supporting information1 | page supporting information boric acid catalyzed chemoselective reduction...

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Supporting InformationBoric acid catalyzed chemoselective reduction of quinolines

Dipanjan Bhattacharyya,‡a Sekhar Nandi,‡a Priyanka Adhikaria, Bikash Kumar Sarmah,a Monuranjan Konwara, and Animesh Das*a

aDepartment of Chemistry, Indian Institute of Technology Guwahati, Guwahati-781039, Assam, India

Email: [email protected]

Table of contents Page No.

1. General Information…………………………………………………………………...2

2. General procedure for transfer hydrogenation reaction…………………………….2

3. Procedure for gram scale transfer hydrogenation reaction………………………....3

4. Procedure for Hantzsch pyridine (HE') to Hantzsch-1,4-dihydropyridine (HE)

recovery………………………………………………………………………………....3

5. Applications of synthesized 1,2,3,4-tetrahydroquinoline derivatives…………….....3

6. Proposed pathway for the reduction of quinoline-6-carbaldehyde…………………7

7. Proposed pathway for the reduction of 4,7-dichloroquinoline……………………...78. Synthesized precursors for bioactive molecules……………………………………...8

9. Reaction mechanism studies………………………………………………………….10

10. Crystallographic data of compound 3f……………………………………………….13

11. Analytical data of the products……………………………………………………….15

12. 1H, 13C, and 19F NMR spectra of the products……………………………………….32

13. References………………………………………………………………………………79

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2020

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1. General Information

All the reagents and chemicals were purchased from common commercial suppliers like Sigma-Aldrich, Alfa Aesar, Merck, Spectrochem, Avra Synthesis Pvt. Ltd. and directly used as received without any further purification unless otherwise mentioned. 2-pentylquinoline,[1] quinolin-2-ylmethanol,[2] 2-styrylquinoline,[3] (E)-2-(3,4-dimethoxystyryl)quinoline,[3] 3-methyl-2-phenylquinoline,[1] methyl quinoline-2-carboxylate,[4] 3-cyanoquinoline,[5] 8-(benzyloxy)quinoline,[6] quinolin-8-yl-4-methylbenzenesulfonate,[7] N-(quinolin-8-yl)acetamide,[8] quinolin-8-ylacetate,[9] 2-(2-benzimidazolyl)quinolone[10] and 2-(quinolin-2-yl)benzo[d]thiazole[10] were prepared according to the reported literature. Boric acid, phenyl boronic acid, and 4-methoxy phenyl boronic acid were purchased from Avra Synthesis Private Ltd and used without further purification. Hantzsch ester was prepared according to the reported literature.[11] All the transfer hydrogenation reactions were performed in a pyrex tube and were carried out under air. 1H, 13C, 19F, and 11B NMR spectra of the compounds were measured in CDCl3 and DMSO-d6 as a solvent by using TMS as an internal standard. Chemical shifts, δ (in ppm), are reported relative to TMS δ (1H) 0.0 ppm, δ (13C) 0.0 ppm) which was used as the inner reference. Otherwise the solvents residual proton resonance and carbon resonance (CHCl3, δ (1H) 7.26 ppm, δ (13C) 77.16 ppm; DMSO-d6, (1H) 2.50 ppm, δ (13C) 39.52 ppm) were used for calibration. Bruker Avance III 600 and 400 spectrometers were used to record the NMR spectra. Chemical shifts (δ) are reported in ppm and spin-spin coupling constant (J) are expressed in Hz, and other data are reported as follows: s = singlet, d = doublet, dd = doublet of doublet, dt = doublet of triplet, t = triplet, m = multiplet, q = quartet, sext = sextet, br = broad, and brs = broad singlet. IR spectra were recorded on Perkin Elmer Instrument at normal temperature making KBr pellet grinding the sample with KBr (IR Grade). MS (ESI-HRMS): Mass spectra were recorded on an Agilent Accurate-Mass Q-TOF LC/MS 6520. Merck or Spectrochem silica gel 60-120 was used for column chromatography.

2. General procedure for transfer hydrogenation reaction

NR1

R2

NH

R1

R2B(OH)3 (15 mol%)

60 oC, DCEHE (2.5 equiv.)

1 2

Scheme S1: Transfer hydrogenation of substituted quinolines.

In a pyrex tube (15 mL), substituted quinoline (0.5 mmol), Hantzsch ester (2.5 equiv.), B(OH)3 (15 mol%) and solvent (2 mL) were charged. The reaction tube was closed, without the exclusion of air and placed in a preheated oil bath (60 oC) with continuous stirring. The reaction was monitored by thin layered chromatography (TLC) in n-hexane and ethyl acetate solvent system. After completion of the reaction, the crude compound was purified by column chromatography on silica gel for pure compound.

Note: 1,2,3,4-THQ’s are highly iodine active and easily identified in a reaction mixture.

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3. Procedure for gram scale transfer hydrogenation reaction

B(OH)3 (15 mol%)

12a,95%

NHN

DCE, 60 oC, 15 h2.5 equiv. Hantzsch ester

1 g scale

Scheme S2: Gram scale transfer hydrogenation of quinoline.

In a pyrex tube (100 mL), quinoline (1.09 gm, 8.46 mmol), Hantzsch ester (5.35 gm, 2.5 eqv.), B(OH)3 (79 mg, 15 mol%) and DCE (15 mL) were charged. The reaction tube was closed, without the exclusion of air and placed in a preheated oil bath (60 oC) with continuous stirring. The reaction was monitored by thin layered chromatography (TLC) in hexane and ethyl acetate solvent system. Once the reaction was complete, reaction tube was brought to room temperature and purified by column chromatography for pure product. The final product was then analysed by 1H and 13C NMR. Isolated yield: 1.07 gm, 95%.

4. Procedure for Hantzsch pyridine (HE') to Hantzsch-1,4-dihydropyridine (HE) recovery

NH

CO2EtEtO2C

Me MeN

CO2EtEtO2C

Me Me

NaBH3CN (1.5 eqv.)

CH3CO2H (20 mol%)H2O, ice bath

HE' HE, 91%

Scheme S3: Reduction of Hantzsch pyridine ester to Hantzsch-1,4-dihydropyridine ester.

In a 50 mL round bottom flask, Hantzsch pyridine (1 gm, 3.9 mmol), water (10 mL) and acetic acid (45 μL, 20 mol%) were charged and placed in an ice bath. In the reaction mixture NaBH3CN (294 mg, 1.2 eqv.) was slowly added and stirred for overnight. The reaction was monitored by thin layered chromatography (TLC) in hexane and ethyl acetate solvent system. Once the reaction was completed, solid precipitate was filtered, washed thoroughly by water and ice cold acetone and dried on vacuum desiccator. Isolated yield: 0.9 g, 91%.

5. Applications of synthesized 1,2,3,4-tetrahydroquinoline derivatives

5.1 Synthesis of nicainoprol

Transfer hydrogenation of 8-hydroxyquinoline to 8-hydroxy-1,2,3,4-tetrahydroquinoline

In a pyrex tube (100 mL), 8-hydroxyquinoline (1 g, 6.8 mmol, 1 eqv.), Hantzsch ester (4.3 g, 17 mmol, 2.5 eqv.), B(OH)3 (15 mol%) and DCE (15 mL) were charged. The reaction tube was closed, without the exclusion of air and placed in a preheated oil bath (60 oC) with continuous stirring. The reaction was monitored by thin layered chromatography (TLC) in n-hexane and ethyl acetate solvent system. Once the reaction was completed, reaction tube was brought to room temperature and purified by silica column chromatography using CH2Cl2/ MeOH mixture to get the pure 8-hydroxy-1,2,3,4-tetrahydroquinoline (2n). Isolated yield: 0.882 g, 87%, colourless oil.

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Hantzsch esterNOH

NHOH

NOH

O

N

NO

OHHN O

Nnicainoprol

1n 2n, 87% 5, 82%

6

B(OH)3 (15 mol%)

DCE, 60 oC, air

dry toluene, NEt3, rt

N

O

Cl

i) epichlorohydrin, KOtBu,dry DMF, 5 oC to rt, 24 h

ii) iPrNH2, EtOH, 60 oC72%

Scheme S4: Synthesis of nicainoprol.

Synthesis of compound 5

In a 50 mL schlenk flask, 8-hydroxy-1,2,3,4-tetrahydroquinoline (0.6 g, 4.02 mmol,1 eqv.), nicotinoyl chloride (0.681 g, 4.83 mmol, 1.2 eqv.), triethyl amine (0.611 g, 6.04 mmol, 1.5 eqv.) and dry toluene (20 mL) were charged and stirred overnight in argon atmosphere at room temperature. Once the reaction was complete, toluene was evaporated by using rotary evaporator. The solid reaction crude was purified by liquid-liquid separation method (water/ ethyl acetate), the organic layer was added with Na2SO4 to remove the excess water and concentrated in a rotary evaporator. Afterwards, the solid crude was purified by silica column chromatography using CH2Cl2 : MeOH (5-10% MeOH mixture) solvent system to obtain pure product as white solid (838 mg, 82%); m.p: 121~122 °C.

Synthesis of compound 6

In a 50 mL schlenk flask, compound 5 (0.125 g, 0.49 mmol, 1 eqv.) was dissolved in dry DMF (0.5 mL) and potassium tert-butoxide (0.066 g, 0.59 mmol, 1.2 eqv.) was charged onto it. The entire solution was stirred in ice cold bath (~0-5 oC) for 30 min followed by the dropwise addition of epichlorohydrin (0.068 g, 0.735 mmol, 1.5 eqv.). After complete addition the reaction mixture was continue to stir at ice cold bath for next 30 minutes and then allowed warm to room temperature and stirred for another 24 h. The reaction was monitored by thin layered chromatography (TLC) in CH2Cl2 and methanol solvent system. After completion of the reaction, crude reaction was concentrated in rotary evaporator and purified by using liquid-liquid separation method (water/ ethyl acetate). The organic layer (ethyl acetate fraction) was added with Na2SO4 to remove the excess water and concentrated in a rotary evaporator. Afterwards, the solid crude (0.118 g, 78%) was directly proceeded for the next step without any further purification. The compound was sensitive towards air and moisture, recommendable to store under argon at -20 oC.

In a 50 mL pyrex tube, above crude compound (0.118 g, 0.38 mmol, 1 eqv.) was dissolved in dry ethanol (2 mL) and isopropylamine (0.045 g, 0.76 mmol, 2 eqv.) was charged onto it. The

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tube was closed under argon flow and the entire solution was stirred at 60 oC for 12 hours. The reaction was monitored using thin layered chromatography (TLC). Upon complete consumption of the starting material, the reaction mixture is concentrated in rotary evaporator to remove ethanol and unreacted isopropylamine. Pure compound 6 was obtained by neutral alumina column chromatography using CH2Cl2 : MeOH (4% MeOH mixture) solvent system to obtain pure product as white solid (130 mg, 93%); m.p: 120~122 ℃ . Overall yield in the last step: 75%.

5.2 Synthesis of antitrypanasomal active compound (7)

Hantzsch esterDCE, 60 oC, air

NS

N NH

pyridine, rt

Me Me Me

OO

O2N

B(OH)3 (15 mol%)

O2N SCl

OO

2b, 98%7, 96%

1b

Scheme S5: Synthesis of antitrypanasomal active compound.

Step 1: Transfer hydrogenation of 2-methylquinoline to 2-methyl-1,2,3,4-tetrahydroquinoline

In a pyrex tube (15 mL), 6-methoxyquinoline (159 mg, 1 mmol), Hantzsch ester (633 mg, 2.5 eqv.), B(OH)3 (10 mg, 15 mol%) and dichloroethane (5 mL) were charged. The reaction tube was closed, without the exclusion of air and placed in a preheated oil bath (60 oC) with continuous stirring. The reaction was monitored by thin layered chromatography (TLC) in hexane and ethyl acetate solvent system. Once the reaction was completed, reaction tube was brought to room temperature and purified by column chromatography for pure product. Isolated yield- 144 mg, 98%, colourless oil.

Step 2: Synthesis of 2-methyl-1-((4-nitrophenyl)sulfonyl)-1,2,3,4-tetrahydroquinoline (7)[12]

In a 25 mL round bottom flask, 2-methyl-1,2,3,4-tetrahydroquinoline (100 mg, 0.68 mmol), 4-nitrobenzenesulfonyl chloride (150 mg, 1 eqv.) and pyridine (3 mL) were charged and allowed to stir at room temperature for 20 h. After consuming the substrates, water was added to the reaction mixture and extracted by using ethyl acetate. The organic layer was further washed with diluted HCl solution to remove the pyridine in traces. Afterwards, in the organic layer Na2SO4 was added to remove excess water and finally organic solvent was evaporated by using rotary evaporator. The product was further purified by column chromatography using hexane and ethyl acetate solvent system to obtain the pure product as pale yellow solid (217 mg, 96%); m.p: 160~162 ℃.

5.3 Synthesis of cuspareine (8)

Step 1: Transfer hydrogenation of (E)-2-(3,4-dimethoxystyryl)quinolone (1f) to 2-(3,4-dimethoxyphenethyl)-1,2,3,4-tetrahydroquinoline (2f)

In a pyrex tube (15 mL), (E)-2-(3,4-dimethoxystyryl)quinoline (100 mg, 0.34 mmol), Hantzsch ester (217 mg, 2.5 eqv.), B(OH)3 (4 mg, 15 mol%) and dichloroethane (3 mL) were charged. The reaction tube was closed, without the exclusion of air and placed in a preheated oil bath

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(60 oC) with continuous stirring. The reaction was monitored by thin layered chromatography (TLC) in hexane and ethyl acetate solvent system. Once the reaction was complete, reaction tube was brought to room temperature (30 oC) and purified by column chromatography for pure product. Isolated yield- 93 mg, 92%.

Hantzsch ester

B(OH)3 (15 mol%)

DCE, 60 oC, air

N OMe

OMeMe

Cuspareine8, 95%

NH

OMe

OMe

K2CO3, MeITHF, reflux

N OMe

OMe1f 2f, 92%

Scheme S6: Synthesis of (±) cuspareine.

Step 2: Synthesis of 2-(3,4-dimethoxyphenethyl)-1-methyl-1,2,3,4-tetrahydroquinoline (8)[13]

In a pyrex tube (15 mL), 2-(3,4-dimethoxyphenethyl)-1,2,3,4-tetrahydroquinoline (50 mg, .17 mmol), methyl iodide (32 μL, 3 eqv.), potassium carbonate (1 eqv.) and dry THF (3 mL) were charged. The reaction mixture was allowed to reflux in a pre-heated oil bath for 20 h. Once the substrates were consumed, THF was evaporated using rotary evaporator and directly purified by column chromatography (n-hexane/ ethyl acetate) to afford the pure product as yellow oil (50 mg, 95%).

5.4 Synthesis of tubulin polymerization inhibitor (9)

Hantzsch ester N

MeO

OMeO

MeOOMe

N NH

MeO MeO pyridine, rt

OMeO

MeOOMe

Cl

B(OH)3(15 mol%)

DCE, 60 oC, air2k, 95% 9, 92%

1k

Scheme S7: Synthesis of tubulin polymerization inhibitor.

