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Supporting Information

� Wiley-VCH 2010

69451 Weinheim, Germany

Modular Synthesis of 1,2-Diamine Derivatives by Palladium-CatalyzedAerobic Oxidative Cyclization of Allylic Sulfamides**Richard I. McDonald and Shannon S. Stahl*

anie_200906342_sm_miscellaneous_information.pdf

S1

Table of Contents Page Additional Reaction Optimization Screening Tables S2-S3 IR Studies of Pd(TFA)2•2DMSO S4 NMR Studies S5 General Considerations S6 Representative Procedure for PdII-Catalyzed Aerobic Oxidative Cyclization S6 Synthesis and Characterization Data of Sulfamide Substrates S7-S15 Sulfamide Ring Opening to Yield 1,2-Diamines S15-S16 Synthesis of Allylic Amines S16-S18 Characterization Data for Cyclic Sulfamides S18-S22 NOE Correlation for Sulfamide S39 (Table 3, Entry 8) S24-S26 Crystallographic Characterization of Sulfamide S38 (Table 3, Entry 6) S27-S35 Crystallographic Characterization of 10 S36-S45

S2

Table S1. Additional Reaction Optimization Data.

BnNS

NBn

O O5% PdII

additives

24 hours

O2 (1 atm)

BnNS

NHBn

OO

BnNS

N

OO

Ph+

A B1 Entry Catalyst

(5%) Additive 1 (mol %)a

Additive 2 (mol %)b Solvent Temp

°C % yield A (B)b

1 Pd(OAc)2 10 py -- toluene 80 39 (25)

2 Pd(OAc)2 10 py 3Å MS THF 25 0

3 Pd(OAc)2 -- -- DMSO 80 45

4 Pd(OAc)2 10 DMSO 3Å MS THF 25 10

5 Pd(OAc)2 -- 200 NaOBz DMSO 80 24

6 Pd(OAc)2 -- 200 NaOBz DMSO 25 22

7 Pd(OAc)2 20 py 20 NaOBz / 3Å MS dioxane 80 25

8 Pd(OAc)2 10 Et3N 3Å MS 15% THF / toluene 80 4 (7)

9 Pd(OAc)2 10 Et3N 3Å MS 15% THF / toluene 25 5 (14)

10 Pd(TFA)2 10 py -- toluene 80 10

11 Pd(TFA)2 10 py 3Å MS toluene 80 51

12 Pd(TFA)2 20 py 3Å MS toluene 80 49

13 Pd(TFA)2 20 py 50 NaOAc / 3Å MS toluene 80 66 (12)




17 Pd(TFA)2 20 py 200 NaOAc toluene 80 76 (8)

18 Pd(TFA)2 20 py 20 Na2CO3 dioxane 80 0

19 Pd(TFA)2 20 py 20 NaOBz dioxane 80 25

20 Pd(TFA)2 10 py / 5 CuCl2

20 NaOAc / 3Å MS dioxane 80 0

21 Pd(TFA)2 10 py / 5 Cu(OAc)2


22 Pd(TFA)2 10 py / 5 Cu(TFA)2


23 Pd(TFA)2 10 ethyl nicotinate


24 Pd(TFA)2 -- 20 NaOBz / 3Å MS DMSO 25 47

S3

25 Pd(TFA)2 -- 20 NaOBz DMSO 25 39

25 Pd(TFA)2 -- 3Å MS DMSO 25 25

26 Pd(TFA)2 -- 20 NaOBz / 3Å MS THF 25 9c

27 Pd(TFA)2 20 py / 10 DMSO

20 NaOBz / 3Å MS dioxane 80 48

28 Pd(TFA)2 10 DMSO 20 NaOBz / 3Å MS dioxane 80 92

29 Pd(TFA)2 10 DMSO 20 NaOBz / 3Å MS THF 25 99c



32 Pd(TFA)2 10 DMSO 20 NaOBz / 3Å MS THF 25 75d

33 Pd(OBz)2 10 DMSO 3Å MS THF 25 16

34 Pd(OBz)2 10 DMSO 20 NaOBz / 3Å MS THF 25 43

Conditions: 1 (0.075 mmole), 1 atm O2, solvent (0.75 mL), 24 hr., if noted 3Å MS (20 mg). apy = pyridine. bDetermined by 1H NMR spectroscopy, internal standard = 1,3,5-trimethoxybenzene. c10 hr. dOpen to air.

Table S2. Solvent Screen.

BnNS

NBn

O O

5% Pd(TFA)2

10% DMSO20% NaOBz, 3Å MS

10 hours, room tempO2, solvent (0.1M)

BnNS

NHBn

OO

1

Entry Solvent % Yielda 1 tetrahydrofuran 100 2 1,4-dioxane 91 3 diethyl ether 69 4 dimethoxyethane 79 5 toluene 80 6 hexane 20 7 MeOH 63 8 t-BuOH 27 9 t-amyl alcohol 34 10 chloroform 19 11 dichloromethane 25 12 dichloroethane 28 13 acetone 91 14 acetonitrile 30

Conditions: 1 (0.075 mmole), 3Å MS (20 mg), 1 atm O2, solvent (0.75 mL), 24 hr. aDetermined by 1H NMR spectroscopy, internal standard = 1,3,5-trimethoxybenzene.

S4

IR Studies of Pd(TFA)2•2DMSO. A crystal structure of PdII(DMSO)2(TFA)2 has been reported previously and the complex exhibits one O-bound and one S-bound DMSO ligand.1 In order to ensure that this coordination mode is not an artifact of crystallization (e.g., crystal packing effects, different solubilities of complexes with different DMSO linkage isomers), we analyzed the 2:1 DMSO:PdII(TFA)2 mixture by FTIR spectroscopy. Infrared spectroscopy is an effective method to distinguish between S- vs O-bound DMSO ligands coordinated to transition metals.2 Relative to the S–O vibrational frequency of free DMSO (νS-O = 1055 cm-1), the S–O vibration for S-bound DMSO occurs at higher frequency (1080-1154 cm-1), whereas the S–O vibration for O-bound DMSO occurs at lower frequency (862-997 cm-1).3 Pd(TFA)2 was mixed with 2 equiv of DMSO in THF, followed by removal of the solvent at reduced pressure to provide an orange solid. An infrared spectrum of this material was obtained (shown below). The infrared spectrum revealed the presence of new absorption bands at frequencies both higher and lower than that of free DMSO that are similar to frequencies observed in S- and O-coordinated DMSO ligands in previously characterized Pd complexes, such as Pd(DMSO)2Cl2,4 [Pd(DMSO)4](BF4)2

2a and [Pd(DMSO)4](ClO4)2.2a These results confirm the presence of both S- and O-bound DMSO in the PdII(DMSO)2(TFA)2 catalyst system.

Infrared absorption bands: Pd(TFA)2 IR (cm-1): 657, 745, 874, 1171, 1575. Pd(TFA)2•2DMSO IR (cm-1): 731, 789, 845, 925, 992, 1026, 1149, 1182, 1405, 1687, 1701

1 Bancroft, D. P.; Cotton, F. A.; Verbruggen, M. Acta Crystallogr., Sect. C: Cryst. Struct. Commun. 1989, 45, 1289-1292. 2 See for example: (a) Wayland, B. B.; Schramm, R. F. Inorg. Chem. 1969, 8, 971-976. (b) Price, J. H.; Schramm, R. F.; Wayland, B. B. J. Chem. Soc. (D): Chem. Comm. 1970, 1377-1378. (c) Price, J. H.; Williamson, A. N.; Schramm, R. F.; Wayland, B. B. Inorg. Chem. 1972, 1 1, 1280-1284. 3 Calligaris, M. Coord. Chem. Rev. 2004, 248, 351-375. 4 Cotton, F. A.; Francis, R.; Horrocks, Jr. W. D. J. Phys. Chem. 1960, 1534-1536.

Pd(TFA)2 Pd(TFA)2 • 2DMSO

S5

NMR Spectroscopic Studies of Pd(TFA)2•2DMSO and (py)2Pd(TFA)2 in THF-d8. A 2:1 mixture of DMSO (1.1 µL, 15.4 µmol) and Pd(TFA)2 (2.56 mg, 7.7 µmol) was dissolved in THF-d8 (500 µL). Independently, a solution of (py)2Pd(TFA)2 (synthesized as described previously5) (4.9 mg, 10.0 µmol) was prepared in THF-d8 (650 µL, 15.4 mM). 1H NMR spectra (500 MHz) of these two solutions were obtained at temperatures ranging from -60 – 40 °C. The variable-temperature 1H NMR spectra are shown in the stacked plots below. The assignments of S- and O-bound DMSO ligand resonances are made on the basis of previously characterized PdII- and PtII-DMSO complexes.6

5 Trend, R. M.; Ramtohul, Y. K.; Stoltz, B. M. J. Am. Chem. Soc. 2005, 127, 17778-17788. 6 (a) Davies, J. A.; Hartley, F. R.; Murray, S. G.; J. Chem. Soc. Dalton Trans. 1979, 1705-1708. (b) Annibale, G.;

Cattalini, L.; Bertolasi, V.; Ferretti, V.; Gilli, G.; Tobe, M. L. J. Chem. Soc. Dalton Trans. 1989, 1265-1271.

N

H1 H2

H3PdpyTFA

TFAPd(TFA)2 • 2DMSO

H1 H2 H3-60 ºC

-40 ºC

-20 ºC

0 ºC

+24 ºC

+40 ºC

HDMSO (S-bound) HDMSO (O-bound) THF

S6

Experimental. 1. General Considerations. All commercially available compounds were purchased and used as received. Solvents were dried over alumina columns prior to use; however, purification and drying of commercial solvents is not required for the catalytic reactions described here. 1H and 13C NMR spectra were recorded on Bruker or Varian 300 MHz spectrometers. Chemical shift values are given in parts per million relative to internal TMS (0.00 ppm for 1H) or CDCl3 (77.23 ppm for 13C). Infrared spectra were obtained as neat powders on a Bruker Tensor 27 FTIR spectrometer using an ATR accessory with a germanium crystal. Flash chromatography was performed using SiliaFlash® P60 (Silicycle, particle size 40-63 µm, 230-400 mesh). 2. Representative Procedure for PdII-Catalyzed Aerobic Cyclization.

5% Pd(TFA)2

10% DMSO

20% NaOBz3Å MS (80 mg)

THF (0.1M), 24 h 25°C, O2 (1 atm)

BnNS

NBn

O OBnN

SNHBn

OO

Most of the catalytic aerobic oxidation reactions were performed using a custom reaction apparatus that enabled several reactions to be performed simultaneously under a constant pressure of O2 (approx 1 atm) with controlled temperature and orbital agitation. Control experiments (see below) demonstrated that similar results can be obtained using a standard round-bottom flask equipped with a stir bar and a balloon of O2. Procedure for reactions performed in a custom parallel reactor: The sulfamide starting material (99.1 mg, 0.3 mmole, 1 equiv), Pd(TFA)2, (5.0 mg, 0.015 mmole, 0.05 equiv), sodium benzoate (8.6 mg, 0.06 mmole, 0.2 equiv), and powdered 3Å molecular sieves (80 mg) were combined in a 30 mL glass reaction vessel (note: the powdered 3Å molecular sieves were stored on the benchtop; glovebox storage was not required7). The headspace was purged with O2 for 10 min, after which a solution of DMSO (2.1 µL, 0.03 mmole, 0.1 equiv) in tetrahydrofuran (3 mL, 0.1M) was added via syringe. The solution was stirred vigorously at room temperature for 10 h or for a time determined by 1H NMR spectroscopic monitoring of the reaction progress. After 10 h, the O2 was purged from the vessel, and the solution was loaded directly onto a silica gel column and purified by flash chromatography (3.5:1 hexanes/EtOAc mixture) to yield 97.7 mg of the product (99.2% yield, white solid). Alternatively, the crude reaction solution was filtered through a pad of basic alumina, eluting with a 1:1 hexanes/EtOAc mixture. Removal of solvent at reduced pressure provided analytically pure product (98.7% yield). Procedure for reactions performed in a round-bottom flask: All solids were combined in a large 3-necked round-bottom flask equipped with a large stir bar, to which was attached a reflux condenser and three rubber septa (a large stir bar and oversized round bottom flask are required is needed to ensure good gas-liquid mixing). The system was then purged with a flow of O2 via a needle through the rubber septum, followed by attachment of an O2 filled balloon to the top of the reflux condensor. After injection of a DMSO / THF solution via syringe, the reaction mixture was stirred vigorously for 24 hours at room temperature, at which point the compound was purified as described above. 7 For a study of the possible role of molecular sieves in Pd-catalyzed aerobic oxidation reactions, see: Steinhoff, B. A.; King, A. E.; Stahl, S. S. J. Org. Chem. 2006, 71, 1861-1868.

S7

3. Synthesis of Sulfamide Substrates. The sulfamide substrates were prepared according to previously reported procedures via the representative two-step sequence shown below.8,9 Pertinent yields, purification methods, and characterization data for the individual sulfamyl oxazolidinones and sulfamide substrates is provided below.

NH

Bn

S1

Et3N

CH3CN

reflux, 17 h1

O NS

NH

O O

Bn

O

BnNS

NHBn

OO

CSI, 2-chloroethanol

Et3N

CH2Cl2

H2N Ph

CSI = chlorosulfonyl isocyanate

S1

O NSNH

O OO

Ph

99% yield; white solid (recrystallized from EtOAc). 1H NMR (300 MHz, CDCl3) δ 3.78 (t, J = 7.8 Hz, 2H), δ 4.17 (t, J = 7.8 Hz, 2H), δ 4.31 (s, 2H), δ 5.91 (bs, 1H), δ 7.3 – 7.43 (m, 5H); 13C NMR (75 MHz, 3:1 CDCl3:DMSO) δ 44.1, δ 46.3, δ 61.2, δ 126.9, δ 127.0, δ 127.7, δ 136.1, δ 151.7; HRMS: m/z (ESI) calculated [M+H]+ = 257.0591, measured 257.0595 (∆ = 1.6 ppm).

1

NSNH

OO

Ph Ph

93% yield; white solid (elution solvent – hexanes:EtOAc = 3:1). 1H NMR (300 MHz, CDCl3) δ 1.69 (dd, J = 6.1, 1.0 Hz, 3H), δ 3.69 (d, J = 6.5 Hz, 2H), δ 4.16 (d, J = 6 Hz, 2H), δ 4.35 – 4.39 (m, 3H), δ 5.45 (dtq, J = 15.2, 6.5, 1.0 Hz, 1H), δ 5.58 (dq, J = 15.2, 6.4 Hz, 1H), δ 7.25 – 7.37 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 17.9, δ 47.5, δ 49.4, δ 50.5, δ 125.6, δ 127.9, δ 128.2, δ 128.7, δ 128.8, δ 129.0, δ 136.7, δ 136.9; HRMS: m/z (ESI) calculated [M+H]+ = 331.1475, measured 331.1473 (∆ < 1 ppm).

S2

O NSNH

O OO

93% yield; white solid. 1H NMR (300 MHz, 3:1 CDCl3:d6-DMSO) δ 0.93 (t, J = Hz, 3H), δ 1.39 (sextet, J = 7.2 Hz, 2H), δ 1.57 (pentet, J = 7.3 Hz, 2H), δ 3.11 (t, J = 7.0 Hz, 2H), δ 4.07 (dd, J = 8.3, 6.6 Hz, 2H), δ 4.45 (dd, J = 9.2, 7.5 Hz, 2H), δ 5.62 (m, 1H); 13C NMR (75 MHz, 3:1 CDCl3:d6-DMSO) δ 13.7, δ 19.8, δ 31.3, δ 44.0, δ 45.5, δ 62.8, δ 153.7; HRMS: m/z (ESI) calculated [M+H]+ = 223.0748, measured 223.0750 (∆ < 1 ppm).

8 Borghese, A.; Antoine, L.; Van Hoeck, J. P.; Mockel, A.; Merschaert, A. Org. Process Res. Dev. 2006, 10, 770-775. 9 Zabawa, T. P.; Chemler, S. R. Org. Lett. 2007, 9, 2035-2038.

S8

S3

NSNH

OO

Ph

92% yield; colorless oil (elution solvent – hexanes:EtOAc = 3:1). 1H NMR (300 MHz, CDCl3) δ 0.91 (t, 7.2 Hz, 3H), δ 1.34 (sextet, J = 7.0 Hz, 2H), δ 1.48 (pent, J = 7.0 Hz, 2H), δ 1.70 (d, J = 5.8 Hz, 3H), δ 2.98 (q, J = 7.0Hz, 2H), δ 3.67 (d, J = 6.0 Hz, 2H), δ 4.16 (t, J = 5.9 Hz, 1H), δ 4.35 (s, 2H), δ 5.44 – 5.62 (m, 2H), δ 7.26 – 7.37 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 13.8, δ 17.9, δ 20.1, δ 31.8, δ 43.1, δ 49.3, δ 50.4, δ 125.7, δ 127.8, δ 128.68, δ 128.73, δ 131.1, δ 136.9; HRMS: m/z (ESI) calculated [M+H]+ = 297.1632, measured 297.1635 (∆ = 1.0 ppm).

