S1

Synthesis of Enantioenriched 1,2-trans-Diamines using the Borono-Mannich Reaction with N-protected α -Amino Aldehydes Stéphanie Norsikian,*a Margaux Beretta,a Alexandre Cannillo,a Amélie Martin,a Pascal Retailleaua and Jean-Marie Beau*a,b

Supporting Information

Table of contents : I. Crystallographic Studies II. Correlation between ees, chemical yields and pKas III. Experimental and Spectral data IV. HPLC and Copies of 1H NMR and 13C NMR

Electronic Supplementary Material (ESI) for Chemical Communications.This journal is © The Royal Society of Chemistry 2015

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I- RX of compound 5

The crystal structure presented herein was solved from a colourless block suitable to X-ray single crystal diffraction, obtained by slow evaporation from a pentane/ether solvent mixture. X-ray crystallographic data were collected at room temperature on an Enraf-Nonius Kappa-CCD diffractometer with graphite-monochromated Mo Kα radiation (λ = 0.71070 Å) at ambient temperature (293(2) K). A preliminary orientation matrix and unit cell parameters were determined from a ϕ−scan of ten one-degree oscillations, followed by spot integration and least-squares refinement using the DENZO1 program as implemented in the COLLECT package.2 One hemisphere of data around the phi axis completed by two ω−scans spanning a total of angular sector of 344° with 2° oscillation, and with the detector at a distance of 31.0 mm from the crystal coupled with a θ offset in the range of 1.2-7.3° were designed for complete collection of data up to a resolution of 0.83 Å in the 2/m Laue group. «Dezingering» action was accomplished by measuring each frame twice with a total exposure of 20s per degree. Data reduction and cell dimension post-refinement were performed, altogether with multi-scan absorption correction (Tmin = 0.91, Tmax = 0.95) with SCALEPACK.1

The non-centrosymmetric space group assignment, P 21/c (n° 14), was based upon systematic absences, E-statistics, agreement factors for equivalent reflections, and successful refinement of the structure. The structure was solved by Direct methods (SIR97),3 followed by subsequent difference Fourier syntheses, and refined by full matrix least squares on F2 using the SHELXL-2014.4 Anisotropic thermal parameters were used for all non-hydrogen atoms whereas hydrogen atoms attached to carbon atoms, located from difference Fourier maps, were refined as a riding model with Uiso = 1.2Ueq of the parent atom (1.5 for the methyl hydrogen atoms). The H atom of the protonated amine group was refined also with Uiso = 1.2Ueq and with a soft 1,2 distance restraint by means of DFIX (sd 0.02Å). The intramolecular centroid distance between the phenyl group at C1 and the tolyl group at S1 is 3.63Å. Statistics for 5. C30 H34 N2 O2 S, Mr= 486.65, crystal size 0.55 x 0.49 x 0.38 mm, monoclinic, space group P 21/c (n°14), a = 11.426(1) Å, b = 16.485(1)Å, c = 15.147(1) Å, b = 100.185(2)°, V= 2808.1(4) Å3, Z= 4, ρcalcd= 1.151 g.cm-3, µ = 0.143 mm-1, F(000)= 1040, λ = 0.7170 Å, 2θmax= 52.4 ° (dmin = 0.83Å), -14 ≤ h ≤ 14, -20 ≤ k ≤ 20, -18 ≤ l ≤ 18, 28991 measured reflections, 5723 independent, R(int)= 0.025, 320 parameters were refined against 5714 reflections, R1= 0.074, wR2= 0.149 (using all data) based on observed F values, R1= 0.049, wR2= 0.126 (4122 reflections with I>2σ(I)), , Δρmin and Δρmax= -0.297 and 0.198 e.Å-3, GOF= 1.024 based on F2. CCDC-1044004 (for 5) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge on application to the Director, CCDC 12 Union Road, Cambridge CB2 1EZ, UK (fax (+44) 1223-336033; or e-mail deposit@ccdc.cam.uk) or via www.ccdc.cam.ac.uk/data_request/cif.