Step 1: Transfer hydrogenation of 6-methoxyquinoline to 6-methoxy-1,2,3,4-tetrahydroquinoline

In a pyrex tube (15 mL), 6-methoxyquinoline (159 mg, 1 mmol), Hantzsch ester (633 mg, 2.5 eqv.), B(OH)3 (10 mg, 15 mol%) and dichloroethane (5 mL) were charged. The reaction tube was closed, without the exclusion of air and placed in a preheated oil bath (60 oC) with continuous stirring. The reaction was monitored by thin layered chromatography (TLC) in

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hexane and ethyl acetate solvent system. Once the reaction was complete, reaction tube was brought to room temperature and purified by column chromatography for pure product 2k. Isolated yield: 155 mg, 95%.

Step 2: Synthesis of compound 9[14]

In a 50 mL schlenk flask, 6-methoxy-1,2,3,4-tetrahydroquinoline (100 mg, 0.61 mmol), was dissolved in pyridine (2 mL). Next, 3,4,5-trimethoxybenzoyl chloride (0.92 mmol, 1.5 eqv.) was added to the above solution and resulting mixture was allowed to stir at room temperature for overnight. Once the reaction was completed, water was added to the reaction mixture and extracted by using ethyl acetate. The organic layer was further washed with diluted HCl solution to remove the pyridine in traces. Afterwards, in the organic layer Na2SO4 was added to remove excess water and finally organic solvent was evaporated by using rotary evaporator. The product was further purified by column chromatography using hexane and ethyl acetate solvent system to obtain the pure product as light yellow viscous liquid (200 mg, 92%).

6. Proposed pathway for the reduction of quinoline-6-carbaldehyde

The reduction of quinoline-6-carbaldehyde possibly possesses in stepwise manner, first, both quinoline ring and carbaldehyde unit were reduced to give intermediate I-1, then converted to 6-methylene-2,3,4,6-tetrahydroquinoline (I-2) via hydroxo-group liberation by the activation of boric acid, subsequently further reduction leads to 6-methyl-1,2,3,4-tetrahydroquinoline 2j.

B(OH)3 (15 mol%)

NHN

DCE, 60 oC, 7 hHantzsch ester

OHC HO

1'v I-1N

H

H

I-2

NH

H3C

2j

Scheme S8: Proposed pathway for the reduction of quinoline-6-carbaldehyde

7. Proposed pathway for the reduction of 4,7-dichloroquinoline

The proposed pathway for the reduction of 4,7-dichloroquinoline is given below.

B(OH)3 (15 mol%)

N 3.5 eqv. Hantzsch esterDCE, 60 oC, 7 h

NH

3h, 91%

proposed pathway-2

Cl

Cl Cl

NH

Cl-HE' HCl

NH

Cl

Cl

H

N

Cl

Cl

H

NCl-HE' HCl

proposed pathway-1

NH

Cl

Cl

H

Scheme S9: Proposed pathway for the reduction of 4,7-dichloroquinoline

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8. Synthesized precursors for bioactive molecules

Table S1: Some reduced quinoline compound as an active intermediate for the synthesis of biological active molecules.

Entry 1,2,3,4-THQderivative

Bioactive compound Application Ref.

1 NH2a

N

ON

NO

N

Aspernigerin, Natural alkaloid 15

2 NH2b

N MeS O

O

O2N

Anti trypanasomal

activity12

3 NH 42c

N4Me

(±)Angustureine Natural alkaloid 16

4 2f N OMe

OMeMe

Cuspareine(natural

alkaloids)13

5NH

Me

2iN

Me

O

CNS depressant agent 17

6 NH

MeO

2k

N

MeO

OMeO

MeOOMe

Tubulin polymerization

Inhibitor14

7 NH

HO

2lN

O

SOO

N3 Histanime H3-

Receptor antagonist

18

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8 NH

HO

2l

N

O

O

HN

4AChE inhibitor 19

9 NHOH 2n

NO OMe

Oxygen radical scavenger 20

10 NH

F

Me3g

N

F

Me

COOHO

Flumequine antibiotic 21

9. Reaction mechanism studies

9.1 Observations from substrate scope studies

N

Br

N

CN

N

Cl

Cl

NH

Br

NH

CN

NH

Cl

Reaction 1

Reaction 2

Reaction 3

DCE, 60 oCHantzsch ester

B(OH)3 (15 mol%)


B(OH)3 (15 mol%)


B(OH)3 (15 mol%)

1'c 3c

1'd 3d

3h1'h

Scheme S10: Transfer hydrogenation of 3-bromo, 3-cyano and 4,7-dichloroquinoline with Hantzsch ester.

While conducting the substrate scope studies, few substrates like 3-bromo, 3-cyano and 4,7-dichloroquinolines surprises us because 4,7-dicholoroquinoline ends with 7-chloro-1,2,3,4-tetrahydroquinoline, whereas 3-bromo quinoline gives 3-bromo-1,2,3,4-tetrahydro quinoline and no dehalogenated product. However, the reaction of 3-cyanoquinoline experiment ends with 3-cyano-1,4-dihydroquinoline which might be due to stabilization of conjugation of π electrons. These results suggest, the reaction might proceed via 1,4 addition of hydride into quinoline moiety.

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9.2 1H NMR spectrum of crude reaction mixture

Further, with close inspection of 1H NMR spectrum of reaction mixture, we found two of the interesting peaks at δ = 4.65 and 3.43 ppm (H3 and H4 respectively). The chemical shifts are well matched with the previous report[22] and probably due to the presence of 1,4-dihydroquinoline as an intermediate on the crude reaction.

Figure S1: 1H NMR spectra of quinoline reduction crude. NMR experiment and reaction conditions: In a quartz NMR tube, quinoline (54 mg, 0.42 mmol), Hantzsch ester (2.5 eqv.), B(OH)3 (15 mol%), CDCl3 (600 μL) were charged. The NMR tube was properly closed and placed in a preheated oil bath (50 oC) for 1 h. Then, the reaction crude was analysed by 1H NMR at 50 oC in 400 MHz Bruker NMR instrument.

9.3 Interactions between quinoline, catalyst and Hantzsch ester (1H and 11B NMR)

9.3A. The reaction conditions for the 1H and 11B NMR experiment of quinolines, phenyl boronic acid and Hantzsch ester

The reaction conditions for the 1H NMR experiment of quinolines and phenyl boronic acid: In a quartz NMR tube, quinoline (26 mg, 0.2 mmol), PhB(OH)2 (24 mg, 0.2 mmol), CDCl3 (600 μL) were charged. The NMR tube was properly closed and placed in a preheated oil bath (50 oC) for 1 h. Then, the reaction crude was analysed by 1H NMR at 50 oC in 400 MHz Bruker NMR instrument.

The reaction conditions for the 11B NMR experiment of phenyl boronic acid and Hantzsch ester: In a quartz NMR tube, Hantzsch ester (86 mg, 0.34 mmol), PhB(OH)2 (12 mg, 0.1 mmol), CDCl3 (600 μL) were charged. The NMR tube was properly closed and placed in a preheated oil bath (50 oC) for 1 h. Then, the reaction crude was analysed by 1H NMR at 50 oC in 400 MHz Bruker NMR instrument.

The reaction conditions for the 11B NMR experiment of phenyl boronic acid and quinolines: In a quartz NMR tube, quinoline (44 mg, 0.34 mmol), PhB(OH)2 (12 mg, 0.1 mmol), CDCl3 (600 μL) were charged. The NMR tube was properly closed and placed in a preheated oil bath (50 oC) for 1 h. Then, the reaction crude was analysed by 1H NMR at 50 oC in 400 MHz Bruker NMR instrument.

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9.3B. 1H NMR experiment of phenyl boronic acid and Hantzsch ester

B OH

OH

NH

EtO2C CO2Et

Me Me

NH

EtO2C CO2Et

Me MeB OH

OH+

a

b

c

Figure S2: Comparative 1H NMR spectra of (a) phenylboronic acid; (b) Hantzsch ester; and (c) combination of phenylboronic acid with Hantzsch ester (NMR experiment and reaction conditions: In a quartz NMR tube, Hantzsch ester (50 mg, 0.2 mmol), PhB(OH)2 (24 mg, 0.2 mmol), CDCl3 (600 μL) were charged. The NMR tube was properly closed and placed in a preheated oil bath (50 oC) for 1 h. Then, the reaction crude was analysed by 1H NMR at 50 oC in 400 MHz Bruker NMR instrument).

9.4 Deuterium-labelling experiment

Reaction conditions: In a pyrex tube (15 mL), substituted quinoline (1 mmol), Hantzsch ester (2.5 eqv.), B(OH)3 (15 mol%), dichloroethane (3 mL) and D2O (0.60 mmol) were charged. The reaction tube was closed, without the exclusion of air and placed in a preheated oil bath (60 oC) with continuous stirring. The reaction was monitored by thin layered chromatography (TLC) in n-hexane and ethyl acetate solvent system. Once the reaction complete, reaction tube was brought to room temperature and purified by column chromatography for pure compound. The final product was then analysed by 1H and 13C NMR.

N

B(OH)3 (15 mol%)

HE (2.5 eqv.)60 oC, DCE, D2O1a

2a'

NH/D

NH/D

D

D-2a

+

N

B(OH)3 (15 mol%)

HE (2.5 eqv.)60 oC, DCE, D2O1g

NH/D

D-2g

D (59%)

NH/D2g'

H+

96% yield

95% yield

a)

b)

Scheme S10: Deuterium labelled experiment for quinoline (a) and 3-methyl quinolone (b).

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1H NMR spectrum of deuterated 1,2,3,4-tetrahydroquinoline (2a' + D-2a):1H NMR (600 MHz, Chloroform-d): δ 6.96–6.92 (m, 4H, 2a' + D-2a), 6.60–6.58 (t, J = 7.3 Hz, 2H, 2a' + D-2a), 6.45–6.44 (d, J = 7.9 Hz, 2H, 2a' + D-2a), 3.66 (br, 2H, 2a' + D-2a), 3.27–3.25 (m, 4H, 2a' + D-2a), 2.76–2.73 (t, J = 6.8 Hz, 2H, 2a' + D-2a), 1.94–1.90 (m, 3H, 2a' + D-2a)

1H NMR spectrum of deuterated 3-methyl-1,2,3,4-tetrahydroquinoline (2g' + D-2g):1H NMR (400 MHz, Chloroform-d): δ 6.97-6.92 (dd, J = 12.6, 7.1 Hz, 4H, 2g' + D-2g), 6.61–6.57 (m, 2H, 2g' + D-2g), 6.47–6.45 (d, J = 7.9 Hz, 2H, 2g' + D-2g), 3.52 (br, 2H, 2g' + D-2g), 3.26-3.22 (m, 2H, 2g' + D-2g), 2.90–2.85 (m, 2H, 2g' + D-2g), 2.79–2.73 (m, 2H, 2g' + D-2g), 2.45–2.39 (m, 2H, 2g' + D-2g), 2.07–2.02 (m, 1H, 2g') 1.04 (s, 6H, 2g' + D-2g).

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

1E+05

1E+05

1E+05

5.8

6

0.8

2

1.9

2

1.9

21

.91

2.0

0

1.2

6

1.5

51

.67

3.5

5

1.0

21

.04

2.3

92

.41

2.4

32

.45

2.7

32

.74

2.7

72

.85

2.8

62

.87

2.8

82

.90

3.2

23

.23

3.2

33

.24

3.2

53

.25

3.2

63

.26

3.5

2

6.4

56

.47

6.5

76

.58

6.5

96

.59

6.6

16

.61

6.9

26

.94

6.9

56

.97

7.2

1

NH/D

D-2g

D (59%)

NH/D2g'

H+

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

-5000

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

50000

55000

2.8

3

4.0

6

4.0

0

1.0

6

1.8

31

.85

3.7

5

1.9

01

.91

1.9

21

.93

1.9

4

2.7

32

.74

2.7

63

.25

3.2

63

.27

3.6

6

6.4

46

.45

6.5

86

.59

6.6

06

.92

6.9

46

.95

6.9

67

.19

2a'

NH/D

NH/D

D

D-2a

+

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13C NMR spectrum of deuterated 3-methyl-1,2,3,4-tetrahydroquinoline (2g' + D-2g):13C NMR (101 MHz, Chloroform-d): δ 144.39, 129.63, 126.79, 126.68, 121.22, 117.02, 113.97, 48.95, 48.85, 35.58, 35.46, 27.28, 27.03, 26.83, 26.63, 19.14, 19.03.

10. Crystallographic study of compound 3f

The crystal was obtained by crystallisation of compound 3f in the presence of chloroform as solvent at room temperature using slow evaporation technique. X-ray crystallographic data were collected using Supernova, single source at offset, Eos diffractometer. Data refinement and cell reduction were carried out by CrysAlisPro. Structures were solved by direct methods using SHELXL-2014/7 and WinGX and refined by a full-matrix least-squares method using SHELXL-2014/7. All of the non-H atoms were refined anisotropically. The ORTEP diagram was obtained with the help of ORTEP software with 40% thermal ellipsoid (see in below, Figure S5). The crystallographic parameters and refinement data were listed in Table S2.

Figure S3: Molecular structure of compound 3f (thermal ellipsoid 40% probability level).

2030405060708090100110120130140f1 (ppm)

-1000

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

19

.03

19

.14

26

.63

26

.83

27

.03

27

.28

35

.46

35

.58

48

.85

48

.95

76

.84

77

.16

77

.48

11

3.9

71

17

.02

12

1.2

2

12

6.6

81

26

.79

12

9.6

3

14

4.3

9

NH/D

D-2g

D (59%)

NH/D2g'

H+

14 | P a g e

Selected bond lengths (in Å): O(2)-N(2) 1.236(2), O(1)-N(2) 1.237(2), N(1)-C(9) 1.354(2), N(1)-C(1) 1.450(2), C(4)-C(5) 1.377(3), C(4)-C(9) 1.426(3), C(4)-C(3) 1.505(2), C(9)-C(8) 1.402(2), C(5)-C(6) 1.386(3), C(6)-C(7) 1.396(3), C(8)-C(7) 1.365(3), C(1)-C(2) 1.508(3), C(3)-C(2) 1.520(3).

Table S2. Crystal data and structure refinement for 3fIdentification code shelxCCDC: 1946184Empirical formula C9H10N2O2

Formula weight 178.19Temperature 293(2) KWavelength 0.71073 ÅCrystal system MonoclinicSpace group P21/nUnit cell dimensions a = 7.5569(7) Å α = 90°.

b = 7.5729(6) Å β = 101.729(9)°.c = 15.4076(14) Å γ = 90°.