S4

O NSNH

O O

Ph

O

91% yield; white solid. 1H NMR (300 MHz, 3:1 CDCl3:d6-DMSO) δ 3.89 (dd, J = 8.3, 6.7 Hz, 2H), δ 4.25 (dd, J = 9.2, 7.5 Hz, 2H), δ 7.14 – 7.19 (m, 1H), δ 7.26 – 7.35 (m, 4H), δ 10.60 (bs, 1H); 13C NMR (75 MHz, 3:1 CDCl3:d6-DMSO) δ 45.9, δ 61.9, δ 121.1, δ 125.0, δ 135.8, δ 152.0; HRMS: m/z (ESI) calculated [M+H]+ = 243.0435, measured 243.0433 (∆ < 1 ppm).

S5

NSNH

OO

PhPh

93% yield; white solid (elution solvent – hexanes:EtOAc = 3:1). 1H NMR (300 MHz, CDCl3) δ 1.63 (dd, J = 6.4, 1.4 Hz, 3H), δ 3.65 (d, J = 6.8 Hz, 2H), δ 4.34 (s, 2H), δ 5.20 (dtq, J = 15.3, 6.8, 1.4 Hz, 1H), δ 5.50 (dq, J = 15.3, 6.4 Hz, 1H), δ 6.48 (s, 1H), δ 7.09 – 7.17 (m, 5H), δ 7.26 – 7.34 (m, 5H); 13C NMR (125 MHz, CDCl3) δ 17.9, δ 49.4, δ 50.7, δ 120.6, δ 124.8, δ 125.2, δ 128.0, δ 128.75, δ 128.79, δ 129.6, δ 131.5, δ 136.1, δ 137.4; HRMS: m/z (ESI) calculated [M+H]+ = 317.1319, measured 317.1317 (∆ < 1 ppm).

S6

NSNH

OOOMe

Ph

90% yield; light yellow solid (elution solvent – hexanes:EtOAc = 3:1). 1H NMR (300 MHz, CDCl3) δ 1.56 (d, J = 6.1 Hz, 3H), δ 3.61 (d, J = 6.8 Hz, 2H), δ 3.75 (s, 3H), δ 4.30 (s, 2H), δ (dtq, J = 15.2, 6.8, 1.6 Hz, 1H) δ (dq, J = 15.3, 6.4 Hz, 1H), δ 6.79 – 6.85 (m, 2H), δ 7.10 – 7.25 (m, 8H); 13C NMR (75 MHz, CDCl3) δ 17.7, δ 49.1, δ 50.3, δ 55.5, δ 114.5, δ 124.0, δ 125.2, δ 127.6, δ 128.5, δ 130.0, δ 130.9, δ 136.2, δ 157.3; HRMS: m/z (ESI) calculated [M–H]- = 345.1278, measured 345.1271 (∆ = 2.0 ppm).

S9

S7

NSNH

OOCO2Et

Ph

40% yield; white solid (elution solvent – hexanes:EtOAc = 3:1). 1H NMR (300 MHz, CDCl3) δ 1.40 (t, J = 7.2 Hz, 3H), δ 1.63 (d, J = 6.3 Hz, 3H), δ 3.70 (d, J = 6.7 Hz, 2H), δ 4.34 – 4.41 (m, 4H), δ 5.25 (dtq, J = 15.3, 6.8, 1.6 Hz, 1H), δ 5.53 (dq, J = 15.3, 6.5 Hz, 1H), δ 7.03 (bs, 1H), δ 7.09 (d, J = 8.7 Hz, 2H), δ 7.15 – 7.18 (m, 2H), δ 7.26 – 7.28 (m, 3H), δ 8.00 (d, J = 8.7 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 14.6, δ 17.9, δ 49.6, δ 50.9, δ 61.2, δ 118.2, δ 124.8, δ 126.0, δ 128.2, δ 128.7, δ 128.9, δ 131.3, δ 131.9, δ 135.8, δ 141.7, δ 166.3; HRMS: m/z (ESI) calculated [M+Na]+ = 411.1349, measured 411.1336 (∆ = 3.2 ppm).

NO

O

SNH

OO

CO2Et

S8 99% yield; white solid (recrystallized from EtOAc). 1H NMR (300 MHz, CDCl3) δ 1.39 (t, J = 7.1 Hz, 3H), δ 3.94 (dd, J = 8.6, 6.8 Hz, 2H), δ 4.30 – 4.42 (m, 4H), δ 7.44 (t, J = 7.7 Hz, 1H), δ 7.55 (d, J = 7.7 Hz, 1H), δ 7.91 (d, J = 7.7 Hz, 1H), δ 8.00 (s, 1H), δ 8.51 (broad s, 1H); 13C NMR (75 MHz, CDCl3) δ 14.4, δ 46.3, δ 61.6, δ 62.9, δ 123.1, δ 126.5, δ 127.5, δ 129.9, δ 132.1, δ 136.0, δ 153.1, δ 166.0; HRMS: m/z (ESI) calculated [M+NH4]+ = 332.0911, measured 332.0913 (∆ < 1 ppm).

NSNH

OO

CO2Et

S9

Ph

75% yield; white solid (elution solvent – hexanes:EtOAc = 3:1). 1H NMR (300 MHz, CDCl3) δ 1.40 (t, J = 7.2 Hz, 3H), δ 1.63 (d, J = 6.5 Hz, 3H), δ 3.68 (d, J = 6.7 Hz, 2H), δ 4.36 (s, 2H), δ 4.40 (q, J = 7.2 Hz, 2H), δ 5.24 (dtq, J = 15.2, 6.8, 1.3 Hz, 1H), δ 5.52 (dq, J = 15.2, 6.6 Hz, 1H), δ 6.91 (s, 1H), δ 7.14 – 7.18 (m, 2H), δ 7.23 – 7.29 (m, 3H), δ 7.36 – 7.42 (m, 2H), δ 7.72 – 7.85 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 14.5, δ 17.9, δ 49.5, δ 50.8, δ 61.5, δ 121.2, δ 124.4, δ 125.0, δ 125.6, δ 128.1, δ 128.7, δ 128.8, δ 129.6, δ 131.7, δ 131.8, δ 136.0, δ 137.8, δ 166.3; HRMS: m/z (ESI) calculated [M+H]+ = 389.1530, measured 389.1533 (∆ < 1 ppm).

S10

NSNH

OO

PhPh

43% yield; white solid (elution solvent – hexanes:EtOAc = 3:1). 1H NMR (300 MHz, CDCl3) δ 1.59 (d, J = 5.0 Hz, 3H), δ 4.15 (dd, J = 5.5, 0.9 Hz, 2H), δ 4.19 (d, J = 6.1 Hz, 2H), δ 4.65 (t, J = 6.1 Hz, 1H), δ 5.41 – 5.56 (m, 2H), δ 7.23 – 7.38 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 17.9, δ 47.8, δ 54.6, δ 126.1, δ 127.8, δ 128.2, δ 128.7, δ 129.0, δ 129.4, δ 130.6, δ 136.8, δ 140.6; HRMS: m/z (ESI) calculated [M+H]+ = 317.1319, measured 317.1313 (∆ = 1.9 ppm).

S10

NO

O

SNH

OO

F

S11 94% yield; white solid (recrystallized from EtOAc). 1H NMR (300 MHz, CDCl3) δ 3.81 (dd, J = 8.4, 6.5 Hz, 2H), δ 4.17 (dd, J = 9.4, 7.5 Hz, 2H), δ 4.26 (d, J = 6.0 Hz, 2H), δ 7.01 – 7.09 (m, 2H), δ 7.34 – 7.41 (m, 2H), δ 8.75 (t, J = 6.1 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 44.3, δ 45.6, δ 61.5, δ 128.9, δ 129.0, δ 132.2, δ 132.2, δ 151.9; HRMS: m/z (ESI) calculated [M+H]+ = 275.0497, measured 275.0510 (∆ = 4.7 ppm).

NSNH

OO

F

S12

Ph

96% yield; white solid (elution solvent – hexanes:EtOAc = 3:1). 1H NMR (300 MHz, CDCl3) δ 1.68 (dd, J = 6.2, 1.1 Hz, 3H), δ 3.65 (d, J = 6.7 Hz, 2H), δ 4.10 (d, J = 6.2 Hz, 2H), δ 4.33 (s, 2H), δ 4.75 (t, J = 6.2 Hz, 1H), δ 5.411 (dtq, 15.2, 6.7, 1.3 Hz, 1H), δ 5.56 (dqt, J = 15.2, 6.4, 0.9 Hz, 1H), δ 6.95 – 7.03 (m, 2H), δ 7.20 – 7.36 (m, 7H); 13C NMR (75 MHz, CDCl3) δ 17.9, δ 40.3, δ 49.2, δ 50.4, δ 108.3, δ 110.7, δ 125.5, δ 127.8, δ 128.7, δ 131.2, δ 136.6, δ 142.7, δ 150.4; HRMS: m/z (ESI) calculated [M+Na]+ = 371.1200, measured 371.1217 (∆ = 4.6 ppm).

NO

O

SNH

OO

NBoc

S13 95% yield; colorless wax (elution solvent – CH2Cl2/MeOH). 1H NMR (300 MHz, CDCl3) ~7.1:1 ratio of rotomers: δ 1.46 (s, 9H + 1.3H), δ 2.90 (s, 3H, minor rotomer δ 2.89), δ 3.32 (broad s, 2H + 0.3H), δ 3.39 – 3.43 (m, 2H + 0.3H), δ 4.06 (dd, J = 8.3, 6.8 Hz, 2H, minor rotomer δ 3.71 – 3.75), δ 4.40 – 4.47 (m, 2H + 0.3H), δ 6.56 (broad s, 1H, minor rotomer δ 6.49); 13C NMR (75 MHz, CDCl3) δ 28.3, δ 35.1, δ 41.5, δ 42.1, δ 42.3, δ 45.4, δ 47.8, δ 48.5, δ 53.6, δ 65.7, δ 80.1, δ 151.5, δ 153.4, δ 155.6, δ 156.5; HRMS: m/z (ESI) calculated [M+H]+ = 324.1224, measured 324.1209 (∆ = 4.6 ppm).

NSNH

OO

NBoc

S14

Ph

82% yield; colorless oil (elution solvent – hexanes:EtOAc = 3:1). 1H NMR (300 MHz, CDCl3) ~1.3:1 ratio of rotomers: δ 1.46 (s, 9H), δ 1.69 (d, J = 5.4 Hz, 3H), δ 2.88 (s, 3H), δ 3.15 (broad s, 2H), δ 3.38 (t, J = 5.9 Hz, 2H), δ 3.65 (d, J = 5.9 Hz, 2H), δ 4.34 (s, 2H), δ 5.27 (broad s, 0.54H, minor rotomer δ 4.93), δ 5.43 – 5.62 (m, 2H), δ 7.24 – 7.36 (m, 5H); 13C NMR (75 MHz, CDCl3) ~1.3:1 ratio of rotomers; δ 17.8, δ 28.5, δ 35.2, δ 41.9, δ 48.2 (minor rotomer δ 48.7), δ 49.1, δ 50.2, δ 80.2, δ 125.5, δ 127.7, δ 128.56, δ 128.63, δ 131.1, δ 136.7, δ 156.9 (minor rotomer δ 155.7); HRMS: m/z (ESI) calculated [M+H]+ = 398.2109, measured 398.2100 (∆ = 2.3 ppm).

S11

NO

O

SNH

OO

S15 62% yield; white solid (recrystallized from EtOAc). 1H NMR (300 MHz, CDCl3) δ 2.36 (apparent qt, J = 6.8, 1 Hz, 2H), δ 3.20 (q, J = 6.6 Hz, 2H), δ 4.07 (dd, J = 8.2, 6.6 Hz, 2H), δ 4.45 (dd, J = 9.3, 7.3 Hz, 2H), δ 5.13 – 5.20 (m, 2H), δ 5.61 (broad s, 1H), δ 5.75 (ddt, J = 17.1, 10.3, 6.8 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 33.5, δ 43.3, δ 45.5, δ 62.8, δ 118.5, δ 134.0, δ 153.6; HRMS: m/z (ESI) calculated [M+H]+ = 221.0591, measured 221.0589 (∆ < 1 ppm).

NSNH

OO

S16

Ph

95% yield; white solid (elution solvent – hexanes:EtOAc = 3:1). 1H NMR (300 MHz, CDCl3) δ 1.71 (dd, J = 5.8, 1 Hz, 3H) δ 2.27 (qt, J = 6.8, 1.1 Hz, 2H), δ 3.06 (q, J = 6.6 Hz, 2H), δ 3.66, (d, J = 6.1 Hz, 2H), δ 4.27 (t, J = 6.1 Hz, 1H), δ 4.35 (s, 2H), δ 5.09 – 5.15 (m, 2H), δ 5.43 – 5.77 (m, 3H), δ 7.26 – 7.38 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 17.9, δ 33.8, δ 42.2, δ 49.3, δ 50.4, δ 118.2, δ 125.6, δ 127.8, δ 128.65, δ 128.73, δ 131.2, δ 134.6, δ 136.8; HRMS: m/z (ESI) calculated [M+H]+ = 295.1475, measured 295.1452 (∆ = 4.4 ppm).

NO

O

SNH

OOCl

S17 55% yield; white solid (recrystallized from EtOAc). 1H NMR (300 MHz, CDCl3) δ 3.06 (t, J = 7.1 Hz, 2H), δ 3.72 (t, J = 7.1 Hz, 2H), δ 3.83 (dd, J = 8.2, 6.7 Hz, 2H), δ 4.29 (dd, J = 9.2, 7.5 Hz, 2H), δ 7.22 – 7.29 (m, 4H), δ 7.68 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 17.9, δ 38.6, δ 45.2, δ 49.3, δ 50.6, δ 120.8, δ 125.1, δ 128.0, δ 128.69, δ 128.72, δ 129.9, δ 131.5, δ 134.6, δ 136.0, δ 136.2; HRMS: m/z (ESI) calculated [M+NH4]+ = 322.0623, measured 322.0613 (∆ = 3.1 ppm).

NSNH

OOCl

S18

Ph

90% yield; colorless oil (elution solvent – hexanes:EtOAc = 2:1). 1H NMR (300 MHz, CDCl3) δ 1.61 (dd, J = 6.5, 1.3 Hz, 3H), δ 3.04 (t, J = 7.2 Hz, 2H), δ 3.64 (d, J = 6.8 Hz, 2H), δ 3.70 (t, J = 7.2 Hz, 2H), δ 4.33 (s, 2H), δ 5.19 (dtq, J = 15.3, 6.8, 1.6 Hz, 1H), δ 5.48 (dq, J = 15.3, 6.5 Hz, 1H), δ 6.61 (broad s, 1H), δ 6.92 (broad s, 1H), δ 7.06 – 7.18 (m, 6H), δ 7.23 – 7.27 (m, 3H); 13C NMR (75 MHz, CDCl3) δ 17.9, δ 38.6, δ 45.2, δ 49.3, δ 50.6, δ 120.8, δ 125.1, δ 127.9, δ 128.69, δ 128.72, δ 129.9, δ 131.5, δ 134.6, δ 136.0, δ 136.2; HRMS: m/z (ESI) calculated [M+Na]+ = 401.1061, measured 401.1055 (∆ = 1.5 ppm).

S12

NO

O

SNH

OO

O

S19 92% yield; yellow solid (elution solvent – CH2Cl2/MeOH). 1H NMR (300 MHz, CDCl3) δ 3.92 (dd, J = 8.5, 6.5 Hz, 2H), δ 4.29 (dd, J = 9.4, 7.5 Hz, 2H), δ 4.35 (s, 2H), δ 6.06 (broad s, 1H), δ 6.35 – 6.37 (m, 2H), δ 7.405 – 7.414 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 39.1, δ 44.4, δ 61.5, δ 107.6, δ 109.8, δ 141.8, δ 149.5, δ 151.9; HRMS: m/z (ESI) calculated [M+NH4]+ = 264.0649, measured 264.0661 (∆ = 4.5 ppm).

NSNH

OO

O

S20

Ph

86% yield; yellow solid (elution solvent – hexanes:EtOAc = 3:1). 1H NMR (300 MHz, CDCl3) δ 1.68 (dd, J = 6.0, 1.0 Hz, 3H), δ 3.64 (d, J = 6.4 Hz, 2H), δ 4.17 (d, J = 6.0 Hz, 2H), δ 4.33 (s, 2H), δ 4.71 (t, J = 6.0 Hz, 1H), δ 5.38 – 5.61 (m, 2H), δ 6.23 (dd, J = 3.2, 0.5 Hz, 1H), δ 6.32 (dd, J = 3.2, 1.9 Hz, 1H), δ 7.25 – 7.36 (m, 6H); 13C NMR (75 MHz, CDCl3) δ 17.9, δ 40.3, δ 49.2, δ 50.4, δ 108.3, δ 110.7, δ 125.5, δ 127.8, δ 128.7, δ 131.2, δ 136.6, δ 142.7, δ 150.4; HRMS: m/z (ESI) calculated [M+H]+ = 321.1268, measured 321.1279 (∆ = 3.4 ppm).

