supporting information for bromomalonate functionalization
TRANSCRIPT
S1
Supporting information for
Visible-Light-Induced Photocatalyst-Free C-3
Functionalization of Indoles with Diethyl
BromomalonateGuangmiao Gu,‡ Mengmeng Huang,‡ Jung Keun Kim, Jianye Zhang, Yabo Li* and Yangjie Wu*
College of Chemistry, Henan Key Laboratory of Chemical Biology and Organic Chemistry, Key Laboratory of Applied Chemistry of Henan Universities, Zhengzhou University, Zhengzhou 450052, P.R. China.
[email protected], [email protected]
Contents
1. General Information...............................................................................................................22. Experimental Procedures .......................................................................................................33. Control Experiments ..............................................................................................................44. The UV-Vis Absorption Spectra, Luminescence Quenching Experiments, Cyclic Voltammetry and Data Processing ..............................................................................................135. Characterization of EDA Complex......................................................................................166. Computational Details .........................................................................................................187. Characterization Data...........................................................................................................348. References............................................................................................................................409. 1H, 13C and 19F NMR Spectra ..............................................................................................4110. Determination of Structure of 3a. ........................................................................................63
Electronic Supplementary Material (ESI) for Green Chemistry.This journal is © The Royal Society of Chemistry 2020
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1. General Information
All reactions were performed using quartz tube. Commercial grade reagents (1a and 2) and EtOH (OCEANPAK, GC ≥ 99.9%) were used without further purification except as indicated below. N-Methylindoles were synthesized from indoles according to the method in the literature.1 2-Arylindoles (1b-1t) were synthesized according to the method in the literature.2 1H NMR and 13C NMR spectral data of 1b-1u are in accordance with those reported2, 3 in the literature. Solvents were dried and degassed by standard methods4 before they were used. Silica gel was purchased from Qing Dao Hai Yang Chemical Industry Co. The LCD Digital Hotplate Magnetic Stirrer MS-H-Pro+ and Digital Single Channel Adjustable Automatic Electronic Pipette Micropipette dPettee+ were purchased from Dragon Laboratory Instruments Limited. 1H NMR spectra was recorded on a Bruker DPX-400 (400 MHz) spectrometer with deuteraterated chloroform as solution, the chemical shifts were quoted in parts per million (ppm) referenced to the appropriate solvent peak or 0.0 ppm for tetramethylsilane. 13C NMR spectra was recorded at 100 MHz on Bruker DPX-400. The chemical shifts δ are reported relative to residual CHCl3 (δC = 77.00 ppm). 19F NMR spectra was recorded at 376.5 MHz on Bruker DPX-400, the chemical shifts δ are reported relative to CFCl3 (δ = 0 ppm) as internal standard. The multiplicity of signals is designated by the following abbreviations: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), dd = doublet of doublet, td = triplet of doublet. Coupling constants J are reported in Hertz (Hz). High resolution mass spectra (HRMS) were obtained on an Agilent LC-MSD-Trap-XCT spectrometer with micromass MS software using electrospray ionisation (ESI). The UV-Vis absorption spectra were recorded in DMF on a Perkin Elmer Lambda 35 spectrometer. The cyclic voltammetry (CV) was recorded in DMF by CHI650A. And the luminescence quenching experiment was recorded using a F-4500 FL spectrophotometer in EtOH. All reactions were carried out with photoreactor (Serial No: PEA12) which was purchased from LUOYANG JINFENG ELECTROMECHANICAL EQUIPMENT CO., LTD.
S3
2. Experimental Procedures
2.1 General procedure for the synthesis of α-indolyl diethyl malonates2-Substitutedindoles 1 (0.2 mmol), diethyl bromomalonate 2 (0.6 mmol, 3.0 equiv.) and
K2HPO4.3H2O (0.4 mmol, 2.0 equiv.) were combined in EtOH (1.5 mL) under Ar atmosphere.
The mixture was stirred at room temperature under 3 W blue LED. After 1 hour, the reaction mixture was extracted with dichloromethane and saturated salt water, the organic phase was dried over Na2SO4 and concentrated under reduced pressure. Then, they were purified by chromatography on silica gel (elute: Ethyl acetate/Petroleum ether = 1/0-10/1, v/v) to give the desired product 3.
2.2 Supplementary reaction with Et3N instead of K2HPO4.3H2O
N+ EtO OEt
O O Et3N (2.0 equiv.)EtOH (1.5 mL)3 W blue LEDs
Ar, 1 h, rtNBr
OEt
OO
N
Br
+
EtO
1a 2 3a, 61% 4a, trace
Scheme S1. Reaction conditions: 1a (0.2 mmol), 2 (3.0 equiv.), Et3N (2.0 equiv.), EtOH (1.5 mL), in a quartz tube under Ar at room temperature for 1 hour. Isolated yield.
S4
3. Control Experiments
a)N
+ EtO OEt
O Ostandard conditionsexp 1: TEMPO (6 equiv.)exp 2: BHT (6 equiv.)exp 3: without 1a, TEMPO (6 equiv.)exp 4: without 1a, BHT (6 equiv.)exp 5: without 1a and base, TEMPO (6 equiv.)exp 6: without 1a and base, BHT (6 equiv.)
N
1aBr
OEt
OO
EtO
2
3a, 0% (for exp 1)3a, trace (for exp 2)3a, 0% (for exp 3)3a, 0% (for exp 4)
b)N
+ EtO OEt
O Ostandard conditions
exp 7: 0.5 hexp 8: 3a (5 mol %), 0.5 h
NBr
OEt
OO
EtO
3a, 38% (for exp 7)3a, 56% (for exp 8)
1a 2
c)N
3a
exp 9: standard conditionsOEt
OO
EtO
+ EtO
O O
3a
Br
2
d) OEtstandard conditions
N
OEt
OO
EtO
exp 10: 4 hexp 11: 6 h N
OEt
OO
EtOEtO
5a, 13% (for exp 7)5a, 35% (for exp 8)
EtO OEt
O O
ON
[I+H]+ exp 1 for 316.2120exp 3 for 316.2121exp 5 for 316.2120
O
O
OEtEtO
O
[II+H]+ exp 2 for 379.2481I II
EtO OEt
O O
[III+H]+ exp 3 for 168.0805exp 4 for 168.0806
[III+Na]+ exp 5 for 183.0626exp 6 for 183.0626
III
OHN
IV
[IV+H]+ exp 1 for 158.1538exp 3 for 158.1539exp 5 for 158.1538
EtO OEt
O O
O O
OEtEtO [V+H]+ exp 4 for 319.1385
V
Scheme S2. Control experiments.
S5
NO
OEt
O
EtO
O H
Figure S1. HRMS spectrum of compound [I + H]+ for exp 1
NO
OEt
O
EtO
O H
Figure S2. HRMS spectrum of compound [I + H]+ for exp 3
S6
NO
OEt
O
EtO
O H
Figure S3. HRMS spectrum of compound [I + H]+ for exp 5
OEtO
O
OEt
O H
Figure S4. HRMS spectrum of compound [II + H]+ for exp 2
S7
EtO
O
OEt
O H
Figure S5. HRMS spectrum of compound [III + H]+ for exp 3
EtO
O
OEt
O H
Figure S6. HRMS spectrum of compound [III + H]+ for exp 4
S8
EtO
O
OEt
O Na
Figure S7. HRMS spectrum of compound [III + Na]+ for exp 5
EtO
O
OEt
O Na
Figure S8. HRMS spectrum of compound [III + Na]+ for exp 6
S9
NOH H
Figure S9. HRMS spectrum of compound [IV + H]+ for exp 1
NOH H
Figure S10. HRMS spectrum of compound [IV + H]+ for exp 3
S10
NOH H
Figure S11. HRMS spectrum of compound [IV + H]+ for exp 5
EtO
O
OEt
O
EtO
O
OEt
O
H
Figure S12. HRMS spectrum of compound [V + H]+ for exp 4
S11
GGM-320-2-1H.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5 -1.0Chemical Shift (ppm)
9.353.002.084.251.031.301.035.161.02
0.00
1.11
1.13
1.15
1.17
1.19
3.46
3.64
3.80
3.813.
833.
85
7.13
7.257.
317.43
7.44
7.45
7.457.467.46
7.47
7.76
7.78
GGM-320-2-1H.ESP
7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1Chemical Shift (ppm)
1.031.301.035.161.02
7.11
7.12
7.13
7.15
7.15
7.23
7.23
7.25
7.25
7.25
7.27
7.27
7.31
7.33
7.43
7.45
7.457.
467.46
7.47
7.76
7.78
N
OO
OEtEtO
EtO
Figure S13. 1H NMR spectrum of compound 5a
GGM-320-2-13C.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
0.00
13.8
915
.47
30.7
4
61.6
261
.96
76.7
577
.07
77.3
9
84.0
6
107.
9010
9.32
120.
0512
1.37
122.
13
126.
4612
7.83
128.
6413
1.41
131.
51
136.
5613
9.20
168.
31
N
OO
OEtEtO
EtO
Figure S14. 13C NMR spectrum of compound 5a
S12
N
EtO
OO
OEtEtO
H
Figure S15. HRMS spectrum of compound [5a + H]+
S13
4. The UV-Vis Absorption Spectra, Luminescence Quenching
Experiments, Cyclic Voltammetry and Data Processing
4.1 The UV-Vis absorption spectraThe UV-Vis absorption spectra were recorded in 10 mm path length quartz cuvette on a
Perkin Elmer Lambda 35 spectrometer.
300 400 500 600 7000.0
0.2
0.4
0.6
0.8
1.0
Abso
rban
ce
Wavelength/nm
1a 2 3a 4a
Figure S16. The UV-Vis absorption spectra of 1-methyl-2-phenylindole 1a (λmax = 355 nm), diethyl bromomalonate 2 (λmax = 302 nm), 3a (λmax = 342 nm), 4a (λmax = 351 nm) in DMF (0.1 mM).
350 400 450 500 550 600
0.0
0.5
1.0
1.5
2.0
2.5
360 380 400 420 440 460 4800.0
0.1
0.2
0.3
0.4
Abso
rban
ce
wavelength/(nm)
Abso
rban
ce
Wavelength/(nm)
1a 2 1a + 2
Figure S17. The UV-Vis absorption spectra of 1-methyl-2-phenylindole 1a (0.13 M) and diethyl bromomalonate 2 (0.4 M) and mixture of 1a (0.13 M) and 2 (0.4 M) in DMF
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250 300 350 400 450 500 550 600
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
350 375 400 425 450 475 500 525
0.00
0.02
0.04
0.06
0.08
0.10
Abso
rban
ce
Wavelength/nm
Abso
rban
ce
Wavelength/nm
2 2 + Et3N
Figure S18. The UV-Vis absorption spectra of diethyl bromomalonate 2 (0.4 M) and mixture of 2 (0.4 M) and triethylamine (0.27 M) in DMF
4.2 Luminescence quenching experimentsEmission intensities were recorded using a F-4500 FL spectrophotometer. First, 3a solution
was excited at 311 nm and the emission/intensity at 378 nm was observed. In a typical experiment, the emission spectrum of a 5×10-5 M solution of 3a and different concentration of diethyl bromomalonate 2 in EtOH in 10 mm path length quartz cuvette were collected.
350 400 450 5000
500
1000
1500
2000
2500
3000
3500
Fluo
resc
ency
Inte
nsity
Wavelength/nm
3a (0.05 mM) 3a, 2 (0.05 mM) 3a, 2 (0.10 mM) 3a, 2 (0.15 mM) 3a, 2 (0.20 mM) 3a, 2 (0.25 mM) 3a, 2 (0.30 mM)
Figure S19. Luminescence quenching experiment of 3a with 2
S15
4.3 Cyclic voltammetryCyclic voltammetry was measured under Ar balloon protection with conventional three-
electrode system (Reference electrode: Ag/AgCl, working electrode: Glassy carbon, counter electrode: Pt wire, Supporting electrolyte: 0.1 M TBAPF6 in DMF) at 50 mV/sec of scan rate.
-3 -2 -1 0 1 2
Ep (1a) = -2.72
Ep (2) = -1.32
Ep (3a) = -2.59
Potential vs Ag/AgCl (V)
Figure S20. CV of reaction reagents (1 mM in DMF)
4.4 Data processingWe could see the reversible reduction waves of all the reagents. With these data in hand we
calculated the excited redox potential, Eg by CV and UV absorption spectrometry theory.