Volume 863.33(13) Å3

ZDensity (calculated) 1.371 Mg/m3

Absorption coefficient 0.099 mm-1

F(000) 376Crystal size 0.35 × 0.32 × 0.30 mm3

Theta range for data collection 2.700 to 24.982°.Index ranges -8<=h<=5, -5<=k<=9, -12<=l<=18Reflections collected 2994Independent reflections 1513 [R(int) = 0.0277]Completeness to theta = 25.242° 97.7 % Refinement method Full-matrix least-squares on F2

Data / restraints / parameters 1513 / 0 / 120Goodness-of-fit on F2 1.139Final R indices [I>2sigma(I)] R1 = 0.0528, wR2 = 0.1192R indices (all data) R1 = 0.0690, wR2 = 0.1387Extinction coefficient n/aLargest diff. peak and hole 0.185 and -0.244 e.Å-3

15 | P a g e

11. Analytical data of the products

1,2,3,4-tetrahydroquinoline (2a)

NH

Colourless oil (65 mg, 98%). 1H NMR (400 MHz, Chloroform-d): δ 6.97 – 6.93 (m, 2H), 6.59 (t, J = 7.4 Hz, 1H), 6.46 (d, J = 7.9 Hz, 1H), 3.30 – 3.28 (m, 2H), 2.76 (t, J = 6.4 Hz, 2H), 1.96 – 1.90 (m, 2H). 13C NMR (101 MHz, Chloroform-d): δ 144.89, 129.64, 126.84, 121.59, 117.08, 114.32, 42.12, 27.09, 22.31. Spectral data is in accordance with the literature.[14]

2-methyl-1,2,3,4-tetrahydroquinoline (2b)

NH

Me

Colourless oil (72 mg, 98%). 1H NMR (400 MHz, Chloroform-d): δ 6.97 – 6.93 (m, 2H), 6.61 – 6.57 (m, 1H), 6.46 – 6.44 (m, 1H), 3.64 (brs, 1H), 3.42 – 3.34 (m, 1H), 2.87-2.79 (m, 1H), 2.74 – 2.68 (m, 1H), 1.94 – 1.88 (m, 1H), 1.62 – 1.53 (m, 1H), 1.20 (d, J = 6.3 Hz, 3H). 13C NMR (101 MHz, Chloroform-d): δ 144.79, 129.26, 126.68, 121.05, 116.95, 114.02, 47.14, 30.14, 26.61, 22.60. Spectral data is in accordance with the literature.[14]

2-pentyl-1,2,3,4-tetrahydroquinoline (2c)

NH

Colourless oil (92 mg, 91%). Isolated yield: 91%. 1H NMR (400 MHz, Chloroform-d): δ 6.97 – 6.93 (m, 2H), 6.59 (td, J = 7.4, 1.2 Hz, 1H), 6.47 (dd, J = 8.4, 1.3 Hz, 1H), 3.76 (brs, 1H), 3.23 (dtd, J = 9.5, 6.3, 2.9 Hz, 1H), 2.87 – 2.66 (m, 2H), 1.99 – 1.93 (m, 1H), 1.49-1.26 (m, 8H), 1.59 – 1.49 (m, 1H), 0.91 (t, J = 6.8 Hz, 3H). 13C NMR (101 MHz, Chloroform-d): δ 144.77, 129.39, 126.84, 121.63, 117.12, 114.25, 51.78, 36.79, 32.10, 28.25, 26.57, 25.55, 22.79, 14.19. Spectral data is in accordance to the reported literature.[23]

(1,2,3,4-tetrahydroquinolin-2-yl) methanol (2d)

NH

CH2OH

Pale yellow oil (70 mg, 87%). 1H NMR (400 MHz, Chloroform-d): δ 7.00 – 6.95 (m, 2H), 6.63 (td, J = 7.4, 1.2 Hz, 1H), 6.54 (dd, J = 7.9, 1.2 Hz, 1H), 3.75 (dd, J = 10.4, 3.8 Hz, 1H), 3.56 (dd, J = 10.4, 7.7 Hz, 1H), 3.47 – 3.44 (m, 1H), 2.84 (ddd, J = 16.4, 10.8, 5.6 Hz, 1H), 2.74 (dt, J = 16.3, 4.9 Hz, 1H), 1.90 (dddd, J = 13.1, 5.6, 4.3, 3.2 Hz, 1H), 1.71 (dddd, J = 12.9, 10.8,

16 | P a g e

9.4, 5.4 Hz, 1H). 13C NMR (101 MHz, Chloroform-d): δ 144.27, 129.37, 127.02, 121.58, 117.61, 114.68, 66.90, 52.90, 26.03, 24.46. Spectral data is in accordance to the reported literature.[24]

2-phenethyl-1,2,3,4-tetrahydroquinoline (2e)

NH

Started with a conjugated double bond containing substrate 2-styrylquinoline. For this, 3.5 equiv. of Hantzsch ester was used. White sticky liquid (105 mg, 89%). 1H NMR (400 MHz, Chloroform-d): δ 7.31 – 7.27 (m, 2H), 7.24 – 7.18 (m, 3H), 6.97-6.93 (m, 2H), 6.60 (t, J = 7.3 Hz, 1H), 6.44 (d, J = 7.8 Hz, 1H), 3.74 (brs, 1H), 3.31-3.28 (m, 1H), 2.79 – 2.72 (m, 4H), 1.99 (ddd, J = 16.0, 8.3, 4.6 Hz, 1H), 1.86 – 1.80 (m, 2H), 1.69 –1.65 (m, 1H). 13C NMR (101 MHz, Chloroform-d): δ 144.65, 141.98, 129.38, 128.62, 128.49, 126.87, 126.10, 121.42, 117.16, 114.27, 51.25, 38.39, 32.31, 28.12, 26.35. Spectral data is in accordance with the literature.[25]

2-(3,4-dimethoxyphenethyl)-1,2,3,4-tetrahydroquinoline (2f)

NH

OMe

OMe

Started with a conjugated double bond containing substrate (E)-2-(3,4-dimethoxy styryl)quinoline. For this, 3.5 equiv. of Hantzsch ester was used. Yellow sticky solid (136 mg, 92%); m.p: 52~54 ᵒC. 1H NMR (600 MHz, Chloroform-d): δ 6.96 – 6.94 (m, 2H), 6.79 (d, J = 8.1 Hz, 1H), 6.74 (d, J = 8.1 Hz, 1H), 6.73 (d, J = 1.6 Hz, 1H), 6.60 (t, J = 7.3 Hz, 1H), 6.44 (d, J = 7.7 Hz, 1H), 3.87 (s, 3H), 3.85 (s, 3H), 3.29 (td, J = 9.2, 6.4 Hz, 1H), 2.79 (dd, J = 10.6, 5.5 Hz, 1H), 2.76 – 2.72 (m, 1H), 2.68 (t, J = 8.0 Hz, 2H), 1.99 (dd, J = 8.7, 3.4 Hz, 1H), 1.80 (td, J = 8.9, 7.4, 3.4 Hz, 2H), 1.69 (dd, J = 10.5, 5.3 Hz, 1H). 13C NMR (151 MHz, Chloroform-d) δ 148.94, 147.30, 144.57, 134.51, 129.32, 126.80, 121.34, 120.16, 117.08, 114.20, 111.62, 111.30, 55.99, 55.89, 51.25, 38.49, 31.88, 28.06, 26.26. Spectral data is in accordance with the literature.[13]

3-methyl-1,2,3,4-tetrahydroquinoline (2g)

NH

Me

Colourless oil (71 mg, 96%). 1H NMR (400 MHz, Chloroform-d): δ 6.96-6.93 (m, 2H), 6.60 (t, J = 6.9 Hz, 1H), 6.48 (d, J = 7.9 Hz, 1H), 3.84 (brs, 1H), 3.26 (ddd, J = 11.0, 3.6, 2.0 Hz, 1H), 2.91 – 2.86 (m, 1H), 2.77 (ddd, J = 16.0, 4.8, 1.6 Hz, 1H), 2.43 (dd, J = 16.0, 10.3 Hz,

17 | P a g e

1H), 2.07 – 1.98 (m, 1H), 1.04 (d, J = 6.6 Hz, 3H). 13C NMR (101 MHz, Chloroform-d): δ 144.39, 129.62, 126.78, 121.19, 117.00, 113.96, 48.94, 35.57, 27.28, 19.14. Spectral data is in accordance with the literature.[14]

3-methyl-2-phenyl-1,2,3,4-tetrahydroquinoline (2h)

NH

Ph

Me

White solid (99 mg, 89%); m.p: 84~86 ᵒC. cis : trans = 10:1. 1H NMR (400 MHz, Chloroform-d): δ 7.32 – 7.22 (m, 5H, major + minor), 7.04 – 6.98 (m, 2H, major + minor), 6.65 (td, J = 7.4, 1.2 Hz, 1H, major + minor), 6.54 (dd, J = 8.0, 1.2 Hz, 1H, minor major + minor), 4.50 (d, J = 3.6 Hz, 1H, major, 90%), 4.39 (d, J = 3.6 Hz, 1H, minor, 10%), 4.11 (brs, 1H, major, 90%), 3.94 (d, J = 12.4 Hz, 1H, minor, 10%), 3.38 (d, J = 12.4 Hz, 1H, minor, 10%), 2.96 (dd, J = 16.1, 5.0 Hz, 1H, major, 90%), 2.49 (dd, J = 16.1, 6.8 Hz, 2H, major 90% + minor 10%), 2.44-2.39 (m, 1H, minor, 10%), 2.31-2.28 (m, 1H, major, 90%), 0.88 (d, J = 6.4 Hz, 3H, minor, 10%), 0.81 (d, J = 6.9 Hz, 3H, major, 90%). 13C NMR (101 MHz, Chloroform-d): δ 144.28, 143.05, 129.83, 128.24, 127.29, 127.23, 127.00, 120.14, 117.19, 113.79, 59.48, 33.50, 32.01, 15.27 (for major 90%). HRMS (ESI) m/z: calculated for C16H18N (M+H+): 224.1434; found: 224.1446. Spectral data is in accordance to the literature.[26] The relative cis- configuration was tentatively assigned by comparison with literature data.[26]

4-methyl-1,2,3,4-tetrahydroquinoline (2i)

NH

Me

Colourless oil (69 mg, 94%). 1H NMR (400 MHz, Chloroform-d): δ 7.05 (d, J = 7.5 Hz, 1H), 6.96 (t, J = 7.3 Hz, 1H), 6.63 (t, J = 7.4 Hz, 1H), 6.47 (d, J = 7.9 Hz, 1H), 3.36-3.27 (m, 2H), 2.94 – 2.89 (m, 1H), 2.02 – 1.95 (m, 1H), 1.71 – 1.65 (m, 1H), 1.29 (d, J = 6.9 Hz, 3H). 13C NMR (101 MHz, Chloroform-d): δ 144.39, 128.58, 126.87, 126.78, 117.11, 114.31, 39.17, 30.38, 30.04, 22.76. Spectral data is in accordance to the reported literature.[14]

6-methyl-1,2,3,4-tetrahydroquinoline (2j)

NH

Me

Colourless oil (71 mg, 97%). 1H NMR (400 MHz, Chloroform-d): δ 6.78 – 6.76 (m, 2H), 6.39 (d, J = 8.6 Hz, 1H), 3.43 (brs, 1H), 3.31 – 3.20 (m, 2H), 2.72 (t, J = 6.5 Hz, 2H), 2.19 (s, 3H), 1.94 – 1.88 (m, 2H). 13C NMR (101 MHz, Chloroform-d): δ 142.52, 130.16, 127.34, 126.33,

18 | P a g e

121.69, 114.56, 42.29, 27.02, 22.55, 20.50. Spectral data is in accordance to the reported literature.[27]

6-methoxy-1,2,3,4-tetrahydroquinoline (2k)

NH

MeO

Colourless oil (77 mg, 95%). 1H NMR (400 MHz, Chloroform-d): δ 6.60 – 6.55 (m, 2H), 6.45 – 6.43 (d, J = 8.5 Hz, 1H), 3.72 (s, 3H), 3.26 – 3.23 (m, 2H), 3.14 (brs, 1H), 2.75 (t, J = 6.5 Hz, 2H), 1.95-1.89 (m, 2H). 13C NMR (101 MHz, Chloroform-d): δ 151.97, 138.97, 123.03, 115.71, 115.02, 113.03, 55.94, 42.46, 27.28, 22.56. Spectral data is in accordance to the reported literature.[27]

6-hydroxy-1,2,3,4-tetrahydroquinoline (2l)

NH

HO

White solid (65 mg, 88%); m.p: 160~162 ᵒC. 1H NMR (400 MHz, DMSO-d6): δ 8.47 (s, 1H), 6.47 – 6.34 (m, 3H), 3.10 – 3.07 (m, 2H), 2.58 (t, J = 6.4 Hz, 2H), 1.79 – 1.73 (m, 2H). 13C NMR (101 MHz, DMSO-d6): δ 149.30, 135.57, 123.05, 116.33, 115.66, 113.69, 41.43, 26.43, 21.64. Spectral data is in accordance to the reported literature.[28]

8-methyl-1,2,3,4-tetrahydroquinoline (2m)

NHMe

Colourless oil (70 mg, 95%). 1H NMR (400 MHz, Chloroform-d): δ 6.88 – 6.84 (m, 2H), 6.55 (t, J = 7.4 Hz, 1H), 3.65 (brs, 1H), 3.38 – 3.36 (m, 2H), 2.79 (t, J = 6.4 Hz, 2H), 2.07 (s, 3H), 1.97-1.91 (m, 2H). 13C NMR (101 MHz, Chloroform-d): δ 142.81, 127.95, 127.49, 121.29, 120.98, 116.50, 42.46, 27.40, 22.27, 17.27. Spectral data is in accordance to the reported literature.[14]

8-hydroxy-1,2,3,4-tetrahydroquinoline (2n)

NHOH

White solid (65 mg, 87%); m.p: 120~122 ᵒC. 1H NMR (400 MHz, DMSO-d6): δ 8.94 (s, 1H), 6.45 – 6.26 (m, 3H), 4.60 (s, 1H), 3.20 (brs, 2H), 2.63 (brs, 2H), 1.78 (brs, 2H). 13C NMR (101

19 | P a g e

MHz, DMSO-d6): δ 143.18, 133.73, 120.37, 119.86, 114.71, 111.39, 40.80, 26.43, 21.79. Spectral data is in accordance to the reported literature.[28]

2-methyl-1,2,3,4-tetrahydroquinolin-8-ol (2o)

NHOH

Me

White solid (69 mg, 85%); m.p: 75~77 ᵒC. 1H NMR (400 MHz, Chloroform-d): δ 6.60 – 6. 46 (m, 3H), 4.61 (s, 1H), 3.33 (s, 1H), 2.86 – 2.71 (m, 2H), 1.94 – 1.90 (m, 1H), 1.62 – 1.57 (m, 1H), 1.23 – 1.22 (d, J = 6.3 Hz, 3H). 13C NMR (101 MHz, Chloroform-d): δ 142.96, 133.69, 123.28, 121.72, 117.29, 112.75, 47.27, 30.19, 26.44, 22.41. Spectral data is in accordance to the reported literature.[29]

8-amino-1,2,3,4-tetrahydroquinoline (2p)

NHNH2

Brown oil (65 mg, 87%). 1H NMR (400 MHz, Chloroform-d): δ 6.59 – 6.51 (m, 3H), 3.32 – 3.29 (m, 2H), 2.76 (t, J = 6.4 Hz, 2H), 1.93 – 1.87 (m, 2H). 13C NMR (101 MHz, Chloroform-d): δ 133.99, 133.93, 123.31, 121.19, 118.09, 114.15, 42.65, 27.11, 22.48. HRMS (ESI) m/z: calculated for C9H13N2 (M+H+): 149.1073; found: 149.1086. Spectral data is in accordance to the reported literature.[30]

1,2,3,4-tetrahydroquinolin-5-amine (2q)

NH

NH2

Yellow solid (62 mg, 83%); m.p: 96~98 ᵒC. 1H NMR (400 MHz, Chloroform-d): δ 6.81 (t, J = 8.0 Hz, 1H), 6.09 (d, J = 7.9 Hz, 1H), 6.01 (d, J = 8.0 Hz, 1H), 3.26 – 3.23 (m, 2H), 2.85 (s, 1H), 2.48 (t, J = 6.7 Hz, 2H), 2.06 – 1.95 (m, 2H). 13C NMR (101 MHz, Chloroform-d): δ 145.89, 145.05, 127.15, 106.95, 105.71, 104.82, 41.52, 22.48, 21.66. Spectral data is in accordance with literature.[31]

Methyl 1,2,3,4-tetrahydroquinoline-2-carboxylate (3a)