S21

NSNH

OO

Ph Ph

94% yield; white solid (elution solvent – hexanes:EtOAc = 3:1). 1H NMR (300 MHz, CDCl3) δ 1.57 – 1.59 (m, 6H), δ 3.70 (s, 2H), δ 4.08 (d, J = 6.1 Hz, 2H), δ 4.29 (s, 2H), δ 4.46 – 4.51 (m, 1H), δ 5.33 – 5.39 (m, 1H), δ 7.20 – 7.33 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 13.5, δ 14.0, δ 47.4, δ 50.7, δ 56.0, δ 124.7, δ 127.8, δ 128.0, δ 128.1, δ 128.6, δ 128.8, δ 129.0, δ 130.9, δ 136.9, δ 137.0; HRMS: m/z (ESI) calculated [M+H]+ = 345.1632, measured 345.1626 (∆ = 1.7 ppm).

S22

NSNH

OO

Et

Ph Ph

82% yield; white solid (elution solvent – hexanes:EtOAc = 3:1). 1H NMR (300 MHz, CDCl3) δ 0.92 (t, J = 7.5 Hz, 3H), δ 1.97 (p, J = 7.0Hz, 2H), δ 3.63 (d, J = 6.4 Hz, 2H) δ 4.11 (d, J = 6.2 Hz, 2H), δ 4.30 (s, 2H), δ 5.00 (t, J = 6.4 Hz, 2H), δ 5.34 (dt, J = 15.3. 6.6 Hz, 1H), δ 5.52 (dt, J = 15.3, 6.4 Hz, 1H) δ 7.22 – 7.27 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 13.7, δ 25.6, δ 47.4, δ 49.5, δ 50.6, δ 123.5, δ 127.9, δ 128.0, δ 128.3, δ 128.7, δ 128.8, δ128.9, δ 136.9, δ 137.4, δ 138.2; HRMS: m/z (ESI) calculated [M+H]+ = 345.1632, measured 345.1637 (∆ = 1.4 ppm).

S13

NSNH

OO

OTIPS

PhPh

S23 85% yield; coloress oil (elution solvent – hexanes:EtOAc = 4:1). 1H NMR (300 MHz, CDCl3) δ 1.04 – 1.09 (m, 21H), δ 3.77 (d, J = 5.7 Hz, 2H), δ 4.11 – 4.29 (m, 5H), δ 4.39 (s, 2H), δ 5.65 – 5.81 (m, 2H), δ 7.26 – 7.37 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 12.2, δ 18.2, δ 47.5, δ 48.9, δ 50.7, δ 63.2, δ 123.9, δ 128.0, δ 128.1, δ 128.2, δ 128.8, δ 128.8, δ 128.9, δ 135.3, δ 136.5, δ 136.9; HRMS: m/z (ESI) calculated [M+H]+ = 503.2761, measured 503.2742 (∆ = 3.8 ppm).

S24

O NSNH

O OO

Ph

Me

93% yield; white solid (recrystallized from EtOAc). 1H NMR (300 MHz, 3:1 CDCl3:d6-DMSO) δ 1.48 (d, J = 6.9 Hz, 3H), δ 3.22 – 3.34 (m, 1H), δ 3.60 – 3.74 (m, 2H), δ 3.95 – 4.04 (m, 1H), δ 4.52 (pent, J = 7.1 Hz, 1H), δ 7.26 – 7.39 (m, 5H), δ 8.91 (d, J = 8.0Hz, 1H); 13C NMR (75 MHz, 3:1 CDCl3:d6-DMSO) δ 22.5, δ 44.0, δ 53.4, δ 60.9, δ 125.2, δ 126.7, δ 127.7, δ 141.9, δ 151.3; HRMS: m/z (ESI) calculated [M–H]- = 269.0601, measured 269.0608 (∆ = 2.6 ppm).

S25

NSNH

OO

Ph

Me

Ph

80% yield; colorless oil (elution solvent – hexanes:EtOAc = 3:1). 1H NMR (300 MHz, CDCl3) δ 1.49 (d, J = 6.9 Hz, 3H), δ 1.58 (dd, J = 6.4, 1.1 Hz, 3H), δ 3.43 – 3.62 (m, 2H), δ 4.19 (ABq, ∆νAB = 19.14 Hz, JAB = 15.1 Hz, 2H), δ 4.50 (pent, J = 6.9 Hz, 1H), δ 5.02 (d, J = 6.9 Hz, 1H), δ 5.21 (dtq, J = 15.3, 6.7, 1.3 Hz, 1H), δ 5.41 (dq, J = 15.3, 6.4 Hz, 1H), δ 7.18 – 7.34 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 17.8, δ 24.4, δ 49.2, δ 50.4, δ 53.8, δ 125.6, δ 126.3, δ 127.7, δ 128.5, δ 128.7, δ 128.8, δ 136.7, δ 143.5; HRMS: m/z (ESI) calculated [M+Na]+ = 367.1451, measured 367.1451 (∆ < 1 ppm).

S26

NSNH

OO

Me

Ph Ph

78% yield; white solid (elution solvent – hexanes:EtOAc = 3:1). 1H NMR (300 MHz, CDCl3) δ 1.28 (d, J = 6.9 Hz, 3H), δ 1.71 (dd, J = 5.0, 1.1 HZ, 3H), δ 3.96 – 4.04 (m, 3H), δ 4.31 (ABq, ∆νAB = 32.8 Hz, JAB = 15.6 Hz, 2H), δ 4.44 – 4.52 (m, 1H), δ 5.56 – 5.72 (m, 2H), δ 7.15 – 7.18 (m, 2H), δ 7.23 – 7.40 (m, 8H); 13C NMR (75 MHz, CDCl3) δ 18.1, δ 18.8, δ 47.4, δ 48.2, δ 56.3, δ 127.7, δ 128.0, δ 128.2, δ 128.5, δ 128.7, δ 128.9, δ 131.4, δ 136.8, δ 138.7; HRMS: m/z (ESI) calculated [M+H]+ = 345.1632, measured 345.1631 (∆ < 1 ppm).

S14

S27

NSNH

OO

Ph

Ph Ph

82% yield; white solid (elution solvent – hexanes:EtOAc = 3:1). 1H NMR (300 MHz, CDCl3) δ 1.75 (dd, J = 6.1, 0.6 Hz, 3H), δ 3.78 – 3.86 (m, 1H), δ 3.91 – 3.99 (m, 2H), δ 4.31 (ABq, ∆νAB = 32.47 Hz, JAB = 15.1 Hz, 2H), δ 5.49 (d, 7.7 Hz, 1H), δ 5.77 (dqd, J = 15.3, 6.1, 0.6 Hz, 1H), δ 5.90 (ddq, J =15.3, 7.9, 1.5 Hz, 1H), δ 7.05 – 7.08 (m, 2H), δ 7.14 – 7.34 (m, 11H), δ 7.38 – 7.41 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 18.1, δ 47.2, δ 49.7, δ 64.6, δ 127.7, δ 127.9, δ 127.9, δ 128.0, δ 128.1, δ 128.45, δ 128.52, δ 128.6, δ 128.7, δ 128.8, δ 131.1, δ 136.7, δ 137.8, δ 139.8; HRMS: m/z (ESI) calculated [M+H]+ = 407.1788, measured 407.1791 (∆ < 1 ppm).

NSNH

OO

BnO

Ph Ph

S28 % yield; colorless oil (elution solvent – hexanes:EtOAc = 3:1). 1H NMR (300 MHz, CDCl3) δ 1.60 (d, J = 6.5 Hz, 3H), δ 3.50 (dd, J = 10.3, 5.2 Hz, 1H), δ 3.68 (apparent t, J = 9.6 Hz, 1H), δ 4.00 – 4.15 (m, 2H), δ 4.30 – 4.47 (m, 4H), δ 4.54 – 4.61 (m, 2H), δ 5.35 (ddq, J = 15.6, 7.,1, 1.6 Hz, 1H), δ 5.63 (dqd, J = 15.6, 6.4, 0.5 Hz, 1H), δ 7.09 – 7.14 (m, 2H), δ 7.21 – 7.33 (m, 11H), δ 7.36 – 7.39 (m, 2H); , J = , H); 13C NMR (75 MHz, CDCl3) δ 18.1, δ 47.2, δ 49.2, δ 60.2, δ 70.6, δ 73.3, δ 126.9, δ 127.6, δ 127.7, δ 128.06, δ 128.09, δ 128.48, δ 128.53, δ 128.6, δ 128.7, δ 130.5, δ 137.3, δ 137.6, δ 138.2; HRMS: m/z (ESI) calculated [M+Na]+ = 473.1870, measured 473.1882 (∆ = 2.5 ppm).

S29

NSNH

OO

Ph Ph

82% yield; white solid (elution solvent – hexanes:EtOAc = 3:1). 1H NMR (300 MHz, CDCl3) δ 1.73 – 1.82 (m, 1H), δ 2.19 – 2.40 (m, 3H), δ 4.04 (ABX, ∆νA+ = 19.65 Hz, ∆νA- = 19.78 Hz, JAB = 13.6 Hz, JAX = 6.31 Hz, JBX = 6.19 Hz, 2H), δ 4.21 – 4.29 (m, 3H), δ 5.07 – 5.11 (m, 1H), δ 5.59 – 5.61 (m, 1H), δ 5.97 – 5.99 (m, 1H), δ 7.17 – 7.20 (m, 2H), δ 7.24 – 7.37 (m, 8H); 13C NMR (75 MHz, CDCl3) δ 27.9, δ 31.7, δ 47.5, δ 47.8, δ 65.7, δ 127.5, δ 1280.1, δ 128.2, δ 128.6, δ 128.9, δ 130.3, δ 136.2, δ 136.9, δ 139.1; HRMS: m/z (ESI) calculated [M+Na]+ = 365.1295, measured 365.1295 (∆ < 1 ppm).

S30

NSNH

OO

Ph Ph

94% yield; yellow solid (elution solvent – hexanes:EtOAc = 3:1). 1H NMR (300 MHz, CDCl3) δ 1.56 – 1.66 (m, 2H), δ 1.74 – 1.80 (m, 1H), δ 1.98 – 2.04 (m, 3H), δ 3.94 – 4.07 (m, 3H), δ 4.33 (ABq, ∆νAB = 59.41 Hz, JAB = 15.8 Hz, 2H), δ 4.53 – 4.59 (m, 1H), δ 5.64 (d, 9.9 Hz, 1H), δ 5.92 – 5.97 (m, 1H), δ 7.14 – 7.17 (m, 2H), δ 7.23 – 7.34 (m, 6H), δ 7.41 (d, J = 7.0Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 21.9, δ

S15

24.7, δ 28.8, δ 47.5, δ 48.3, δ 58.9, δ 127.6, δ 128.1, δ 128.2, δ 128.3, δ 128.4, δ 128.7, δ 128.9, δ132.7, δ 136.8, δ 139.0; HRMS: m/z (ESI) calculated [M+Na]+ = 379.1451, measured 379.1450 (∆ < 1 ppm).

8

NSNH

OO

O

O

Ph Ph

The reaction of sulfamyl oxazolidinone S1 and allyl amine S3210,11 (1.35:1 ratio of trans:cis isomers) provided the desired sulfamide as a colorless oil (85% yield, 1.35:1 ratio of trans:cis isomers). HRMS: m/z (ESI) calculated [M–H]- = 429.1853, measured 429.1855 (∆ < 1 ppm). Trans isomer: 1H NMR (300 MHz, CDCl3) δ 1.21 (s, 3H), δ 1.28 (s, 3H), δ 1.76 (d, J = 6.0 Hz, 3H), δ 3.64 – 4.58 (m, 8H), δ 5.66 – 5.96 (m, 2H), δ 7.15 – 7.40 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 18.6, δ 25.7, δ 26.7, δ 47.6, δ 50.1, δ 63.1, δ 67.6, δ 77.9, δ 110.1, δ 125.6, δ 128.1 – 129.0, δ 133.0, δ 138.1. Cis isomer: 1H NMR (300 MHz, CDCl3) δ 1.23 (s, 3H), δ 1.30 (s, 3H), δ 1.73 (dd, J = 6.8, 1.7 Hz, 3H), δ 3.64 – 4.58 (m, 8H), δ 5.66 – 5.96 (m, 2H), δ 7.15 – 7.40 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 14.2, δ 25.5, δ 26.7, δ 47.5, δ 50.1, δ 63.1, δ 67.4, δ 77.9, δ 110.1, δ 124.5, δ 128.1, δ 128.2 – 129.0, δ 131.3, δ 136.9, δ 137.0. 4. Sulfamide Ring Opening to Yield 1,2-Diamines.

O

O

NBn

SBnNO

ONHBn

O

O NHBn

LiAlH4

Et2O

9 10 To a dry 3-neck round bottom flask attached with a reflux condenser was added cyclic sulfamide 9 (128.5 mg, 0.3 mmole, 1 equiv), which was subsequently put under a N2 atmosphere. Diethyl ether (3 mL) was then added via syringe. A rubber septum was removed, followed by addition of LiAlH4 (45.5 mg, 1.2 mmole, 4 equiv). The solution was then submerged in a pre-heated oil bath (45°C) and refluxed until TLC indicated complete consumption of starting material (~24 hours). The flask was removed from the oil bath and cooled to 0°C, followed by stepwise slow, drop-wise addition of H2O (45 µL mL), 15% NaOH (45 µL), and H2O (135 µL). –CAUTION—Vigorous H2 gas evolution, add quenching agents carefully. MgSO4was then added, the reaction mixture filtered, and the solvent removed in vacuo. The resulting oil was further purified by silica gel column chromatography to provide 1,2-diamine 10 as a colorless oil (97.9 mg, 89% yield). 1H NMR (300 MHz, CDCl3) δ 1.33 (s, 3H), δ 1.42 (s, 3H), δ 1.84 (bs, 2H), δ 2.88 (t, J = 5.7 Hz, 1H), δ 3.07 (dd, J = 8.5, 5.3 Hz, 1H), δ 3.59 (d, J = 13.2 Hz, 1H), δ 3.81 – 3.91 (m, 4H), δ 4.02 (dd, J = 8.2, 6.5 Hz, 1H), δ 4.15 (q, J = 6.4 Hz, 1H), δ 5.14 (dd, J = 17.1, 1.3 Hz, 1H), δ 5.25 (dd, J =

10 Allyl amine S32 was synthesized using 3 equivalents of trans-1-bromo-1-propene according to the protocol described by Gálvez and coworkers (see eqtn below): Badorrey, R.; Cativiela, C.; Diaz-De-Villegas, M. D.; Diez, R.; Galvez, J. A. Eur. J. Org. Chem. 2003, 2268-2275. Following column chromatography (elution solvent – hexanes:EtOAc = 3:1), this procedure provided the desired product as a colorless oil (66% yield, 1.9:1 ratio of trans:cis isomers, only one diastereomer observed by 1H NMR spectroscopy).

NHBn

OO

NBn

OO

+

S32

BrMg

THFO

O

OH

OH

OO

S31 11 For the synthesis of imine S31 in 2 steps from 1,2:5,6-Di-O-isopropylidene-D-mannitol, see: Leyes, A. E.; Poulter, C. D. Org. Lett. 1999, 1, 1067-1070 and de Jorge, L.; Domingos, O.; de Guilherme, M.; Vilela, A.; Costa, P. R.; Dias, A. G. Synth. Commun. 2004, 34, 589-598.

S16

10.2, 1.6 Hz), δ 5.76 (ddd, J = 17.1, 10.2, 8.7 Hz, 1H), δ 7.20 – 7.34 (m, 10H); 13C NMR (125 MHz, CDCl3) δ 25.4, δ 26.8, δ 51.2, δ 53.9, δ 62.5, δ 62.6, δ 66.9, δ 77.5, δ 108.8, δ 117.9, δ 127.0, δ 127.1, δ 128.2, δ 128.4, δ 128.48, δ 128.53, δ 138.8, δ 140 .8, δ 141.0; HRMS: m/z (ESI) calculated [M+H]+ = 367.2381, measured 367.2385 (∆ = 1.1 ppm). 5. Synthesis of Allylic Amines.

HO

Cl3CCN, NaH

Et2O OCl3C

NH reflux

tolueneNH

CCl3

O

NH2

KOH (aq)

EtOH (E)-Crotylamine was prepared by modification of a previously reported procedure.12 An oven-dried

500 mL round bottom flask was charged with NaH (60% dispersion in mineral oil, 1.398 g, 45.94 mmole, 0.1 equiv), followed by cannula addition of Et2O (130 mL). An addition funnel was then used to slowly add 3-buten-2-ol (25.2 g, 349.5 mmole, 1 equiv) to the NaH mixture – CAUTION – H2 evolution, use a large round bottom flask to account for vigorous foaming and perform the reaction in a well ventilated fume hood. After stirring for 15 minutes, this sodium alkoxide solution was transferred slowly in a dropwise manner via cannula to a preformed 0 °C solution of trichloroacetonitrile (35.05 mL, 349.5 mmole, 1 equiv) and Et2O (25 mL). This orange solution was then removed from the ice bath and stirred at room temperature for 2 hours, at which point the Et2O was removed at reduced pressure.

The resulting brown oil was dissolved in dry toluene (400 mL), a reflux condenser was attached to the flask, and the solution was refluxed for 24 hours. The dark brown solution was then filtered through a pad of celite, which was washed three more times with toluene. The toluene was then removed at reduced pressure to yield 71.3 g of a brown oil.