1 Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Volume 276, Macromolecular Crystallography, part A, edited by C.W. Carter, Jr. & R.M. Sweet, 307-326, 1997, New York: Academic Press. 2 Nonius, B. V. (1999). COLLECT, data collection software. 3 Altomare, A., Burla, M. C., Camalli, M., Cascarano, G. L., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G., Polidori, G. & Spagna, R. (1999). J. Appl. Cryst. 32, 115-119. 4 Sheldrick, G. M. (2008). Acta Crystallogr., A64, 112-122.

S3

Figure 1. An ORTEP-3 5 plot of 5, showing the atom-labelling scheme. Ellipsoids are drawn at the 50% probability level and H atoms are shown as spheres of arbitrary radius.

5 Burnett M.N. and Johnson, C. K. (1996) Oak Ridge National Laboratory Report ORNL-6895

S4

II. Correlation between ees, chemical yields and pKas The following graphical representation illustrates the dependence of the chemical yields and ee's of the diamine products as a function of the pKa of the corresponding NH-groups in the starting aldehydes 3 (with the condensation of vinyl boronic acid 1a and N,N-diallylamine 2a with N-protected aldehydes 3 derived from L-phenylalanine). The experimental results found for the NHTFA aldehyde 3k (calculated pKa of 9.88) have also been included in the following graphical representations (diamine product in 42% yield and 4% ee ; they are not reported in the main text). The pKa were calculated in an aqueous medium using the ACD/pKa DB program,6,7 a method based on linear free-energy relationships. The same histogram with the corresponding methyl esters is also shown for comparison.

6 Advanced Chemistry Development, Inc.: https://ilab.acdlabs.com/ilab2/ 7 See also C. Liao and M. C. Nicklaus, J. Chem. Inf. Model. 2009, 49, 2801.

NHPG

O

0  

2  

4  

6  

8  

10  

12  

14  

16  

0  

10  

20  

30  

40  

50  

60  

70  

80  

90  

100  

NHAc   NHBoc   NHMtr   NHTFA   NHSES   NHTs   NHNs  

ee  

Yield  

pKa  

pKa Ee (%) Yield (%) PG 14,95 3 23 NHAc 11,38 15 21 NHBoc 9,97 20 28 NHMtr 9,88 4 42 NHTFA 9,54 71 39 NHSES 9,54 93 54 NHTs 8,18 94 71 NHNs

S5

NHPG

O

OMe

0  

2  

4  

6  

8  

10  

12  

14  

16  

0  

10  

20  

30  

40  

50  

60  

70  

80  

90  

100  

NHAc   NHBoc   NHMtr   NHTFA   NHSES   NHTs   NHNs  

ee  

Yield  

pKa  

pKa Ee (%) Yield (%) PG 14,74 3 23 NHAc 11,17 15 21 NHBoc 9,61 20 28 NHMtr 9,67 4 42 NHTFA 9,25 71 39 NHSES 9,18 93 54 NHTs 7,81 94 71 NHNs

S6

III. Experimental procedure General. Reactions were monitored with analytical thin-layer chromatography (TLC) on silica gel 60 F254 plates and visualized under UV (254 nm) and/or by staining with KMNO4. Silica gel SDS 60 ACC 35-70 mm was used for column chromatography. Preparative TLC was done using Merck 60 F254 0.5 mm. NMR spectra were recorded with AM 300, AVANCE 300 and AVANCE 500 Brüker spectrometers. Chemical shifts are given in parts per million, referenced to the solvent peak of CDCl3, defined at 77.23 ppm (13C NMR) and 7.26 ppm (1H NMR). Microwave reactions were carried out with a CEM Discover S-Class. Melting points (uncorrected) were determined with the aid of a Büchi B-540 apparatus. IR spectra were recorded on a Perkin-Elmer Spectrum BX instrument with an FT-IR system. Optical rotations were measured on an Anton Paar MCP300 polarimeter using a cell of 1 dm-length path. All the reagent grade chemicals obtained from commercial sources were used as received excepted for(E)-phenyl vinyl boronic acid (1a), which was purchased from the Aldrich Chemical Company. It was diluted with Et2O, the ethereal phase was washed with water and dried with Na2SO4. After evaporation of the solvent, the solid was washed with pentane. For the oxidation reaction with TEMPO, CH2Cl2 stabilised with ethanol was used. A- Synthesis of the α-aminoaldehydes