-6
-5
-4
-3
-2
-1
3a2
Eg = 3.86 Eg = 2.22
Eg = 3.92
Ener
gy le
vel/e
V
-1.68
-5.60
-2.82
-5.04
-1.67
-5.53
1a
Figure S21. The EHOMO, ELUMO and Eg of different reagents
S16
5. Characterization of EDA Complex
5.1 Stoichiometry of the EDA complex in solutionA Job’s plot5 was drawn to evaluate the stoichiometry of the EDA complex between the
diethyl bromomalonate (2) and triethylamine in DMF. We measured the absorption at 430 nm in DMF solutions of triethylamine and 2 having a constant total concentration of 0.2 M but different donor/acceptor ratios. All the absorption spectra were recorded in 10 mm path length quartz cuvette using a Perkin Elmer Lambda 35 spectrometer. The absorbance values were plotted against the molar fraction (%) of diethyl bromomalonate (2). The maximum absorbance is obtained for a 1 : 1 mixture of triethylamine : 2, indicating that this is the stoichiometry of the EDA complex in solution.
0 20 40 60 80 100
0.000
0.002
0.004
0.006
0.008
0.010
0.012
0.014
0.016
0.018
Abso
rban
ce
Molar Fraction of 2 (%)
Figure S22. Job’s plot in DMF
5.2 Determination of the association constant (KEDA)The association constant of the EDA complex formed between diethyl bromomalonate (2)
and 1-methyl-2-phenylindole (1a) was determined spectrophotometrically in DMF, employing the Benesi-Hildebrand methodology6. We measured the absorption at 430 nm of solutions with constant concentration of the diethyl bromomalonate (2, 0.05 M) but increased donor/acceptor ratios by adding excess of 1-methyl-2-phenylindole (1a). All the absorption spectra were recorded in 10 mm path length quartz cuvette using a Perkin Elmer Lambda 35 spectrometer. According to the methodology, a straight line is obtained when the reciprocal of the absorbance (A) is plotted against the reciprocal of the concentration of the partner in excess. The association constant (KEDA), calculated dividing the intercept by the slope, is 2.4 ± 0.19 M-1 for the solution in DMF.
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1.0 1.5 2.0 2.5 3.0 3.5
100
110
120
130
140
150
160
170
1/A
(a.u
.)
1/Et3N (M-1)
y = 71.27006+29.15027*xR2 = 0.91583
Figure S23. The Benesi-Hildebrand plot in DMF
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6. Computational Details
All the calculations were conducted by using the Gaussian 16 program package.7 The B3LYP8 functional together with Becke-Johnson damping corrections9 (abbreviated as B3LYP-D3BJ) and the 6-311+G(d,p) basis sets10 were used for all the calculations. The polarizable continuum model (PCM)11 was employed to consider the solvent effect of EtOH. The intrinsic reaction coordinate (IRC)11 analysis was carried out to confirm that all the saddle point connected the correct reactant and product on the potential energy surface. With the help of Multiwfn 3.7-dew12 and VMD version 1.9.3 programs13, we drawn and analysed TS and intermediate A1, A2, A3, A4.
1a Sum of electronic and zero-point Energies= -634.176039 Sum of electronic and thermal Energies= -634.163453 Sum of electronic and thermal Enthalpies= -634.162509 Sum of electronic and thermal Free Energies= -634.215499 C -1.86451500 -0.94430500 -0.16239700 C -1.84581500 0.46057800 0.06992200 C -3.02079300 1.20936600 0.18224800 C -4.22932300 0.53488500 0.04883700 C -4.26952000 -0.85354100 -0.19047900 C -3.10140900 -1.59627100 -0.29738600 C -0.49929000 -1.36834100 -0.20471000 C 0.29151200 -0.25394500 -0.01199400 H -2.99748000 2.27800000 0.35731900 H -5.15769800 1.08866600 0.12644700 H -5.23008000 -1.34548300 -0.29163900 H -3.14105900 -2.66462700 -0.47880400 H -0.13206700 -2.36367800 -0.39972800 C -0.12098100 2.20516200 0.54481500 H -0.15177100 2.89138700 -0.30545600 H -0.79065700 2.57605600 1.32207100 H 0.88990000 2.18077100 0.94386700 C 1.75772500 -0.18588300 -0.02009300 C 2.44836200 0.81799300 -0.71690000 C 2.50038900 -1.17690900 0.64010400 C 3.84011200 0.83282100 -0.74452100 H 1.89615000 1.57502800 -1.25957400 C 3.89172800 -1.16395200 0.60499800 H 1.97849700 -1.95041200 1.19048900 C 4.56753800 -0.15664500 -0.08364400 H 4.35646700 1.61314500 -1.29135300 H 4.44875100 -1.93557600 1.12360600 H 5.65080200 -0.14363100 -0.10633500
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N -0.52772500 0.86204100 0.15947000
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1a* Sum of electronic and zero-point Energies= -634.053453 Sum of electronic and thermal Energies= -634.040548 Sum of electronic and thermal Enthalpies= -634.039604 Sum of electronic and thermal Free Energies= -634.092681 C -1.84319000 -0.95412000 -0.04498200 C -1.86139700 0.47718400 0.02129000 C -3.03013400 1.20329600 0.00572300 C -4.25043900 0.47650300 -0.06598900 C -4.26295700 -0.92017700 -0.13129600 C -3.07826900 -1.65459900 -0.12305100 C -0.50846700 -1.34816300 -0.02868400 C 0.33003600 -0.15119200 0.03341900 H -3.03851400 2.28471600 0.03589900 H -5.18557600 1.02312200 -0.07260000 H -5.21289900 -1.43841800 -0.18928800 H -3.09025600 -2.73672000 -0.17108300 H -0.13026800 -2.35450500 -0.10074400 C -0.20082700 2.30450600 0.40795800 H -0.05223600 2.89920900 -0.49665400 H -1.02203700 2.73533900 0.97999900 H 0.70016000 2.33709000 1.01614200 C 1.74295300 -0.12343900 0.00319300 C 2.53562100 1.02362100 -0.35032200 C 2.46075900 -1.35001700 0.26702100 C 3.91117600 0.95522100 -0.38199000 H 2.05738600 1.94562000 -0.64592400 C 3.84037800 -1.38665600 0.24531500 H 1.91166200 -2.24623400 0.52385700 C 4.59340100 -0.24193000 -0.06727300 H 4.47646600 1.83535500 -0.66843100 H 4.34791100 -2.31850500 0.47119700 H 5.67543200 -0.28191300 -0.09152000 N -0.52987000 0.92223100 0.09531000
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2 Sum of electronic and zero-point Energies= -3148.461476 Sum of electronic and thermal Energies= -3148.447380 Sum of electronic and thermal Enthalpies= -3148.446436 Sum of electronic and thermal Free Energies= -3148.505054 C 0.61633600 0.65089300 1.35747400 C 0.17095800 -0.63264000 0.64749300 H -0.08355700 -1.33554900 1.43699600 C -1.05986400 -0.50322000 -0.25220200 O -1.91719800 0.32513900 0.34208100 O 0.90957500 1.74396600 0.65501800 C -3.22300200 0.53023300 -0.29112300 H -3.53220000 1.50707400 0.07448300 H -3.07250000 0.57365000 -1.36902600 C -4.19386200 -0.56119700 0.10917000 H -5.17265700 -0.34382100 -0.32561400 H -3.86641600 -1.53566900 -0.25663800 H -4.30268500 -0.60465000 1.19461600 C 0.67259500 1.88644200 -0.77941500 H -0.39128500 2.08084900 -0.91819900 H 0.95048500 0.96563900 -1.29017100 C 1.51651400 3.04578000 -1.25780200 H 2.57801800 2.84050800 -1.10750200 H 1.34086400 3.19962100 -2.32495200 H 1.25287100 3.96335700 -0.72872300 O -1.23831500 -1.08487100 -1.29001700 O 0.73340900 0.66113100 2.56055900 Br 1.69717800 -1.45633400 -0.27794200
S22
3a Sum of electronic and zero-point Energies= -1207.919103 Sum of electronic and thermal Energies= -1207.893584 Sum of electronic and thermal Enthalpies= -1207.892640 Sum of electronic and thermal Free Energies= -1207.976084 C 2.18405100 -1.86902500 0.05701600 C 2.09047800 -0.60271200 0.69183600 C 3.21143200 -0.08546600 1.35991600 C 4.38338900 -0.83026700 1.37894200 C 4.45781500 -2.08385200 0.74028700 C 3.36260200 -2.62018200 0.07245200 C 0.09146100 -1.07896800 -0.27508600 C 0.75641000 -0.12052800 0.47059200 H 3.16951100 0.88123700 1.84930700 H 5.25680800 -0.44325400 1.89065900 H 5.38567200 -2.64282500 0.77227900 H 3.42490000 -3.58790100 -0.40966300 C -1.29873500 -1.11639200 -0.75564400 C -1.83535300 -0.04360800 -1.47925200 C -2.10865600 -2.23602100 -0.50744100 C -3.14803700 -0.09151800 -1.94353100 H -1.21533000 0.81763600 -1.68472300 C -3.41465600 -2.28503100 -0.98092700 H -1.71661300 -3.06305000 0.07193500 C -3.93947000 -1.21223500 -1.70202800 H -3.54875100 0.74696900 -2.50119000 H -4.02758500 -3.15500900 -0.77639200 H -4.95889000 -1.24917500 -2.06771300 N 0.96349600 -2.14144800 -0.52321200 C 0.72195300 -3.29786800 -1.37397000 H 1.59984400 -3.47376600 -1.99697400 H 0.52180300 -4.19405700 -0.78137300 H -0.12921300 -3.10478700 -2.02144500 C 0.30068500 1.21232800 0.99247000 H 0.80642800 1.37739800 1.94938300 C -1.18097800 1.36077300 1.33538800 C 0.73524900 2.39937200 0.12670200 O 1.20102600 3.41666200 0.59013700 O -1.88516200 2.25887700 0.93180400 O 0.55004300 2.17552200 -1.17365900 O -1.56058900 0.43086400 2.21180000 C 0.94994600 3.21983900 -2.10798300 H 0.31282200 3.05349000 -2.97514000 H 0.71732300 4.18828700 -1.66678600
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C 2.42004000 3.09130800 -2.45714900 H 2.68176300 3.84381300 -3.20537800 H 3.04706000 3.24905500 -1.57805000 H 2.63400500 2.10433500 -2.87270400 C -2.91020100 0.53737800 2.75975700 H -3.13442000 1.59337100 2.90779000 H -2.83401900 0.04472100 3.72774700 C -3.92956100 -0.13674900 1.86540400 H -4.91683400 -0.05944200 2.32881600 H -3.96962500 0.33653300 0.88436600 H -3.69286500 -1.19230600 1.73056600
S24
A1
Sum of electronic and zero-point Energies= -4991.641568 Sum of electronic and thermal Energies= -4991.616226 Sum of electronic and thermal Enthalpies= -4991.615282 Sum of electronic and thermal Free Energies= -4991.703725C 1.56782700 1.02399500 -1.40117600