EtOH (15 mL) was added to the brown oil, followed by slow addition of aq. 3N KOH (300 mL). This solution was stirred for 24 hours, during which time the mixture turned bright red. The reaction was extracted 3 times with CH2Cl2 (organic fractions totaled approximately 225 mL), dried with MgSO4 and filtered –NOTE—In the first CH2Cl2 extraction, the organic layer was the top layer. This solution was analyzed by 1H NMR spectroscopy to determine the quantity of product present in the mixture with toluene, EtOH, CH2Cl2 (crotyl amine is 6.04% by mass). This solution was used for reductive amination with benzaldehyde.13

NH

Bn

S33

OHCPh NH2 +

1. Mg2SO4 / CH2Cl2

2. NaBH4 / MeOH

An oven-dried 2-neck round-bottom flask was put under an N2 atmosphere then charged with tiglic aldehyde (3.00 mL, 31.0 mmole, 1 equiv) and dry CH2Cl2 (30 mL). Under a positive flow of N2, a septa was quickly removed and MgSO4 (approx. 2 g) added, followed by syringe addition of benzyl amine (3.72 mL, 34.1 mmole, 1.1 equiv). The mixture was refluxed for 1.5 hours, cooled to room temperature then filtered (wash with dry CH2Cl2). The oil remaining after removal of the solvent at reduced pressure was put under an N2 atmosphere, followed by addition of dry MeOH (40 mL). This mixture was cooled to 0°C, the septa quickly removed, and NaBH4 (1.17 g, 30.96 mmole, 1 equiv) added in portions – CAUTION – H2 evolution, this mixture foams vigorously. After addition of NaBH4, the solution was removed from the ice bath and allowed to stir at room temperature overnight. At this point, the mixture was poured into H2O (100 mL) and extracted 3 times with CH2Cl2. The solution was then dried with MgSO4, filtered, and the solvent removed at reduced pressure to give 5.10 g (94.0% yield) of S33 as a colorless oil, which was suitable for use in the next step without further purification. 1H NMR (300 MHz, CDCl3) δ 1.52 (bs, 1H), δ 1.61 (d, J = 6.6 Hz, 3H), δ 1.66 (s, 3H), δ 3.15 (s, 2H), δ 3.72 (s, 2H), δ 5.40 (q, J = 6.6 Hz, 1H), δ 7.20 – 7.32 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 13.7, δ 14.7, δ 53.1, δ 57.2, δ 120.5,

12 Clizbe, L. A.; Overman, L. E.; Organic Syntheses, 1978, 58, 4-11. 13 Klein, J. E. M. N.; Müller-Bunz, H.; Evans, P. Org. Biomol. Chem., 2009, 7, 986-995.

S17

δ 127.0, δ 128.3, δ 128.5, 134.2, δ 140.8; HRMS: m/z (ESI) calculated [M+H]+ = 176.1434, measured 176.1427 (∆ = 4.0 ppm).

NH

Ph

S34 Aryl amination of phenyl iodide with (E)-crotyl benzyl amine was performed as described by Ma and coworkers14 to provide S34 as a light yellow oil (76% yield). 1H NMR (300 MHz, CDCl3) δ 1.69 (dd, J = 6.2, 1.3 Hz, 3H), δ 3.65 – 3.67 (m, 3H), δ 5.53 – 5.62 (m, 1H), δ 5.65 – 5.77 (m, 1H), δ 6.68 (dd, J = 8.6, 1.0 Hz, 2H), δ 6.69 (tt, J = 7.4, 1.0 Hz, 1H), δ 7.13 – 7.20 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 17.9, δ 46.2, δ 113.1, δ 117.5, δ 128.0, δ 128.3, δ 129.4, δ 148.4; HRMS: m/z (ESI) calculated [M+H]+ = 148.1121, measured 148.1125 (∆ = 2.7 ppm).

NH

PhEt

OH

H2NPh H

O1.

2. NaBH4

, MgSO4

S35

1. CCl3CN, NaH

2. toluene, reflux

3. KOH, EtOH

Intermediate (E)-2-pentenylamine was synthesized from the commercially available allyl alcohol (3 steps, 73% yield) and was used as a CH2Cl2 solution in the next step. Following the protocol described above, reductive amination with benzaldehyde provided allylic amine S35 (93% yield) as a light yellow oil. 1H NMR (300 MHz, CDCl3) δ 0.98 (t, J = 7.4 Hz, 3H), δ 1.48 (bs, 1H), δ 2.04 (pd, J = 7.4, 1.0 Hz, 2H), δ 3.20 (dd, J = 6.0, 1.0 Hz, 2H), δ 3.76 (s, 2H), δ 5.48 – 5.68 (m, 2H), δ 7.19 – 7.31 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 13.7, δ 25.5, δ 51.2, δ 53.4, δ 126.9, δ 127.3, δ 128.2, δ 128.4, δ 134.5, δ 140.5; HRMS: m/z (ESI) calculated [M+H]+ = 176.1434, measured 176.1430 (∆ = 2.3 ppm).

NH

Ph

OH

H2N

Ph H

O1.

2. NaBH4

, MgSO4

S36

1. CCl3CN, NaH

2. toluene, reflux

3. KOH, EtOH

Intermediate (±)-(E)-1-methyl-2-butenylamine was synthesized from (±)-(E)-3-penten-2-ol15 in three steps (71% overall yield) and was used as a CH2Cl2 solution in the next step. Following the protocol described above, reductive amination with benzaldehyde provided allyl amine S36 (91% yield) as a light yellow oil.1H NMR (300 MHz, CDCl3) δ 1.15 (d, J = 6.5 Hz, 3H), δ 1.70 (dd, J = 6.3, 1.5 Hz, 3H), δ 3.17 (p, J = 6.8 Hz, 1H), δ 3.72 (ABq, ∆νAB = 33.9 Hz, JAB = 13.1 Hz, 2H), δ 5.33 (ddq, J = 15.3, 7.7, 1.4 Hz, 1H), δ 5.55 (dqd, J = 15.3, 6.3, 0.6 Hz, 1H), δ 7.20 – 7.34 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 17.9, δ 22.2, δ 51.6, δ 55.4, δ 125.9, δ 127.0, δ 128.3, δ 128.6, δ 135.7, δ 141.0; HRMS: m/z (ESI) calculated [M+H]+ = 176.1434, measured 176.1432 (∆ = 1.1 ppm).

NH

Ph

OH1. CCl3CN, NaH

2. toluene, reflux

3. KOH, EtOHH2N

Ph H

O1.

2. NaBH4

, MgSO4

S37

Ph

Ph Ph

Intermediate (±)-(E)-1-phenyl-2-butenylamine was synthesized from (±)-(E)-4-phenyl-3-buten-2-ol16 in three steps (75% overall yield). Following the protocol described above, reductive amination with 14 Ma, D. W.; Cai, Q.; Zhang, H. Org. Lett. 2003, 5, 2453-2455. 15 (±)-(E)-3-penten-2-ol was synthesized via methyl Grignard addition to the crotonaldehyde. 16 (±)-(E)-4-phenyl-3-buten-2-ol was synthesized via Luche reduction of the corresponding ketone. For Luche reduction conditions, see the following: Becker, N.; Carreira, E. M. Org. Lett. 2007, 9, 3857-3858. The alcohol was purified by column chromatography (2:1 Hex:EtOAc) to give a colorless oil (87% yield).

S18

benzaldehyde provided allyl amine S37 (92% yield) as a light yellow oil. 1H NMR (300 MHz, CDCl3) δ 1.67 (d, J = 4.7 Hz, 3H), δ 2.00 (bs, 1H), δ 3.70 (ABq, ∆νAB = 7.44 Hz, JAB = 13.3 Hz, 2H), δ 4.17 (d, J = 5.9 Hz, 1H), δ 5.59 – 5.69 (m, 2H), δ 7.20 – 7.38 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 18.0, δ 51.4, δ 64.7, δ 126.6, δ 127.0, δ 127.2, δ 127.4, δ 128.3, δ 1285, δ 128.7, 134.3, δ 140.6, δ 143.6; HRMS: m/z (ESI) calculated [M+Na]+ = 238.1591, measured 238.1591 (∆ < 1 ppm). 6. Characterization Data of Cyclic Sulfamides.

NSN

O O

Ph Ph

Table 2, 7a. 99% yield; white solid. 1H NMR (300 MHz, CDCl3) δ 2.89 (dd, J = 9.4, 7.4 Hz, 1H), δ 3.27 (dd, J = 9.4, 6.8 Hz, 1H), δ 3.78 (apparent q, J = 7.6 Hz, 1H), δ 4.02 (d, J = 13.8 Hz, 1H), δ 4.29 (s, 2H), δ 4.35 (d, J = 13.8 Hz, 1H), δ 5.14 – 5.22 (m, 2H), δ 5.69 (ddd, J = 17.0, 10.2, 8.6 Hz, 1H), δ 7.27 – 7.41 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 49.0, δ 50.5, δ 51.4, δ 59.7, δ 121.0, δ 128.0, δ 128.3, δ 128.6, δ 128.9, δ 129.1, δ 134.6, δ 135.0, δ 135.5; HRMS: m/z (ESI) calculated [M+Na]+ = 351.1095, measured 351.1095 (∆ < 1 ppm).

NSN

O O

Ph

Table 2, 7b. 99% yield; colorless oil. 1H NMR (300 MHz, CDCl3) δ 0.92 (t, J = 7.3 Hz, 3H), δ 1.34 – 1.42 (m, 2H), δ 1.61 – 1.71 (m, 2H), δ 2.82 – 2.98 (m, 2H), δ 3.12 – 3.21 (m, 1H), δ 3.25 (dd, J = 9.1, 6.7 Hz, 1H), δ 3.76 (q, J = 7.6 Hz, 1H), δ 3.96 (d, J = 14.0 Hz, 1H), δ 4.37 (d, J = 14.0 Hz, 1H), δ 5.28 (d, J = 9.7 Hz, 1H), δ 5.32 (d, J = 16.7 Hz, 1H), δ 5.71 (ddd, J = 16.7, 9.7, 8.4 Hz, 1H), δ 7.30 – 7.38 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 13.8, δ 20.2, δ 30.1, δ 46.0, δ 50.6, δ 51.4, δ 60.8, δ 120.8, δ 128.2, δ 128.8, δ 135.1, δ 135.2; HRMS: m/z (ESI) calculated [M+Na]+ = 317.1295, measured 317.1295 (∆ < 1 ppm).

NSN

O O

PhPh

Table 2, 7c. 97% yield; white solid. 1H NMR (300 MHz, CDCl3) δ 2.88 (dd, J = 9.3, 7.5 Hz, 1H), δ 3.26 (dd, J = 9.3, 6.6 Hz, 1H), δ 3.78 (q, J = 7.6 Hz, 1H), δ 4.02 (d, J = 13.8 Hz, 1H), δ 4.28 (s, 2H), δ 4.34 (d, J = 13.8 Hz, 1H), δ 5.16 (d, J = 17.1 Hz, 1H), δ 5.20 (d, J = 10.1 Hz, 1H), δ (ddd, J = 17.1, 10.1, 8.6 Hz, 1H), δ 7.23 – 7.40 (m, 10H); 13C NMR (125 MHz, CDCl3) δ 50.4, δ 51.6, δ 59.1, δ 120.9, δ123.2, δ126.2, δ128.5, δ 129.0, δ129.5, δ129.6, δ 134.4, δ 137.8, δ 136.6; HRMS: m/z (ESI) calculated [M+Na]+ = 337.0982, measured 337.0989 (∆ = 2.1 ppm).

NSN

O OOMe

Ph

Table 2, 7d. 96% yield; light yellow solid. 1H NMR (300 MHz, CDCl3) δ 3.01 (t, J = 8.9 Hz, 1H), δ 3.41 (dd, J = 9.4, 6.4 Hz, 1H), δ 3.77 (s, 3H), δ 4.04 (d, J = 13.9 Hz, 1H), δ 4.41 (q, J = 7.5 Hz, 1H), δ 4.48 (d, J = 13.9 Hz, 1H), δ 5.16 (d, J = 17.6 Hz, 1H), δ 5.21 (d, J = 10.1 Hz, 1H), δ 5.64 (ddd, J = 17.6, 10.1, 7.9 Hz, 1H), δ 6.87 – 6.92 (m, 2H), δ 7.25 – 7.43 (m, 7H); 13C NMR (75 MHz, CDCl3) δ 50.5, δ 51.7, δ 55.5,

S19

δ 60.4, δ 114.8, δ 121.0, δ 127.5, δ 128.4, δ 128.6, δ 128.91, δ 128.93, δ 134.3, δ 134.9, δ 158.9; HRMS: m/z (ESI) calculated [M+Na]+ = 367.1087, measured 367.1093 (∆ = 1.6 ppm).

NSN

O OCO2Et

Ph

Table 2, 7e. 30% yield; white solid. 1H NMR (300 MHz, CDCl3) δ 1.38 (t, J = 7.1 Hz, 3H), δ 3.10 (dd, J = 9.8, 6.9 Hz, 1H), δ 3.51(dd, J = 9.8 , 6.5 Hz, 1H), δ 4.18 (d, J = 14.0 Hz, 1H), δ 4.32 – 4.42 (m, 3H), δ 4.62 (q, J = 6.7 Hz, 1H), δ 5.31 (d, J = 10.3 Hz, 1H), δ 5.38 (d, J = 17.2 Hz, 1H), δ 5.73 (ddd, J = 17.2, 10.3, 6.9 Hz, 1H), δ 7.28 (d, J = 9.1 Hz, 2H), δ 7.34 – 7.40 (m, 5H), δ 8.04 (d, J = 9.1 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 14.5, δ 50.0, δ 51.4, δ 58.4, δ 61.1, δ 119.4, δ 120.8, δ 126.5, δ 128.7, δ 129.04, δ 129.09, δ 131.1, δ 134.1, δ 134.4, δ 141.0, δ 166.2; HRMS: m/z (ESI) calculated [M]• + = 386.1295, measured 386.1304 (∆ = 2.3 ppm).

NS

N

OO

CO2EtPh

Table 2, 7f. 70% yield; white solid. 1H NMR (300 MHz, CDCl3) δ 1.39 (t, J = 6.8 Hz, 3H), δ 3.09 (dd, J = 9.7, 8.0 Hz, 1H), δ 3.49 (dd, J = 9.6, 6.6 Hz, 1H), δ 4.11 (d, J = 13.7 Hz, 1H), δ 4.38 (q, J = 6.9 Hz, 2H), δ 4.47 (d, J = 13.7 Hz, 1H), δ 4.62 (q, J = 7.1 Hz, 1H), δ 5.27 (d, J = 10.2 Hz, 1H), δ 5.36 (d, J = 17.2 Hz, 1H), δ 5.69 (ddd, J = 17.2, 10.2, 7.7 Hz, 1H), δ 7.35 – 7.49 (m, 6H), δ 7.58 (ddd, J = 8.1, 2.3, 1.2 Hz, 1H), 7.87 – 7.92 (m, 2H); HRMS: m/z (ESI) calculated [M+Na]+ = 409.1193, measured 409.1182 (∆ = 2.7 ppm).

NSN

O O

PhPh

Table 2, 7g. 92% yield; 1H NMR (500 MHz, CDCl3) δ 3.61 (dd, J = 8.8, 7.1 Hz, 1H), δ 3.86 (dd, J = 8.8, 6.6 Hz, 1H), δ 4.00 (apparent q, J = 7.4 Hz, 1H), δ 4.33 (ABq, ∆νAB = 18.2 Hz, JAB = 14.9 Hz, 2H), δ 5.32 (d, J = 17.1 Hz, 1H), δ 5.35 (d, J = 10 Hz, 1H), δ (ddd, J = 17.1, 10, 8.8 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 48.9, δ 49.6, δ 59.1, δ 129.2, δ 132.0, δ 125.0, δ 128.2, δ 128.8, δ 129.3, δ 129.7, δ 134.1, δ 135.2, δ 138.0; HRMS: m/z (ESI) calculated [M+Na]+ = 337.0982, measured 337.0984 (∆ < 1 ppm).

NS

N

OO

F

Ph

Table 2, 7h. 99% yield; colorless oil. 1H NMR (300 MHz, CDCl3) δ 2.89 (dd, J = 9.4, 7.8 Hz, 1H), δ 3.27 (dd, J = 9.4, 6.7 Hz, 1H), δ 3.77 (apparent quartet, J = 7.7 Hz, 1H), δ 3.77 (d, J = 13.8 Hz, 1H), δ 4.24 (s, 2H), δ 4.35 (d, J = 13.8 Hz, 1H), δ 5.19 (d, J = 17.2 Hz, 1H), δ 5.23 (d, J = 10.2 Hz, 1H), δ 5.67 (ddd, J = 17.2, 10.2, 8.7 Hz, 1H), δ 6.97 – 7.04 (m, 2H), δ 7.28 – 7.38 (m, 7H); 13C NMR (75 MHz, CDCl3) δ 48.4, δ 50.5, δ 51.3, δ 59.9, δ 115.3, δ 115.6, δ 121.1, δ 128.3, δ 128.8, δ 128.9, δ 130.8, δ 130.9, δ 131.25, δ 131.29, δ 134.6, δ 134.8, 160.9, δ 164.1; HRMS: m/z (ESI) calculated [M+Na]+ = 369.1044, measured 369.1057 (∆ = 3.5 ppm).