General Procedure (A) for sulfonylation

To a stirred solution of methyl ester hydrochloride (1.0 equiv) in dry CH2Cl2 (0.4 M) under inert atmosphere at 0 °C was added triethylamine (2.2 equiv) then arylsulfonyl chloride (1.1 equiv). The resulting mixture was stirred at room temperature for 12 h. Solvent was then removed under reduced pressure and the residue was diluted with AcOEt (50 mL). The organic phase was washed with a 1:1 solution of water and saturated aqueous NaHCO3 (50 mL), dried over Na2SO4 and filtered.

General Procedure (B) for the reduction of ester to alcohol using LiBH4

To a stirred solution of methyl ester (1.0 equiv) in dry THF (0.15-0.2 M) at 0 °C under argon atmosphere was added portionwise LiBH4 (3.5-4 equiv). The resulting mixture was stirred at room temperature. Saturated aqueous NH4Cl was then added and the aqueous phase was extracted with EtOAc (3 x). Organic layers were combined, washed with water, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel to afford the corresponding alcohol.

General Procedure (C) for the oxidation to α-amino aldehyde To a stirred solution of alcohol (1.0 equiv) in CH2Cl2 (0.035 M) at -5 °C was added saturated aqueous NaHCO3 (0.5 x V CH2Cl2 mL), KBr (1.0 equiv) and TEMPO (0.05 equiv). NaOCl (0.5 M, 2.0 equiv) was

RH

O

NHGP

TEMPO cat.NaOCl, KBr

CH2Cl2/NaHCO30 °C, 30 minR

NHGP

OH

34

R

NHGP

O

MeOReduction

R

NH3

O

MeOCl

E

Protection

S7

then added with a syringe pump over 30 min. Saturated aqueous Na2S2O3 (V Na2S2O3 = V NaHCO3) was added, the phases were separated and the aqueous layer was extracted with DCM (3 x). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to afford the corresponding crude α-amino aldehyde which was used directly in the next step.

4-methyl-N-[(2S)-1-oxo-3-phenylpropan-2-yl]benzenesulfonamide 3a. The General Procedure (A) was followed using L-phenylalanine methyl ester (400 mg, 1.85 mmol,) triethylamine (0.57 mL, 4.02 mmol) and para-toluenesulfonyl chloride (388 mg, 2.04 mmol,). in CH2Cl2 (4 mL) to afford Ea (563 mg, 1.84 mmol, 99%) as a white powder (NMR data consistent with those reported in the literature).8 To a stirred solution of Ea (575 mg, 1.72 mmol, 1.0 equiv) in dry THF (25 mL) at 0 °C under argon atmosphere was added portionwise LiAlH4 ((131 mg, 3.45 mmol, 2.0 equiv). The resulting mixture was stirred for 2 h at room temperature. Water (80 µL) was added dropwise, then aqueous 15% NaOH (160

µL) and water (160 µL) were added and the mixture was stirred at 20°C for 30 min and filtered on Celite. The Celite pad was washed with hot ethanol (5 x 30 mL) and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (AcOEt/heptane 3:7 to 4:6) to afford the corresponding alcohol 4a (516 mg, 1.69 mmol, 98%) as white powder (NMR data consistent with those reported in the literature).9 The General Procedure (C) was followed using 4a (215 mg, 0.7 mmol), TEMPO (6 mg, 0.035 mmol), KBr (84 mg, 0.7 mmol), NaOCl (0.5 M, 2.4 mL, 1.2 mmol), saturated aqueous NaHCO3 (7 mL) in CH2Cl2 (14 mL) to afford 3a (206 mg, 0.68 mmol, 96%). 1H NMR (500 MHz, CDCl3) δ 9.58 (s, 1H, CHO), 7.63 (d, J = 7.0 Hz, 2H, HAr), 7.31-7.24 (m, 5H, HAr), 7.07 (d, J = 7.0 Hz, 2H, HAr), 5.09 (d, 1H, NH), 4.09-4.02 (m, 1H, CHNH), 3.13-3.03 (m, 2H, CH2Ph), 2.45 (s, 3H, CH3).