C 1.44771405 -0.45016549 -0.83346115 H 1.62380700 -1.05236200 -1.69548400 C 2.42670000 -0.77443500 0.23364000 O 3.59100800 -0.15609400 0.00022500 O 1.48064000 2.07844300 -0.58290600 C 4.71430600 -0.46474700 0.88245500 H 5.34912000 0.41628900 0.80976900 H 4.33431300 -0.55686500 1.89936700 C 5.43355000 -1.71892400 0.42755600 H 6.30377800 -1.88555700 1.06755000 H 4.78464700 -2.59328700 0.49839200 H 5.78034500 -1.61487400 -0.60263400 C 1.40013200 1.97722600 0.86946000 H 2.41335600 1.82914200 1.24479600 H 0.77670500 1.12784600 1.14451800 C 0.80110000 3.26944300 1.37775700 H -0.21238000 3.40217300 0.99457000 H 0.75710300 3.23997300 2.46905000 H 1.40948000 4.12567300 1.07964800 O 2.22400600 -1.55108900 1.13264500 O 1.71263700 1.21595400 -2.58915800 Br -0.27096163 -0.70443375 -0.38593287 P -4.06841434 -1.43613573 0.45305011 O -2.59267368 -1.18944370 0.09379717 O -4.40994284 -3.01979726 -0.09878623 O -5.18316425 -0.51244102 -0.43808441 O -4.37856025 -1.46044914 2.12434254 K -5.20164448 1.98163882 -0.60903531 K -2.79934601 -4.61894985 0.94939736 H -4.07758035 -0.63828504 2.51811569
S25
A2
Sum of electronic and zero-point Energies= -4991.639454Sum of electronic and thermal Energies= -4991.613949Sum of electronic and thermal Enthalpies= -4991.613005Sum of electronic and thermal Free Energies= -4991.702887C 1.56782700 1.02399500 -1.40117600
C 1.43201600 -0.38957200 -0.85396100 H 1.62380700 -1.05236200 -1.69548400 C 2.42670000 -0.77443500 0.23364000 O 3.59100800 -0.15609400 0.00022500 O 1.48064000 2.07844300 -0.58290600 C 4.71430600 -0.46474700 0.88245500 H 5.34912000 0.41628900 0.80976900 H 4.33431300 -0.55686500 1.89936700 C 5.43355000 -1.71892400 0.42755600 H 6.30377800 -1.88555700 1.06755000 H 4.78464700 -2.59328700 0.49839200 H 5.78034500 -1.61487400 -0.60263400 C 1.40013200 1.97722600 0.86946000 H 2.41335600 1.82914200 1.24479600 H 0.77670500 1.12784600 1.14451800 C 0.80110000 3.26944300 1.37775700 H -0.21238000 3.40217300 0.99457000 H 0.75710300 3.23997300 2.46905000 H 1.40948000 4.12567300 1.07964800 O 2.22400600 -1.55108900 1.13264500 O 1.71263700 1.21595400 -2.58915800 Br -0.46285200 -0.74452000 -0.34628300 P -4.10701900 -0.33254900 0.13573600 O -4.19774100 0.25033900 -1.28544000 O -3.65773500 0.98148400 1.13604100 H -4.30062100 1.69156500 1.03290100 O -2.92574484 -1.31989597 0.36197600 O -5.46577596 -0.83935520 0.69998260 K -3.28525848 -3.51262849 -1.15419485 K -6.51061312 -2.66361567 -0.97825727
S26
A3
Sum of electronic and zero-point Energies= -4991.640489Sum of electronic and thermal Energies= -4991.615328Sum of electronic and thermal Enthalpies= -4991.614383Sum of electronic and thermal Free Energies= -4991.701267C 2.96947917 1.63711844 1.61943053
C 2.96888138 1.43499740 3.19074309 H 3.65269323 0.62847219 3.32731244 C 3.41154480 2.62504935 3.95891919 O 4.36816944 3.28089027 3.29020157 O 2.27219034 2.63215083 1.06021072 C 5.01408490 4.40882992 3.95798912 H 5.37940622 5.02083557 3.13550148 H 4.25364522 4.95886135 4.51133109 C 6.14076219 3.93628677 4.85493184 H 6.64308118 4.80510925 5.28792005 H 5.76253010 3.31829385 5.67079257 H 6.87569645 3.36382801 4.28524138 C 1.57647370 3.66502439 1.81865912 H 2.31596322 4.41104232 2.11198718 H 1.12257393 3.22633895 2.70595535 C 0.52008247 4.25460976 0.91121402 H -0.21238790 3.49644148 0.62791339 H 0.00023423 5.05731051 1.43956423 H 0.96970682 4.67063551 0.00739682 O 3.02238446 2.90745873 5.06403703 O 3.58003649 0.87515508 0.90127246 Br 1.35105775 0.80319993 3.64047487 P -2.67021842 -0.77774266 4.94813079 O -3.34999039 0.05097672 6.05215271 O -3.68133405 -0.61995805 3.57630788 O -2.69308983 -2.45852430 5.20200078 O -1.15433901 -0.17728728 4.46692091 K -1.80930196 -3.63919460 7.22064801 K -3.96112100 1.80531465 3.03800351 H -0.57762914 -0.11305723 5.23169554
S27
A4
Sum of electronic and zero-point Energies= -3440.799378 Sum of electronic and thermal Energies= -3440.774036 Sum of electronic and thermal Enthalpies= -3440.773092 Sum of electronic and thermal Free Energies= -3440.859337 C -1.90515000 1.07452400 1.45341600 C -1.47778000 -0.29782500 0.95467900 H -1.52603900 -0.96182200 1.81494300 C -2.34385000 -0.91874300 -0.13300100 O -3.59981300 -0.48330800 0.00167400 O -1.99846500 2.10442300 0.60668700 C -4.61309000 -1.03577900 -0.89696700 H -5.38319600 -0.26721600 -0.91892400 H -4.17027400 -1.13665400 -1.88717900 C -5.14310700 -2.35424300 -0.37069000 H -5.94135000 -2.70758900 -1.02824900 H -4.35918800 -3.11282000 -0.34618600 H -5.55444800 -2.23344800 0.63353200 C -1.88334800 1.99467300 -0.84217000 H -2.88375600 1.79852100 -1.22892100 H -1.22428500 1.16921800 -1.10502700 C -1.32517100 3.30357900 -1.35466900 H -0.32362200 3.47853200 -0.95694300 H -1.26280000 3.26606100 -2.44481800 H -1.96954200 4.13892700 -1.07424300 O -1.96726500 -1.71755800 -0.95382100 O -2.11523700 1.26262000 2.63187500 Br 0.45948200 -0.25471800 0.45682400 N 3.16054900 -0.12631200 -0.15149400 C 3.75223100 -0.49175000 1.14668100 H 3.39512200 0.24399400 1.87234700 H 3.32886100 -1.45086800 1.45085300 C 5.28308500 -0.56788100 1.20448800 H 5.74930100 0.38840000 0.95719800 H 5.59521900 -0.83869300 2.21658800 H 5.67765800 -1.32461100 0.52207400
S28
C 3.48062100 -1.05728900 -1.24380100 H 2.89362400 -0.75205900 -2.11106400 H 4.54025000 -0.96649300 -1.53616500 C 3.15769000 -2.51490400 -0.93015700 H 2.12198900 -2.62255600 -0.60049400 H 3.29247100 -3.11619700 -1.83248500 H 3.80908000 -2.92974000 -0.15829200 C 3.45205500 1.27148800 -0.50657000 H 3.23605600 1.87298400 0.38066600 H 4.52303900 1.40491000 -0.72915600 C 2.63201100 1.80517800 -1.67942200 H 2.80226600 2.88020100 -1.77819300 H 2.91087700 1.34176500 -2.62758900 H 1.56601800 1.64098300 -1.51486800
S29
B Sum of electronic and zero-point Energies= -574.267217 Sum of electronic and thermal Energies= -574.254550 Sum of electronic and thermal Enthalpies= -574.253606 Sum of electronic and thermal Free Energies= -574.308265 C 1.60795700 -1.15820000 -0.07973700 C 0.22639200 -1.14970200 -0.59763900 H 0.02246200 -1.77007300 -1.45988300 C -0.88472900 -0.56974300 0.14484100 O -2.03511500 -0.68288500 -0.53821900 O 2.23118700 -0.03052600 0.25088400 C -3.23254000 -0.12204300 0.07431900 H -4.04657000 -0.67335700 -0.39272300 H -3.21005200 -0.34196500 1.14133900 C -3.33656500 1.36772900 -0.19390700 H -4.27409900 1.74320700 0.22396400 H -2.51266000 1.91063600 0.27197700 H -3.33426200 1.56893600 -1.26723400 C 1.66858200 1.27952500 -0.07594500 H 0.98981300 1.55588000 0.72899900 H 1.10481800 1.19898700 -1.00775600 C 2.82303100 2.24624000 -0.21021900 H 3.49294000 1.94780000 -1.01893400 H 2.43220400 3.24190900 -0.43335300 H 3.39291400 2.30171500 0.71946800 O -0.78245300 -0.06431700 1.25077500 O 2.17509600 -2.22808400 0.05204200
S30
C Sum of electronic and zero-point Energies= -1208.471247 Sum of electronic and thermal Energies= -1208.445318 Sum of electronic and thermal Enthalpies= -1208.444373 Sum of electronic and thermal Free Energies= -1208.529713 C 1.97499700 -0.92223900 -0.31006300 C 1.83266900 -2.29228100 -0.03558000 C 2.94186300 -3.12416200 0.10879300 C 4.20816400 -2.55502800 -0.04988600 C 4.36174200 -1.20000200 -0.34607200 C 3.23644800 -0.37435300 -0.47423000 C 0.59638600 -0.29445500 -0.31105100 C -0.30804000 -1.51174800 -0.25164200 H 2.83732600 -4.17647700 0.33847800 H 5.08458000 -3.18364400 0.05694700 H 5.35290400 -0.78309300 -0.47589200 H 3.35766900 0.67479400 -0.70991200 N 0.47940200 -2.63164500 0.01859600 C 0.04348100 -4.01711000 -0.09090900 H 0.83975500 -4.60541400 -0.54650000 H -0.19493200 -4.44709100 0.88504800 H -0.83534300 -4.07588200 -0.73001500 C -1.72721000 -1.49822900 -0.38704700 C -2.58884800 -2.42680200 0.25973200 C -2.34751400 -0.49222500 -1.17823700 C -3.96551100 -2.35198700 0.11205400 H -2.17542200 -3.17598800 0.92010800 C -3.72430500 -0.43015000 -1.31852700 H -1.73249000 0.23281300 -1.69475000 C -4.55210800 -1.35852000 -0.67832000 H -4.59222300 -3.06694300 0.63372100 H -4.15970600 0.34551400 -1.93886200 H -5.62841100 -1.30472800 -0.78726700 H 0.41266000 0.33229600 -1.18482600 C 0.45342500 0.60402700 0.97434900 H 0.75399900 0.01163700 1.83705100 C 1.36057900 1.82907700 0.95340100 C -0.97500200 1.05400900 1.26490800 O -1.64337300 0.60878700 2.16972100 O 1.87871600 2.28264700 1.95071800 O 1.49895500 2.34714900 -0.26599300 O -1.38260600 1.99991600 0.41784500 C -2.74561400 2.48875800 0.57564200 H -3.41425300 1.62790700 0.57836500
S31
H -2.81445300 2.99231700 1.54136900 C 2.29880300 3.55868800 -0.38833700 H 3.30049500 3.34714700 -0.01063500 H 1.84737900 4.32748900 0.24050300 C 2.30726900 3.94495600 -1.84984600 H 2.89861800 4.85426300 -1.97988800 H 2.75160200 3.15607900 -2.46036500 H 1.29422000 4.13914300 -2.20808300 C -3.02300400 3.42238700 -0.58009500 H -4.03871200 3.81509800 -0.49273800 H -2.32753800 4.26432700 -0.58128500 H -2.93908500 2.89628300 -1.53330800
S32