S20

NS

N

OONBocPh

Table 2, 7i. 99% yield; colorless oil. 1H NMR (300 MHz, CDCl3) δ (, J = , H); 13C NMR (75 MHz, CDCl3) ~1.2:1 ratio of rotomers; minor rotomer: δ 28.5, δ 35.5, δ 43.3, δ 47.1, δ 50.6, δ 51.4, δ 60.4, δ 79.5, δ 121.4, δ 128.9, δ 134.8, δ 155.9; major rotomer: δ 28.5, δ 35.5, δ 44.0, δ 47.9, δ 50.6, δ 51.4, δ 61.3, δ 79.8, δ 128.3, δ 128.8, δ134.7, δ 155.5; HRMS: m/z (ESI) calculated [M+H]+ = 396.1952, measured 396.1967 (∆ = 3.8 ppm).

NS

N

OO

Ph

Table 2, 7j. 99% yield; colorless oil. 1H NMR (300 MHz, CDCl3) δ 2.44 (qt, J = 7.4, 1.3 Hz, 2H), δ 2.86 (dd, J = 9.2, 8.3 Hz, 1H), δ 3.01, (dt, J = 13.5, 7.9 Hz, 1H), δ 3.22 (td, J = 7.3, 0.9 Hz, 1H), δ 3.26 (dd, J = 9.2, 6.7 Hz, 1H), δ 3.79 (td, J = 8.3, 6.7 Hz, 1H), δ 3.96 (d, 13.8 Hz, 1H), δ 4.38 (d,, 13.8 Hz, 1H), δ 5.03 – 5.15 (m, 2H), δ 5.28 – 5.37 (m, 2H), δ 5.65 – 5.86 (m, 2H), δ 7.27 – 7.38 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 32.4, δ 45.6, δ 50.6, δ 51.4, δ 60.7, δ 117.1, δ 121.0, δ 128.3, δ 128.82, δ 128.84, δ 134.9, δ 135.0; HRMS: m/z (ESI) calculated [M+H]+ = 293.1319, measured 293.1326 (∆ = 1.7 ppm).

NS

N

OOCl

Ph

Table 2, 7k. 91% yield; colorless oil. 1H NMR (300 MHz, CDCl3) δ 3.05 (td, J = 7.5, 1.3 Hz, 3H), δ 3.45 (dd, J = 9.6, 6.6 Hz, 1H), δ 3.69 (t, J = 7.2 Hz, 2H), δ 4.08 (d, J = 13.8 Hz, 1H), δ 4.47 (d, J = 13.8 Hz, 1H), δ 4.53 (q, J = 7.6 Hz, 1H), δ 5.24 (d, J = 10.2 Hz, 1H), δ 5.31 (d, J = 17.2 Hz, 1H), δ 5.69 (ddd, J = 17.2, 10.2, 7.6 Hz, 1H), δ 7.21 – 7.28 (m, 4H), δ 7.32 – 7.43 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 38.8, δ 44.8, δ 51.6, δ 59.1, δ 120.9, δ 123.4, δ 128.5, δ 129.0, δ 130.0, δ 134.4, δ 134.8, δ 135.3, δ 136.1; HRMS: m/z (ESI) calculated [M+Na]+ = 399.0905, measured 399.0889 (∆ = 4 ppm).

NS

N

OOOPh

Table 2, 7l. 80% yield; colorless oil. 1H NMR (300 MHz, CDCl3) δ 2.86 (dd, J = 9.4 8.1 Hz, 1H), δ 3.26 (dd, J = 9.4, 6.8 Hz, 1H), δ 3.82, (apparent quartet, J = 7.7 Hz, 1H), δ 3.95 (d, J = 13.8 Hz, 1H), δ 4.26 (s, 2H), δ 4.36 (d, J = 13.8 Hz, 1H), δ 5.25 (dd, J = 10.0, 1.2 Hz, 1H), δ 5.27 (dd, J = 17.2, 0.9 Hz, 1H), δ 5.68 (ddd, J = 17.2, 10.0, 8.4 Hz, 1H), δ 6.32 – 6.39 (m, 2H), δ 7.28 – 7.38 (m, 6H); 13C NMR (75 MHz, CDCl3) δ 41.9, δ 50.4, δ 51.3, δ 59.7, δ 110.4, δ 110.7, δ 128.3, δ 128.8, δ 134.3, δ 134.9, δ 142.7, δ148.9; HRMS: m/z (ESI) calculated [M+H]+ = 319.1111, measured 319.1097 (∆ = 4.4 ppm).

NSN

O O

Ph Ph

Table 3, Entry 1. 99% yield; white solid. 1H NMR (300 MHz, CDCl3) δ 1.29 (s, 3H), δ 3.02 (ABq, ∆νAB = 15.39 Hz, JAB = 9.2 Hz, 2H), δ 4.20 (ABq, ∆νAB = 62.46 Hz, JAB = 15.8 Hz, 2H), δ 4.19 (ABq, ∆νAB = 19.15 Hz, JAB = 13.8 Hz, 2H), δ 5.24 (d, J = 17.4 Hz, 1H), δ 5.27 (d, J = 10.6 Hz, 1H), δ 5.93 (d, J = 17.4,

S21

10.6 Hz, 1H), δ 7.22 – 7.42 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 21.1, δ 45.7, δ 50.7, δ 57.3, δ 62.1, δ 117.9, δ 127.7, δ 128.2, δ128.5, δ 128.5, δ 128.7, δ 128.9, δ 135.0, δ 137.1, δ 138.8; HRMS: m/z (ESI) calculated [M+Na]+ = 365.1295, measured 365.1292 (∆ < 1 ppm).

NSN

O O

Ph Ph

Table 3, Entry 2. 96% yield; white solid. 1H NMR (300 MHz, CDCl3) δ 1.60 (dd, J = 6.4, 1.1 Hz, 3H), δ 2.85 (dd, J = 8.9, 8.1 Hz, 1H), δ 3.22 (dd, J = 9.2, 6.7 Hz, 1H), δ 3.99 (d, J = 13.9 Hz, 1H), δ 4.24 (s, 2H), δ 4.33 (d, J = 13.9 Hz, 1H), δ 5.27 (ddq, J = 15.3, 8.9, 1.1 Hz, 1H), δ 5.56 (dq, J = 15.3, 6.4 Hz, 1H), δ 7.23 – 7.43 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 17.6, δ 48.7, δ 50.9, δ 51.3, δ 59.3, δ 127.5, δ 127.8, δ 128.2, δ 128.5, δ 128.78, δ 128.82, δ 129.0, δ 132.9, δ 135.0, δ 135.8; HRMS: m/z (ESI) calculated [M+Na]+ = 365.1295, measured 365.1307 (∆ = 3.3 ppm).

NS

N

OO

OTIPS

Ph Ph

Table 3, Entry 3. 81% yield, light yellow oil. 1H NMR (300 MHz, CDCl3) cis:trans mixture (2:1 ratio) δ 0.95 – 1.11 (m, 21H), δ 2.82 – 2.92 (m, 1H), δ 3.21 – 3.31 (m, 1H), δ 3.68 – 3.76 (m, 1H), δ 3.99 – 4.05 (m, 1H), δ4.17 – 4.61 (m, 4H), δ 4.88 (dd, J = 11.7, 9.9 Hz, 1H), trans δ 6.34 (d, J = 11.9 Hz, 0.66H), cis δ 6.42 (dd, J = 5.6, 0.8 Hz, 0.33H), δ 7.23 – 7.41 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 12.1 (cis δ 11.9), δ 17.8 (cis δ 18.1), δ 48.0 (cis δ 49.2), δ 51.4 (cis δ 49.2), δ 51.4 (cis δ 51.6), δ 51.98 (cis δ 52.03), δ 56.1, δ 106.8 (cis δ 106.8), δ 127.9 (cis δ 127.8), δ 128.3 (cis δ 128.2), δ 128.7 (cis 128.5), δ 128.8, δ 128.88, δ 128.92, δ 129.0, δ 129.3, δ 135.3, δ 136.0, δ 147.0 (cis δ 144.8).

NSN

O O

Ph Ph

Me

Table 3, Entry 4. 90% yield, colorless oil. 1H NMR (300 MHz, CDCl3) δ 1.70 (d, J = 6.8 Hz, 3H), δ 2.73 (dd, J = 9.5, 6.8 Hz, 1H), δ 3.12 (dd, J = 9.5, 7.1 Hz), δ 3.65 (q, J = 7.5 Hz, 1H), δ 3.96 (d, J = 13.9 Hz, 1H), δ 4.27 (d, J = 13.9Hz, 1H), δ 4.93 – 4.99 (m, 2H), δ 5.05 (d, J = 10.2 Hz, 1H), δ 5.76 (ddd, J = 17.3, 10.0, 8.4 Hz, 1H), δ 7.25 – 7.48 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 19.9, δ 50.6, δ 51.2, δ 55.4, δ 57.0, δ 118.5, δ 127.8, δ 128.5, δ 128.8, 128.9, δ 137.4, δ 138.7; HRMS: m/z (ESI) calculated [M+H]+ = 343.1475, measured 343.1475 (∆ < 1 ppm).

NSN

O O

Ph Ph

Me Table 3, Entry 5. 93% yield; colorless oil. 1H NMR (300 MHz, CDCl3) δ 1.08 (d, J = 6.2 Hz, 3H), δ 3.16 (dq, J = 7.5, 6.3 Hz, 1H), δ 3.37 (t, J = 8.1 Hz, 1H), δ 4.09 (d, J = 14.8 Hz, 1H), δ 4.14 (d, J = 15.3 Hz, 1H), δ 4.31 (d, J = 14.8 Hz, 1H), δ 4.47 (d, J = 15.3 Hz, 1H), δ 5.22 – 5.28 (m, 2H), δ 5.51 – 5.63 (m, 1H), δ 7.25 – 7.44 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 17.1, δ 49.5, δ 58.5, δ 68.1, δ 122.0, δ 127.95, δ 128.01, δ 128.6, δ 128.7, δ 128.8, δ 129.0, δ 129.2, δ 134.4, δ 135.7, δ 136.0; HRMS: m/z (ESI) calculated [M+H]+ = 343.1475, measured 343.1463 (∆ = 3.5 ppm).

S22

NSN

O O

Ph Ph

Ph

S38 Table 3, Entry 6 (Sulfamide S38). 95% yield; white solid. 1H NMR (300 MHz, CDCl3) δ 3.65 (t, J = 8.2 Hz, 1H), δ 4.00 (d, J = 7.9 Hz, 1H), δ 4.08 – 4.20 (m, 3H), δ 4.33 (d, J = 14.9 Hz, 1H), δ 4.91 (d, J = 17.1 Hz, 1H), δ 5.12 (d, J = 10.0 Hz, 1H), δ 5.60 (ddd, J = 17.1, 10.0, 8.4 Hz, 1H), δ 7.21 – 7.32 (m, 13H), δ 7.37 – 7.39 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 49.9, δ 50.1, δ 66.7, δ 68.9, δ 122.3, δ 128.10, δ 128.13, δ 128.4, δ 128.6, δ 128.7, δ 129.0, δ 129.2, δ 129.4, δ 129.6, δ 133.4, δ 134.9, δ 135.7, δ 136.0; HRMS: m/z (ESI) calculated [M+Na]+ = 427.1451, measured 427.1459 (∆ = 1.9 ppm).

NS

N

OO

O

PhPh

Ph

Table 3, Entry 7. 99% yield; colorless oil. 1H NMR (300 MHz, CDCl3) δ 3.25 (apparent q, J = 5.4 Hz, 1H), δ 3.38 (d, J = 5.0 Hz, 2H), δ 3.62 (dd, J = 8.5, 6.0 Hz, 1H), δ 4.15 – 4.30 (m, 5H), δ 4.51 (d, J = 15.0 Hz, 1H), δ 5.12 – 5.20 (m, 2H), δ 5.60 (ddd, J = 17.1, 10.2, 8.5 Hz, 1H), δ 7.14 – 7.17 (m, 2H), δ 7.24 – 7.40 (m, 13H); 13C NMR (75 MHz, CDCl3) δ 18.1, δ 47.2, δ 49.2, δ 60.2, δ 70.6, δ 73.3, δ 126.9, δ 127.6, δ 127.7, δ 128.06, δ 128.09, δ 128.48, δ 128.53, δ 128.6, δ 128.7, δ 130.5, δ 137.3, δ 137.6, δ 138.2; HRMS: m/z (ESI) calculated [M+H]+ = 449.1894, measured 449.1904 (∆ = 2.2 ppm).

S39

NSN

O O

Ph Ph

Table 3, Entry 8 (Sulfamide S39). 90% yield; white solid. 1H NMR (300 MHz, CDCl3) δ 2.29 (ddt, J = 17.6, 7.3, 2.2 Hz, 1H), δ 2.42 (apparent dp J = 17.6, 2.2 Hz, 1H), δ 3.90 (td, J = 7.8, 3.2, Hz, 1H), δ 4.17 – 4.25 (m, 3H), δ 4.40 (d, J = 14.2 Hz, 1H), δ 4.43 (d, J = 14.2 Hz, 1H), δ 5.27 – 5.30 (m, 1H), δ 5.76 – 5.78 (m, 1H), δ 7.31 – 7.42 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 37.5, δ 50.0, δ 50.6, δ 57.7, δ 65.9, δ 127.8, δ 128.3, δ 128.4, δ 128.9, δ 129.1, δ 129.3, δ 134.0, δ 135.3, δ 135.6; HRMS: m/z (ESI) calculated [M+Na]+ = 363.1138, measured 363.1128 (∆ = 2.8 ppm). For NOE correlation data, see page S18.

NSN

O O

Ph Ph

Table 3, Entry 9. 73% yield; white solid. 1H NMR (500 MHz, CDCl3) δ 1.74 – 1.82 (m, 1H), δ 1.95 – 2.05 (m, 3H), δ 3.93 – 4.04 (m, 3H), δ 4.24 (d, J = 15.8 Hz, 1H), δ 4.34 (d, J = 15.8 Hz, 1H), δ 4.55 – 4.58 (m, 1H), δ 5.63 – 5.67 (m, 1H), δ 5.92 – 5.96 (m, 1H), δ 7.14 – 7.16 (m, 2H), δ 7.24 – 7.33 (m, 6H), δ 7.40 (d, 7.4 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 21.9, δ 24.7, δ 28.8, δ 47.5, δ 48.3, δ 56.9, δ 127.6, δ 128.1, δ 128.2, δ 128.3, δ 128.4, δ 128.7, δ 128.9, δ 132.8, δ 136.7, δ 139.0; HRMS: m/z (ESI) calculated [M+Na]+ = 377.1295, measured 377.1281 (∆ = 3.7 ppm).

S23

O

O

N

SNO

O

9

Ph

Ph

Sulfamide 9. Colorless oil. 1H NMR (300 MHz, CDCl3) δ 1.24 (s, 3H), δ 1.27 (s, 3H), δ 3.23 (dd, J = 6.5, 4,4 Hz, 1H), δ 3.51 – 3.59 (m, 2H), δ 3.83 (dd, J = 8.6, 6.2 Hz, 1H), δ 4.14 – 4.24 (m, 3H), δ 4.41 (ABq, ∆νAB = 50.64 Hz, JAB = 14.5 Hz, 2H), δ 5.16 (d, J = 10 Hz, 1H), δ 5.20 (d, J = 17.2 Hz, 1H), δ 5.52 (ddd, J = 17.2, 10, 8.2 Hz, 1H), δ 7.25 – 7.43 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 26.1, δ 26.7, δ 49.0, δ 54.5, δ 62.7, δ 62.8, δ 66.0, δ 76.3, δ 109.5, δ 120.2, δ128.0, δ 128.4, δ 128.5, δ 128.8, δ 129.2, δ 129.6, δ 135.1, δ 135.25, δ 135.32; HRMS: m/z (ESI) calculated [M+Na]+ = 451.5295, measured 451.5295 (∆ < 1 ppm).

S24

NOE Correlation for S39 (Table 3, Entry 8).

S27

Crystallographic Characterization of S38 (Table 3, Entry 6).

Data Collection A colorless crystal with approximate dimensions 0.15 x 0.10 x 0.05 mm3 was selected under oil

under ambient conditions and attached to the tip of a Micromount©. The crystal was mounted in a stream of cold nitrogen at 100(2) K and centered in the X-ray beam by using a video camera.

The crystal evaluation and data collection were performed on a Bruker SMART APEXII diffractometer with Cu Kα (λ = 1.54178 Å) radiation and the diffractometer to crystal distance of 4.03 cm.

The initial cell constants were obtained from three series of ω scans at different starting angles. Each series consisted of 50 frames collected at intervals of 0.5º in a 25º range about ω with the exposure time of 30 seconds per frame. The reflections were successfully indexed by an automated indexing routine built in the SMART program. The final cell constants were calculated from a set of 6460 strong reflections from the actual data collection. The data were collected by using the full sphere data collection routine to survey the reciprocal space to the extent of a full sphere to a resolution of 0.82 Å. A total of 15410 data were harvested by collecting 18 sets of frames with 0.69º scans in ω and φ with an exposure time 20-60 sec per frame. These highly redundant datasets were corrected for Lorentz and polarization effects. The absorption correction was based on fitting a function to the empirical transmission surface as sampled by multiple equivalent measurements. [1] Structure Solution and Refinement

The systematic absences in the diffraction data were consistent for the space groups P1̄ and P1. The E-statistics strongly suggested the centrosymmetric space group P1̄ that yielded chemically reasonable and computationally stable results of refinement [2].