NH

CO2Me

20 | P a g e

Pale yellow oil (85 mg, 89%). 1H NMR (400 MHz, Chloroform-d): δ 7.02 – 6.94 (m, 2H), 6.65 (td, J = 7.4, 1.2 Hz, 1H), 6.59 (dd, J = 8.0, 1.2 Hz, 1H), 4.05 (dd, J = 8.8, 3.8 Hz, 1H), 3.78 (s, 3H), 2.83 – 2.73 (m, 2H), 2.28 (dtd, J = 13.0, 5.6, 3.8 Hz, 1H), 2.01 (dtd, J = 12.9, 9.0, 5.2 Hz, 1H). 13C NMR (101 MHz, Chloroform-d): δ 173.86, 143.08, 129.27, 127.20, 120.69, 117.83, 114.73, 54.06, 52.50, 25.95, 24.85. Spectral data is in accordance to the reported literature.[32]

2-(pyridin-2-yl)-1,2,3,4-tetrahydroquinoline (3b)

NH N

Brown oil (86 mg, 82%). 1H NMR (400 MHz, Chloroform-d): δ 8.58 (d, J = 4.9 Hz, 1H), 7.70 – 7.66 (td, J = 7.7, 1.8 Hz, 1H), 7.43 (d, J = 7.9 Hz, 1H), 7.21 – 7.18 (m, 1H), 7.05 – 6.99 (m, 2H), 6.68 – 6.62 (m, 2H), 4.59 (dd, J = 8.8, 3.5 Hz, 1H), 2.92-2.89 (m, 1H), 2.70 (dt, J = 16.3, 5.2 Hz, 1H), 2.29 – 2.24 (m, 1H), 2.06 – 2.02 (m, 1H). 13C NMR (101 MHz, Chloroform-d): δ 163.22, 149.25, 144.28, 136.91, 129.38, 127.10, 122.32, 121.24, 120.74, 117.43, 114.60, 57.00, 28.90, 26.12. HRMS (ESI) m/z: calculated for C14H15N2 (M+H+): 211.1235; found: 211.1244. Spectral data is in accordance to the reported literature.[25]

3-bromo-1,2,3,4-tetrahydroquinoline (3c)

NH

Br

Brown oil (97 mg, 92%). 1H NMR (400 MHz, Chloroform-d): δ 7.05 – 7.00 (m, 1H), 6.93 (d, J = 7.4 Hz, 1H), 6.67 (td, J = 7.5, 0.9 Hz, 1H), 6.53 (d, J = 7.9 Hz, 1H), 4.52 – 4.46 (m, 1H), 3.65 (ddd, J = 12.1, 3.2, 1.8 Hz, 1H), 3.48 (ddd, J = 12.1, 7.6, 0.9 Hz, 1H), 3.39 (dd, J = 16.5, 4.7 Hz, 1H), 3.19 (dd, J = 16.4, 7.6 Hz, 1H). 13C NMR (101 MHz, Chloroform-d): δ 142.73, 129.58, 127.68, 118.71, 118.20, 114.66, 49.52, 44.32, 37.96. HRMS (ESI) m/z: calculated for C9H11BrN (M+H+): 212.0069; found: 212.0081.

1,4-dihydroquinoline-3-carbonitrile (3d)

NH

CN

White solid (71 mg, 91%); m.p: 106~107 ℃. 1H NMR (400 MHz, Chloroform-d): δ 7.10 – 7.06 (m, 1H), 6.98 – 6.92 (m, 2H), 6.82 (d, J = 5.9 Hz, 1H), 6.58 (d, J = 8.0 Hz, 1H), 6.14 (brs, 1H), 3.72 (s, 2H). 13C NMR (101 MHz, Chloroform-d): δ 139.43, 135.82, 129.48, 127.81, 123.93, 121.24, 118.59, 115.30, 78.06, 27.03. HRMS (ESI) m/z: calculated for C10H9N2 (M+H+): 157.0765; found: 157.0778.

6-chloro-1,2,3,4-tetrahydroquinoline (3e)

21 | P a g e

NH

Cl

Pale yellow sticky liquid (77 mg, 93%). 1H NMR (400 MHz, Chloroform-d): δ 6.89 (s, 1H), 6.87 (d, J = 2.4 Hz, 1H), 6.35(d, J = 8.0 Hz, 1H), 3.76 (brs, 1H), 3.27 – 3.24 (m, 2H), 2.70 (t, J = 6.4 Hz, 2H), 1.92 – 1.86 (m, 2H). 13C NMR (101 MHz, Chloroform-d): δ 143.40, 129.10, 126.58, 122.95, 121.20, 115.17, 41.94, 26.96, 21.83. Spectral data is in accordance to the reported literature.[27]

6-nitro-1,2,3,4-tetrahydroquinoline (3f)

NH

O2N

White solid (77 mg, 87%); m.p: 160~162 ℃. 1H NMR (400 MHz, Chloroform-d): δ 7.90 – 7.87 (m, 2H), 6.36 (m, J = 9.6 Hz,1H), 4.75 (brs, 1H), 3.42 (td, J = 6.0, 2.0 Hz, 2H), 2.79 (t, J = 6.3 Hz, 2H), 1.95 (dt, J = 12.4, 6.1 Hz, 2H). 13C NMR (101 MHz, Chloroform-d): δ 150.52, 137.32, 126.04, 124.41, 119.95, 112.27, 41.85, 27.00, 20.92. Spectral data is in accordance to the reported literature. [33]

6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline (3g)

NH

F

Me

Colourless sticky liquid (73 mg, 89%). 1H NMR (400 MHz, Chloroform-d): δ 6.70-6.65 (m, 2H), 6.41 – 6.38 (m, 1H), 3.72 (brs, 1H), 3.36 – 3.32 (m, 1H), 2.85 – 2.81 (m, 1H), 2.79-2.71 (m, 1H), 1.94 – 1.89 (m, 1H), 1.58 – 1.56 (m, 1H), 1.20 (d, J = 6.3 Hz, 3H). 13C NMR (101 MHz, Chloroform-d): δ 155.63 (d, J = 235.3 Hz), 141.1 (d, J = 1.8 Hz), 122.61 (d, J = 6.6 Hz), 115.51 (d, J = 21.6 Hz), 114.84 (d, J = 7.7 Hz), 113.28 (d, J = 22.5 Hz), 47.44, 30.02, 26.84, 22.63. Spectral data is in accordance to the reported literature.[27]

7-chloro-1,2,3,4-tetrahydroquinoline (3h)

NH

Cl

4,7-dichloroquinoline was used as the substrate. Colourless oil (76 mg, 91%). For this, 3.5 equiv. of Hantzsch ester was used. 1H NMR (400 MHz, Chloroform-d): δ 6.83 (d, J = 8 Hz, 1H), 6.53 (dd, J = 8.0, 2.1 Hz, 1H), 6.42 (d, J = 2.1 Hz, 1H), 3.84 (brs, 1H), 3.29 – 3.26 (m, 2H), 2.70 (t, J = 6.4 Hz, 2H), 1.93 – 1.87 (m, 2H). 13C NMR (101 MHz, Chloroform-d): δ

22 | P a g e

145.80, 132.03, 130.51, 119.72, 116.63, 113.49, 41.79, 26.66, 21.92. Spectral data is in accordance to the reported literature.[34]

8-bromo-1,2,3,4-tetrahydroquinoline (3i)

NHBr

Colourless oil (90 mg, 86%). 1H NMR (400 MHz, Chloroform-d): δ 7.22 (d, J = 8.0 Hz, 1H), 6.88 (dd, J = 7.4, 0.7 Hz, 1H), 6.44 (t, J = 7.7 Hz, 1H), 4.42 (brs, 1H), 3.39 – 3.37 (m, 2H), 2.77 (t, J = 6.3 Hz, 2H), 1.95 – 1.89 (m, 2H). 13C NMR (101 MHz, Chloroform-d): δ 141.85, 130.15, 128.52, 122.97, 117.03, 108.84, 42.18, 27.57, 21.83. Spectral data is in accordance to the reported literature.[14]

8-(benzyloxy)-1,2,3,4-tetrahydroquinoline (3j)

NHO

Colourless oil (110 mg, 92%). 1H NMR (400 MHz, Chloroform-d): δ 7.43 – 7.22 (m, 5H), 6.65 (dd, J = 16.2, 7.7 Hz, 2H), 6.54 (t, J = 7.7 Hz, 1H), 5.03 (s, 2H), 4.29 (brs, 1H), 3.32 – 3.29 (m, 2H), 2.78 (t, J = 6.4 Hz, 2H), 1.98 – 1.92 (m, 2H). 13C NMR (101 MHz, Chloroform-d): δ 145.53, 137.42, 134.89, 128.64, 128.05, 127.77, 122.12, 121.62, 115.66, 108.88, 70.36, 41.56, 26.82, 22.17. Spectral data is in accordance to the reported literature.[14]

1,2,3,4-tetrahydroquinolin-8-yl-4′-methylbenzenesulfonate (3k)

NHOSO

O

Me

White solid (130 mg, 86%); m.p: 62~64 ℃. 1H NMR (400 MHz, Chloroform-d): δ 7.77 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H)), 6.80 (d, J = 7.2 Hz, 2H), 6.59 (dd, J = 8.2, 1.4 Hz, 1H), 6.39 (t, J = 7.8 Hz, 1H), 4.18 (brs, 1H), 3.20-3.16 (m, 2H), 2.72 – 2.68 (t, J = 6.4 Hz, 2H), 2.45 (s, 3H), 1.85 – 1.79 (m, 2H). 13C NMR (101 MHz, Chloroform-d): δ 145.45, 137.95, 136.07, 133.04, 129.79, 128.66, 127.87, 123.65, 120.16, 115.22, 41.36, 27.01, 21.85, 21.50. HRMS (ESI) m/z: calculated for C16H18NO3S (M+H+): 304.1007; found: 304.1037.

23 | P a g e

N-(1,2,3,4-tetrahydroquinolin-8-yl)acetamide (3l)

NHN

MeOH

NHNHMe

Oacyclic cyclic

acyclic : cyclic = 2 : 1

White solid (80 mg, 84%); m.p: 113~115 ℃. 1H NMR (400 MHz, Chloroform-d): δ 7.11 (brs, 1H, acyclic, 67%), 7.01 (d, J = 7.8 Hz, 1H, acyclic, 67%), 6.93 (d, J = 7.2 Hz, 1H, cyclic, 33%), 6.87 (d, J = 7.2 Hz, 1H, acyclic, 67%), 6.83 (d, J = 7.2 Hz, 1H, cyclic, 33%), 6.68 (brs, 1H, cyclic, 33%), 6.63 (t, J = 7.6 Hz, 1H, acyclic, 67%), 6.55 (t, J = 7.2 Hz, 1H, cyclic, 33%), 4.14 (brs, 1H, acyclic, 67%), 3.32-3.29 [(m, 2H, acyclic, 67%) + (m, 2H, cyclic, 33%)], 2.78 [(t, 2H, acyclic, 67%) + (t, 2H, cyclic, 33%)], 2.17 (s, 3H, acyclic 67%), 1.91-1.87 [(m, 2H, acyclic, 67%) + (m, 2H, cyclic, 33%) + (s, 3H, cyclic, 33%)]. 13C NMR (101 MHz, Chloroform-d): δ 169.25, 139.36, 129.29, 127.87, 126.61, 124.34, 123.42, 123.33, 117.41, 115.95, 42.30, 41.76, 27.45, 27.15, 23.88, 22.00, 21.76, 20.51. HRMS (ESI) m/z: calculated for C11H14N2O (M+): 190.1106; found: 190.1185.

8-(allyloxy)-1,2,3,4-tetrahydroquinoline (3m)

NHO

Colourless oil (80 mg, 85%). 1H NMR (400 MHz, Chloroform-d): δ 6.66-6.62 (m, 2H), 6.58 – 6.54 (m, 1H), 6.10-6.05 (m, 1H), 5.42 (dd, J = 17.3, 1.6 Hz, 1H), 5.30 (dd, J = 10.5, 1.5 Hz, 1H), 4.55 (dt, J = 5.4, 1.6 Hz, 2H), 3.37– 3.35 (m, 2H), 2.80 (t, J = 6.4 Hz, 2H), 1.97 – 1.91 (m, 2H). 13C NMR (101 MHz, Chloroform-d): δ 145.29, 134.88, 133.82, 122.03, 121.64, 117.45, 115.68, 108.94, 69.21, 41.59, 26.82, 22.19. Spectral data is in accordance to the reported literature.[14]

1,2,3,4-tetrahydroquinolin-8-yl acetate (3n)

NHOO

Yellow oil (84 mg, 88%). 1H NMR (400 MHz, Chloroform-d): δ 7.80 (s, 1H), 7.11 (t, J = 7.8 Hz, 1H), 6.92 (d, J = 8.0 Hz, 1H), 6.74 (d, J = 7.4 Hz, 1H), 3.72 – 3.69 (m, 2H), 2.85 (t, J = 7.0 Hz, 2H), 2.38 (s, 3H), 2.10 – 2.04 (p, J = 6.9 Hz, 2H). 13C NMR (101 MHz, Chloroform-d): δ 171.66, 150.52, 133.24, 128.94, 127.43, 121.04, 118.38, 47.87, 26.52, 24.24, 23.36. HRMS (ESI) m/z: calculated for C11H14NO2 (M+H+): 192.1024; found: 192.1016.

24 | P a g e

1,2,3,4-tetrahydroquinolin-8-yl trifluoromethanesulfonate (3o)

NHOTf

Yellow oil (151 mg, 85%). 1H NMR (600 MHz, Chloroform-d): δ 6.95 (dd, J = 19.0, 7.9 Hz, 2H), 6.55 (t, J = 7.8 Hz, 1H), 4.17 (brs, 1H), 3.38-3.36 (m, 2H), 2.79 (t, J = 6.3 Hz, 2H), 1.96-1.92 (m, 2H). 13C NMR (101 MHz, Chloroform-d): δ 137.25, 136.39, 128.99, 124.58, 120.31, 119.22, 115.73, 41.56, 27.01, 21.35. 19F NMR (377 MHz, Chloroform-d): δ -73.98. HRMS (ESI) m/z: calculated for C10H11F3NO3S (M+H+): 282.0406; found: 282.0425.

8-ethynyl-1,2,3,4-tetrahydroquinoline (3p)

NH

Colourless oil (69 mg, 88%). 1H NMR (400 MHz, Chloroform-d): δ 7.15 (d, J = 7.6 Hz, 1H), 6.92 (d, J = 7.3 Hz, 1H), 6.49 (t, J = 7.5 Hz, 1H), 4.74 (brs, 1H), 3.41-3.38 (m, 2H), 3.37 (s, 1H), 2.76-2.75 (t, J = 6.4 Hz, 2H), 1.96 – 1.90 (m, 2H). 13C NMR (101 MHz, Chloroform-d): δ 146.56, 130.48, 130.22, 120.84, 115.61, 104.80, 82.42, 81.20, 41.89, 27.26, 21.74. HRMS (ESI) m/z: calculated for C11H12N (M+H+): 158.0969; found: 158.0975.