D Sum of electronic and zero-point Energies= -1208.333914 Sum of electronic and thermal Energies= -1208.308389 Sum of electronic and thermal Enthalpies= -1208.307445 Sum of electronic and thermal Free Energies= -1208.391112 C 2.06717900 -0.79453700 -0.22912600 C 1.98602100 -2.18172800 -0.11564400 C 3.09242800 -3.01015500 -0.02864700 C 4.34127300 -2.38731900 -0.06514700 C 4.44924000 -1.00089400 -0.19039400 C 3.31352500 -0.18883000 -0.27289000 C 0.65999700 -0.24553100 -0.24217900 C -0.17539100 -1.51059600 -0.23885700 H 3.00576100 -4.08395900 0.06427100 H 5.23638300 -2.99246900 0.00077100 H 5.43035200 -0.54435100 -0.22684600 H 3.41499300 0.88123000 -0.38000500 N 0.60830800 -2.55940700 -0.14317800 C 0.21051400 -3.97038700 -0.17681600 H 0.88254300 -4.49397400 -0.85348300 H 0.29201900 -4.39366000 0.82401100 H -0.80988500 -4.04984200 -0.53647300 C -1.62404200 -1.54812600 -0.34582000 C -2.40611000 -2.34821600 0.50434300 C -2.24829800 -0.73757500 -1.30944700 C -3.78881400 -2.33584700 0.38617300 H -1.93841600 -2.93639900 1.28229400 C -3.63061400 -0.75472800 -1.43754700 H -1.65347200 -0.12071800 -1.96947400 C -4.40169000 -1.54822400 -0.58858300 H -4.38874000 -2.93665700 1.05774800 H -4.10623900 -0.14534600 -2.19543600 H -5.48073300 -1.54766300 -0.68195300 H 0.43982900 0.34249900 -1.13608500 C 0.38692100 0.63269600 1.01856300 H 0.69891200 0.08646500 1.90677600 C 1.17639300 1.94409600 1.00078100 C -1.08819900 0.98899600 1.23869900 O -1.73879500 0.57174600 2.16583200 O 1.50020600 2.51389600 2.01625400 O 1.41126700 2.38030200 -0.23140200 O -1.52970500 1.82267800 0.30200000 C -2.91843300 2.26643300 0.40531800 H -3.55168900 1.38041100 0.44789100
S33
H -3.02220700 2.81847900 1.34018700 C 2.06872100 3.67911200 -0.36920000 H 3.03483100 3.62443400 0.13424100 H 1.45118200 4.42000800 0.13971900 C 2.20287300 3.95721500 -1.84810300 H 2.68971700 4.92493500 -1.98821700 H 2.81044900 3.19340600 -2.33768700 H 1.22331900 3.99217900 -2.32896900 C -3.20610300 3.12236200 -0.80546800 H -4.23868100 3.47548400 -0.75852400 H -2.54629200 3.99162000 -0.83657800 H -3.08022400 2.55146000 -1.72746700
S34
TS
Sum of electronic and zero-point Energies= -1208.457859 Sum of electronic and thermal Energies= -1208.431918 Sum of electronic and thermal Enthalpies= -1208.430974 Sum of electronic and thermal Free Energies= -1208.517730 C 2.23884300 -0.43903500 -0.47780800 C 2.39635200 -1.78736800 -0.09154900 C 3.65381500 -2.34861000 0.12134600 C 4.76513300 -1.53205700 -0.08704700 C 4.62560100 -0.19774900 -0.49286600 C 3.36077600 0.35923400 -0.68308800 C 0.79791500 -0.16938900 -0.52153500 C 0.16971200 -1.45817000 -0.37001100 H 3.77513000 -3.37709700 0.43556300 H 5.75633200 -1.94212800 0.06643900 H 5.50940700 0.40728000 -0.65466300 H 3.25624900 1.39384000 -0.98469500 N 1.13684400 -2.38257200 -0.01651600 C 0.95640400 -3.81747200 0.15039300 H 1.83274700 -4.33108300 -0.24295800 H 0.83105300 -4.08524000 1.20213200 H 0.08377800 -4.14550400 -0.40969100 C -1.24736400 -1.74141000 -0.51990900 C -1.93925500 -2.65864100 0.29494000 C -1.98048800 -1.04673700 -1.50336700 C -3.29893500 -2.88463500 0.11573400 H -1.42400400 -3.16145800 1.10128600 C -3.33850500 -1.27642200 -1.67792000 H -1.47467100 -0.33386100 -2.14197300 C -4.00641000 -2.20078700 -0.87323700 H -3.81166800 -3.58646600 0.76297100 H -3.87774000 -0.73455600 -2.44583600 H -5.06655300 -2.37803100 -1.00852500 H 0.37022700 0.57107700 -1.18334200 C 0.48524400 0.90448600 1.15036400 H 1.12400100 0.39651000 1.86204700
S35
C 1.03414900 2.22958500 0.80971200 C -0.93119300 0.69773900 1.49895900 O -1.27954700 -0.09515700 2.36082400 O 2.05386400 2.67927200 1.31210800 O 0.36119300 2.86504300 -0.16470100 O -1.80142900 1.39652200 0.75542000 C -3.21015000 1.15627500 1.00491000 H -3.40605100 0.09132200 0.87857200 H -3.43217200 1.42976000 2.03834400 C 0.85238900 4.16960000 -0.56357400 H 1.88480700 4.06634800 -0.90294300 H 0.84372300 4.82588400 0.30885500 C -0.05731600 4.67530100 -1.66194200 H 0.27941000 5.66181000 -1.98948700 H -0.04040900 4.00329600 -2.52289800 H -1.08635800 4.76309300 -1.30677500 C -3.98963100 1.99479600 0.01659200 H -5.06004400 1.83678400 0.16931000 H -3.77617100 3.05784300 0.14886000 H -3.74409000 1.71192300 -1.00877800
S36
B-anione Sum of electronic and zero-point Energies= -574.443488 Sum of electronic and thermal Energies= -574.431070 Sum of electronic and thermal Enthalpies= -574.430126 Sum of electronic and thermal Free Energies= -574.483915 C 1.55027000 -1.20859800 -0.05948900 C 0.15675300 -1.25253300 -0.30199700 H -0.17709500 -2.11876300 -0.85774200 C -0.85974000 -0.44336600 0.25804000 O -2.11015200 -0.82059000 -0.23903400 O 2.16385600 -0.05351900 0.39813600 C -3.25029800 -0.08276000 0.22756500 H -4.09089400 -0.77201000 0.12628600 H -3.12044400 0.16143900 1.28291200 C -3.48310800 1.17618200 -0.59475100 H -4.38851000 1.68597000 -0.25185000 H -2.64141900 1.86396300 -0.49346900 H -3.60929100 0.92980400 -1.65231200 C 1.75031900 1.24502400 -0.07741800 H 1.07173000 1.68915600 0.64893100 H 1.20066900 1.11964500 -1.01385400 C 2.99353700 2.09168900 -0.27936300 H 3.65435100 1.65135100 -1.03031600 H 2.70795300 3.09321200 -0.61481800 H 3.55122200 2.19374600 0.65531900 O -0.78818000 0.46114400 1.09740800 O 2.32139200 -2.16845300 -0.23583500
S37
III Sum of electronic and zero-point Energies= -574.916055 Sum of electronic and thermal Energies= -574.903243 Sum of electronic and thermal Enthalpies= -574.902299 Sum of electronic and thermal Free Energies= -574.958443 C -1.13965000 -1.01701500 -0.76035300 C -0.34472700 -1.65176000 0.36664700 H -0.91745300 -1.70322800 1.29358800 H -0.11339400 -2.67458800 0.06792500 C 0.97687700 -0.96817500 0.68133200 O 1.69116200 -1.29981500 1.59856900 O -1.17236600 -1.49264000 -1.87339200 O 1.24929800 0.01613900 -0.17604500 O -1.83802100 0.10074100 -0.51320300 C 2.49510500 0.75146100 0.01715500 H 3.32191200 0.05045000 -0.10498100 H 2.50794100 1.13237000 1.03904900 C 2.52504800 1.86082100 -1.00876800 H 1.68042300 2.53963300 -0.87401200 H 3.44827900 2.43324800 -0.89293600 H 2.49547100 1.45765000 -2.02300600 C -1.84819000 0.73576900 0.79732700 H -2.28013000 0.04356400 1.52251200 H -0.82317200 0.97293900 1.08497500 C -2.68069000 1.99278300 0.67805700 H -3.70219400 1.75543700 0.37476000 H -2.71586700 2.49525500 1.64744500 H -2.24503100 2.67856400 -0.05112500
S38
K2HPO4
Sum of electronic and zero-point Energies= -1843.168590 Sum of electronic and thermal Energies= -1843.159364 Sum of electronic and thermal Enthalpies= -1843.158420 Sum of electronic and thermal Free Energies= -1843.205478P 3.02730200 0.98618500 -0.05468800
O 3.19753800 -0.39536000 0.63423200 O 2.09200100 1.93131200 0.97569000 H 2.59944300 2.16635500 1.76060000 O 2.16505700 0.89176600 -1.32373400 O 4.37933000 1.70473700 -0.19630800 K 1.84255600 -1.82912900 -1.11799400 K 5.83354500 -0.20751400 0.95718000
S39
(KHPO4·)O P
OOH
OK
Sum of electronic and zero-point Energies= -1243.060487 Sum of electronic and thermal Energies= -1243.052875 Sum of electronic and thermal Enthalpies= -1243.051931 Sum of electronic and thermal Free Energies= -1243.094859P -0.13825792 0.94817854 -0.21603893
O 0.09023146 -0.63932274 0.37703128 O 0.32995249 2.07655444 0.98047553 H 1.25584659 1.94645717 1.19817901 O -1.78750679 1.17991430 -0.60382326 O 0.69998528 1.14828141 -1.44962323 K 2.68466390 -1.00386613 0.98705459
S40
(K2HPO4·+)OK
OHO P
OK
Sum of electronic and zero-point Energies= -1842.941727 Sum of electronic and thermal Energies= -1842.931402 Sum of electronic and thermal Enthalpies= -1842.930458 Sum of electronic and thermal Free Energies= -1842.983607P -0.13825792 0.94817854 -0.21603893
O 0.09023146 -0.63932274 0.37703128 O 0.32995249 2.07655444 0.98047553 H 1.25584659 1.94645717 1.19817901 O -1.78750679 1.17991430 -0.60382326 O 0.69998528 1.14828141 -1.44962323 K 2.68466390 -1.00386613 0.98705459 K -1.98231242 2.55618946 -2.90686851
S41
(KHPO4-)
O PO
OHOK
Sum of electronic and zero-point Energies= -1243.259438 Sum of electronic and thermal Energies= -1243.252268 Sum of electronic and thermal Enthalpies= -1243.251324 Sum of electronic and thermal Free Energies= -1243.292128P -0.11178239 0.76830822 -0.33698095
O 0.09148210 -0.62388789 0.63491080 O 0.31779997 2.15837582 0.56150170 H 1.23520562 2.09099750 0.83614153 O -1.74591120 0.88832583 -0.82618315 O 0.76934574 0.66456579 -1.55241246 K 2.66212918 -0.81268753 1.40447450
S42
KH2PO4
Sum of electronic and zero-point Energies= -1243.713913Sum of electronic and thermal Energies= -1243.706008Sum of electronic and thermal Enthalpies= -1243.705064Sum of electronic and thermal Free Energies= -1243.748799P 1.03349442 -0.02029189 0.11596816
O 1.46897675 -0.48447894 1.47577473 O -0.41482948 0.24999786 -0.21627161 O 1.92246696 1.33117553 -0.21100166 H 1.62351359 1.77587104 -1.01384763 O 1.54171776 -1.08543161 -1.03939683 H 2.41631138 -1.44150001 -0.83933482 K -2.93099459 -0.00632082 0.00214858
S43
7. Characterization Data
N
EtOOCCOOEt
diethyl 2-(1-methyl-2-phenyl-1H-indol-3-yl)malonate (3a)White solid (59.3 mg, 87%), mp. 89.9-90.3 °C. 1H NMR (400 MHz, CDCl3): δ 7.79 (d, J = 7.95 Hz, 1H), 7.53-7.45 (m, 5H), 7.34 (d, J = 8.19 Hz, 1H), 7.26 (t, J = 7.09 Hz, 1H), 7.16 (t, J = 7.21 Hz, 1H), 4.74 (s, 1H), 4.20-4.12 (m, 4H), 3.59 (s, 3H), 1.23 (t, J = 7.09 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 168.8, 140.2, 137.3, 131.0, 130.7, 128.7, 128.6, 126.4, 122.1, 121.2, 120.0, 109.5, 105.0, 61.5, 50.3, 31.0, 14.1. HRMS (ESI) calcd. for C22H24NO4 (M+H)+: 366.1700, found: 366.1704.
N
Br
3-bromo-1-methyl-2-phenyl-1H-indole (4a)Gray solid (1.7 mg, 3%), mp. 61.5-61.8 °C. 1H NMR (400 MHz, CDCl3): δ 7.62 (d, J = 7.82 Hz, 1H), 7.54-7.44 (m, 5H), 7.36-7.28 (m, 2H), 7.23 (td, J1 = 7.34 Hz, J2 = 1.10 Hz, 1H), 3.66 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 138.0, 136.8, 130.7, 130.4, 128.7, 128.5, 127.2, 122.9, 120.6, 119.4, 109.7, 90.1, 31.7. HRMS (ESI) calcd. for C15H13BrN (M+H)+: 286.0226, found: 286.0225.