A successful solution by the direct methods provided most non-hydrogen atoms from the E-map. The remaining non-hydrogen atoms were located in an alternating series of least-squares cycles and difference Fourier maps. All non-hydrogen atoms were refined with anisotropic displacement coefficients. All hydrogen atoms were included in the structure factor calculation at idealized positions and were allowed to ride on the neighboring atoms with relative isotropic displacement coefficients. Atoms C19-24 are disordered over two positions with a major component of 87.6%(16) and were refined with restraints and constraints.

The final least-squares refinement of 281 parameters against 3674 data resulted in residuals R (based on F2 for I≥2σ) and wR (based on F2 for all data) of 0.0356 and 0.0944, respectively. The final difference Fourier map was featureless.

The molecular diagrams are drawn with 50% probability ellipsoids [3]. References [1] Bruker-AXS. (2000-2007) SADABS, SAINT, and SMART 5.622 Software Reference Manuals.

Bruker-AXS, Madison, Wisconsin, USA. [2] Sheldrick, G. M. (2008). SHELXL. Acta Cryst. A64, 112-122. [3] Pennington, W.T. (1999) J. Appl. Cryst. 32(5), 1028-1029.

S28

Figure S1. A molecular drawing of S38 shown with 50% probability ellipsoids [3]. All hydrogen atoms and the minor component of the disordered atoms were omitted for clarity.

S29

Table S3. Crystal data and structure refinement for S38. Identification code stahl77 Empirical formula C24H24N2O2S Formula weight 404.51 Temperature 100(2) K Wavelength 1.54178 Å Crystal system Triclinic Space group P Unit cell dimensions a = 9.6725(4) Å �= 75.090(2)°. b = 10.3611(4) Å �= 74.004(2)°. c = 11.2703(4) Å � = 79.625(2)°. Volume 1041.92(7) Å3 Z 2 Density (calculated) 1.289 Mg/m3 Absorption coefficient 1.554 mm-1 F(000) 428 Crystal size 0.15 x 0.10 x 0.05 mm3 Theta range for data collection 4.18 to 69.45°. Index ranges -10<=h<=11, -12<=k<=12, -13<=l<=13 Reflections collected 15410 Independent reflections 3674 [R(int) = 0.0260] Completeness to theta = 67.00° 95.0 % Absorption correction Multi-scan with SADABS Max. and min. transmission 0.9263 and 0.8003 Refinement method Full-matrix least-squares on F2 Data / restraints / parameters 3674 / 15 / 281 Goodness-of-fit on F2 0.997 Final R indices [I>2sigma(I)] R1 = 0.0356, wR2 = 0.0900 R indices (all data) R1 = 0.0429, wR2 = 0.0944 Largest diff. peak and hole 0.295 and -0.293 e.Å-3

S30

Table S4. Atomic coordinates ( x 104) and equivalent isotropic displacement parameters (Å2x 103) for S38. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor. ________________________________________________________________________________ x y z U(eq) ______________________________________________________________________________ S(1) 2628(1) 934(1) 9394(1) 24(1) O(1) 3974(1) 1452(1) 9190(1) 28(1) O(2) 1440(1) 1913(1) 9123(1) 28(1) N(1) 2149(2) -6(1) 10846(1) 25(1) N(2) 2872(2) -306(1) 8648(1) 26(1) C(1) 1805(2) -3584(2) 9031(2) 32(1) C(2) 2335(2) -4802(2) 8680(2) 37(1) C(3) 3808(2) -5197(2) 8379(2) 36(1) C(4) 4754(2) -4364(2) 8421(2) 38(1) C(5) 4227(2) -3150(2) 8774(2) 34(1) C(6) 2759(2) -2755(2) 9092(2) 26(1) C(7) 2162(2) -1462(2) 9531(2) 26(1) C(8) 2503(2) -1453(2) 10780(2) 25(1) C(9) 1597(2) -2303(2) 11907(2) 29(1) C(10) 2129(2) -3121(2) 12817(2) 34(1) C(11) 2717(2) 354(2) 11805(2) 28(1) C(12) 1795(2) 1512(2) 12332(2) 29(1) C(13) 762(2) 1275(2) 13472(2) 42(1) C(14) -56(3) 2329(2) 13991(2) 50(1) C(15) 138(2) 3641(2) 13370(2) 46(1) C(16) 1142(2) 3899(2) 12227(2) 38(1) C(17) 1967(2) 2843(2) 11713(2) 32(1) C(18) 2521(2) 103(2) 7393(2) 32(1) C(19) 3546(3) 1058(6) 6474(7) 36(1) C(20) 3035(5) 2370(3) 5954(4) 60(1) C(21) 4011(7) 3226(4) 5105(5) 80(2) C(22) 5471(6) 2793(4) 4796(4) 66(1) C(23) 5969(4) 1498(6) 5311(3) 47(1) C(24) 5017(3) 632(5) 6151(3) 36(1) C(19A) 3394(15) 1180(40) 6480(50) 36(1) C(20A) 2740(20) 2230(20) 5690(20) 60(1) C(21A) 3580(30) 3140(20) 4760(30) 80(2) C(22A) 5070(30) 2960(30) 4560(30) 66(1) C(23A) 5710(20) 1940(30) 5370(20) 47(1) C(24A) 4899(13) 960(30) 6220(20) 36(1) ________________________________________________________________________________

S31

Table S5. Bond lengths [Å] and angles [°] for S38. _____________________________________________________ S(1)-O(2) 1.4343(12) S(1)-O(1) 1.4345(12) S(1)-N(2) 1.6580(14) S(1)-N(1) 1.6624(14) N(1)-C(11) 1.489(2) N(1)-C(8) 1.493(2) N(2)-C(18) 1.484(2) N(2)-C(7) 1.484(2) C(1)-C(2) 1.386(3) C(1)-C(6) 1.395(2) C(1)-H(1) 0.9500 C(2)-C(3) 1.381(3) C(2)-H(2) 0.9500 C(3)-C(4) 1.384(3) C(3)-H(3) 0.9500 C(4)-C(5) 1.383(3) C(4)-H(4) 0.9500 C(5)-C(6) 1.378(3) C(5)-H(5) 0.9500 C(6)-C(7) 1.510(2) C(7)-C(8) 1.535(2) C(7)-H(7) 1.0000 C(8)-C(9) 1.498(2) C(8)-H(8) 1.0000 C(9)-C(10) 1.312(3) C(9)-H(9) 0.9500 C(10)-H(10A) 0.9500 C(10)-H(10B) 0.9500 C(11)-C(12) 1.510(2) C(11)-H(11A) 0.9900 C(11)-H(11B) 0.9900 C(12)-C(13) 1.388(3) C(12)-C(17) 1.393(3) C(13)-C(14) 1.387(3) C(13)-H(13) 0.9500

C(14)-C(15) 1.380(3) C(14)-H(14) 0.9500 C(15)-C(16) 1.378(3) C(15)-H(15) 0.9500 C(16)-C(17) 1.388(3) C(16)-H(16) 0.9500 C(17)-H(17) 0.9500 C(18)-C(19A) 1.511(8) C(18)-C(19) 1.515(3) C(18)-H(18A) 0.9900 C(18)-H(18B) 0.9900 C(18)-H(18C) 0.9900 C(18)-H(18D) 0.9900 C(19)-C(24) 1.387(4) C(19)-C(20) 1.394(4) C(20)-C(21) 1.400(4) C(20)-H(20) 0.9500 C(21)-C(22) 1.378(5) C(21)-H(21) 0.9500 C(22)-C(23) 1.374(5) C(22)-H(22) 0.9500 C(23)-C(24) 1.389(3) C(23)-H(23) 0.9500 C(24)-H(24) 0.9500 C(19A)-C(24A) 1.392(8) C(19A)-C(20A) 1.399(10) C(20A)-C(21A) 1.394(8) C(20A)-H(20A) 0.9500 C(21A)-C(22A) 1.381(9) C(21A)-H(21A) 0.9500 C(22A)-C(23A) 1.375(9) C(22A)-H(22A) 0.9500 C(23A)-C(24A) 1.391(8) C(23A)-H(23A) 0.9500 C(24A)-H(24A) 0.9500

O(2)-S(1)-O(1) 115.74(7) O(2)-S(1)-N(2) 111.73(7) O(1)-S(1)-N(2) 110.25(7) O(2)-S(1)-N(1) 109.98(7) O(1)-S(1)-N(1) 111.51(7) N(2)-S(1)-N(1) 95.92(7) C(11)-N(1)-C(8) 114.17(13) C(11)-N(1)-S(1) 114.31(10) C(8)-N(1)-S(1) 108.74(10) C(18)-N(2)-C(7) 115.29(13) C(18)-N(2)-S(1) 114.59(11) C(7)-N(2)-S(1) 109.04(10) C(2)-C(1)-C(6) 120.03(18)

C(2)-C(1)-H(1) 120.0 C(6)-C(1)-H(1) 120.0 C(3)-C(2)-C(1) 120.43(17) C(3)-C(2)-H(2) 119.8 C(1)-C(2)-H(2) 119.8 C(2)-C(3)-C(4) 119.46(17) C(2)-C(3)-H(3) 120.3 C(4)-C(3)-H(3) 120.3 C(3)-C(4)-C(5) 120.22(19) C(3)-C(4)-H(4) 119.9 C(5)-C(4)-H(4) 119.9 C(6)-C(5)-C(4) 120.72(17) C(6)-C(5)-H(5) 119.6

S32

C(4)-C(5)-H(5) 119.6 C(5)-C(6)-C(1) 119.12(16) C(5)-C(6)-C(7) 121.48(15) C(1)-C(6)-C(7) 119.39(16) N(2)-C(7)-C(6) 111.45(13) N(2)-C(7)-C(8) 102.22(12) C(6)-C(7)-C(8) 112.95(14) N(2)-C(7)-H(7) 110.0 C(6)-C(7)-H(7) 110.0 C(8)-C(7)-H(7) 110.0 N(1)-C(8)-C(9) 110.24(13) N(1)-C(8)-C(7) 102.88(13) C(9)-C(8)-C(7) 112.98(14) N(1)-C(8)-H(8) 110.2 C(9)-C(8)-H(8) 110.2 C(7)-C(8)-H(8) 110.2 C(10)-C(9)-C(8) 123.11(18) C(10)-C(9)-H(9) 118.4 C(8)-C(9)-H(9) 118.4 C(9)-C(10)-H(10A) 120.0 C(9)-C(10)-H(10B) 120.0 H(10A)-C(10)-H(10B) 120.0 N(1)-C(11)-C(12) 112.87(14) N(1)-C(11)-H(11A) 109.0 C(12)-C(11)-H(11A) 109.0 N(1)-C(11)-H(11B) 109.0 C(12)-C(11)-H(11B) 109.0 H(11A)-C(11)-H(11B) 107.8 C(13)-C(12)-C(17) 117.95(17) C(13)-C(12)-C(11) 120.48(16) C(17)-C(12)-C(11) 121.56(15) C(12)-C(13)-C(14) 121.14(19) C(12)-C(13)-H(13) 119.4 C(14)-C(13)-H(13) 119.4 C(15)-C(14)-C(13) 120.10(19) C(15)-C(14)-H(14) 120.0 C(13)-C(14)-H(14) 120.0 C(14)-C(15)-C(16) 119.69(19) C(14)-C(15)-H(15) 120.2 C(16)-C(15)-H(15) 120.2 C(15)-C(16)-C(17) 120.15(18) C(15)-C(16)-H(16) 119.9 C(17)-C(16)-H(16) 119.9 C(16)-C(17)-C(12) 120.96(17) C(16)-C(17)-H(17) 119.5 C(12)-C(17)-H(17) 119.5 N(2)-C(18)-C(19A) 113(2) N(2)-C(18)-C(19) 110.8(3)

N(2)-C(18)-H(18A) 109.5 C(19)-C(18)-H(18A) 109.5 N(2)-C(18)-H(18B) 109.5 C(19A)-C(18)-H(18B) 113.2 C(19)-C(18)-H(18B) 109.5 H(18A)-C(18)-H(18B) 108.1 N(2)-C(18)-H(18C) 108.9 C(19A)-C(18)-H(18C) 108.9 N(2)-C(18)-H(18D) 108.9 C(19A)-C(18)-H(18D) 108.9 H(18C)-C(18)-H(18D) 107.7 C(24)-C(19)-C(20) 119.2(2) C(24)-C(19)-C(18) 119.9(2) C(20)-C(19)-C(18) 120.9(3) C(19)-C(20)-C(21) 119.5(3) C(19)-C(20)-H(20) 120.2 C(21)-C(20)-H(20) 120.2 C(22)-C(21)-C(20) 120.7(3) C(22)-C(21)-H(21) 119.7 C(20)-C(21)-H(21) 119.7 C(21)-C(22)-C(23) 119.6(2) C(21)-C(22)-H(22) 120.2 C(23)-C(22)-H(22) 120.2 C(22)-C(23)-C(24) 120.6(3) C(22)-C(23)-H(23) 119.7 C(24)-C(23)-H(23) 119.7 C(19)-C(24)-C(23) 120.4(2) C(19)-C(24)-H(24) 119.8 C(23)-C(24)-H(24) 119.8 C(24A)-C(19A)-C(20A) 118.7(8) C(24A)-C(19A)-C(18) 119.5(8) C(20A)-C(19A)-C(18) 120.3(10) C(21A)-C(20A)-C(19A) 119.6(6) C(21A)-C(20A)-H(20A) 120.2 C(19A)-C(20A)-H(20A) 120.2 C(22A)-C(21A)-C(20A) 120.8(6) C(22A)-C(21A)-H(21A) 119.6 C(20A)-C(21A)-H(21A) 119.6 C(21A)-C(22A)-C(23A) 119.1(6) C(21A)-C(22A)-H(22A) 120.4 C(23A)-C(22A)-H(22A) 120.4 C(22A)-C(23A)-C(24A) 120.2(6) C(22A)-C(23A)-H(23A) 119.9 C(24A)-C(23A)-H(23A) 119.9 C(23A)-C(24A)-C(19A) 119.8(7) C(23A)-C(24A)-H(24A) 120.1 C(19A)-C(24A)-H(24A) 120.1

_____________________________________________________________ Symmetry transformations used to generate equivalent atoms:

S33

Table S6. Anisotropic displacement parameters (Å2x 103) for S38. The anisotropic displacement factor exponent takes the form: -2�2[ h2 a*2U11 + ... + 2 h k a* b* U12 ] ______________________________________________________________________________ U11 U22 U33 U23 U13 U12 ______________________________________________________________________________ S(1) 26(1) 24(1) 21(1) -6(1) -4(1) -6(1) O(1) 27(1) 31(1) 28(1) -8(1) -4(1) -9(1) O(2) 29(1) 29(1) 27(1) -7(1) -7(1) -3(1) N(1) 30(1) 25(1) 22(1) -7(1) -6(1) -7(1) N(2) 32(1) 26(1) 21(1) -6(1) -6(1) -7(1) C(1) 35(1) 33(1) 31(1) -8(1) -6(1) -9(1) C(2) 46(1) 32(1) 36(1) -9(1) -8(1) -14(1) C(3) 49(1) 26(1) 31(1) -8(1) -7(1) -5(1) C(4) 37(1) 36(1) 42(1) -14(1) -4(1) -3(1) C(5) 34(1) 33(1) 39(1) -13(1) -6(1) -8(1) C(6) 33(1) 26(1) 20(1) -5(1) -4(1) -8(1) C(7) 26(1) 28(1) 24(1) -7(1) -4(1) -6(1) C(8) 27(1) 25(1) 23(1) -8(1) -4(1) -5(1) C(9) 32(1) 28(1) 26(1) -8(1) -2(1) -8(1) C(10) 43(1) 29(1) 28(1) -7(1) -4(1) -6(1) C(11) 35(1) 29(1) 22(1) -6(1) -8(1) -7(1) C(12) 32(1) 34(1) 26(1) -11(1) -7(1) -9(1) C(13) 54(1) 40(1) 32(1) -12(1) 3(1) -19(1) C(14) 54(1) 58(1) 39(1) -24(1) 12(1) -21(1) C(15) 46(1) 48(1) 50(1) -28(1) -6(1) -5(1) C(16) 46(1) 35(1) 41(1) -13(1) -13(1) -9(1) C(17) 34(1) 35(1) 30(1) -10(1) -7(1) -10(1) C(18) 43(1) 32(1) 24(1) -8(1) -11(1) -6(1) C(19) 54(1) 35(2) 21(1) -6(1) -9(1) -8(1) C(20) 72(2) 49(2) 42(2) 6(1) -4(1) -2(1) C(21) 105(3) 54(2) 57(2) 24(2) -11(2) -13(2) C(22) 84(3) 71(2) 34(2) 14(2) -9(2) -35(2) C(23) 59(2) 64(2) 24(1) -10(1) -8(1) -26(2) C(24) 49(1) 42(2) 25(1) -8(1) -13(1) -15(1) C(19A) 54(1) 35(2) 21(1) -6(1) -9(1) -8(1) C(20A) 72(2) 49(2) 42(2) 6(1) -4(1) -2(1) C(21A) 105(3) 54(2) 57(2) 24(2) -11(2) -13(2) C(22A) 84(3) 71(2) 34(2) 14(2) -9(2) -35(2) C(23A) 59(2) 64(2) 24(1) -10(1) -8(1) -26(2) C(24A) 49(1) 42(2) 25(1) -8(1) -13(1) -15(1) ______________________________________________________________________________