4-nitro-N-[(2S)-1-hydroxy-3-phenylpropan-2- yl]benzenesulfonamide 4b. The General Procedure (A) was followed using L-phenylalanine methyl ester hydrochloride (2 g, 9.27 mmol), triethylamine (2.8 mL, 20.4 mmol) and para-nitrobenzenesulfonyl chloride (2.25 g, 10.2 mmol) in CH2Cl2 (25 mL). After work-up and concentration under reduced pressure, the residue was diluted with Et2O (100 mL), stirred for 15 min, filtrated and concentrated to afford the corresponding ester Eb (2.9 g, 7.9 mmol, 86%) as a white powder (NMR data consistent with those reported in the literature).10 The General Procedure (B) was then followed using Eb (1 g, 2.7 mmol) and LiBH4 (227 mg, 10.4 mmol) in THF (15 mL).

After purification (AcOEt/heptane 3:7 to 5:5), 4b (0.87 g, 2.6 mmol, 94%) was obtained as yellow powder. Mp = 157-159 °C (recrystallisation in Et2O/CH2Cl2 1/1). [α]D25 −51.7 (c 0.2, CHCl3). 1H NMR (300 MHz, CDCl3) δ 8.17 (d, J = 10.0 Hz, 1H, HAr), 7.75 (d, J = 10.0 Hz, 1H, HAr), 7.20-7.10 (m, 3H, HAr), 7.01-6.95 (m, 2H, HAr), 4.92 (d, J = 8.0 Hz, 1H, NH), 3.81-3.63 (m, 2H, CH2OH), 3.62-3.50 (m, 1H, CHNH), 2.89 (dd, J = 14.0 and 6.0 Hz, 1H, CH2Ph), 2.60 (dd, J = 14.0 and 9.0 Hz, 1H, CH2Ph). 13C NMR (75 MHz, CDCl3) δ 145.8 (CqAr), 136.6 (CqAr), 129.0 (CAr), 128.7 (CAr), 127.9 (CAr), 126.8 (CAr), 124.1 (CAr), 64.7 (CH2OH), 57.4 (CHNH), 38.0 (CH2Ph). IR 3675, 3498, 3106, 2971, 1607, 1525 cm-1. ESIHRMS m/z = 337.0863 [M+H]+. C15H17N2O5S requires 337.0858.

8 (a) Davis, F. A.; Zhou, P.; Reddy, G. V. J. Org. Chem. 1994, 59, 3243. (b) Sridhar, R.; Srinivas, B.; Kumar, V. P.; Narender, M.; Rao, K. R. Adv. Synth. Catal. 2007, 349, 1873. 9 a) Bonini, B.F.; Comes-Franchini, M.; Fochi, M.; Gawronski, J.; Mazzanti, G.; Ricci, A.; Varchi, G. Eur. J. Org. Chem. 1999, 1999, 437. (b) Pyne, S. G.; Hensel, M.J.; Fuchs, P.L. J. Am. Chem. Soc. 1982, 21, 5719. 10 (a) Di Gioia, M.L. ; Leggio, A.; Le Pera, A.; Liguori, A.; Napoli, A.; Siciliano, C.; Sindona, G. J. Org. Chem. 2003, 68, 7416. (b) Reichwein, J.F.; Liskamp, R.M.J. Eur. J. Org. Chem. 2000, 2000, 2335.