N
EtOOCCOOEt
diethyl 2-(1,5-dimethyl-2-phenyl-1H-indol-3-yl)malonate (3b)Yellow liquid (64.7mg, 86%). 1H NMR (400 MHz, CDCl3): δ 7.57 (s, 1H), 7.52-7.43 (m, 5H), 7.22 (d, J = 8.44 Hz, 1H), 7.08 (d, J = 8.44 Hz, 1H), 4.71 (s, 1H), 4.21-4.11 (m, 4H), 3.55 (s, 3H), 2.47 (s, 3H), 1.23 (t, J = 7.09 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 168.9, 140.2, 135.7, 131.0, 130.9, 129.1, 128.6, 128.5, 126.6, 123.7, 120.7, 109.6, 104.4, 61.5, 50.3, 31.0, 21.7, 14.1. HRMS (ESI) calcd. for C23H26NO4 (M+H)+: 380.1856, found: 380.1855.
N
EtOOCCOOEt
MeO
diethyl 2-(5-methoxy-1-methyl-2-phenyl-1H-indol-3-yl)malonate (3c)Yellow solid (47.0 mg, 59%), mp. 61.3-62.5 °C. 1H NMR (400 MHz, CDCl3): δ 7.52-7.42 (m, 5H), 7.26 (d, J = 2.45 Hz, 1H), 7.23 (d, J = 8.80 Hz, 1H), 6.92 (dd, J1 = 8.80 Hz, J2 = 2.45 Hz,
S44
1H), 4.71 (s, 1H), 4.16 (q, J = 7.09 Hz, 4H), 3.86 (s, 3H), 3.55 (s, 3H), 1.23 (t, J = 7.09 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 168.8, 154.3, 140.7, 132.7, 130.9, 130.8, 128.7, 128.6, 126.7, 112.5, 110.2, 104.6, 102.9, 61.5, 55.9, 50.3, 31.1, 14.2. HRMS (ESI) calcd. for C23H26NO5 (M+H)+: 396.1805, found: 396.1803.
N
EtOOCCOOEt
F
diethyl 2-(5-fluoro-1-methyl-2-phenyl-1H-indol-3-yl)malonate (3d)Yellow solid (37.6mg, 49%), mp. 64.5-65.4 °C. 1H NMR (400 MHz, CDCl3): δ 7.54-7.43 (m, 6H), 7.26-7.23 (m, 1H), 7.00 (td, J1 = 9.05 Hz, J2 = 2.57 Hz, 1H), 4.68(s, 1H), 4.22-4.14 (m, 4H), 3.57 (s, 3H), 1.24 (t, J = 7.09 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 168.6, 158.0 (d, 1J = 234.0 Hz), 141.8, 133.9, 130.9, 130.4, 128.9, 128.7, 126.6 (d, 3J = 10.3 Hz), 110.5 (d, 2J = 26.4 Hz), 110.1 (d, 3J = 9.5 Hz), 106.2 (d, 2J = 24.2 Hz), 105.0 (d, 4J = 5.1 Hz), 61.6, 50.2, 31.2, 14.1. 19F NMR (376.5 MHz, CDCl3): δ -124.1. HRMS (ESI) calcd. for C22H23FNO4 (M+H)+: 384.1606, found: 384.1605.
N
NCCOOEt
EtOOC
diethyl 2-(5-cyano-1-methyl-2-phenyl-1H-indol-3-yl)malonate (3e)Yellow solid (15.7 mg, 20%), mp. 92.4-93.4 °C. 1H NMR (400 MHz, CDCl3): δ 8.18 (s, 1H), 7.55-7.52 (m, 3H), 7.49 (dd, J1 = 8.56 Hz, J2 = 1.59 Hz, 1H), 7.45-7.43 (m, 2H), 7.39 (d, J = 8.56 Hz, 1H), 4.70 (s, 1H), 4.23-4.15 (m, 4H), 3.62 (s, 3H), 1.26 (t, J = 7.09 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 168.2, 142.5, 138.8, 130.8, 129.6, 129.5, 128.9, 127.2, 126.1, 125.0, 120.9, 110.4, 106.1, 103.1, 61.9, 50.1, 31.3, 14.1. HRMS (ESI) calcd. for C23H23N2O4 (M+H)+: 391.1652, found: 391.1653.
N
EtOOCCOOEt
diethyl 2-(1,6-dimethyl-2-phenyl-1H-indol-3-yl)malonate (3f)White solid (64.2 mg, 85%), mp. 113.8-114.5 °C. 1H NMR (400 MHz, CDCl3): δ 7.67 (d, J = 8.19 Hz, 1H), 7.50-7.42 (m, 5H), 7.12 (s, 1H), 6.99 (d, J = 8.19 Hz, 1H), 4.71 (s, 1H), 4.21-4.09 (m, 4H), 3.54 (s, 3H), 2.49 (s, 3H), 1.22 (d, J = 7.09 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 168.9, 139.6, 137.7, 131.9, 131.0, 130.9, 128.6, 128.6, 124.3, 121.7, 120.9, 109.5, 104.9, 61.5, 50.3, 30.9, 21.9, 14.1. HRMS (ESI) calcd. for C23H26NO4 (M+H)+: 380.1856, found: 380.1858.
S45
NCl
EtOOCCOOEt
diethyl 2-(6-chloro-1-methyl-2-phenyl-1H-indol-3-yl)malonate (3g)Yellow solid (58.5mg, 73%), mp. 77.5-77.9 °C. 1H NMR (400 MHz, CDCl3): δ 7.71 (d, J = 8.56 Hz, 1H), 7.54-7.48 (m, 3H), 7.44-7.42 (m, 2H), 7.34 (d, J = 1.83 Hz, 1H), 7.13 (dd, J1 = 8.56 Hz, J2 = 1.71 Hz, 1H), 4.69 (s, 1H), 4.21-4.13 (m, 4H), 3.54 (s, 3H), 1.22 (t, J = 7.09 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 168.7, 140.9, 137.8, 130.9, 130.2, 129.0, 128.7, 128.0, 124.9, 122.2, 120.6, 109.6, 105.2, 61.6, 50.1, 31.1, 14.1. HRMS (ESI) calcd. for C22H23ClNO6 (M+H)+: 400.1310, found: 400.1308.
N
EtOOCCOOEt
diethyl 2-(1,7-dimethyl-2-phenyl-1H-indol-3-yl)malonate (3h)White solid (59.6 mg, 85%), mp. 118.2-119.1 °C. 1H NMR (400 MHz, CDCl3): δ 7.80 (d, J = 7.95 Hz, 1H), 7.51-7.42 (m, 5H), 7.01 (t, J = 7.82 Hz, 1H), 6.94 (d, J = 7.09 Hz, 1H), 4.68 (s, 1H), 4.17-4.10 (m, 4H), 3.79 (d, J = 1.10 Hz, 3H), 2.78 (s, 3H), 1.21 (td, J1 = 7.09 Hz, J2 = 1.59 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 168.8, 141.2, 136.3, 131.2, 131.0, 128.7, 128.5, 127.2, 125.1, 121.2, 120.0, 119.0, 105.3, 61.4, 50.3, 34.4, 20.4, 14.1. HRMS (ESI) calcd. for C23H26NO4 (M+H)+: 380.1856, found: 380.1857.
N
EtOOCCOOEt
diethyl 2-(1,4-dimethyl-2-phenyl-1H-indol-3-yl)malonate (3i)White solid (54.7 mg, 66%), mp. 105.4-106.8 °C. 1H NMR (400 MHz, CDCl3): δ 7.49-7.43 (m, 5H), 7.19-7.11 (m, 2H), 5.19 (s, 1H), 4.04-3.92 (m, 4H), 3.49 (s, 3H), 2.65 (s, 3H), 1.17 (t, J = 7.09 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 169.4, 140.1, 137.3, 131.5, 131.2, 130.2, 128.8, 128.1, 125.7, 122.4, 122.0, 107.6, 105.4, 61.4, 51.0, 31.0, 20.7, 14.0. HRMS (ESI) calcd. for C23H26NO4 (M+H)+: 380.1856, found: 380.1858.
N
EtOOCCOOEt
diethyl 2-(1-methyl-2-(p-tolyl)-1H-indol-3-yl)malonate (3j)Yellow solid (54.6 mg, 87%), mp. 115.9-117.8 °C. 1H NMR (400 MHz, CDCl3): δ 7.79 (d, J = 7.95 Hz, 1H), 7.35-7.30 (m, 5H), 7.24 (td, J1 = 8.19 Hz, J2 = 1.10 Hz, 1H), 7.15 (td, J1 = 6.97 Hz, J2 = 0.98 Hz, 1H), 4.73 (s, 1H), 4.20-4.12 (m, 4H), 3.58 (s, 3H), 2.44 (s, 3H), 1.22 (t,
S46
J = 7.1 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 168.9, 140.3, 138.6, 137.2, 130.8, 129.3, 127.6, 126.4, 121.9, 121.1, 119.9, 109.4, 104.8, 61.4, 50.3, 30.9, 21.4, 14.1. HRMS (ESI) calcd. for C23H26NO4 (M+H)+: 380.1856, found: 380.1857.
N
EtOOCCOOEt
diethyl 2-(2-(4-ethylphenyl)-1-methyl-1H-indol-3-yl)malonate (3k)Yellow solid (61.4 mg, 78%), mp. 77.4-78.5 °C. 1H NMR (400 MHz, CDCl3): δ 7.78 (d, J = 7.95 Hz, 1H), 7.38-7.32 (m, 5H), 7.24 (t, J = 7.09 Hz, 1H), 7.15 (t, J = 7.09 Hz, 1H), 4.75 (s, 1H), 4.22-4.10 (m, 4H), 3.58 (s, 3H), 2.74 (q, J = 7.58 Hz, 2H), 1.31 (t, J = 7.58 Hz, 3H), 1.23 (t, J = 7.09 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 168.9, 144.8, 140.4, 137.2, 130.9, 128.1, 127.8, 126.3, 121.9, 121.1, 119.8, 109.4, 104.8, 61.4, 50.3, 31.0, 28.7, 15.4, 14.1. HRMS (ESI) calcd. for C24H28NO4 (M+H)+: 394.2013, found: 394.2015.
N
EtOOCCOOEt
OMe
diethyl 2-(2-(4-methoxyphenyl)-1-methyl-1H-indol-3-yl)malonate (3l)Yellow solid (52.3 mg, 66%), mp. 114.7-117.8 °C. 1H NMR (400 MHz, CDCl3): δ 7.78 (d, J = 7.95 Hz, 1H), 7.37 (d, J = 8.80 Hz, 2H), 7.32 (d, J = 8.07 Hz, 1H), 7.24 (t, J = 8.07 Hz, 1H), 7.15 (t, J = 8.07 Hz, 1H), 7.03 (d, J = 8.80 Hz, 2H), 4.73 (s, 1H), 4.22-4.10 (m, 4H), 3.88 (s, 3H), 3.57 (s, 3H), 1.23 (t, J = 7.09 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 168.9, 160.0, 140.1, 137.1, 132.2, 126.4, 122.8, 121.9, 121.0, 119.9, 114.0, 109.4, 104.8, 61.5, 55.4, 50.4, 30.9, 14.1. HRMS (ESI) calcd. for C23H26NO5 (M+H)+: 396.1805, found: 396.1807.
N
EtOOCCOOEt
Cl
diethyl 2-(2-(4-chlorophenyl)-1-methyl-1H-indol-3-yl)malonate (3m)Yellow solid (51.1 mg, 64%), mp. 132.6-115.9 °C. 1H NMR (400 MHz, CDCl3): δ 7.79 (d, J = 7.95 Hz, 1H), 7.50-7.39 (m, 4H), 7.33 (d, J = 8.19 Hz, 1H), 7.26 (t, J = 6.97 Hz, 1H), 7.17 (t, J = 6.97 Hz, 1H), 4.69 (s, 1H), 4.23-4.10 (m, 4H), 3.57 (s, 3H), 1.23 (t, J = 7.09 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 168.7, 138.8, 137.3, 135.0, 132.3, 129.2, 128.9, 126.3, 122.4, 121.2, 120.1, 109.5, 105.4, 61.6, 50.2, 31.0, 14.1. HRMS (ESI) calcd. for C22H23ClNO4 (M+H)+: 400.1310, found: 400.1311.