8-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline (3q)

NHF

Me

Colourless sticky liquid (71 mg, 86%). 1H NMR (400 MHz, Chloroform-d): δ 6.81 – 6.73 (m, 2H), 6.52 – 6.47 (m, 1H), 3.88 (brs, 1H), 3.45-3.37 (m, 1H), 2.88 – 2.72 (m, 2H), 1.95 – 1.92 (m, 1H), 1.64 –1.61 (m, 1H), 1.25 (d, J = 6.2 Hz, 3H). 13C NMR (101 MHz, Chloroform-d): δ 150.83 (d, J = 238.3 Hz), 133.35 (d, J = 12.2 Hz), 124.4 (d, J = 2.8 Hz), 123.5 (d, J = 3.8 Hz), 115.74 (d, J = 7.5 Hz), 112.25 (d, J = 18.4 Hz), 46.8, 29.86, 26.35 (d, J = 3 Hz), 22.64. HRMS (ESI) m/z: calculated for C10H13FN (M+H+): 166.1027; found: 166.1037.

8-(benzyloxy)-2-methyl-1,2,3,4-tetrahydroquinoline (3r)

25 | P a g e

NHO

Me

Colourless oil (112 mg, 89%).1H NMR (400 MHz, Chloroform-d): δ 7.43-7.30 (m, 5H), 6.65 (t, J = 8.6 Hz, 2H), 6.53 (t, J = 7.8 Hz, 1H), 5.07 – 5.01 (m, 2H), 4.18 (brs, 1H), 3.40 – 3.35 (m, 1H), 2.85 (ddd, J = 16.8, 11.2, 5.7 Hz, 1H), 2.77 – 2.71 (m, 1H), 1.94 – 1.90 (m, 1H), 1.63 – 1.56 (m, 1H), 1.22 – 1.21 (d, J = 6.3 Hz, 3H). 13C NMR (101 MHz, Chloroform-d): δ 145.33, 137.52, 134.93, 128.64, 128.01, 127.73, 121.95, 121.40, 115.76, 109.11, 70.50, 46.79, 30.15, 26.48, 22.69. HRMS (ESI) m/z: calculated for C17H20NO (M+H+): 254.1544; found: 254.1538.

2-(1H-benzo[d]imidazol-2-yl)-1,2,3,4-tetrahydroquinoline (3s)

NH HN

N

Pale yellow solid (103 mg, 83%); m.p: 156~157 ℃. 1H NMR (400 MHz, Chloroform-d): δ 7.56 (brs, 2H), 7.25-7.23 (m, 2H), 7.05 (t, J = 7.5 Hz, 1H), 6.99 (d, J = 7.4 Hz, 1H), 6.72 (t, J = 7.3 Hz, 1H), 6.60 (d, J = 7.9 Hz, 1H), 4.88 (t, J = 4 Hz, 1H), 2.86 – 2.79 (m, 1H), 2.63-2.56 (m, 1H), 2.36 (dd, J = 13.0, 6.6 Hz, 1H), 2.22 (d, J = 4.6 Hz, 1H). 13C NMR (101 MHz, Chloroform-d): δ 157.18, 142.79, 129.63, 127.32, 122.68, 121.67, 118.59, 114.98, 50.93, 27.80, 25.07. HRMS (ESI) m/z: calculated for C16H16N3 (M+H+): 250.1344; found: 250.1338.

2-(1,2,3,4-tetrahydroquinolin-2-yl)benzo[d]thiazole (3t)

NH S

N

Yellow oil (113 mg, 85%). 1H NMR (400 MHz, Chloroform-d): δ 7.99 (dd, J = 8.2, 1.1 Hz, 1H), 7.86 (dt, J = 8.0, 0.9 Hz, 1H), 7.48 (ddd, J = 8.3, 7.2, 1.3 Hz, 1H), 7.37 (ddd, J = 8.3, 7.2, 1.2 Hz, 1H), 7.07 (td, J = 7.7, 1.6 Hz, 1H), 7.00 (d, J = 7.5 Hz, 1H), 6.74 – 6.67 (m, 2H), 4.97 (ddd, J = 6.2, 4.9, 3.1 Hz, 1H), 4.61 (brs, 1H), 2.95 – 2.82 (m, 1H), 2.78-2.71 (m, 1H), 2.38-2.33 (m, 2H). 13C NMR (101 MHz, Chloroform-d): δ 177.39, 153.78, 142.86, 135.08, 129.43, 127.30, 126.19, 125.01, 122.99, 121.97, 121.34, 118.45, 114.85, 54.60, 29.09, 25.22. HRMS (ESI) m/z: calculated for C16H15N2S (M+H+): 267.0955; found: 267.0981.

6-methylene-2,3,4,6-tetrahydroquinoline (I-2) + 6-methyl-1,2,3,4-tetrahydroquinoline (2j)

26 | P a g e

N NH

H3C+

2j

H

H

I-2

Yellow oil (I-2 + 2j): (53 mg, 73%), I-2:2j = 1:3 ratio; 1H NMR (400 MHz, Chloroform-d): δ 7.18-7.21 (m, 2H, minor, 25%), 6.77-6.79 [(m, 2H, major, 75%) + (m, 1H, minor, 25%)], 6.40-6.42 (m, 1H, major, 75%), 6.37-3.39 (m, 2H, minor, 25%), 4.28-4.42 (m, 1H, major, 75%), 3.35-3.37 (m, 2H, minor, 25%), 3.25-3.28 (m, 2H, major, 75%), 2.71-2.75 [(m, 2H, major, 75%) + (m, 2H, minor, 25%)], 2.2 (s, 3H, major, 75%), 1.90-1.96 [(m, 2H, major, 75%) + (m, 2H, minor, 25%)]. 13C NMR (101 MHz, Chloroform-d): δ 163.01, 142.53, 133.39, 131.43, 130.22, 127.39, 126.45, 121.78, 114.63, 113.39, 42.34, 41.74, 27.05, 26.87, 22.59, 21.13, 20.54. HRMS (ESI) m/z: calculated for C10H12N (M+H+) for I-2: 146.0970; found: 146.0963. calculated for C10H14N (M+H+) for 2j: 148.1126; found: 148.1127.

9,10-dihydroacridine (4a)

NH

White solid (89 mg, 98%); m.p: 171~173 ℃. 1H NMR (400 MHz, Chloroform-d): δ 7.10 – 7.05 (m, 4H), 6.84 (td, J = 7.4, 1.2 Hz, 2H), 6.65 (dd, J = 7.8, 1.2 Hz, 2H), 5.93 (brs, 1H), 4.04 (s, 2H). 13C NMR (101 MHz, Chloroform-d) δ 140.25, 128.73, 127.12, 120.76, 120.16, 113.57, 31.51. Spectral data is in accordance to the reported literature.[14]

1,2,3,4,7,8,9,10-octahydro-1,10-phenanthroline (4b)

NH HN

For this, 5 eqv. of Hantzsch ester was used. Yellow solid (81 mg, 86%); m.p: 69~71 ᵒC. 1H NMR (400 MHz, Chloroform-d): δ 6.45 (s, 2H), 3.31 – 3.28 (m, 4H), 2.73 (t, J = 6.3 Hz, 4H), 1.89 – 1.87 (m, 4H). 13C NMR (101 MHz, Chloroform-d): δ 132.88, 120.51, 119.20, 42.69, 26.99, 22.59. spectral data is matched with the literature.[30]

1,2,3,4-tetrahydrobenzo[h]quinoline (4c)

HN

Light brown oil (89 mg, 97%). 1H NMR (400 MHz, Chloroform-d): δ 7.73 – 7.71 (m, 1H), 7.67 – 7.65 (m, 1H), 7.40 – 7.34 (m, 2H), 7.16 (d, J = 8.3 Hz, 1H), 7.10 (d, J = 8.3 Hz, 1H),

27 | P a g e

4.23 (brs, 1H), 3.46 – 3.44 (m, 2H), 2.89 (t, J = 6.4 Hz, 2H), 2.04 – 1.98 (m, 2H). 13C NMR (101 MHz, Chloroform-d): δ 139.03, 133.13, 128.68, 128.62, 125.02, 124.83, 123.37, 119.54, 117.08, 115.96, 42.52, 27.55, 22.22. Spectral data is in accordance to the reported literature.[27]

1,1',2,2',3,3',4,4'-octahydro-8,8'-biquinoline (4d)

NHH

N

For this, 5 eqv. of Hantzsch ester was used. Isolated yield: 92%. Yellow oil (121 mg, 92%). 1H NMR (400 MHz, Chloroform-d): δ 6.97 (d, J = 7.3 Hz, 2H), 6.91 (d, J = 7.3 Hz, 2H), 6.66 (t, J = 7.4 Hz, 2H), 3.29 – 3.22 (m, 4H), 2.83 (t, J = 6.4 Hz, 4H), 1.98 – 1.89 (m, 4H). 13C NMR (101 MHz, Chloroform-d): δ 142.49, 128.98, 128.83, 123.4, 121.59, 116.63, 42.10, 27.58, 22.07. HRMS (ESI) m/z: calculated for C18H21N2 (M+H+): 265.1704; found: 265.1709.

(8-hydroxy-3,4-dihydroquinolin-1(2H)-yl)(pyridin-3-yl)methanone (5)

NOH

O

N

Isolated yield: 82%. 1H NMR (400 MHz, DMSO-d6): δ 9.43 (s, 1H), 8.46 (dd, J = 4.8, 1.7 Hz, 1H), 8.38 (d, J = 2.2 Hz, 1H), 7.58 (dt, J = 7.9, 2.0 Hz, 1H), 7.23 (dd, J = 7.9, 4.8 Hz, 1H), 6.89 (t, J = 7.8 Hz, 1H), 6.72 (dd, J = 7.5, 1.3 Hz, 1H), 6.42 (dd, J = 8.1, 1.3 Hz, 1H), 3.4 (brs, 2H), 2.73 (t, J = 6.4 Hz, 2H), 1.91 (brs, 2H). 1H NMR (400 MHz, CD3CN): δ 8.48 (br, 2H), 7.68 – 7.66 (m, 1H), 7.23 – 7.21 (m, 1H), 6.98 (t, J = 7.5 Hz, 1H), 6.78 (d, J = 7.4 Hz, 1H), 6.53 – 6.51 (m, 1H), 3.64 (brs, 2H), 2.78 (t, J = 6.6 Hz, 2H), 1.91 (m, 2H). 13C NMR (101 MHz, DMSO-d6): δ 167.62, 150.20, 149.24, 148.17, 136.31, 134.96, 133.27, 127.11, 126.56, 122.63, 118.22, 114.24, 42.86, 26.28, 24.47. HRMS (ESI) m/z: calculated for C15H15N2O2 (M+H+): 255.1133; found: 255.1132.

(8-(2-hydroxy-3-(isopropylamino)propoxy)-3,4-dihydroquinolin-1(2H)-yl)(pyridin-3-yl)methanone (6)

NO

OHHN O

N

28 | P a g e

Isolated yield: 75%. 1H NMR (400 MHz, Chloroform-d): δ 8.62 – 8.55 (m, 2H), 7.73 (br, 1H), 7.20 – 7.17 (m, 1H), 7.08 (t, J = 7.9 Hz, 1H), 6.85 (d, J = 7.5 Hz, 1H), 6.64 – 6.61 (m, 1H), 4.22 (br, 1H), 3.80 – 3.76 (m, 2H), 3.58 – 3.48 (m, 2H), 2.86 – 2.66 (m, 4H), 2.56 – 2.51 (m, 1H), 2.22 (br, 2H), 1.89 – 1.80 (m, 2H), 1.05 (d, 6H). 13C NMR (101 MHz, Chloroform-d): δ 168.57, 151.13, 151.07, 149.09, 135.67, 132.44, 128.64, 127.04, 122.87, 122.79, 120.79, 111.32, 71.92, 70.98, 68.68, 68.06, 49.10, 26.75, 24.82, 23.07, 22.98. HRMS (ESI) m/z: calculated for C21H28N3O3 (M+H+): 370.2125; found: 370.2141.

2-methyl-1-((4-nitrophenyl)sulfonyl)-1,2,3,4-tetrahydroquinoline (7)

NS

Me

OO

O2N

Isolated yield: 96%. 1H NMR (400 MHz, Chloroform-d): δ 8.21 (d, J = 8.9 Hz, 2H), 7.75 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 8.9 Hz, 2H), 7.29 (d, J = 7.4 Hz, 1H), 7.16 (t, J = 7.9 Hz, 1H), 7.00 (d, J = 7.4 Hz, 1H), 4.43 – 4.35 (hext, J = 6.4 Hz, 1H), 2.44 – 2.37 (m, 1H), 1.89 – 1.81 (m, 1H), 1.71 – 1.64 (m, 1H), 1.41 – 1.36 (m, 1H), 1.34 – 1.32 (d, J = 6.5 Hz, 3H). 13C NMR (151 MHz, Chloroform-d): δ 144.85, 134.40, 133.80, 128.36, 128.28, 127.62, 127.28, 126.55, 124.17, 53.43, 30.61, 25.02, 22.03. Spectral data is in accordance to the reported literature.[12]

2-(3,4-dimethoxyphenethyl)-1-methyl-1,2,3,4-tetrahydroquinoline (8)

N

OMe

OMe

Me

Isolated yield: 95%. 1H NMR (400 MHz, Chloroform-d): δ 7.10-7.06 (m, 1H), 6.98 (d, J = 7.4 Hz, 1H), 6.80 – 6.78 (m, 1H), 6.74 – 6.70 (m, 2H), 6.58 (t, J = 7.3, 1.1 Hz, 1H), 6.52 (d, J = 8.2 Hz, 1H), 3.87 (s, 3H), 3.85 (s, 3H), 3.30 – 3.27 (dq, J = 8.6, 4.3 Hz, 1H), 2.91 (s, 3H), 2.82 – 2.87 (m, 1H), 2.72-2.66 (m, 2H), 2.55 – 2.53 (m, 1H), 1.96 – 1.92 (m, 3H), 1.74 – 1.73 (m, 1H). 13C NMR (101 MHz, Chloroform-d): δ 149.08, 147.40, 145.47, 134.82, 128.83, 127.27, 121.90, 120.22, 115.55, 111.79, 111.49, 110.78, 58.58, 56.11, 56.04, 38.24, 33.25, 32.08, 24.58, 23.74. The obtained spectroscopic data were in agreement with the reported data for this compound.[16]

29 | P a g e

(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)(3,4,5-trimethoxyphenyl)methanone (9)

N

O

MeO

OMeMeO

MeO

Isolated yield: 92%. 1H NMR (400 MHz, Chloroform-d): δ 6.66 (d, J = 2.4 Hz, 1H), 6.55 (d, J = 1.7 Hz, 2H), 6.45 (dd, J = 7.0, 4.3 Hz, 1H), 3.83 (td, J = 6.5, 2.1 Hz, 2H), 3.79 (s, J = 2.1 Hz, 3H), 3.70 (d, J = 2.3 Hz, 3H), 3.65 (d, J = 2.1 Hz, 6H), 2.76 (td, J = 6.7, 2.1 Hz, 2H), 2.02 –1.97 (m, 2H). 13C NMR (101 MHz, Chloroform-d): δ 169.37, 156.60, 152.71, 139.56, 132.99, 132.57, 131.24, 126.27, 113.12, 111.44, 106.25, 60.86, 56.04, 55.40, 44.58, 27.18, 24.15. Spectra data is in accordance to the reported literature.[14]

30 | P a g e

NH

20253035404550556065707580859095100105110115120125130135140145f1 (ppm)

-1000

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

11000

12000

22

.31

27

.09

42

.12

76

.84

77

.16

77

.48

11

4.3

21

17

.08

12

1.5

9

12

6.8

41

29

.64

14

4.8

9

NH

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.0f1 (ppm)