O

NH

Ph

O2S

H

NH

Ph

O2S

NO2

HO

S8

4-nitro-N-[(2S)-1-oxo-3-phenylpropan-2- yl]benzenesulfonamide 3b. The General Procedure (C) was followed using alcohol 4b (101 mg, 0.3 mmol), TEMPO (2.3 mg, 0.015 mmol), KBr (35.4 mg, 0.3 mmol), NaOCl (1.2 mL, 0.6 mmol) and saturated solution of NaHCO3 (2.5 mL) in CH2Cl2 (5 mL). 3b was obtained as a beige powder (95.1 mg, 0.28 mmol, 95%). 1H NMR (300 MHz, CDCl3) δ 9.62 (s, 1H, CHO) 8.25 (d, J = 9.0 Hz, 1H, HAr), 7.85 (d, J = 9.0 Hz, 1H, HAr), 7.32-7.22 (m, 3H, HAr), 7.10-7.02 (m, 2H, HAr), 5.29 (bs, 1H, NH), 4.25-4.17 (m, 1H, CHNH), 3.27 (dd, J = 14.0 and 6.0 Hz, 1H, CH2Ph), 3.07-2.98 (dd, J = 14.0 and 7.0 Hz, 1H, CH2Ph).

(S)-methyl 2-(4-methoxy-2,3,6-trimethylphenylsulfonamido)-3-phenylpropanoate Ec. To a stirred solution of L-phenylalanine methyl ester hydrochloride (363 mg, 1.68 mmol, 1.0 equiv) in dry CH2Cl2 (10 mL) under argon atmosphere at 0 °C was added triethylamine (0.5 mL, 3.7 mmol, 2.2 equiv) then [4-methoxy-2,3,6-trimethyl)phenyl]sulfonyl chloride (440 mg, 1.77 mmol, 1.1 equiv) and 4-dimethylaminopyridine (25 mg, 0.2 mmol, 0.12 equiv.). The resulting mixture was stirred for 12 h at room temperature. Then, water (5 mL) was added and the aqueous phase was extracted with AcOEt (3 x 20 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated under reduce pressure. The residue was purified by flash

chromatography on silica gel (AcOEt/heptane 20:80 to 25:75) to afford product Ec (384 mg, 0.98 mmol, 58%) as a white powder. Mp = 113-115 °C. [α]D25 −4.5 (c 0.2, CHCl3). 1H NMR (300 MHz, CDCl3) δ 7.25-7.15(m, 3H, HAr), 7.07-6.95 (m, 2H, HAr), 6.55 (s, 1H, HAr), 5.11 (d, J = 9.0 Hz, 1H, NH), 4.15-4.01 (m, 1H, CHNH), 3.87 (s, 3H, OCH3), 3.57 (s, 3H, OCH3), 3.04 (dd, J = 6.0 and 13.0 Hz, 1H, CH2Ph), 2.99 (dd, J = 6.5 and 13.0 Hz, 1H, CH2Ph), 2.65 (s, 3H, CH3), 2.42 (s, 3H, CH3), 2.10 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3) δ 171.7 (CO2Me), 159.4 (CqAr), 139.3 (CqAr), 139.0 (CqAr), 135.2 (CqAr), 129.2 (CAr), 128.5 (CAr), 127.1 (CAr), 125.2 (CqAr), 111.9 (CAr), 56.5 (CHNH), 55.5 (OCH3), 52.4 (OCH3), 39.2 (CH2Ph), 24.3 (CH3), 17.7 (CH3), 11.9 (CH3). IR 3311, 1744, 1585, 1560, 1456, 1328, 1307, 1119, 1104 cm-1. ESIMS m/z = 392.15 ([M+H]+, 100%), 455.16 ([M+CH3CN+Na]+, 50%), 805.26 ([2M+ Na]+, 50%). ESIHRMS m/z = 392.1535 [M+H]+. C20H25NO5S requires 392.1532. Anal. Calcd for C20H25NO5S: C, 61.36; H, 6.44; N, 3.58; O, 20.43; S, 8.19. Found: C, 61.38; H, 6.58; N, 3.70; O, 20.20; S, 8.15