S34

Table S7. Hydrogen coordinates ( x 104) and isotropic displacement parameters (Å2x 10 3) for S38. ________________________________________________________________________________ x y z U(eq) ________________________________________________________________________________ H(1) 791 -3315 9229 39 H(2) 1681 -5368 8648 44 H(3) 4168 -6034 8144 43 H(4) 5769 -4626 8207 46 H(5) 4885 -2583 8797 41 H(7) 1092 -1289 9615 31 H(8) 3555 -1748 10738 30 H(9) 590 -2247 11965 34 H(10A) 3133 -3195 12780 41 H(10B) 1511 -3640 13513 41 H(11A) 3713 595 11413 34 H(11B) 2769 -441 12508 34 H(13) 614 375 13903 51 H(14) -752 2147 14776 61 H(15) -418 4363 13728 55 H(16) 1269 4801 11791 46 H(17) 2660 3031 10928 38 H(18A) 1513 548 7486 38 H(18B) 2592 -705 7054 38 H(18C) 1478 441 7509 38 H(18D) 2698 -697 7021 38 H(20) 2032 2680 6173 72 H(21) 3662 4116 4738 96 H(22) 6129 3384 4232 79 H(23) 6973 1193 5090 56 H(24) 5377 -258 6507 43 H(20A) 1718 2336 5783 72 H(21A) 3131 3891 4262 96 H(22A) 5652 3521 3871 79 H(23A) 6703 1912 5342 56 H(24A) 5371 152 6621 43 ________________________________________________________________________________

S35

Table S8. Torsion angles [°] for S38. ________________________________________________________________ O(2)-S(1)-N(1)-C(11) -102.49(12) O(1)-S(1)-N(1)-C(11) 27.30(14) N(2)-S(1)-N(1)-C(11) 141.81(12) O(2)-S(1)-N(1)-C(8) 128.63(11) O(1)-S(1)-N(1)-C(8) -101.58(11) N(2)-S(1)-N(1)-C(8) 12.93(12) O(2)-S(1)-N(2)-C(18) 33.14(14) O(1)-S(1)-N(2)-C(18) -97.05(13) N(1)-S(1)-N(2)-C(18) 147.41(12) O(2)-S(1)-N(2)-C(7) -97.77(12) O(1)-S(1)-N(2)-C(7) 132.03(11) N(1)-S(1)-N(2)-C(7) 16.50(12) C(6)-C(1)-C(2)-C(3) -0.6(3) C(1)-C(2)-C(3)-C(4) -0.4(3) C(2)-C(3)-C(4)-C(5) 0.6(3) C(3)-C(4)-C(5)-C(6) 0.2(3) C(4)-C(5)-C(6)-C(1) -1.2(3) C(4)-C(5)-C(6)-C(7) 177.47(17) C(2)-C(1)-C(6)-C(5) 1.4(3) C(2)-C(1)-C(6)-C(7) -177.30(16) C(18)-N(2)-C(7)-C(6) 69.31(19) S(1)-N(2)-C(7)-C(6) -160.15(11) C(18)-N(2)-C(7)-C(8) -169.77(14) S(1)-N(2)-C(7)-C(8) -39.23(15) C(5)-C(6)-C(7)-N(2) 50.8(2) C(1)-C(6)-C(7)-N(2) -130.50(16) C(5)-C(6)-C(7)-C(8) -63.6(2) C(1)-C(6)-C(7)-C(8) 115.08(17) C(11)-N(1)-C(8)-C(9) 73.52(18) S(1)-N(1)-C(8)-C(9) -157.53(12) C(11)-N(1)-C(8)-C(7) -165.75(13) S(1)-N(1)-C(8)-C(7) -36.80(15) N(2)-C(7)-C(8)-N(1) 46.58(16) C(6)-C(7)-C(8)-N(1) 166.45(13) N(2)-C(7)-C(8)-C(9) 165.43(14) C(6)-C(7)-C(8)-C(9) -74.70(18) N(1)-C(8)-C(9)-C(10) -109.58(19)

C(7)-C(8)-C(9)-C(10) 135.95(18) C(8)-N(1)-C(11)-C(12) -150.74(14) S(1)-N(1)-C(11)-C(12) 83.18(15) N(1)-C(11)-C(12)-C(13) 97.0(2) N(1)-C(11)-C(12)-C(17) -84.3(2) C(17)-C(12)-C(13)-C(14) -1.1(3) C(11)-C(12)-C(13)-C(14) 177.6(2) C(12)-C(13)-C(14)-C(15) 0.6(4) C(13)-C(14)-C(15)-C(16) 0.4(3) C(14)-C(15)-C(16)-C(17) -0.9(3) C(15)-C(16)-C(17)-C(12) 0.3(3) C(13)-C(12)-C(17)-C(16) 0.6(3) C(11)-C(12)-C(17)-C(16) -178.06(17) C(7)-N(2)-C(18)-C(19A) -174(2) S(1)-N(2)-C(18)-C(19A) 59(2) C(7)-N(2)-C(18)-C(19) -167.0(3) S(1)-N(2)-C(18)-C(19) 65.2(3) N(2)-C(18)-C(19)-C(24) 62.0(8) N(2)-C(18)-C(19)-C(20) -117.5(7) C(24)-C(19)-C(20)-C(21) 0.7(11) C(18)-C(19)-C(20)-C(21) -179.8(6) C(19)-C(20)-C(21)-C(22) -1.1(7) C(20)-C(21)-C(22)-C(23) 1.1(6) C(21)-C(22)-C(23)-C(24) -0.9(6) C(20)-C(19)-C(24)-C(23) -0.5(11) C(18)-C(19)-C(24)-C(23) -180.0(5) C(22)-C(23)-C(24)-C(19) 0.6(7) N(2)-C(18)-C(19A)-C(24A) 55(6) N(2)-C(18)-C(19A)-C(20A) -139(4) C(24A)-C(19A)-C(20A)-C(21A) -8(7) C(18)-C(19A)-C(20A)-C(21A) -173(4) C(19A)-C(20A)-C(21A)-C(22A) 4(6) C(20A)-C(21A)-C(22A)-C(23A) -6(5) C(21A)-C(22A)-C(23A)-C(24A) 12(5) C(22A)-C(23A)-C(24A)-C(19A) -16(5) C(20A)-C(19A)-C(24A)-C(23A) 13(7) C(18)-C(19A)-C(24A)-C(23A) 179(4)

________________________________________________________________ Symmetry transformations used to generate equivalent atoms:

S36

Crystallographic Characterization of 10.

Data Collection

A colorless crystal with approximate dimensions 0.16 x 0.13 x 0.12 mm3 was selected under oil under ambient conditions and attached to the tip of a MiTeGen MicroMount©. The crystal was mounted in a stream of cold nitrogen at 100(1) K and centered in the X-ray beam by using a video camera.

The crystal evaluation and data collection were performed on a Bruker SMART APEXII diffractometer with Cu Kα (λ = 1.54178 Å) radiation and the diffractometer to crystal distance of 4.03 cm.

The initial cell constants were obtained from three series of ω scans at different starting angles. Each series consisted of 50 frames collected at intervals of 0.5º in a 25º range about ω with the exposure time of 10 seconds per frame. The reflections were successfully indexed by an automated indexing routine built in the SMART program. The final cell constants were calculated from a set of 9886 strong reflections from the actual data collection. The data were collected by using the full sphere data collection routine to survey the reciprocal space to the extent of a full sphere to a resolution of 0.83 Å. A total of 22026 data were harvested by collecting 23 sets of frames with 0.6º scans in ω with an exposure time 12-20 sec per frame. These highly redundant datasets were corrected for Lorentz and polarization effects. The absorption correction was based on fitting a function to the empirical transmission surface as sampled by multiple equivalent measurements. [1] Structure Solution and Refinement

The systematic absences in the diffraction data were consistent for the space groups P21 and P21/m. The E-statistics strongly suggested the non-centrosymmetric space group P21 that yielded chemically reasonable and computationally stable results of refinement [2,3].

A successful solution by the direct methods provided most non-hydrogen atoms from the E-map. The remaining non-hydrogen atoms were located in an alternating series of least-squares cycles and difference Fourier maps. All non-hydrogen atoms were refined with anisotropic displacement coefficients. All hydrogen residing on carbon atoms were included in the structure factor calculation at idealized positions and were allowed to ride on the neighboring atoms with relative isotropic displacement coefficients. The hydrogen residing on nitrogen atoms were found in the difference map and refined independently. Atoms O1, C14, C15 and C16 are disordered over two positions with a ratio of 77.4(3)%: 22.6(3)% and were refined with restraints. The chiral centers were confirmed to be R at C8 and S at C11 and C12. There are several hydrogen bonding interactions of the type N-H···Cl present.

The final least-squares refinement of 280 parameters against 3999 data resulted in residuals R (based on F2 for I≥2σ) and wR (based on F2 for all data) of 0.0264 and 0.0711, respectively. The final difference Fourier map was featureless.

The molecular diagram is drawn with 50% probability ellipsoids. References [1] Bruker-AXS. (2007) APEX2, SADABS, and SAINT Software Reference Manuals. Bruker-AXS,

Madison, Wisconsin, USA. [2] Sheldrick, G. M. (2008) SHELXL. Acta Cryst. A64, 112-122. [3] Dolomanov, O.V.; Bourhis, L.J.; Gildea, R.J.; Howard, J.A.K.; Puschmann, H. "OLEX2: a

complete structure solution, refinement and analysis program". J. Appl. Cryst. (2009) 42, 339-341.

S37

Figure S8. A molecular drawing of 10. All H atoms riding on C atoms are omitted. Only the major component of the disordered atoms is shown. The dashed line represents a hydrogen bond.

S38

Table S9. Crystal data and structure refinement for 10. Identification code stahl75 Empirical formula [C23H31N2O2]+ Cl-

Formula weight 402.95 Temperature 100(2) K Wavelength 1.54178 Å Crystal system Monoclinic Space group P21 Unit cell dimensions a = 8.9393(2) Å �= 90°. b = 8.4273(2) Å �= 95.2660(10)°. c = 14.4703(3) Å � = 90°. Volume 1085.51(4) Å3 Z 2 Density (calculated) 1.233 Mg/m3 Absorption coefficient 1.710 mm-1 F(000) 432 Crystal size 0.16 x 0.13 x 0.12 mm3 Theta range for data collection 3.07 to 69.63°. Index ranges -10<=h<=10, -10<=k<=10, -17<=l<=17 Reflections collected 22026 Independent reflections 3999 [R(int) = 0.0270] Completeness to theta = 67.00° 99.8 % Absorption correction Empirical with SADABS Max. and min. transmission 0.8211 and 0.7715 Refinement method Full-matrix least-squares on F2 Data / restraints / parameters 3999 / 15 / 280 Goodness-of-fit on F2 1.030 Final R indices [I>2sigma(I)] R1 = 0.0264, wR2 = 0.0705 R indices (all data) R1 = 0.0272, wR2 = 0.0711 Absolute structure parameter 0.028(9) Largest diff. peak and hole 0.239 and -0.125 e.Å-3

S39

Table S10. Atomic coordinates ( x 104) and equivalent isotropic displacement parameters (Å2x 103) for 10. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor. ________________________________________________________________________________ x y z U(eq) ________________________________________________________________________________ Cl(1) 9458(1) 864(1) 5491(1) 24(1) N(1) 8568(1) 4372(2) 5939(1) 20(1) N(2) 11449(1) 5638(2) 6962(1) 25(1) C(1) 4374(2) 3714(2) 5558(1) 25(1) C(2) 3217(2) 2855(2) 5896(1) 27(1) C(3) 3532(2) 1731(2) 6581(1) 26(1) C(4) 5005(2) 1468(2) 6930(1) 25(1) C(5) 6172(2) 2288(2) 6576(1) 22(1) C(6) 5866(2) 3417(2) 5883(1) 21(1) C(7) 7061(2) 4275(2) 5403(1) 24(1) C(8) 8616(2) 5384(2) 6805(1) 20(1) C(9) 8368(2) 7081(2) 6516(1) 23(1) C(10) 7215(2) 7931(2) 6730(1) 31(1) C(11) 10125(2) 5155(2) 7406(1) 22(1) C(12) 10315(2) 3452(2) 7750(1) 23(1) C(13) 11561(2) 3184(2) 8527(1) 29(1) O(2) 9001(1) 3008(1) 8188(1) 28(1) O(1) 11047(2) 1794(2) 8979(1) 38(1) C(14) 9436(2) 1763(3) 8826(2) 31(1) C(15) 8736(4) 2118(5) 9718(2) 50(1) C(16) 8997(3) 170(3) 8408(2) 40(1) O(1A) 10838(5) 2618(9) 9304(3) 38(1) C(14A) 9389(6) 2025(8) 8968(4) 31(1) C(15A) 8269(12) 2301(18) 9675(7) 50(1) C(16A) 9469(12) 330(8) 8648(8) 40(1) C(17) 12141(2) 7156(2) 7235(1) 30(1) C(18) 13476(2) 7004(2) 7964(1) 26(1) C(19) 14404(2) 5671(2) 7983(1) 26(1) C(20) 15660(2) 5576(2) 8618(1) 32(1) C(21) 16017(2) 6811(3) 9235(1) 41(1) C(22) 15103(2) 8136(2) 9214(1) 40(1) C(23) 13830(2) 8233(2) 8584(1) 33(1) ________________________________________________________________________________

S40

Table S11. Bond lengths [Å] and angles [°] for 10. _____________________________________________________ N(1)-C(7) 1.4939(18) N(1)-C(8) 1.5129(19) N(1)-H(1A) 0.90(2) N(1)-H(1B) 0.89(2) N(2)-C(11) 1.4559(18) N(2)-C(17) 1.459(2) N(2)-H(2) 0.884(19) C(1)-C(2) 1.388(2) C(1)-C(6) 1.396(2) C(1)-H(1) 0.9500 C(2)-C(3) 1.382(2) C(2)-H(2A) 0.9500 C(3)-C(4) 1.385(2) C(3)-H(3) 0.9500 C(4)-C(5) 1.388(2) C(4)-H(4) 0.9500 C(5)-C(6) 1.390(2) C(5)-H(5) 0.9500 C(6)-C(7) 1.511(2) C(7)-H(7A) 0.9900 C(7)-H(7B) 0.9900 C(8)-C(9) 1.501(2) C(8)-C(11) 1.549(2) C(8)-H(8) 1.0000 C(9)-C(10) 1.315(2) C(9)-H(9) 0.9500 C(10)-H(10A) 0.9500 C(10)-H(10B) 0.9500 C(11)-C(12) 1.523(2) C(11)-H(11) 1.0000 C(12)-O(2) 1.4343(18) C(12)-C(13) 1.525(2) C(12)-H(12) 1.0000 C(13)-O(1A) 1.430(4) C(13)-O(1) 1.437(2) C(13)-H(13A) 0.9900

C(13)-H(13B) 0.9900 O(2)-C(14) 1.428(2) O(2)-C(14A) 1.417(4) O(1)-C(14) 1.437(2) C(14)-C(15) 1.515(3) C(14)-C(16) 1.509(3) C(15)-H(15A) 0.9800 C(15)-H(15B) 0.9800 C(15)-H(15C) 0.9800 C(16)-H(16A) 0.9800 C(16)-H(16B) 0.9800 C(16)-H(16C) 0.9800 O(1A)-C(14A) 1.432(5) C(14A)-C(15A) 1.514(5) C(14A)-C(16A) 1.505(5) C(15A)-H(15D) 0.9800 C(15A)-H(15E) 0.9800 C(15A)-H(15F) 0.9800 C(16A)-H(16D) 0.9800 C(16A)-H(16E) 0.9800 C(16A)-H(16F) 0.9800 C(17)-C(18) 1.523(2) C(17)-H(17A) 0.9900 C(17)-H(17B) 0.9900 C(18)-C(23) 1.387(2) C(18)-C(19) 1.395(2) C(19)-C(20) 1.387(2) C(19)-H(19) 0.9500 C(20)-C(21) 1.389(3) C(20)-H(20) 0.9500 C(21)-C(22) 1.383(3) C(21)-H(21) 0.9500 C(22)-C(23) 1.394(3) C(22)-H(22) 0.9500 C(23)-H(23) 0.9500

C(7)-N(1)-C(8) 114.64(11) C(7)-N(1)-H(1A) 104.3(11) C(8)-N(1)-H(1A) 109.5(12) C(7)-N(1)-H(1B) 111.6(12) C(8)-N(1)-H(1B) 112.2(12) H(1A)-N(1)-H(1B) 103.7(17) C(11)-N(2)-C(17) 117.83(13) C(11)-N(2)-H(2) 111.5(12) C(17)-N(2)-H(2) 112.5(13) C(2)-C(1)-C(6) 120.51(15) C(2)-C(1)-H(1) 119.7 C(6)-C(1)-H(1) 119.7 C(3)-C(2)-C(1) 120.10(14)