N
EtOOCCOOEt
COOMe
S47
diethyl 2-(2-(4-(methoxycarbonyl)phenyl)-1-methyl-1H-indol-3-yl)malonate (3n)Yellow solid (59.7 mg, 70%), mp. 96.1-97.5 °C. 1H NMR (400 MHz, CDCl3): δ 8.19 (d, J = 8.07 Hz, 2H), 7.80 (d, J = 8.68 Hz, 1H), 7.56 (d, J = 7.95 Hz, 2H), 7.35 (d, J = 8.19 Hz, 1H), 7.27 (td, J1 = 8.19 Hz, J2 = 1.10 Hz, 1H), 7.17 (t, J = 7.09 Hz, 1H), 4.71 (s, 1H), 4.20-4.11 (m, 4H), 3.96 (s, 3H), 3.59 (s, 3H), 1.22 (s, J = 7.09 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 168.6, 166.7, 138.9, 137.6, 135.4, 131.0, 130.3, 129.8, 126.4, 122.6, 121.3, 120.2, 109.6, 105.7, 61.6, 52.4, 50.2, 31.1, 14.1. HRMS (ESI) calcd. for C24H26NO6 (M+H)+: 424.1755, found: 424.1757.
N
EtOOCCOOEt
diethyl 2-(1-methyl-2-(m-tolyl)-1H-indol-3-yl)malonate (3o)Yellow solid (58.6 mg, 77%), mp. 78.1-78.9 °C. 1H NMR (400 MHz, CDCl3): δ 7.79 (d, J = 7.95 Hz, 1H), 7.39 (t, J = 7.89 Hz, 1H), 7.33 (d, J = 8.07 Hz, 1H), 7.28-7.23 (m, 4H), 7.16 (t, J = 7.95 Hz, 1H), 4.74 (s, 1H), 4.21-4.13 (m, 4H), 3.58 (s, 3H), 2.43 (s, 3H), 1.23 (t, J = 7.09 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 168.9, 140.4, 138.3, 137.2, 131.6, 130.6, 129.5, 128.4, 128.0, 126.4, 122.0, 121.2, 119.9, 109.5, 104.9, 61.5, 50.3, 31.0, 21.5, 14.1. HRMS (ESI) calcd. for C23H26NO4 (M+H)+: 380.1856, found: 380.1857.
N
EtOOCCOOEt
Cldiethyl 2-(2-(3-chlorophenyl)-1-methyl-1H-indol-3-yl)malonate (3p)Yellow solid (55.2 mg, 69%), mp. 84.7-85.6°C. 1H NMR (400 MHz, CDCl3): δ 7.79 (d, J = 7.95 Hz, 1H), 7.49-7.45 (m, 3H), 7.37-7.33 (m, 2H), 7.27 (td, J1 = 7.43 Hz, J2 = 1.10 Hz, 1H), 7.17 (td, J1 = 8.01 Hz, J2 = 1.04 Hz, 1H), 4.71 (s, 1H), 4.21-4.13 (m, 4H), 3.59 (s, 3H), 1.24 (t, J = 7.09 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 168.6, 138.5, 137.3, 134.5, 132.5, 131.0, 129.9, 129.2, 128.9, 126.3, 122.5, 121.3, 120.2, 109.6, 105.6, 61.6, 50.1, 31.1, 14.1. HRMS (ESI) calcd. for C22H23ClNO4 (M+H)+: 400.1310, found: 400.1312.
N
EtOOCCOOEt
diethyl 2-(2-(3,5-dimethylphenyl)-1-methyl-1H-indol-3-yl)malonate (3r)Yellow solid (69.0 mg, 88%), mp. 111.9-112.7 °C. 1H NMR (400 MHz, CDCl3): δ 7.79 (d, J = 7.82 Hz, 1H), 7.32 (d, J = 8.19 Hz, 1H), 7.24 (t, J = 7.09 Hz, 1H), 7.15 (t, J = 7.82 Hz, 1H), 7.09 (s, 1H), 7.06 (s, 2H), 4.75 (s, 1H), 4.21-4.13 (m, 4H), 3.58 (s, 3H), 2.39 (s, 6H), 1.24 (t, J = 7.09 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 169.0, 140.6, 138.1, 137.2, 130.5, 130.4, 128.7, 126.4, 121.9, 121.2, 119.9, 109.4, 104.8, 61.5, 50.3, 31.0, 21.4, 14.1. HRMS (ESI) calcd. for C24H28NO4 (M+H)+: 394.2013, found: 394.2015.
S48
N
EtOOCCOOEt
diethyl 2-(1-methyl-2-(o-tolyl)-1H-indol-3-yl)malonate (3s)Yellow oil (31.1 mg, 40%). 1H NMR (400 MHz, CDCl3): δ 7.81 (d, J = 8.07 Hz, 1H), 7.42-7.23 (m, 6H), 7.17 (t, J = 7.09 Hz, 1H), 4.49 (s, 1H), 4.17-4.09 (m, 4H), 3.44 (s, 3H), 2.09 (s, 3H), 1.22 (t, J = 7.09 Hz, 3H), 1.18 (t, J = 7.21 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 168.8, 168.7, 139.8, 139.2, 137.1, 131.6, 130.3, 130.1, 129.5, 126.4, 125.9, 121.8, 121.1, 119.9, 109.3, 104.9, 61.4, 61.4, 50.3, 30.3, 19.7, 14.1. HRMS (ESI) calcd. for C23H26NO4 (M+H)+: 380.1856, found: 380.1859.
N
EtOOCCOOEt
diethyl 2-(1-methyl-2-(naphthalen-2-yl)-1H-indol-3-yl)malonate (3t)White solid (44.3 mg, 53%), mp. 129.6-130.8 °C. 1H NMR (400 MHz, CDCl3): δ 7.98-7.90 (m, 4H), 7.84 (d, J = 7.95 Hz, 1H), 7.57-7.52 (m, 3H), 7.36 (d, J = 8.19 Hz, 1H), 7.27 (td, J1 = 8.19 Hz, J2 = 1.10 Hz, 1H), 7.19 (td, J1 = 6.97 Hz, J2 = 0.98 Hz, 1H), 4.81 (s, 1H), 4.20-4.12 (m, 4H), 3.62 (s, 3H),1.22 (t, J = 7.09 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 168.9, 140.2, 137.4, 133.1, 133.1, 130.7, 128.4, 128.3, 128.1, 127.9, 127.0, 126.8, 126.5, 122.2, 121.3, 120.1, 109.5, 105.4, 61.6, 50.3, 31.2, 14.1. HRMS (ESI) calcd. for C26H26NO4 (M+H)+: 416.1856, found: 416.1858.
N
EtOOCCOOEt
diethyl 2-(1,2-dimethyl-1H-indol-3-yl)malonate (3u)Yellow solid (21.5 mg, 35%), mp. 78.0-78.8 °C. 1H NMR (400 MHz, CDCl3): δ 7.60 (d, J = 7.95 Hz, 1H), 7.24 (d, J = 8.07 Hz, 1H), 7.15 (td, J1 = 7.52 Hz, J2 = 1.22 Hz, 1H), 7.09 (td, J1 = 8.01 Hz, J2 = 1.22 Hz, 1H), 4.89 (s, 1H), 4.23-4.16 (m, 4H), 3.65 (s, 3H), 2.41 (s, 3H), 1.25 (t, J = 7.09 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 168.9, 136.6, 135.4, 126.8, 121.0, 119.5, 119.1, 108.8, 103.1, 61.6, 49.7, 29.7, 14.1, 10.9. HRMS (ESI) calcd. for C17H22NO4 (M+H)+: 304.1543, found: 304.1544.
S49
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Mori-Sánchez, J. Contreras-García, A. J. Cohen and W. Yang, J. Am. Chem. Soc., 2010, 132, 6498.
(13) W. Humphrey, A. Dalke and K. Schluten, J. Molec. Graphics, 1996, 14, 33.
S50
9. 1H, 13C and 19F NMR Spectra
18-W-HMM-GGM-122-4-1H.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5 -1.0Chemical Shift (ppm)
6.103.004.030.960.981.210.995.010.96
7.80
7.78
7.53 7.
517.
497.
477.
457.
35 7.33
7.26 7.24
7.16
4.74
4.19 4.
184.
17 4.16
4.16
4.15
4.14
4.13
3.59
1.24
1.23
1.21
0.00
18-W-HMM-GGM-122-4-1H.ESP
7.9 7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1Chemical Shift (ppm)
0.981.210.995.010.96
7.80 7.78
7.53
7.51
7.49
7.48
7.47
7.45
7.35
7.33
7.27
7.26 7.
247.
247.
24 7.18 7.
167.
14
3a
N
EtOOCCOOEt
Figure S24. 1H NMR spectrum of compound 3a
18-W-HMM-122-4-13C.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
0.03
14.0
9
31.0
0
50.2
8
61.5
0
76.7
477
.06
77.3
8
105.
00
109.
47
119.
9512
1.17
122.
07
126.
3712
8.5713
0.99
137.
2514
0.19
168.
84
18-W-HMM-122-4-13C.ESP
142 140 138 136 134 132 130 128 126 124 122 120 118Chemical Shift (ppm)
119.
95
121.
17
122.
07
126.
37
128.
5712
8.73
130.
7113
0.99
137.
25
140.
19
3a
N
EtOOCCOOEt
S51
Figure S25. 13C NMR spectrum of compound 3a
18-W-HMM-125-1.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5Chemical Shift (ppm)
3.001.161.040.985.030.94
0.00
3.66
7.237.24
7.257.
307.34
7.49
7.50
7.51
7.52
7.61
7.63
18-W-HMM-125-1.ESP
7.65 7.60 7.55 7.50 7.45 7.40 7.35 7.30 7.25 7.20Chemical Shift (ppm)
1.161.040.985.030.94
7.21
7.22
7.237.24
7.25
7.25
7.28
7.297.
307.
317.
327.
327.
347.
367.49
7.49
7.50
7.51
7.52
7.61
7.63
4a
N
Br
Figure S26. 1H NMR spectrum of compound 4a
GGM-127-13C.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
0.03
31.7
0
76.7
277
.04
77.3
6
90.1
4109.
74
119.
3612
0.57
122.
87
127.
2112
8.48
130.
73
136.
8113
8.03
GGM-127-13C.ESP
131 130 129 128 127 126 125 124 123 122 121 120Chemical Shift (ppm)
119.
36
120.
57
122.
87
127.
21
128.
4812
8.71
130.
4313
0.73
4a
N
Br
S52
Figure S27. 13C NMR spectrum of compound 4a
GGM-248-2 1H.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5Chemical Shift (ppm)
6.132.993.004.090.960.991.105.010.95
0.00
1.21
1.23
1.25
2.47
3.55
4.114.
124.13
4.14
4.15
4.16
4.16
4.17
4.18
4.19
4.20
4.21
4.71
7.077.
097.21
7.237.
237.
437.
457.
487.
497.
57
GGM-248-2 1H.ESP
7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7Chemical Shift (ppm)
0.991.105.010.95
7.077.
097.21
7.23
7.23
7.437.43
7.45
7.48
7.49
7.51
7.52
7.57 3b
N
EtOOCCOOEt
Figure S28. 1H NMR spectrum of compound 3b
GGM-248-2 13C.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
14.0
8
21.6
7
31.0
1
50.2
7
61.4
5
76.7
777
.09
77.4
0
104.
44
109.
15
120.
7312
3.70
126.
5712
8.53
130.
98
135.
74
140.
22
168.
91
GGM-248-2 13C.ESP
140 138 136 134 132 130 128 126 124 122 120 118Chemical Shift (ppm)
120.
73
123.
70
126.
57
128.
5312
8.64
129.
12
130.
8713
0.98
135.
74
140.
22
3b
N
EtOOCCOOEt
S53
Figure S29. 13C NMR spectrum of compound 3b
GGM-249-2-1H.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5 -1.0Chemical Shift (ppm)
5.993.003.024.010.930.950.950.955.05
0.00
1.22
1.23
1.25
3.553.
86
4.14
4.16
4.17
4.19
4.71
6.93
6.937.
217.
247.26
7.26
7.43
7.447.45
7.48
7.507.
507.
52
3c
N
EtOOCCOOEt
MeO
GGM-249-2-1H.ESP
7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7Chemical Shift (ppm)
0.950.950.955.05
6.90
6.916.93
6.93
7.21
7.247.
267.
26
7.42
7.43
7.447.
457.
457.
487.
487.
507.
527.
52
Figure S30. 1H NMR spectrum of compound 3c
GGM-249-2-13C.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
14.1
5
31.1
1
50.2
8
55.9
4
61.4
6
76.7
677
.08
77.3
9
102.
8710
4.59
110.
2011
2.49
126.
7212
8.56
130.
9313
2.65
140.
73154.
31
168.
83
GGM-249-2-13C.ESP
133 132 131 130 129 128 127 126Chemical Shift (ppm)
126.