N-[(2S)-1-hydroxy-3-phenylpropan-2-yl]-2- (4-methoxy-2,3,6- trimethyl)phenylsulfonamide 4c. The General Procedure (B) was followed using methyl ester Ec (384 mg, 0.98 mmol) and LiBH4 (107 mg, 4.9 mmol) in dry THF (4.3 mL). After purification (AcOEt/heptane 3:7 to 4:6), 4c (315 mg, 0.87 mmol, 88 %) was obtained. [α]D25 −22.2 (c 0.3, CHCl3). 1H NMR (300 MHz, CDCl3) δ 7.26-6.96 (m, 5H, HAr), 6.57 (s, 1H, HAr), 4.89 (d, J = 7.0 Hz, 1H, NH), 3.88 (s, 3H, OCH3), 3.71 (dd, J = 11.0 and 3.0 Hz, CH2OH), 3.55 (dd, J = 11.0 and 4.0 Hz, CH2OH), 3.49-3.37 (m, 1H, CHNH), 2.82 (dd, J = 14.0 and 7.0 Hz, 1H, CH2Ph), 2.72 (dd, J = 14.0 and 8.0 Hz, 1H, CH2Ph), 2.65 (s, 3H, CH3),

2.31 (s, 3H, CH3), 2.09 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3) δ 159.6 (CqAr), 139.1 (CqAr), 138.9 (CqAr), 137.1 (CAr), 129.3 (CAr), 129.2 (CAr), 129.1 (CAr), 128.8 (CAr), 128.7 (CAr), 126.9 (CAr), 125.5 (CqAr), 112.2 (CAr), 64.4 (CH2OH), 56.6, 55.7 (OCH3, CHNH), 38.2 (CH2Ph), 24.7 (CH3), 17.9 (CH3), 12.2 (CH3). IR 3669, 3329, 2937, 1585 cm-1. ESIHRMS m/z = 364.1566 [M+H]+. C19H26NO4S requires 364.1583.

O

NH

Ph

O2S

NO2

H

NH

Ph

O2S

OMe

MeO

O

NH

Ph

O2S

OMe

HO

S9

N-[(2S)-1-oxo-3-phenylpropan-2-yl]-2- (4-methoxy-2,3,6- trimethyl)phenylsulfonamide 3c. The General Procedure (C) was followed using 4c (107 mg, 0.3 mmol), TEMPO (2.3 mg, 0.015 mmol), KBr (35 mg, 0.3 mmol), NaOCl (1.2 mL, 0.82 mmol) and saturated solution of NaHCO3 (2.1 mL) in CH2Cl2 (4.9 mL). The α-amino aldehyde 3c (105.2 mg, 0.29 mmol, 99 %) was obtained as a yellow oil. 1H NMR (500 MHz, CDCl3) δ 9.63 (s, 1H, CHO), 7.31-7.22 (m, 3H, HAr), 7.08-7.01 (m, 2H, HAr), 6.58 (s, 1H, HAr), 5.23 (bs, 1H, NH), 3.93-3.84 (m, 4H, CHNH, OCH3), 3.06 (dd, J =14.0 and 6.0 Hz, 1H, CH2Ph), 2.98 (dd, J =14.0 and 7.5 Hz, 1H, CH2Ph), 2.63 (s, 3H, CH3), 2.28 (s, 3H,

CH3), 2.09 (s, 3H, CH3).

Methyl N-{[2-(trimethylsilyl)ethyl]sulfonyl}-L-phenylalaninate Ed. To a stirred solution of L-phenylalanine methyl ester hydrochloride (200 mg, 0.93 mmol, 1.0 equiv) in dry DMF (2 mL) under argon atmosphere at 0°C was added triethylamine (0.6 mL, 4.6 mmol, 5 equiv) then 2-(trimethylsilyl)ethanesulfonyl chloride (0.26 mL, 1.4 mmol, 1.5 equiv) in dry DMF (1 mL) using a syringe pump (15 min). The resulting mixture was stirred for 1 h 30 allowing the temperature to raise 20°C. Water (10 mL) was then added and the aqueous phase was extracted with AcOEt (3 x 15 mL). Organic layers were