C(3)-C(2)-H(2A) 120.0 C(1)-C(2)-H(2A) 120.0 C(2)-C(3)-C(4) 119.72(14) C(2)-C(3)-H(3) 120.1 C(4)-C(3)-H(3) 120.1 C(3)-C(4)-C(5) 120.46(15) C(3)-C(4)-H(4) 119.8 C(5)-C(4)-H(4) 119.8 C(4)-C(5)-C(6) 120.19(13) C(4)-C(5)-H(5) 119.9 C(6)-C(5)-H(5) 119.9 C(5)-C(6)-C(1) 118.95(13) C(5)-C(6)-C(7) 123.97(13)

S41

C(1)-C(6)-C(7) 116.93(13) N(1)-C(7)-C(6) 115.39(12) N(1)-C(7)-H(7A) 108.4 C(6)-C(7)-H(7A) 108.4 N(1)-C(7)-H(7B) 108.4 C(6)-C(7)-H(7B) 108.4 H(7A)-C(7)-H(7B) 107.5 C(9)-C(8)-N(1) 108.29(11) C(9)-C(8)-C(11) 111.94(12) N(1)-C(8)-C(11) 110.61(11) C(9)-C(8)-H(8) 108.6 N(1)-C(8)-H(8) 108.6 C(11)-C(8)-H(8) 108.6 C(10)-C(9)-C(8) 123.48(14) C(10)-C(9)-H(9) 118.3 C(8)-C(9)-H(9) 118.3 C(9)-C(10)-H(10A) 120.0 C(9)-C(10)-H(10B) 120.0 H(10A)-C(10)-H(10B) 120.0 N(2)-C(11)-C(12) 109.71(12) N(2)-C(11)-C(8) 114.75(12) C(12)-C(11)-C(8) 111.44(12) N(2)-C(11)-H(11) 106.8 C(12)-C(11)-H(11) 106.8 C(8)-C(11)-H(11) 106.8 O(2)-C(12)-C(11) 108.58(12) O(2)-C(12)-C(13) 102.02(11) C(11)-C(12)-C(13) 115.59(13) O(2)-C(12)-H(12) 110.1 C(11)-C(12)-H(12) 110.1 C(13)-C(12)-H(12) 110.1 O(1A)-C(13)-C(12) 106.1(2) O(1)-C(13)-C(12) 102.35(13) O(1A)-C(13)-H(13A) 135.4 O(1)-C(13)-H(13A) 111.3 C(12)-C(13)-H(13A) 111.3 O(1A)-C(13)-H(13B) 77.7 O(1)-C(13)-H(13B) 111.3 C(12)-C(13)-H(13B) 111.3 H(13A)-C(13)-H(13B) 109.2 C(14)-O(2)-C(12) 106.94(13) C(12)-O(2)-C(14A) 110.7(2) C(14)-O(1)-C(13) 107.60(14) O(2)-C(14)-O(1) 107.22(15) O(2)-C(14)-C(15) 107.2(2) O(1)-C(14)-C(15) 110.6(2)

O(2)-C(14)-C(16) 110.43(17) O(1)-C(14)-C(16) 107.3(2) C(15)-C(14)-C(16) 113.8(2) C(13)-O(1A)-C(14A) 108.0(3) C(15A)-C(14A)-C(16A) 114.0(6) C(15A)-C(14A)-O(2) 108.7(6) C(16A)-C(14A)-O(2) 109.0(5) C(15A)-C(14A)-O(1A) 110.5(6) C(16A)-C(14A)-O(1A) 111.6(5) O(2)-C(14A)-O(1A) 102.4(3) C(14A)-C(15A)-H(15D) 109.5 C(14A)-C(15A)-H(15E) 109.5 H(15D)-C(15A)-H(15E) 109.5 C(14A)-C(15A)-H(15F) 109.5 H(15D)-C(15A)-H(15F) 109.5 H(15E)-C(15A)-H(15F) 109.5 C(14A)-C(16A)-H(16D) 109.5 C(14A)-C(16A)-H(16E) 109.5 H(16D)-C(16A)-H(16E) 109.5 C(14A)-C(16A)-H(16F) 109.5 H(16D)-C(16A)-H(16F) 109.5 H(16E)-C(16A)-H(16F) 109.5 N(2)-C(17)-C(18) 113.58(14) N(2)-C(17)-H(17A) 108.8 C(18)-C(17)-H(17A) 108.8 N(2)-C(17)-H(17B) 108.8 C(18)-C(17)-H(17B) 108.8 H(17A)-C(17)-H(17B) 107.7 C(23)-C(18)-C(19) 119.20(15) C(23)-C(18)-C(17) 120.18(15) C(19)-C(18)-C(17) 120.53(14) C(20)-C(19)-C(18) 120.28(16) C(20)-C(19)-H(19) 119.9 C(18)-C(19)-H(19) 119.9 C(19)-C(20)-C(21) 120.43(17) C(19)-C(20)-H(20) 119.8 C(21)-C(20)-H(20) 119.8 C(22)-C(21)-C(20) 119.39(16) C(22)-C(21)-H(21) 120.3 C(20)-C(21)-H(21) 120.3 C(21)-C(22)-C(23) 120.45(16) C(21)-C(22)-H(22) 119.8 C(23)-C(22)-H(22) 119.8 C(18)-C(23)-C(22) 120.24(17) C(18)-C(23)-H(23) 119.9 C(22)-C(23)-H(23) 119.9

_____________________________________________________________ Symmetry transformations used to generate equivalent atoms:

S42

Table S12. Anisotropic displacement parameters (Å2x 103) for 10. The anisotropic displacement factor exponent takes the form: -2�2[ h2 a*2U11 + ... + 2 h k a* b* U12 ] ______________________________________________________________________________ U11 U22 U33 U23 U13 U12 ______________________________________________________________________________ Cl(1) 23(1) 20(1) 29(1) -2(1) 10(1) 0(1) N(1) 20(1) 20(1) 22(1) 1(1) 6(1) -1(1) N(2) 20(1) 27(1) 28(1) -2(1) 3(1) -2(1) C(1) 24(1) 24(1) 26(1) -4(1) -2(1) 3(1) C(2) 19(1) 28(1) 34(1) -11(1) 1(1) 1(1) C(3) 22(1) 23(1) 35(1) -10(1) 11(1) -4(1) C(4) 27(1) 21(1) 29(1) -2(1) 10(1) 2(1) C(5) 17(1) 22(1) 28(1) -1(1) 4(1) 2(1) C(6) 20(1) 19(1) 25(1) -4(1) 4(1) -1(1) C(7) 23(1) 24(1) 23(1) 2(1) 2(1) 0(1) C(8) 21(1) 20(1) 21(1) -1(1) 6(1) 0(1) C(9) 24(1) 20(1) 24(1) 1(1) 3(1) -1(1) C(10) 33(1) 24(1) 38(1) 5(1) 10(1) 4(1) C(11) 22(1) 22(1) 23(1) -3(1) 5(1) 0(1) C(12) 22(1) 25(1) 23(1) -2(1) 3(1) 1(1) C(13) 26(1) 32(1) 28(1) 2(1) -1(1) 2(1) O(2) 25(1) 32(1) 28(1) 8(1) 4(1) 0(1) O(1) 30(1) 42(1) 42(1) 17(1) -8(1) -5(1) C(14) 31(1) 35(1) 26(1) 5(1) -2(1) -3(1) C(15) 60(2) 60(2) 30(1) 8(1) 7(1) -4(2) C(16) 36(2) 32(1) 50(2) 3(1) -14(1) 4(1) O(1A) 30(1) 42(1) 42(1) 17(1) -8(1) -5(1) C(14A) 31(1) 35(1) 26(1) 5(1) -2(1) -3(1) C(15A) 60(2) 60(2) 30(1) 8(1) 7(1) -4(2) C(16A) 36(2) 32(1) 50(2) 3(1) -14(1) 4(1) C(17) 27(1) 25(1) 39(1) 2(1) 2(1) -3(1) C(18) 23(1) 28(1) 26(1) 1(1) 9(1) -7(1) C(19) 24(1) 30(1) 25(1) -2(1) 6(1) -6(1) C(20) 24(1) 42(1) 31(1) 4(1) 6(1) -2(1) C(21) 34(1) 59(1) 28(1) -1(1) 0(1) -14(1) C(22) 44(1) 47(1) 29(1) -12(1) 6(1) -16(1) C(23) 36(1) 31(1) 33(1) -4(1) 14(1) -6(1) ______________________________________________________________________________

S43

Table S13. Hydrogen coordinates ( x 104) and isotropic displacement parameters (Å2x 10 3) for 10. ________________________________________________________________________________ x y z U(eq) ________________________________________________________________________________ H(1A) 9160(20) 4800(20) 5540(12) 24 H(1B) 8960(20) 3420(30) 6053(12) 24 H(2) 11312(19) 5520(20) 6352(14) 30 H(1) 4149 4510 5101 30 H(2A) 2208 3041 5655 33 H(3) 2740 1141 6812 32 H(4) 5219 721 7416 30 H(5) 7181 2077 6806 27 H(7A) 7178 3734 4806 28 H(7B) 6706 5367 5257 28 H(8) 7779 5049 7176 25 H(9) 9082 7568 6159 27 H(10A) 6484 7474 7086 37 H(10B) 7113 9002 6529 37 H(11) 10084 5839 7968 26 H(12) 10452 2725 7218 28 H(13A) 12538 2991 8275 34 H(13B) 11658 4100 8956 34 H(15A) 9127 1374 10201 75 H(15B) 7642 2004 9613 75 H(15C) 8984 3206 9916 75 H(16A) 7900 100 8307 61 H(16B) 9377 -675 8832 61 H(16C) 9430 52 7814 61 H(15D) 8534 1639 10223 75 H(15E) 7259 2021 9403 75 H(15F) 8289 3421 9858 75 H(16D) 9919 294 8056 61 H(16E) 8454 -119 8567 61 H(16F) 10087 -288 9113 61 H(17A) 11375 7846 7483 36 H(17B) 12478 7680 6678 36 H(19) 14173 4826 7560 32 H(20) 16281 4660 8631 39 H(21) 16881 6745 9668 49 H(22) 15345 8987 9632 48 H(23) 13202 9142 8579 39 ________________________________________________________________________________

S44

Table S14. Torsion angles [°] for 10. ___________________________________________________________________ C(6)-C(1)-C(2)-C(3) 2.1(2) C(1)-C(2)-C(3)-C(4) 0.1(2) C(2)-C(3)-C(4)-C(5) -2.1(2) C(3)-C(4)-C(5)-C(6) 1.9(2) C(4)-C(5)-C(6)-C(1) 0.3(2) C(4)-C(5)-C(6)-C(7) -175.04(14) C(2)-C(1)-C(6)-C(5) -2.3(2) C(2)-C(1)-C(6)-C(7) 173.37(13) C(8)-N(1)-C(7)-C(6) -66.87(16) C(5)-C(6)-C(7)-N(1) -24.0(2) C(1)-C(6)-C(7)-N(1) 160.55(13) C(7)-N(1)-C(8)-C(9) -67.76(15) C(7)-N(1)-C(8)-C(11) 169.23(12) N(1)-C(8)-C(9)-C(10) 117.50(16) C(11)-C(8)-C(9)-C(10) -120.31(16) C(17)-N(2)-C(11)-C(12) -131.16(13) C(17)-N(2)-C(11)-C(8) 102.48(15) C(9)-C(8)-C(11)-N(2) -58.41(16) N(1)-C(8)-C(11)-N(2) 62.45(16) C(9)-C(8)-C(11)-C(12) 176.13(12) N(1)-C(8)-C(11)-C(12) -63.01(15) N(2)-C(11)-C(12)-O(2) 179.74(11) C(8)-C(11)-C(12)-O(2) -52.04(15) N(2)-C(11)-C(12)-C(13) 65.88(16) C(8)-C(11)-C(12)-C(13) -165.91(12) O(2)-C(12)-C(13)-O(1A) 0.4(4) C(11)-C(12)-C(13)-O(1A) 118.0(4) O(2)-C(12)-C(13)-O(1) 36.62(16) C(11)-C(12)-C(13)-O(1) 154.21(14) C(11)-C(12)-O(2)-C(14) -155.65(14) C(13)-C(12)-O(2)-C(14) -33.14(17) C(11)-C(12)-O(2)-C(14A) -143.2(4) C(13)-C(12)-O(2)-C(14A) -20.7(4) O(1A)-C(13)-O(1)-C(14) 73.4(3) C(12)-C(13)-O(1)-C(14) -27.02(19) C(12)-O(2)-C(14)-O(1) 17.2(2) C(14A)-O(2)-C(14)-O(1) -92.5(11) C(12)-O(2)-C(14)-C(15) 136.0(2) C(14A)-O(2)-C(14)-C(15) 26.3(11) C(12)-O(2)-C(14)-C(16) -99.41(19) C(14A)-O(2)-C(14)-C(16) 150.9(11) C(13)-O(1)-C(14)-O(2) 7.3(2) C(13)-O(1)-C(14)-C(15) -109.3(2) C(13)-O(1)-C(14)-C(16) 125.96(19) O(1)-C(13)-O(1A)-C(14A) -69.3(5) C(12)-C(13)-O(1A)-C(14A) 19.5(6) C(14)-O(2)-C(14A)-C(15A) -136.1(13) C(12)-O(2)-C(14A)-C(15A) 149.6(6) C(14)-O(2)-C(14A)-C(16A) -11.3(10)

C(12)-O(2)-C(14A)-C(16A) -85.6(5) C(14)-O(2)-C(14A)-O(1A) 107.0(13) C(12)-O(2)-C(14A)-O(1A) 32.7(6) C(13)-O(1A)-C(14A)-C(15A) -147.0(6) C(13)-O(1A)-C(14A)-C(16A) 85.0(7) C(13)-O(1A)-C(14A)-O(2) -31.4(6) C(11)-N(2)-C(17)-C(18) 97.18(16) N(2)-C(17)-C(18)-C(23) -151.13(14) N(2)-C(17)-C(18)-C(19) 32.3(2) C(23)-C(18)-C(19)-C(20) 0.2(2) C(17)-C(18)-C(19)-C(20) 176.79(14) C(18)-C(19)-C(20)-C(21) -0.6(2) C(19)-C(20)-C(21)-C(22) 0.3(2) C(20)-C(21)-C(22)-C(23) 0.4(3) C(19)-C(18)-C(23)-C(22) 0.5(2) C(17)-C(18)-C(23)-C(22) -176.14(14) C(21)-C(22)-C(23)-C(18) -0.8(2)

S45

________________________________________________________________ Symmetry transformations used to generate equivalent atoms: Table S15. Hydrogen bonds for 10 [Å and °]. ____________________________________________________________________________ D-H...A d(D-H) d(H...A) d(D...A) <(DHA) ____________________________________________________________________________ N(1)-H(1A)...Cl(1)#1 0.90(2) 2.21(2) 3.1060(12) 177.5(16) N(1)-H(1B)...Cl(1) 0.89(2) 2.36(2) 3.1449(13) 148.0(15) N(2)-H(2)...Cl(1)#1 0.884(19) 2.71(2) 3.5720(14) 165.9(17) ____________________________________________________________________________ Symmetry transformations used to generate equivalent atoms: #1 -x+2,y+1/2,-z+1

NH

Ph

NH

Ph

NH

Ph

Me

NH

Ph

Me

NH

Ph

Ph

NH

Ph

Ph

ONS

NH

OO O

Ph

ONS

NH

OO O

Ph

NH

SN

OO

Ph

Ph

NH

SN

OO

Ph

Ph

ONS

NH

OO O

ONS

NH

OO O

NH

SN

OO

Ph

NH

SN

OO

Ph

ONS

NH

OO O

Ph

ONS

NH

OO O

Ph

NH

SN

OO

Ph

Ph

NH

SN

OO

Ph

Ph

ONS

NH

OO OMeO

ONS

NH

OO OMeO

NH

SN

OO

Ph

MeO

NH

SN

OO

Ph

MeO

BnNS

NH

CO2EtOO

BnNS

NH

CO2EtOO

NO

O

SNH

OO

CO2Et

NO

O

SNH

OO

CO2Et

BnNS

NH

OO

CO2Et

BnNS

NH

OO

CO2Et

NH

SN

OO

Ph

Ph

NH

SN

OO

Ph

Ph

BnNS

NH

OO

F

BnNS

NH

OO

F

NO

O

SNH

OO

NBoc

NO

O

SNH

OO

NBoc

BnNS

NH

OO

NBoc

BnNS

NH

OO

NBoc

NO

O

SNH

OO

NO

O

SNH

OO

BnNS

NH

OO

BnNS

NH

OO

BnNS

NH

OOCl

BnNS

NH

OOCl

NO

O

SNH

OO

O

NO

O

SNH

OO

O

BnNS

NH

OO

O

BnNS

NH

OO

O

NS

Ph

NH

OO

Ph

NS

Ph

NH

OO

Ph

BnNS

NHBn

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OTIPS

BnNS

NHBn

OO

OTIPS

NS

Ph

NH

OO

Ph

Me

NS

Ph

NH

OO

Ph

Me

NS

Ph

NH

OO

Ph

Ph

NS

Ph

NH

OO

Ph

Ph

BnNS

NHBn

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BnO

BnNS

NHBn

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BnO

NS

Ph

NH

OO

Ph

NS

Ph

NH

OO

Ph

ONS

NH

OO O

Ph

Me

ONS

NH

OO O

Ph

Me

NS

Ph

NH

OO

Ph

Me

NS

Ph

NH

OO

Ph

Me