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

2.0

8

2.1

8

1.9

5

1.0

01

.07

2.2

1

0.0

0

1.9

01

.92

1.9

31

.95

1.9

6

2.7

42

.76

2.7

7

3.2

83

.29

3.3

0

6.4

56

.47

6.5

76

.59

6.6

16

.93

6.9

56

.97

7.2

4

12. 1H, 13C, and 19F NMR spectra of the products

Figure S4: 1H NMR Spectrum of 2a (CDCl3, 400 MHz, 298 K)

Figure S5: 13C NMR Spectrum of 2a (CDCl3, 101 MHz, 298 K)

31 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.0f1 (ppm)

0

500

1000

1500

2000

2500

3000

3500

4000

4500

3.0

0

1.0

6

1.0

4

1.0

51

.06

1.0

6

0.7

2

0.9

50

.95

1.9

1

1.1

91

.20

1.5

41

.55

1.5

71

.58

1.6

01

.61

1.6

21

.88

1.8

91

.90

1.9

01

.91

1.9

21

.93

1.9

41

.94

2.6

82

.69

2.6

92

.70

2.7

22

.73

2.7

32

.74

2.7

92

.80

2.8

12

.83

2.8

42

.85

3.3

63

.36

3.3

73

.38

3.3

93

.40

3.4

06

.44

6.4

46

.46

6.5

76

.58

6.6

16

.61

6.9

36

.93

6.9

56

.97

7.2

1

NH

1.51.61.71.81.92.02.12.22.32.42.52.62.72.82.93.03.13.23.33.4f1 (ppm)

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

1400

1500

1600

1700

1800

1.0

6

1.0

4

1.0

5

1.0

6

1.0

6

1.5

31

.54

1.5

51

.57

1.5

81

.60

1.6

11

.62

1.8

81

.89

1.9

01

.90

1.9

11

.92

1.9

31

.94

1.9

4

2.6

82

.69

2.6

92

.70

2.7

22

.73

2.7

32

.74

2.7

92

.80

2.8

12

.83

2.8

42

.85

2.8

73

.34

3.3

53

.36

3.3

63

.37

3.3

83

.39

3.4

03

.40

3.4

13

.42

Figure S6: 1H NMR Spectrum of 2b (CDCl3, 400 MHz, 298 K)

NH

253035404550556065707580859095100105110115120125130135140145f1 (ppm)

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

22

.60

26

.61

30

.14

47

.14

76

.84

77

.16

77

.48

11

4.0

21

16

.95

12

1.0

5

12

6.6

81

29

.26

14

4.7

9

Figure S7: 13C NMR Spectrum of 2b (CDCl3, 101 MHz, 298 K)

32 | P a g e

Figure S8: 1H NMR Spectrum of 2c (CDCl3, 400 MHz, 298 K)

0102030405060708090100110120130140f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

14

.19

22

.79

25

.55

26

.57

28

.25

32

.10

36

.79

51

.78

76

.84

77

.16

77

.48

11

4.2

51

17

.12

12

1.6

31

26

.84

12

9.3

9

14

4.7

7

NH

Figure S9: 13C NMR Spectrum of 2c (CDCl3, 101 MHz, 298 K)

NH

33 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

0

50

100

150

200

250

300

350

400

450

1.2

3

1.1

1

1.2

21

.26

1.0

51

.07

1.0

7

1.0

00

.98

2.0

1

-0.0

01

.72

1.8

81

.88

1.8

81

.89

1.8

91

.89

1.9

02

.72

2.7

52

.76

2.7

72

.80

2.8

22

.83

2.8

43

.44

3.4

53

.45

3.4

63

.46

3.4

73

.53

3.5

53

.56

3.5

83

.73

3.7

43

.75

3.7

66

.53

6.5

36

.55

6.5

56

.61

6.6

26

.63

6.6

46

.65

6.6

56

.95

6.9

56

.96

6.9

76

.97

6.9

86

.99

7.0

07

.00

7.2

6

NH

CH2OH

Figure S10: 1H NMR Spectrum of 2d (CDCl3, 400 MHz, 298 K)

253035404550556065707580859095100105110115120125130135140145f1 (ppm)

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

24

.46

26

.03

52

.90

66

.90

76

.84

77

.16

77

.48

11

4.6

81

17

.61

12

1.5

8

12

7.0

21

29

.37

14

4.2

7

NH

CH2OH

Figure S11: 13C NMR Spectrum of 2d (CDCl3, 101 MHz, 298 K)

34 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1.1

72

.27

1.1

7

3.9

8

1.1

8

0.6

5

1.0

01

.00

2.0

22

.99

2.1

9

1.6

51

.66

1.6

71

.68

1.6

91

.80

1.8

21

.84

1.8

41

.86

1.9

71

.98

1.9

92

.00

2.0

12

.72

2.7

42

.76

2.7

72

.78

2.7

9

3.2

83

.29

3.3

03

.30

3.3

13

.74

6.4

36

.45

6.5

86

.60

6.6

16

.93

6.9

56

.97

7.1

87

.20

7.2

27

.24

7.2

77

.29

7.3

1

NH

Figure S12: 1H NMR Spectrum of 2e (CDCl3, 400 MHz, 298 K)

253035404550556065707580859095100105110115120125130135140145f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

26

.35

28

.12

32

.31

38

.39

51

.25

76

.84

77

.16

77

.48

11

4.2

71

17

.16

12

1.4

21

26

.10

12

6.8

71

28

.49

12

8.6

21

29

.38

14

1.9

81

44

.65

NH

Figure S13: 13C NMR Spectrum of 2e (CDCl3, 101 MHz, 298 K)

35 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.0f1 (ppm)

-1000

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

11000

12000

13000

14000

15000

16000

17000

18000

19000

1.1

32

.15

1.0

9

2.1

61

.14

1.1

2

1.0

7

3.2

73

.00

1.0

41

.04

2.0

91

.05

2.0

9

1.6

51

.66

1.6

71

.68

1.6

91

.78

1.7

91

.80

1.8

01

.81

1.8

21

.83

1.9

71

.97

1.9

81

.99

1.9

92

.00

2.6

72

.68

2.6

92

.72

2.7

42

.75

2.7

62

.78

2.7

92

.79

2.8

03

.27

3.2

83

.29

3.3

03

.30

3.8

53

.87

6.4

36

.45

6.5

96

.60

6.6

16

.72

6.7

36

.74

6.7

56

.79

6.8

06

.94

6.9

56

.96

7.2

3

NH

OMe

OMe

Figure S14: 1H NMR Spectrum of 2f (CDCl3, 600 MHz, 298 K)

253035404550556065707580859095100105110115120125130135140145150f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

6500

26

.26

28

.06

31

.88

38

.49

51

.25

55

.89

55

.99

76

.95

77

.16

77

.37

11

1.3

01

11

.62

11

4.2

01

17

.08

12

0.1

61

21

.34

12

6.8

01

29

.32

13

4.5

1

14

4.5

71

47

.30

14

8.9

4

NH

OMe

OMe

Figure S15: 13C NMR Spectrum of 2f (CDCl3, 151 MHz, 298 K)

36 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.0f1 (ppm)

-200

0

200

400

600

800

1000

1200

1400

1600

1800

2000

2200

2400

2600

2800

3000

3200

3400

3.0

0

1.1

1

1.1

3

1.1

21

.16

1.0

7

0.8

4

0.9

60

.97

1.9

4

1.0

31

.05

2.0

32

.05

2.0

62

.07

2.3

92

.42

2.4

32

.46

2.7

42

.75

2.7

52

.76

2.7

82

.79

2.7

92

.80

2.8

62

.89

2.9

1

3.2

43

.24

3.2

53

.25

3.2

73

.27

3.2

73

.28

3.8

4

6.4

76

.49

6.5

86

.60

6.6

26

.93

6.9

46

.96

7.2

5

NH

Me

1.952.052.152.252.352.452.552.652.752.852.953.053.153.25f1 (ppm)

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

1.1

1

1.1

3

1.1

2

1.1

6

1.0

7

2.0

12

.02

2.0

32

.03

2.0

52

.06

2.0

72

.08

2.1

0

2.3

92

.42

2.4

32

.46

2.7

42

.75

2.7

52

.76

2.7

82

.79

2.7

92

.80

2.8

62

.89

2.9

1

3.2

43

.24

3.2

53

.25

3.2

73

.27

3.2

73

.28

Figure S16: 1H NMR Spectrum of 2g (CDCl3, 400 MHz, 298 K)

NH

Me

0102030405060708090100110120130140f1 (ppm)

-200

0

200

400

600

800

1000

1200

1400

1600

1800

2000

2200

2400

2600

19

.14

27

.28

35

.57

48

.94

76

.84

77

.16

77

.48

11

3.9

61

17

.00

12

1.1

91

26

.78

12

9.6

2

14

4.3

9

Figure S17: 13C NMR Spectrum of 2g (CDCl3, 101 MHz, 298 K)

37 | P a g e

Figure S18: 1H NMR Spectrum of 2h (CDCl3, 400 MHz, 298 K)

Figure S19: 13C NMR Spectrum of 2h (CDCl3, 101 MHz, 298 K)

NH

Ph

Me

NH

Ph

Me

38 | P a g e

Figure S20: 1H NMR Spectrum of 2i (CDCl3, 400 MHz, 298 K)

Figure S21: 13C NMR Spectrum of 2i (CDCl3, 101 MHz, 298 K)

NH

Me

102030405060708090100110120130140f1 (ppm)

-1000

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

11000

12000

13000

14000

150002

2.7

6

30

.04

30

.38

39

.17

76

.84

77

.16

77

.48

11

4.3

11

17

.11

12

6.7

81

26

.87

12

8.5

8

14

4.3

9

NH

Me

39 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.0f1 (ppm)

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

2.0

0

2.9

0

1.9

9

2.0

9

0.5

3

0.9

3

1.8

5

1.8

81

.89

1.9

01

.91

1.9

11

.91

1.9

21

.92

1.9

31

.93

1.9

31

.94

2.1

92

.70

2.7

22

.74

3.2

43

.24

3.2

53

.26

3.2

63

.43

6.3

86

.40

6.7

66

.77

6.7

76

.77

6.7

87

.21

NH

Me

Figure S22: 1H NMR Spectrum of 2j (CDCl3, 400 MHz, 298 K)

0102030405060708090100110120130140f1 (ppm)

0

1000

2000

3000

4000

5000

6000

7000

8000

90002

0.5

02

2.5

52

7.0

2

42

.29

76

.84

77

.16

77

.48

11

4.5

6

12

1.6

91

26

.33

12

7.3

41

30

.16

14

2.5

2

NH

Me

Figure S23: 13C NMR Spectrum of 2j (CDCl3, 101 MHz, 298 K)

40 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

2.0

9

2.1

10

.90

2.0

8

3.0

0

0.9

41

.87

1.8

91

.91

1.9

21

.93

1.9

5

2.7

32

.75

2.7

63

.23

3.2

43

.26

3.7

2

6.4

36

.45

6.5

56

.56

6.5

76

.58

6.6

06

.60

7.2

5

NH

MeO

1.81.92.02.12.22.32.42.52.62.72.82.93.03.13.23.3f1 (ppm)

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

2.0

9

2.1

1

0.9

0

2.0

8

1.8

91

.91

1.9

21

.93

1.9

5

2.7

32

.75

2.7

6

3.2

33

.24

3.2

6

Figure S24: 1H NMR Spectrum of 2k (CDCl3, 400 MHz, 298 K)

0102030405060708090100110120130140150f1 (ppm)

-200

0

200

400

600

800

1000

1200

1400

1600

1800

2000

2200

2400

2600

2800

30002

2.5

6

27

.28

42

.46

55

.94

76

.84

77

.16

77

.48

11

3.0

31

15

.02

11

5.7

1

12

3.0

3

13

8.9

7

15

1.9

7

NH

MeO

Figure S25: 13C NMR Spectrum of 2k (CDCl3, 101 MHz, 298 K)

41 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

-50

0

50

100

150

200

250

300

350

400

450

500

550

600

650

700

750

1.9

3

1.8

9

2.0

0

2.7

9

0.8

4

1.7

31

.75

1.7

61

.77

1.7

92

.50

2.5

72

.59

2.6

03

.07

3.0

93

.10

3.3

7

6.3

46

.37

6.3

7

8.4

7

NH

HO

Figure S26: 1H NMR Spectrum of 2l (DMSO-d6, 400 MHz, 298 K)

Figure S27: 13C NMR Spectrum of 2l (DMSO-d6, 101 MHz, 298 K)

NH

HO

42 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.0f1 (ppm)

-200

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

1400

1500

1600

1700

1800

1900

2000

2100

2200

2300

2.1

03

.00

2.0

3

2.0

3

0.7

3

0.9

5

1.9

0

1.9

11

.93

1.9

41

.95

1.9

72

.07

2.7

72

.79

2.8

0

3.3

63

.37

3.3

83

.65

6.5

36

.55

6.5

76

.84

6.8

66

.86

6.8

87

.25

NHMe

Figure S28: 1H NMR Spectrum of 2m (CDCl3, 400 MHz, 298 K)

102030405060708090100110120130140150f1 (ppm)

-1000

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

11000

12000

13000

14000

17

.27

22

.27

27

.40

42

.46

76

.84

77

.16

77

.48

11

6.5

01

20

.98

12

1.2

9

12

7.4

91

27

.95

14

2.8

1

NHMe

Figure S29: 13C NMR Spectrum of 2m (CDCl3, 101 MHz, 298 K)

43 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

-200

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

1400

1500

1600

1700

1800

1900

2000

2100

2200

2.0

0

2.0

3

2.0

0

0.8

3

3.1

3

0.8

5

1.7

8

2.6

3

3.2

0

4.6

0

6.2

66

.35

6.3

76

.45

8.9

4

NHOH

Figure S30: 1H NMR Spectrum of 2n (DMSO-d6, 400 MHz, 298 K)

20253035404550556065707580859095100105110115120125130135140145f1 (ppm)

-5000

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

50000

5500021

.79

26

.43

38

.90

39

.10

39

.31

39

.52

39

.73

39

.94

40

.15

40

.80

11

1.3

9

11

4.7

1

11

9.8

61

20

.37

13

3.7

3

14

3.1

8

NHOH

Figure S31: 13C NMR Spectrum of 2n (DMSO-d6, 101 MHz, 298 K)

44 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.0f1 (ppm)

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

3.0

0

1.1

2

1.0

6

2.3

0

1.0

0

1.4

8

3.0

0

1.2

21

.23

1.5

71

.57

1.5

81

.58

1.5

91

.59

1.6

01

.60

1.6

11

.61

1.6

21

.62

1.9

01

.92

1.9

4

2.7

12

.71

2.7

42

.78

2.7

92

.82

2.8

63

.33

4.6

1

6.4

66

.48

6.5

96

.60

7.2

2

NHOH

Figure S32: 1H NMR Spectrum of 2o (CDCl3, 400 MHz, 298 K)

20253035404550556065707580859095100105110115120125130135140145f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

22

.41

26

.44

30

.19

47

.27

76

.84

77

.16

77

.48

11

2.7

51

17

.29

12

1.7

21

23

.28

13

3.6

9

14

2.9

6

NHOH

Figure S33: 13C NMR Spectrum of 2o (CDCl3, 101 MHz, 298 K)

45 | P a g e

Figure S34: 1H NMR Spectrum of 2p (CDCl3, 400 MHz, 298 K)

Figure S35: 13C NMR Spectrum of 2p (CDCl3, 101 MHz, 298 K)

NHNH2

NHNH2

46 | P a g e

Figure S36: 1H NMR Spectrum of 2q (CDCl3, 400 MHz, 298 K)