combined, washed with water (2 x 10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (AcOEt/heptane 1:9 to 4:6) to afford product Ed (165 mg, 0.48 mmol, 52 %) as a green yellow oil. [α]D25 −1.7 (c 0.6, CHCl3).1H NMR (300 MHz, CDCl3) δ 7.38-7.18 (m, 5H, HAr), 4.89 (bs, 1H, NH), 4.35 (ddd, J = 9.0, 8.0 and 5.0 Hz, CHNH), 3.79 (s, 3H, OCH3), 3.17 (dd, J = 14.0 and 5.0 Hz, 1H, CH2Ph), 2.99 (dd, J = 14.0 Hz and 8.0 Hz, 1H, CH2Ph), 2.76-2.54 (m, 2H, CH2SO2), 0.91-0.74 (m, 2H, CH2Si), -0,04 (s, 9H, Si(CH3)3). 13C NMR (75 MHz, CDCl3) δ 172.4 (CO2Me), 135.8 (CqAr), 129.8 (CAr), 129.7 (CAr), 129.0 (CAr), 127.7 (CAr), 57.6 (CHNH), 53.0 (OCH3), 50.2 (CH2SO2), 39.9 (CH2Ph), 10.4 (CH2Si), -1.9 (Si(CH3)3). IR 3273, 2954, 1742, 1320, 1249, 1142, 698 cm-1. ESIMS m/z = 407.14 ([M+CH3CN+Na]+, 100%), 709.25 ([2M+ Na]+, 40%). ESIHRMS m/z = 407.1438 [M+CH3CN+Na]+. C17H28N2NaO4SSi requires 407.1437.

N-[(2S)-1-hydroxy-3-phenylpropan-2-yl]-2- (trimethylsilyl)ethanesulfonamide 4d. The General Procedure (B) was followed using methyl ester Ed (93 mg, 0.27 mmol) and LiBH4 (22 mg, 1 mmol) in THF (2 mL) for 5 h. After purification by flash chromatography on silica gel (AcOEt/heptane 3:7 to 4:6), 4d (83 mg, 0.26 mmol, 97%)

was obtained. [α]D25 −39.8 (c 0.6, CHCl3).1H NMR (300 MHz, CDCl3) δ 7.38-7.19 (m, 5H, HAr), 4.76 (d, J = 8.0 Hz, 1H, NH), 3.86-3.75 (m, 1H, CH2OH), 3.68-3.57 (m, 2H, CH2OH, CHNH), 2.95 (dd, J = 14.0 and 5.0 Hz, 1H, CH2Ph), 2.78 (dd, J = 14.0 and 9.0 Hz, 1H, CH2Ph), 2.60-2.41 (m, 3H, OH, CH2SO2), 0.83-0.64 (m, 2H, CH2Si), -0.05 (s, 9H, Si(CH3)3). 13C NMR (75 MHz, CDCl3) δ 138.0 (CqAr), 129.7 (CAr), 129.0 (CAr), 127.3 (CAr), 65.7 (CH2OH), 58.0 (CHNH), 49.5 (CH2SO2), 38.7 (CH2Ph), 10.2 (CH2Si), -1.9 (Si(CH3)3). IR 3477, 3273, 2953, 1420, 1310, 1249, 1138 cm-1. ESIMS m/z = 316.18 ([M+H]+, 35%), 379.15 ([M+CH3CN+Na]+, 20%), 631.28 ([2M+H]+, 100%). ESIHRMS m/z = 316.1405 [M+H]+. C14H26NO3SiS requires 316.1403.