72
128.
5612
8.67
130.
7913
0.93
132.
65
3c
N
EtOOCCOOEt
MeO
Figure S31. 13C NMR spectrum of compound 3c
S54
GGM-245-21H ESP.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5 -1.0Chemical Shift (ppm)
6.273.004.060.931.011.276.01
7.54 7.53
7.52 7.
50 7.44
7.43
7.26 7.
257.
247.
237.
007.
00
4.68
4.22 4.
21 4.20
4.19 4.18
4.17
4.16
4.16
4.15
4.14
3.57
1.26
1.24
1.22
0.00
GGM-245-21H ESP.ESP
7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9Chemical Shift (ppm)
1.011.276.01
7.54 7.
537.
527.
507.
497.
487.
45 7.44
7.43
7.26
7.25
7.24
7.23
7.03
7.00
7.00
6.98
6.97
3d
N
EtOOCCOOEt
F
Figure S32. 1H NMR spectrum of compound 3d
GGM-245-2-13C ESP.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
168.
60
159.
1815
6.85 141.
77 133.
9113
0.86
128.
6512
6.67
126.
57 110.
5911
0.32
110.
1411
0.05
106.
3410
6.10
105.
0610
5.01
61.6
0
50.1
8
31.1
9
14.0
6
0.00
GGM-245-2-13C ESP.ESP
135 130 125 120 115 110 105Chemical Shift (ppm)
133.
91
130.
8613
0.36 12
8.92
128.
65
126.
6712
6.57 11
0.59
110.
3211
0.14
110.
05
106.
3410
6.10
105.
0610
5.01
3d
N
EtOOCCOOEt
F
Figure S33. 13C NMR spectrum of compound 3d
S55
GGM-245-219F ESP.ESP
8 0 -8 -16 -24 -32 -40 -48 -56 -64 -72 -80 -88 -96 -104 -112 -120 -128 -136 -144 -152 -160 -168 -176 -184 -192Chemical Shift (ppm)
-124
.09
3d
N
EtOOCCOOEt
F
Figure S34. 19F NMR spectrum of compound 3d
19-W-HMM-9.10-2_8960001r
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5 -1.0Chemical Shift (ppm)
6.433.004.000.971.041.901.312.910.91
0.00
1.24
1.26
1.27
3.62
4.18
4.20
4.22
4.70
7.26
7.387.
407.45
7.48
7.48
7.53
7.558.18
19-W-HMM-9.10-2_8960001r
7.60 7.55 7.50 7.45 7.40 7.35Chemical Shift (ppm)
1.041.901.312.91
7.38
7.40
7.437.
43
7.44
7.45
7.48
7.48
7.50
7.50
7.53
7.54
7.55
7.55
3e
N
EtOOCCOOEt
NC
Figure S35. 1H NMR spectrum of compound 3e
S56
GGM-273-2-13C.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
168.
24
142.
54
138.
79
130.
8012
8.87
127.
1812
6.11
124.
9912
0.88
110.
42
106.
0910
3.06
77.3
577
.03
76.7
2
61.8
9
50.0
6
31.2
7 14.0
7
0.01
GGM-273-2-13C.ESP
131 130 129 128 127 126 125 124 123 122 121Chemical Shift (ppm)
130.
80
129.
45 129.
42
128.
87
127.
18
126.
11
124.
99
120.
88
3e
N
EtOOCCOOEt
NC
Figure S36. 13C NMR spectrum of compound 3e
GGM-256-2-1H.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5 -1.0Chemical Shift (ppm)
6.043.013.003.990.961.020.984.991.01
0.00
1.20
1.22
1.24
2.49
3.54
4.094.
114.124.
134.
144.15
4.15
4.16
4.17
4.18
4.19
4.21
4.71
6.98
7.00
7.12
7.42
7.43
7.44
7.44
7.47
7.50
7.66
7.68
GGM-256-2-1H.ESP
7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8Chemical Shift (ppm)
1.020.984.991.01
6.987.00
7.12
7.22
7.42
7.44
7.44
7.47
7.48
7.48
7.50
7.66
7.68
N
EtOOCCOOEt
3f
Figure S37. 1H NMR spectrum of compound 3f
S57
GGM-256-2-13C.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
168.
90
139.
6113
7.71
131.
9013
1.01
128.
55
124.
2512
1.72
120.
85
109.
50
104.
86
77.4
477
.12
76.8
0
61.4
7
50.3
2
30.9
3
21.9
4
14.1
1
GGM-256-2-13C.ESP
132.0 131.5 131.0 130.5 130.0 129.5 129.0 128.5 128.0 127.5Chemical Shift (ppm)
131.
90
131.
0113
0.88
128.
6112
8.55
N
EtOOCCOOEt
3f
Figure S38. 13C NMR spectrum of compound 3f
GGM-6-Cl-1H.esp
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5Chemical Shift (ppm)
6.023.003.920.930.990.931.942.900.97
7.72 7.70
7.54
7.52
7.50
7.49 7.
447.
447.
347.
33
7.25 7.
14
4.69
4.20 4.
194.
18 4.17
4.16
4.15
4.15
4.14
4.13
3.54
1.24
1.23
1.21
0.00
GGM-6-Cl-1H.esp
7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0Chemical Shift (ppm)
0.990.931.942.900.97
7.72 7.
70
7.54 7.
537.
527.
507.
497.
497.
487.
447.
447.
437.
42
7.34
7.33
7.25
7.14
7.13
7.12
7.11
N
EtOOCCOOEt
Cl
3g
Figure S39. 1H NMR spectrum of compound 3g
S58
GGM-6-Cl-13C.esp
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
168.
66
140.
9213
7.76
130.
89 128.
7012
8.03
124.
9012
2.21
120.
62
109.
56
105.
24
77.4
077
.08
76.7
7
61.6
4
50.1
4
31.1
2
14.0
9
GGM-6-Cl-13C.esp
132 131 130 129 128 127 126 125 124 123 122 121 120Chemical Shift (ppm)
130.
89
130.
16
128.
9912
8.70
128.
03
124.
90
122.
21
120.
62
N
EtOOCCOOEt
Cl
3g
Figure S40. 13C NMR spectrum of compound 3g
1H.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5Chemical Shift (ppm)
5.973.002.984.090.950.981.015.020.97
0.00
1.19
1.20
1.21
1.21
1.23
2.783.
793.
794.
104.11
4.12
4.13
4.14
4.15
4.16
4.17
4.68
6.936.
956.
997.01
7.037.
237.42
7.44
7.48
7.49
7.517.
597.
61
1H.ESP
7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8Chemical Shift (ppm)
0.981.015.020.97
6.93
6.95
6.996.
997.01
7.03
7.23
7.42
7.42
7.44
7.44
7.46
7.48
7.49
7.50
7.51
7.59
7.61
3h
N
EtOOCCOOEt
Figure S41. 1H NMR spectrum of compound 3h
S59
GGM-247-2-13C.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
0.00
14.0
6
20.4
4
34.4
4
50.3
0
61.4
2
105.
31
119.
0212
0.01
121.
19
125.
1212
7.20
128.
5013
1.15
136.
33
141.
17
168.
81
GGM-247-2-13C.ESP
131 130 129 128 127 126 125 124 123 122 121 120 119Chemical Shift (ppm)
119.
02
120.
01
121.
19
125.
12
127.
20
128.
5012
8.68
131.
0013
1.15
3h
N
EtOOCCOOEt
Figure S42. 13C NMR spectrum of compound 3h
1H.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5Chemical Shift (ppm)
6.003.013.004.000.930.992.035.01
7.49 7.48
7.47 7.
477.
457.
45 7.44
7.17
7.15 7.13
6.91
6.90 5.19
4.02 4.01 4.00
3.99 3.99
3.98
3.97
3.96
3.49
2.65
1.19
1.17
1.15
0.00
1H.ESP
7.5 7.4 7.3 7.2 7.1 7.0 6.9Chemical Shift (ppm)
0.992.035.01
7.49
7.48
7.47
7.47
7.45
7.44
7.43
7.43
7.23 7.
197.
177.
15 7.13
7.11
6.91
6.90
N
EtOOCCOOEt
3i
Figure S43. 1H NMR spectrum of compound 3i
S60
13C.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0Chemical Shift (ppm)
169.
44
140.
1113
7.25
131.
5413
1.20
128.
7812
8.11
125.
6712
2.35
122.
00
107.
6210
5.41
77.4
177
.09
76.7
7
61.4
2
51.0
3
30.9
8
20.6
7
13.9
9
13C.ESP
132 131 130 129 128 127 126 125 124 123 122Chemical Shift (ppm)
131.
5413
1.20
130.
22
128.
78
128.
11
125.
67
122.
3512
2.00
N
EtOOCCOOEt
3i
Figure S44. 13C NMR spectrum of compound 3i
GGM-263-2-1H.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5 -1.0Chemical Shift (ppm)
5.973.013.004.090.941.011.135.010.97
7.80
7.78 7.34
7.34
7.33 7.32
7.30 7.
247.
247.
17 7.15
4.73
4.20 4.
19 4.18
4.17 4.16
4.16
4.15
4.14
4.13
4.12
3.58
2.44
1.24
1.22
1.21
0.00
GGM-263-2-1H.ESP
7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1Chemical Shift (ppm)
1.011.135.010.97
7.80 7.78
7.35 7.
347.
347.
33 7.32
7.30
7.26
7.26 7.
24 7.24
7.24
7.22 7.17 7.
157.
157.
137.
13
N
EtOOCCOOEt
3j
Figure S45. 1H NMR spectrum of compound 3j
S61
GGM-263-2-13C.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
168.
88
140.
3213
8.63
137.
19
130.
8212
9.27
127.
6312
6.35
121.
9012
1.10
119.
85
109.
40
104.
80
61.4
4
50.3
0
30.9
2
21.3
7
14.0
6
0.00
N
EtOOCCOOEt
3j
Figure S46. 13C NMR spectrum of compound 3j
GGM-366-P-C2H5-1H.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5 -1.0Chemical Shift (ppm)
6.003.001.983.003.980.941.031.124.860.96
0.00
1.21
1.23
1.24
1.31
1.33
2.71
2.73
2.75
2.77
3.58
4.104.
124.134.
144.
154.16
4.17
4.17
4.18
4.19
4.20
4.22
4.75
7.15
7.177.
247.
247.
267.
327.
347.
357.
387.77
7.79
3k
N
EtOOCCOOEt
GGM-366-P-C2H5-1H.ESP
7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1Chemical Shift (ppm)
1.031.124.860.96
7.13
7.13
7.15
7.17
7.17
7.227.
247.24
7.24
7.26
7.26
7.32
7.34
7.35
7.387.77
7.79
Figure S47. 1H NMR spectrum of compound 3k
S62
GGM-366-P-C2H5-13C.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
0.00
14.0
615
.38
28.7
130
.9650
.30
61.4
4
76.7
277
.04
77.3
6
104.
75
109.
41
119.
8412
1.09
121.
8812
6.34
127.
8212
8.05
130.
88
137.
1714
0.36
144.
82
168.
90
3k
N
EtOOCCOOEt
Figure S48. 13C NMR spectrum of compound 3j
GGM-289-3-1H-ESP.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5Chemical Shift (ppm)
6.003.013.004.060.951.981.021.121.001.980.96
7.79
7.77
7.39
7.38 7.
367.
317.
247.
047.
027.
01
4.73
4.22 4.
19 4.18
4.17 4.16
4.16
4.15
4.14
3.88
3.57
1.25
1.23
1.21
0.00
GGM-289-3-1H-ESP.ESP
7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0Chemical Shift (ppm)
1.981.021.121.001.980.96
7.79 7.77
7.39
7.38
7.36
7.36
7.33
7.31
7.26 7.26
7.24
7.22 7.
17 7.17
7.15
7.15
7.13
7.13
7.05
7.04
7.02
7.01
N
EtOOCCOOEt
OMe
3l
Figure S49. 13H NMR spectrum of compound 3l
S63
GGM-289-3-13C-ESP.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
168.
93
159.
96
140.
1313
7.13
132.
23
126.
3512
2.78
121.
8812
1.04
119.
87
114.
04
109.
42
104.
81
77.4
077
.08
76.7
7
61.4
8
55.3
8
50.3
5
30.9
1
14.1
1
N
EtOOCCOOEt
OMe
3l
Figure S50. 13C NMR spectrum of compound 3l
GGM-262-3-1H.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5 -1.0Chemical Shift (ppm)
6.053.004.280.961.011.131.004.080.98
7.80
7.78
7.50
7.48
7.41
7.39
7.34 7.