Figure S37: 13C NMR Spectrum of 2q (CDCl3, 101 MHz, 298 K)

47 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.0f1 (ppm)

-50

0

50

100

150

200

250

300

350

400

450

500

550

600

650

700

1.1

9

1.1

8

2.1

8

2.9

0

1.0

1

1.0

01

.00

2.0

6

1.9

81

.99

2.0

02

.01

2.0

22

.02

2.0

32

.04

2.2

62

.26

2.2

72

.28

2.2

82

.29

2.2

92

.30

2.3

12

.73

2.7

62

.77

2.7

82

.80

2.8

12

.82

2.8

33

.78

4.0

34

.04

4.0

54

.06

6.5

86

.58

6.6

06

.60

6.6

36

.63

6.6

56

.65

6.6

66

.67

6.9

46

.95

6.9

76

.98

6.9

97

.00

7.0

07

.01

7.0

27

.02

7.2

6

NH

CO2Me

1.851.901.952.002.052.102.152.202.252.302.352.402.452.502.552.602.652.702.752.802.852.902.95f1 (ppm)

-5

0

5

10

15

20

25

30

35

40

45

50

55

1.1

9

1.1

8

2.1

8

1.9

61

.97

1.9

81

.99

2.0

02

.01

2.0

22

.02

2.0

32

.04

2.0

5

2.2

52

.26

2.2

62

.27

2.2

82

.28

2.2

92

.29

2.3

02

.31

2.3

12

.32

2.7

22

.73

2.7

42

.76

2.7

72

.78

2.8

02

.81

2.8

22

.83

2.8

52

.86

2.8

7


0102030405060708090100110120130140150160170f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

6500

70002

4.8

52

5.9

5

52

.50

54

.06

76

.84

77

.16

77

.48

11

4.7

31

17

.83

12

0.6

91

27

.20

12

9.2

7

14

3.0

8

17

3.8

6

NH

CO2Me


48 | P a g e


0102030405060708090100110120130140150160f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

6500

70002

6.1

22

8.9

0

57

.00

76

.84

77

.16

77

.48

11

4.6

01

17

.43

12

0.7

41

21

.24

12

2.3

21

27

.10

12

9.3

8

13

6.9

1

14

4.2

8

14

9.2

5

16

3.2

2

NH N


NH N

49 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.0f1 (ppm)

0

500

1000

1500

2000

2500

3000

3500

1.2

41

.23

1.2

31

.15

1.0

3

1.0

01

.05

0.9

91

.08

3.1

63

.18

3.2

03

.22

3.3

63

.37

3.4

03

.41

3.4

53

.45

3.4

73

.47

3.4

83

.48

3.5

03

.50

3.6

33

.63

3.6

43

.64

3.6

63

.66

3.6

73

.67

4.4

64

.47

4.4

84

.48

4.4

94

.49

4.5

04

.51

4.5

14

.52

6.5

26

.54

6.6

56

.66

6.6

76

.68

6.6

96

.69

6.9

26

.94

7.0

07

.01

7.0

37

.04

7.0

57

.24

NH

Br


0102030405060708090100110120130140150f1 (ppm)

-2000

-1000

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

11000

12000

13000

14000

15000

16000

17000

18000

19000

20000

37

.96

44

.32

49

.52

76

.84

77

.16

77

.48

11

4.6

61

18

.20

11

8.7

1

12

7.6

81

29

.58

14

2.7

3

NH

Br


50 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.0f1 (ppm)

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

1400

2.1

6

0.9

5

1.0

00

.98

2.0

41

.00

3.7

2

6.1

46

.57

6.5

96

.82

6.8

36

.92

6.9

26

.94

6.9

66

.96

6.9

76

.98

7.0

67

.06

7.0

87

.10

7.1

07

.26

NH

CN


1520253035404550556065707580859095100105110115120125130135140145f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

6500

7000

27

.03

76

.84

77

.16

77

.48

78

.06

11

5.3

01

18

.59

12

1.2

41

23

.93

12

7.8

11

29

.48

13

5.8

2

13

9.4

3

NH

CN


51 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

2.0

0

1.9

9

1.9

9

0.5

8

0.9

1

1.7

8

1.8

61

.88

1.8

91

.90

1.9

2

2.6

82

.70

2.7

2

3.2

43

.25

3.2

7

3.7

6

6.3

46

.36

6.8

76

.87

6.8

9

7.2

3

NH

Cl

Figure S46: 1H NMR Spectrum of 3e (CDCl3, 400 MHz, 298 K)

102030405060708090100110120130140150f1 (ppm)

-1000

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

11000

12000

21

.83

26

.96

41

.94

76

.84

77

.16

77

.48

11

5.1

7

12

1.2

01

22

.95

12

6.5

81

29

.10

14

3.4

0

NH

Cl

Figure S47: 13C NMR Spectrum of 3e (CDCl3, 101 MHz, 298 K)

52 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

1400

1500

2.0

0

1.9

7

1.9

6

0.8

8

0.9

3

1.7

7

1.9

21

.94

1.9

51

.97

1.9

8

2.7

82

.79

2.8

13

.40

3.4

03

.41

3.4

23

.43

3.4

3

4.7

5

6.3

56

.36

6.3

76

.38

7.2

7

7.8

77

.89

7.9

0

NH

O2N

Figure S48: 1H NMR Spectrum of 3f (CDCl3, 400 MHz, 298 K)

2030405060708090100110120130140150160f1 (ppm)

0

500

1000

1500

2000

2500

3000

20

.92

27

.00

41

.85

76

.84

77

.16

77

.48

11

2.2

7

11

9.9

51

24

.41

12

6.0

4

13

7.3

2

15

0.5

2

NH

O2N

Figure S49: 13C NMR Spectrum of 3f (CDCl3, 101 MHz, 298 K)

53 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

1400

1500

1600

1700

1800

1900

2000

3.0

0

1.1

6

1.0

6

1.0

71

.33

1.0

6

0.6

4

0.9

3

1.8

6

1.1

91

.21

1.5

61

.58

1.8

91

.90

1.9

01

.91

1.9

21

.93

1.9

42

.71

2.7

12

.72

2.7

32

.78

2.7

82

.79

2.7

92

.81

2.8

12

.82

2.8

22

.82

2.8

53

.32

3.3

33

.34

3.3

43

.35

3.3

53

.36

6.3

86

.39

6.4

06

.40

6.4

06

.41

6.4

16

.65

6.6

66

.67

6.6

76

.67

6.6

76

.68

6.6

96

.69

6.6

96

.70

7.2

6

NH

F

Figure S50: 1H NMR Spectrum of 3g (CDCl3, 400 MHz, 298 K)

Figure S51: 13C NMR Spectrum of 3g (CDCl3, 101 MHz, 298 K)

NH

F

54 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.0f1 (ppm)

-200

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

1400

1500

1600

1700

1800

1900

2000

2100

2200

2300

2.0

0

2.0

0

1.9

7

0.7

3

0.8

70

.88

0.9

2

1.8

71

.88

1.8

81

.89

1.8

91

.90

1.9

01

.91

1.9

11

.92

1.9

21

.93

1.9

32

.68

2.7

02

.71

3.2

63

.27

3.2

83

.29

3.8

4

6.4

26

.43

6.5

26

.52

6.5

46

.54

6.8

16

.82

6.8

26

.83

6.8

46

.84

7.2

5

NH

Cl

Figure S52: 1H NMR Spectrum of 3h (CDCl3, 400 MHz, 298 K)

20253035404550556065707580859095100105110115120125130135140145f1 (ppm)

-1000

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

11000

12000

13000

21

.92

26

.66

41

.79

76

.84

77

.16

77

.48

11

3.4

91

16

.63

11

9.7

2

13

0.5

11

32

.03

14

5.8

0

NH

Cl

Figure S53: 13C NMR Spectrum of 3h (CDCl3, 101 MHz, 298 K)

55 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

-200

0

200

400

600

800

1000

1200

1400

1600

1800

2000

2200

2400

2600

2800

3000

2.0

0

2.0

4

1.9

8

0.8

1

0.9

5

0.9

2

0.9

1

1.8

91

.91

1.9

21

.94

1.9

5

2.7

52

.77

2.7

8

3.3

73

.38

3.3

9

4.4

2

6.4

26

.44

6.4

66

.87

6.8

76

.89

6.8

97

.21

7.2

37

.25

NHBr

Figure S54: 1H NMR Spectrum of 3i (CDCl3, 400 MHz, 298 K)

0102030405060708090100110120130140f1 (ppm)

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

14002

1.8

3

27

.57

42

.18

76

.84

77

.16

77

.48

10

8.8

4

11

7.0

3

12

2.9

71

28

.52

13

0.1

5

14

1.8

5

NHBr

Figure S55: 13C NMR Spectrum of 3i (CDCl3, 101 MHz, 298 K)

56 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

-200

0

200

400

600

800

1000

1200

1400

1600

1800

2000

2200

2400

2600

2800

3000

3200

3400

3600

2.0

0

2.0

1

1.9

3

0.9

0

2.0

1

0.9

91

.95

4.8

8

1.9

21

.93

1.9

51

.96

1.9

8

2.7

62

.78

2.7

9

3.2

93

.31

3.3

2

4.2

9

5.0

3

6.5

26

.54

6.5

66

.62

6.6

46

.66

6.6

87

.22

7.3

07

.32

7.3

47

.36

7.3

87

.39

7.4

27

.43

NHOBn

Figure S56: 1H NMR Spectrum of 3j (CDCl3, 400 MHz, 298 K)

20253035404550556065707580859095100105110115120125130135140145150f1 (ppm)

-1000

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

11000

12000

13000

22

.17

26

.82

41

.56

70

.36

76

.84

77

.16

77

.48

10

8.8

8

11

5.6

6

12

1.6

21

22

.12

12

7.7

71

28

.05

12

8.6

4

13

4.8

91

37

.42

14

5.5

3

NHOBn

Figure S57: 13C NMR Spectrum of 3j (CDCl3, 101 MHz, 298 K)

57 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

1400

1500

1600

1700

1800

2.0

9

3.0

1

2.0

8

2.0

9

0.9

2

1.0

00

.96

0.9

8

1.9

3

1.9

0

1.7

91

.79

1.8

01

.82

1.8

21

.83

1.8

31

.85

2.4

52

.68

2.7

02

.72

3.1

63

.17

3.1

83

.18

3.1

93

.20

4.1

86

.37

6.3

96

.41

6.5

86

.58

6.6

06

.60

6.7

96

.79

6.7

96

.80

6.8

16

.81

7.2

67

.31

7.3

17

.33

7.3

37

.33

7.7

57

.76

7.7

67

.77

7.7

87

.78

NHOSO

O

Figure S58: 1H NMR Spectrum of 3k (CDCl3, 400 MHz, 298 K)

20253035404550556065707580859095100105110115120125130135140145150f1 (ppm)

0

500

1000

1500

2000

2500

3000

21

.50

21

.85

27

.01

41

.36

76

.84

77

.16

77

.48

11

5.2

21

20

.16

12

3.6

51

27

.87

12

8.6

61

29

.79

13

3.0

41

36

.07

13

7.9

5

14

5.4

5

NHOSO

O

Figure S59: 13C NMR Spectrum of 3k (CDCl3, 101 MHz, 298 K)

58 | P a g e

Figure S60: 1H NMR Spectrum of 3l (CDCl3, 400 MHz, 298 K)

0102030405060708090100110120130140150160170f1 (ppm)

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

1400

1500

20

.51

21

.76

22

.00

23

.88

27

.15

27

.45

41

.76

42

.30

76

.84

77

.16

77

.48

11

5.9

51

17

.41

12

3.3

31

23

.42

12

4.3

41

26

.61

12

7.8

71

29

.29

13

9.3

6

16

9.2

5

NHN

MeOH

NHNH

Oacyclic cyclic


Figure S61: 13C NMR Spectrum of 3l (CDCl3, 101 MHz, 298 K)

NHN

MeOH

NHNHMe

Oacyclic cyclic


59 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.0f1 (ppm)

0

500

1000

1500

2000

2500

3000

3500

4000

4500

2.0

0

2.0

0

1.9

6

1.9

5

0.9

30

.91

0.8

7

0.9

31

.81

1.9

11

.92

1.9

31

.94

1.9

41

.94

1.9

51

.95

1.9

61

.96

1.9

72

.75

2.7

72

.78

3.3

13

.32

3.3

44

.51

4.5

14

.51

4.5

24

.52

4.5

35

.24

5.2

55

.27

5.2

75

.36

5.3

75

.41

5.4

16

.03

6.0

46

.06

6.0

66

.07

6.0

76

.09

6.1

06

.50

6.5

26

.54

6.5

96

.59

6.6

06

.60

6.6

16

.61

6.6

26

.62

6.6

2

NHO

Figure S62: 1H NMR Spectrum of 3m (CDCl3, 400 MHz, 298 K)

20253035404550556065707580859095100105110115120125130135140145150f1 (ppm)

-2000

-1000

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

11000

12000

13000

14000

15000

16000

17000

18000

19000

20000

21000

22

.19

26

.82

41

.59

69

.21

76

.84

77

.16

77

.48

10

8.9

4

11

5.6

81

17

.45

12

1.6

41

22

.03

13

3.8

21

34

.88

14

5.2

9

NHO

Figure S63: 13C NMR Spectrum of 3m (CDCl3, 101 MHz, 298 K)

60 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

1400

1500

1600

1700

1800

1900

2000

2100

2.2

3

3.0

0

2.0

9

1.9

9

1.0

31

.00

1.0

4

0.9

8

2.0

42

.05

2.0

72

.09

2.1

02

.38

2.8

42

.85

2.8

7

3.6

93

.70

3.7

2

6.7

46

.76

6.9

16

.93

7.0

97

.11

7.1

37

.26

7.8

0

NHOO

Figure S64: 1H NMR Spectrum of 3n (CDCl3, 400 MHz, 298 K)

30405060708090100110120130140150160170f1 (ppm)

0

500

1000

1500

2000

250023

.36

24

.24

26

.52

47

.87

11

8.3

81

21

.04

12

7.4

31

28

.94

13

3.2

4

15

0.5

2

17

1.6

6

NHOO

Figure S65: 13C NMR Spectrum of 3n (CDCl3, 101 MHz, 298 K)

61 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.0f1 (ppm)

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

100000

110000

2.2

4

2.1

2

2.1

7

0.9

6

1.0

0

2.0

6

1.9

21

.93

1.9

41

.95

1.9

6

2.7

82

.79

2.8

03

.36

3.3

63

.37

3.3

73

.38

3.3

8

4.1

7

6.5

46

.55

6.5

76

.92

6.9

46

.96

6.9

7

NHOTf

Figure S66: 1H NMR Spectrum of 3o (CDCl3, 600 MHz, 298 K)

0102030405060708090100110120130140f1 (ppm)

-1000

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

11000

120002

1.3

5

27

.01

41

.56

76

.84

77

.16

77

.48

11

5.7

31

17

.13

11

9.2

21

20

.31

12

4.5

81

28

.99

13

6.3

91

37

.25

NHOTf

Figure S67: 13C NMR Spectrum of 3o (CDCl3, 101 MHz, 298 K)

62 | P a g e

-135-125-115-105-95-85-75-65-55-45-35-25-15-5f1 (ppm)

-5000

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

50000

55000

60000

65000

70000

75000

80000

85000

90000

-73

.98

NHOTf

Figure S68: 19F NMR Spectrum of 3o (CDCl3, 377 MHz, 298 K)