327.
267.
177.
16
4.69
4.20 4.19 4.
184.
18 4.16
4.14
4.14
4.13 4.13
4.12
3.57
1.25
1.23
1.21
0.00
GGM-262-3-1H.ESP
7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1Chemical Shift (ppm)
1.011.131.004.080.98
7.80 7.78
7.50
7.48
7.41
7.39
7.34
7.32
7.28 7.
26 7.26
7.24
7.19
7.18
7.17
7.16
7.15
7.15
N
EtOOCCOOEt
Cl
3m
Figure S51. 1H NMR spectrum of compound 3m
S64
GGM-262-3-13C.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
168.
66
138.
7913
7.33
135.
0313
2.29
129.
1512
8.91
126.
2912
2.36
121.
2012
0.12
109.
53
105.
41
77.4
077
.08
76.7
7
61.6
0
50.1
9
31.0
1
14.0
9
0.03
N
EtOOCCOOEt
Cl
3m
Figure S52. 13C NMR spectrum of compound 3m
GGM-282-2-1H.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5Chemical Shift (ppm)
6.163.013.124.030.910.971.021.081.981.002.05
0.00
1.21
1.22
1.24
3.593.96
4.12
4.14
4.16
4.18
4.19
4.20
4.71
7.17
7.27
7.27
7.297.
347.
367.
557.57
7.79
7.81
8.18
8.20
GGM-282-2-1H.ESP
8.2 8.1 8.0 7.9 7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0Chemical Shift (ppm)
0.971.021.081.981.002.05
8.20 8.
18
7.81 7.79
7.57
7.55
7.36
7.34
7.29
7.27 7.
277.
25 7.19
7.17
7.16
7.15
3n
N
EtOOCCOOEt
COOMe
Figure S53. 1H NMR spectrum of compound 3n
S65
GGM-282-2-13C.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
168.
6016
6.69
138.
8713
7.55 13
5.37
130.
9912
9.79
126.
3512
2.56
121.
3212
0.21
109.
60
105.
74
77.4
477
.12
76.8
0
61.6
2
52.3
650
.15 31.1
4
14.0
8
N
EtOOCCOOEt
COOMe
GGM-282-2-13C.ESP
138 136 134 132 130 128 126Chemical Shift (ppm)
138.
87
137.
55 135.
37
130.
99
130.
3112
9.79
126.
35
3n
Figure S54. 13C NMR spectrum of compound 3n
GGM-260-2-1H.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5 -1.0Chemical Shift (ppm)
5.963.002.994.070.881.024.051.151.240.93
7.80
7.78
7.78
7.39
7.37 7.
327.
277.
277.
257.
247.
237.
16
4.74
4.21 4.
20 4.19
4.18 4.17
4.16
4.15
4.14
4.13
4.13
3.58
2.43
1.25
1.23
1.21
0.00
GGM-260-2-1H.ESP
7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0Chemical Shift (ppm)
1.024.051.151.240.93
7.80
7.80 7.78
7.78
7.41
7.39
7.37 7.
347.
32
7.28
7.27
7.27
7.25
7.24
7.23 7.23
7.16
7.16
7.14
N
EtOOCCOOEt
3o
Figure S55. 1H NMR spectrum of compound 3o
S66
GGM-260-2-13C.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
168.
90
140.
43 138.
2513
7.24
131.
6412
9.48
128.
4312
8.03
126.
38
121.
9712
1.18
119.
91
109.
45
104.
87
77.3
977
.08
76.7
6
61.4
8
50.3
1
31.0
1
21.5
2
14.1
1
GGM-260-2-13C.ESP
140 138 136 134 132 130 128 126 124 122 120Chemical Shift (ppm)
140.
43 138.
25
137.
24
131.
64
130.
58
129.
48
128.
4312
8.03
126.
38
121.
97
121.
18
119.
91
3o
N
EtOOCCOOEt
Figure S56. 13C NMR spectrum of compound 3o
GGM-259-2.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5Chemical Shift (ppm)
6.133.004.110.951.011.202.022.980.99
7.80
7.78 7.
48 7.46
7.46
7.45 7.45
7.35 7.33
7.25 7.17
4.71
4.21 4.
20 4.19
4.18
4.17
4.16
4.15
4.15
4.14
4.13
3.59
1.26
1.24
1.22
0.00
GGM-259-2.ESP
7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1Chemical Shift (ppm)
1.011.202.022.980.99
7.80 7.78
7.49
7.48
7.48
7.46
7.46
7.45 7.
45
7.37
7.37
7.35 7.
337.
29 7.29
7.28
7.27
7.25
7.25
7.19 7.19
7.17
7.17
7.16
7.15
3p
N
EtOOCCOOEt
Cl
Figure S57. 1H NMR spectrum of compound 3p
S67
GGM-259-2-13C.esp
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
168.
61
138.
4513
7.32
134.
5013
2.54
130.
9812
9.87
129.
1812
8.94
126.
25
122.
4612
1.25
120.
16
109.
55
105.
59
77.3
777
.06
76.7
4
61.6
2
50.1
2
31.0
6
14.0
7
3p
N
EtOOCCOOEt
Cl
GGM-259-2-13C.esp
140 138 136 134 132 130 128 126 124 122 120 118Chemical Shift (ppm)
138.
45
137.
32
134.
50
132.
54
130.
98
129.
8712
9.18
128.
94
126.
25
122.
46
121.
25
120.
16
Figure S58. 13C NMR spectrum of compound 3p
GGM-290-2-1H.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5Chemical Shift (ppm)
6.065.973.004.040.911.921.041.011.100.970.93
7.80
7.78
7.33 7.
31 7.09
7.06
4.75
4.20 4.19
4.18
4.17
4.16
4.16
4.15
4.14
3.58
2.39
1.25
1.24
1.22
0.00
GGM-290-2-1H.ESP
7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0Chemical Shift (ppm)
1.921.041.011.100.970.93
7.80 7.78
7.33
7.31
7.26
7.24
7.22 7.
177.
157.
13
7.09
7.06
3r
N
EtOOCCOOEt
Figure S59. 1H NMR spectrum of compound 3r
S68
GGM-290-2-13C.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
168.
96
140.
6413
8.06
137.
23
130.
4713
0.36
128.
7212
6.41
121.
8812
1.18
119.
86
109.
43
104.
75
77.4
277
.09
76.7
7 61.4
5
50.3
3
31.0
2
21.4
0
14.1
2
3r
N
EtOOCCOOEt
Figure S60. 13C NMR spectrum of compound 3r
GGM-270-3.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5 -1.0Chemical Shift (ppm)
3.182.913.013.003.970.951.056.210.97
7.82
7.80
7.41 7.
397.
387.
357.
33 7.27
7.25
7.24 7.17
7.16
4.49
4.17
4.15 4.
134.
134.
124.
104.
09
3.44
2.09
1.24
1.22
1.18
1.16
0.00
GGM-270-3.ESP
7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1Chemical Shift (ppm)
1.056.210.97
7.82 7.80
7.42 7.41
7.40 7.39
7.38 7.
387.
357.
33
7.29
7.27
7.25
7.24
7.23
7.19 7.
187.
177.
167.
15 7.15
3s
N
EtOOCCOOEt
Figure S61. 1H NMR spectrum of compound 3s
S69
GGM-270-3-13C.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
168.
8016
8.71
139.
75 139.
1713
7.08
131.
6013
0.12
129.
4612
6.39
125.
8712
1.77
121.
0511
9.86
109.
31
104.
93
77.3
977
.07
76.7
5
61.4
2
50.3
0
30.3
1
19.6
5 14.0
8
GGM-270-3-13C.ESP
131.5 131.0 130.5 130.0 129.5Chemical Shift (ppm)
131.
60
130.
33
130.
12
129.
46
GGM-270-3-13C.ESP
62.0 61.5 61.0 60.5 60.0 59.5Chemical Shift (ppm)
61.4
261
.38
3s
N
EtOOCCOOEt
Figure S62. 13C NMR spectrum of compound 3s
GGM-291-2-1H ESP.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5 -1.0Chemical Shift (ppm)
5.903.003.990.941.081.041.053.061.034.09
7.98
7.97 7.95
7.92
7.90
7.57
7.54
7.53
7.52 7.
357.
277.
217.
19
4.81
4.19 4.18
4.17
4.16 4.15
4.14
4.13
4.13
3.62
1.24
1.22
1.21
0.00
GGM-291-2-1H ESP.ESP
8.0 7.9 7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1Chemical Shift (ppm)
1.081.041.053.061.034.09
7.98
7.97 7.
957.
937.
927.
917.
91 7.90
7.85 7.83
7.57
7.54
7.53
7.52
7.37
7.35
7.29 7.
28 7.27
7.25
7.25
7.21
7.19
7.19
7.17
3t
N
EtOOCCOOEt
Figure S63. 1H NMR spectrum of compound 3t
S70
GGM-291-2-13CESP.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
14.1
4
31.1
8
50.3
4
61.5
6
76.8
277
.13
77.4
5
105.
43
109.
54
120.
0712
1.29
122.
21
126.
49
126.
7612
6.95
127.
8812
8.13
128.
2612
8.37
130.
6813
3.14
137.
4314
0.20
168.
883t
N
EtOOCCOOEt
GGM-291-2-13CESP.ESP
136 134 132 130 128 126 124 122 120Chemical Shift (ppm)
137.
43
133.
1413
3.12
130.
68
128.
3712
8.26
128.
1312
7.88
126.
9512
6.76
126.
49
122.
21
121.
29
120.
07
Figure S64. 13C NMR spectrum of compound 3t
GGM-300(2-CH3)ESP.ESP
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5 -1.0Chemical Shift (ppm)
6.183.002.963.980.840.980.951.000.85
7.61
7.59
7.25
7.24 7.
237.
157.
147.
117.
10 7.09
7.07
4.89
4.23 4.
234.
22 4.21
4.20
4.19
4.18
4.17
4.16
3.65 2.41
1.27
1.25
1.23
0.00
GGM-300(2-CH3)ESP.ESP
7.6 7.5 7.4 7.3 7.2 7.1 7.0Chemical Shift (ppm)
0.980.951.000.85
7.61 7.
59
7.25
7.23
7.17 7.
177.
16 7.15
7.14 7.
11 7.10
7.09
7.08
7.07
7.07
3u
N
EtOOCCOOEt
Figure S65. 1H NMR spectrum of compound 3u
S71
GGM-300(2-CH3)13C.ESP
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)
168.
94
136.
5713
5.43
126.
75
120.
96
119.
08
108.
78
103.
07
77.3
977
.08
76.7
6
61.5
9
49.6
5
29.6
7
14.1
310
.88
3u
N
EtOOCCOOEt
Figure S66. 13C NMR spectrum of compound 3u
S72
10.Determination of Structure of 3a
The structure of 3a was determined by the X-ray diffraction. Recrystallized from EtOH/dichloromethane. Further information can be found in the CIF file. This crystal was deposited in the Cambridge Crystallographic Data Centre and assigned as CCDC 1923193.
Table 1 Crystal data and structure refinement for 3aIdentification code 20190478Empirical formula C22H23NO4
Formula weight 365.41Temperature/K 293(2)Crystal system monoclinicSpace group P21/c
a/Å 13.2745(8)b/Å 7.8001(2)c/Å 24.2247(14)α/° 90β/° 129.278(10)γ/° 90
Volume/Å3 1941.6(3)Z 4
ρcalcg/cm3 1.250
S73
μ/mm-1 0.697F(000) 776.0
Crystal size/mm3 0.17 × 0.14 × 0.12Radiation CuKα (λ = 1.54184)
2Θ range for data collection/° 7.76 to 134.144Index ranges -10 ≤ h ≤ 15, -7 ≤ k ≤ 9, -28 ≤ l ≤ 25
Reflections collected 7250Independent reflections 3471 [Rint = 0.0268, Rsigma = 0.0315]
Data/restraints/parameters 3471/0/247Goodness-of-fit on F2 1.040
Final R indexes [I>=2σ (I)] R1 = 0.0490, wR2 = 0.1250Final R indexes [all data] R1 = 0.0630, wR2 = 0.1387
Largest diff. peak/hole / e Å-3 0.22/-0.23