63 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.0f1 (ppm)

-200

0

200

400

600

800

1000

1200

1400

1600

1800

2000

2200

2400

2600

2800

3000

3200

2.4

7

2.3

6

0.9

12

.38

1.0

1

1.0

6

1.0

8

1.0

0

1.9

01

.92

1.9

21

.93

1.9

31

.94

1.9

41

.96

2.7

32

.74

2.7

63

.36

3.3

83

.38

3.3

93

.40

3.4

03

.41

4.7

4

6.4

76

.49

6.5

16

.91

6.9

16

.92

6.9

37

.13

7.1

37

.15

7.1

57

.25

NH

Figure S69: 1H NMR Spectrum of 3p (CDCl3, 400 MHz, 298 K)

0102030405060708090100110120130140150f1 (ppm)

-1000

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

11000

120002

1.7

4

27

.26

41

.89

76

.84

77

.16

77

.48

81

.20

82

.42

10

4.8

0

11

5.6

1

12

0.8

4

13

0.2

21

30

.48

14

6.5

6

NH

Figure S70: 13C NMR Spectrum of 3p (CDCl3, 101 MHz, 298 K)

64 | P a g e

Figure S71: 1H NMR Spectrum of 3q (CDCl3, 400 MHz, 298 K)

Figure S72: 13C NMR Spectrum of 3q (CDCl3, 101 MHz, 298 K)

NHF

NHF

65 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

-200

0

200

400

600

800

1000

1200

1400

1600

1800

2000

2200

2400

2600

2800

3000

3200

3400

3.0

0

1.2

7

1.0

4

1.0

51

.03

1.0

2

0.9

1

2.0

6

1.0

01

.99

5.0

1

1.2

11

.22

1.5

61

.59

1.6

01

.62

1.6

31

.90

1.9

01

.91

1.9

21

.93

1.9

31

.94

2.7

12

.72

2.7

32

.75

2.7

62

.77

2.8

12

.82

2.8

42

.85

3.3

53

.36

3.3

73

.38

3.3

93

.39

3.4

04

.18

5.0

15

.03

5.0

45

.07

6.5

16

.53

6.5

56

.63

6.6

56

.67

7.2

17

.30

7.3

27

.33

7.3

67

.37

7.3

97

.41

7.4

3

NHO

Figure S73: 1H NMR Spectrum of 3r (CDCl3, 400 MHz, 298 K)

20253035404550556065707580859095100105110115120125130135140145f1 (ppm)

-1000

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

22

.69

26

.48

30

.15

46

.79

70

.50

76

.84

77

.16

77

.48

10

9.1

1

11

5.7

6

12

1.4

01

21

.95

12

7.7

31

28

.01

12

8.6

4

13

4.9

31

37

.52

14

5.3

3

NHO

Figure S74: 13C NMR Spectrum of 3r (CDCl3, 101 MHz, 298 K)

66 | P a g e

Figure S75: 1H NMR Spectrum of 3s (CDCl3, 400 MHz, 298 K)

0102030405060708090100110120130140150160f1 (ppm)

-2000

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

20000

22000

24000

260002

5.0

72

7.8

0

50

.93

76

.84

77

.16

77

.48

11

4.9

81

18

.59

12

1.6

71

22

.68

12

7.3

21

29

.63

14

2.7

9

15

7.1

8

NH N

HN

Figure S76: 13C NMR Spectrum of 3s (CDCl3, 101 MHz, 298 K)

NH N

HN

67 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

-50

0

50

100

150

200

250

300

350

400

450

500

550

2.0

9

1.1

41

.30

0.9

9

1.0

5

2.0

30

.99

1.0

31

.02

1.0

3

0.9

61

.00

2.3

32

.35

2.3

52

.36

2.3

72

.37

2.7

62

.85

2.8

84

.61

4.9

74

.97

4.9

74

.98

6.6

76

.67

6.6

96

.69

6.7

06

.72

6.7

26

.74

6.7

46

.99

7.0

17

.05

7.0

77

.07

7.2

67

.37

7.3

77

.37

7.3

97

.39

7.4

67

.46

7.4

77

.48

7.4

87

.50

7.5

07

.85

7.8

57

.85

7.8

77

.87

7.8

77

.98

7.9

88

.00

8.0

0

NH N

S

Figure S77: 1H NMR Spectrum of 3t (CDCl3, 400 MHz, 298 K)

NH N

S

0102030405060708090100110120130140150160170180f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

65002

5.2

22

9.0

9

54

.60

76

.84

77

.16

77

.48

11

4.8

51

18

.45

12

1.3

41

21

.97

12

2.9

91

25

.01

12

6.1

91

27

.30

12

9.4

31

35

.08

14

2.8

6

15

3.7

8

17

7.3

9

Figure S78: 13C NMR Spectrum of 3t (CDCl3, 101 MHz, 298 K)

68 | P a g e

Figure S79: 1H NMR Spectrum of I-2+2j (CDCl3, 400 MHz, 298 K)

Figure S80: 1H NMR Spectrum of I-2+2j (CDCl3, 101 MHz, 298 K)

N NH

H3C+

2j

H

H

I-2I-2:2j = 1:3

N NH

H3C+

2j

H

H

I-2I-2:2j = 1:3

69 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.0f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

6500

2.0

0

0.8

2

1.9

41

.96

3.9

2

4.0

4

5.9

36

.64

6.6

46

.66

6.6

66

.82

6.8

36

.84

6.8

46

.86

6.8

67

.05

7.0

57

.07

7.0

77

.08

7.0

87

.09

7.1

07

.23

NH


3035404550556065707580859095100105110115120125130135140f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

6500

7000

31

.51

76

.84

77

.16

77

.48

11

3.5

7

12

0.1

61

20

.76

12

7.1

21

28

.73

14

0.2

5

NH


70 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.0f1 (ppm)

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

4.6

3

4.2

5

4.3

4

2.0

0

1.8

71

.87

1.8

81

.88

1.8

9

2.7

12

.73

2.7

53

.28

3.2

93

.29

3.3

03

.31

6.4

5

7.2

6

HNNH



NH HN

71 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)

0

500

1000

1500

2000

2500

3000

3500

4000

2.0

0

1.9

8

1.9

5

0.5

6

0.9

30

.93

1.8

30

.99

0.9

8

1.9

82

.00

2.0

02

.01

2.0

12

.01

2.0

22

.02

2.0

32

.04

2.8

82

.89

2.9

1

3.4

43

.45

3.4

6

4.2

37

.09

7.1

17

.15

7.1

77

.21

7.3

47

.36

7.3

67

.36

7.3

77

.38

7.3

87

.40

7.6

57

.65

7.6

67

.66

7.6

77

.71

7.7

17

.72

7.7

37

.73

HN


20253035404550556065707580859095100105110115120125130135140f1 (ppm)

-2000

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

20000

22000

24000

26000

28000

30000

32000

34000

22

.22

27

.55

42

.52

76

.84

77

.16

77

.48

11

5.9

61

17

.08

11

9.5

41

23

.37

12

4.8

31

25

.02

12

8.6

21

28

.68

13

3.1

3

13

9.0

3

HN


72 | P a g e



NHH

N

NHH

N

73 | P a g e

1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

-1000

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

11000

12000

13000

14000

1.7

4

2.1

1

1.0

01

.01

1.0

2

1.0

1

0.9

9

0.9

51

.00

0.9

9

1.9

1

2.5

02

.71

2.7

32

.74

3.4

7

6.4

16

.41

6.4

36

.44

6.7

06

.71

6.7

26

.73

6.8

76

.89

6.9

17

.22

7.2

37

.23

7.2

57

.57

7.5

87

.58

7.5

97

.60

7.6

08

.38

8.3

98

.45

8.4

68

.46

8.4

7

9.4

3

6.46.56.66.76.86.97.07.17.27.37.47.57.67.77.87.98.08.18.28.38.48.5f1 (ppm)

-200

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

1400

1500

1600

1700

1800

1900

2000

2100

2200

2300

1.0

0

1.0

1

1.0

2

1.0

1

0.9

9

0.9

5

1.0

0

6.4

16

.41

6.4

36

.44

6.7

06

.71

6.7

26

.73

6.8

76

.89

6.9

1

7.2

27

.23

7.2

37

.25

7.5

77

.58

7.5

87

.59

7.6

07

.60

8.3

88

.39

8.4

58

.46

8.4

68

.47

NOH

O

N

Figure S89: 1H NMR Spectrum of 5 (DMSO-d6, 400 MHz, 298 K)

Figure S90: 1H NMR Spectrum of 5 (CD3CN, 400 MHz, 298 K)

NOH

O

N

74 | P a g e

30405060708090100110120130140150160170f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

6500

7000

7500

8000

8500

9000

24

.47

26

.28

38

.89

39

.10

39

.31

39

.52

39

.73

39

.94

40

.15

42

.86

11

4.2

41

18

.22

12

2.6

31

26

.56

12

7.1

1

13

3.2

71

34

.96

13

6.3

1

14

8.1

71

49

.24

15

0.2

0

16

7.6

2

NOH

O

N

Figure S91: 13C NMR Spectrum of 5 (DMSO-d6, 101 MHz, 298 K)

Figure S92: 1H NMR Spectrum of 6 (CDCl3, 400 MHz, 298 K)

NO

OHHN O

N

75 | P a g e

Figure S93: 13C NMR Spectrum of 6 (CDCl3, 101 MHz, 298 K)

Figure S94: HRMS Spectrum of 6

NO

OHHN O

N

NO

OHHN O

N

HRMS (ESI) m/z: 370.2125 (M+H+) (calculated mass)

NO

OHHN O

N

HRMS (ESI) m/z: 370.2125 (M+H+)(calculated mass)

76 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

-20

0

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

360

3.1

81

.02

1.1

01

.03

1.0

0

0.9

8

0.8

80

.90

0.7

5

1.7

40

.86

1.7

6

1.3

21

.34

1.3

61

.38

1.3

91

.40

1.4

11

.64

1.6

51

.66

1.6

81

.69

1.7

01

.71

1.8

11

.83

1.8

41

.84

1.8

61

.86

1.8

71

.88

1.8

92

.37

2.3

92

.40

2.4

12

.43

2.4

44

.35

4.3

64

.38

4.4

04

.41

4.4

3

6.9

97

.01

7.1

57

.16

7.1

87

.26

7.2

87

.30

7.6

37

.65

7.7

47

.76

8.2

08

.22

NS O

O

O2N


0102030405060708090100110120130140f1 (ppm)

-200

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

1400

1500

1600

1700

1800

1900

2000

2100

22002

2.0

32

5.0

23

0.6

1

53

.43

76

.95

77

.16

77

.37

12

4.1

71

26

.55

12

7.2

81

27

.62

12

8.2

81

28

.36

13

3.8

01

34

.40

14

4.8

5

NS O

O

O2N


77 | P a g e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.0f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

1.2

5

3.0

1

1.0

32

.09

1.0

63

.07

1.1

2

6.0

1

1.0

01

.09

2.0

61

.02

1.0

21

.04

1.7

31

.74

1.9

21

.93

1.9

31

.94

1.9

51

.96

1.9

62

.53

2.5

42

.55

2.6

62

.67

2.6

72

.68

2.7

02

.71

2.7

22

.85

2.9

13

.27

3.2

83

.29

3.3

03

.85

3.8

76

.52

6.5

46

.57

6.5

76

.59

6.5

96

.61

6.6

16

.70

6.7

16

.71

6.7

26

.73

6.7

46

.78

6.8

06

.97

6.9

86

.99

7.0

67

.06

7.0

87

.10

7.2

5

NMe

OMe

OMe


0102030405060708090100110120130140150f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

65002

3.7

42

4.5

8

32

.08

33

.25

38

.24

56

.04

56

.11

58

.58

76

.84

77

.16

77

.48

11

0.7

81

11

.49

11

1.7

91

15

.55

12

0.2

21

21

.90

12

7.2

71

28

.83

13

4.8

2

14

5.4

71

47

.40

14

9.0

8

NMe

OMe

OMe


78 | P a g e


30405060708090100110120130140150160170f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

6500

7000

7500

8000

8500

24

.15

27

.18

44

.58

55

.40

56

.04

60

.86

76

.84

77

.16

77

.48

10

6.2

51

11

.44

11

3.1

2

12

6.2

71

31

.24

13

2.5

71

32

.99

13

9.5

6

15

2.7

1

15

6.6

0

16

9.3

7

N

O

MeO

OMeMeO

MeO


N

MeO

OMeO

MeOOMe

79 | P a g e

13. References1 M. Maji, K. Chakrabarti, B. Paul, B. C. Roy, S. Kundu, Adv. Synth. Catal. 2018, 360, 722-729.2 Y. Yang, H. Wang, H. Ma, Chem. Asian J. 2017, 12, 239-247.3 C. E. Kaslow, R. D. Stayner, J. Am. Chem. Soc. 1945, 67, 1716-1717.4 S. Wang, Q. Zheng, J. Wang, D. Chen, Y. Yub, W. Liu, Org. Chem. Front. 2016, 3, 496-500.5 C. Yang, J. M. Williams, Org. Lett. 2004, 61, 2837-2840.6 S. Hu, Y. Jin, Y. Liu, M. Ljungman, N. Neamati, Eur. J. Med. Chem. 2018, 158, 884-895.7 T. Ogata, J. F. Hartwig, J. Am. Chem. Soc. 2008, 130, 13848-13849.8 Y. Wang, F. Yu, X. Han, M. Li, Y. Tong, J. Ding, H. Hou, Inorg. Chem. 2017, 56, 5953-5958.9 S. Mastoor, S. Faizi, R. Saleem, B. S. Siddiqui, Magn. Reson. Chem. 2014, 52, 115-121.10 A. Rahim, S. P. Shaik, M. F. Baig, A. Alarifi, A. Kamal, Org. Biomol. Chem. 2018, 16, 635-644.11 A. Hantzsch, Justus Liebigs Ann. Chem. 1882, 215, 1.12 R. J. Pagliero, S. Lusvarghi, A. B. Pierini, R. Brun, M. R. Mazzieri, Bioorg. Med. Chem. 2010, 18, 142-

150.13 S. Shahane, F. Louafi, J. Moreau, J.-P. Hurvois, J.-L. Renaud, P. van de Weghe, T. Roisnel, Eur. J. Org.

Chem. 2008, 4622-4631.14 C-H. Yang, X. Chen, H. Li, W. Wei, Z. Yang, J. Chang, Chem. Commun. 2018, 54, 8622-8625.15 Y.-H. Ye. Shen, X. T. Wang, H. L. Zhu, C. Xu, Y. C. Song, H. Li and R. X. Tan, Chem.–Eur. J. 2006,

12, 4393-4396.16 A. O’Byrne, P. Evans, Tetrahedron, 2008, 64, 8067-8072.17 S.-I. Murahashi, Y. Imada, Y. Hirai, Bull. Chem. Soc. Jpn. 1989, 62, 2968–2976.18 C. D. Jesudason, L. S. Beavers, J. Cramer, J. Dill, D. R. Finley, C. W. Lindsley, F. C. Stevens, R. A.

Gadski, S. W. Oldham, R. T. Pickard, C. S. Siedem, D. K. Sindelar, A. Singh, B. M. Watson, P. A. Hipskind, Bioorg. Med. Chem. Lett. 2006, 16, 3415-3418.

19 S. S. Chaudhaery, K. K. Roy, N. Shakya, G. Saxena, S. R. Sammi, A. Nazir, C. Nath, A. K. Saxena, J. Med. Chem. 2010, 53, 6490-6505.

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