N-[(2S)-1-oxo-3-phénylpropan-2-yl]-2- (triméthylsilyl)éthanesulfonamide 3d. The General Procedure (C) was followed using alcohol 4d (31.6 mg, 0.1 mmol), TEMPO (0.8 mg, 0.005 mmol), KBr (12 mg, 0.1 mmol), NaOCl (0.4 mL, 0.2 mmol) and saturated solution of

NH

Ph

O2S

OMe

O

H

HN

O

PhMeO

SO2

SiMe3

HNPhHO

SO2

SiMe3

NHSO2

O

Ph

SiMe3

S10

NaHCO3 (1 mL) in CH2Cl2 (2 mL). The α-amino aldehyde 3d (31 mg, 0.10 mmol, quantitative) was obtained as an yellow oil. 1H NMR (300 MHz, CDCl3) δ 9.73 (s, 1H, H4), 7.43-6.91 (m, 5H, HAr), 4.73 (d, J = 7.5 Hz, 1H, NH), 4.37-4.30 (m, 1H, CHNH), 3.252 (dd, J =14 and 6.0 Hz, 1H, CH2Ph), 3.04-2.97 (dd, J

=14 and 7.5 Hz, 1H, CH2Ph), 2.74-2.61 (m, 2H, CH2SO2), 0.94-0.73 (m, 2H, CH2Si), 0.00 (s, 9H, Si(CH3)3).

N-[(2S)-1-oxo-3-phenylpropan-2-yl]acetamide 3e. To a stirred solution of L-phenylalanine methyl ester hydrochloride (880 mg, 4.08 mmol, 1.0 equiv) in pyridine (10 mL) was added acetic anhydride (0.77 mL, 8.16 mmol, 2 equiv). The resulting mixture was stirred for 24 h at room temperature. Solvent was then removed under reduced pressure and co-evaporated with toluene (3 x 5 mL). The residue was diluted with AcOEt (10 mL). The organic phase was washed with aqueous HCl 1M (25 mL) then with saturated aqueous NaHCO3 (25 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to afford the clean product Ee (890 mg, 4.03 mmol,

99%) as a white powder (NMR data consistent with those reported in the literature).11 The General Procedure (A) was followed using methyl ester Ee (400 mg, 1.81 mmol) and LiBH4 (200 mg, 9.05 mmol) in MeOH (8 mL). After purification by flash chromatography on silica gel (AcOEt/heptane 1:0 to 95:5), alcohol 4e (329 mg, 1,70 mmol, 94%) was obtained as white powder (NMR data consistent with those reported in the literature).12 The General Procedure (B) was followed using 4e (154 mg, 0.80 mmol), TEMPO (6.22 mg, 0.04 mmol), KBr (94.4 mg, 0.80 mmol), NaOCl (3.2 mL, 1.6 mmol) and saturated aqueous NaHCO3 (3.5 mL) in CH2Cl2 (8.5 mL) to afford α-amino aldehyde 3e (33 mg, 0,17 mmol, 21%) as a beige powder. 1H NMR (500 MHz, CDCl3) δ 9.68 (s, 1H, H5), 7.42-7.17 (m, 5H, HAr), 6.1 (s, 1H, NH), 4.8 (s, 1H, H4), 3.22 (m, 2H, H3), 2.08 (s, 3H, H2).

tert-Butyl [(2S)-1-oxo-3-phenylpropan-2-yl]carbamate 3f. To a stirred solution of Boc-L-phenylalanine (1.0 g, 3.77 mmol, 1.0 equiv) in dry THF (20 mL) under argon atmosphere at 0°C was added borane (11.3 mL, 1M dans le THF, 11.3 mmol, 3.0 equiv) using a syringe pump (30 min). The resulting mixture was stirred at room temperature for 3 h. Then

water (8.6 mL) was added. Aqueous phase was extracted with AcOEt (3 x 40 mL). Organic layers were combined, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (AcOEt/heptane 3:7 to 4:6) to afford alcohol 4f (678 mg, 2.74 mmol, 72%) as a white powder (NMR data consistent with those reported in the literature).13 The General Procedure (B) was followed using the alcohol 4f (150 mg, 0.6 mmol), TEMPO (5.0 mg, 0.032 mmol), KBr (71 mg, 0.6 mmol), NaOCl (2.4 mL, 1.2 mmol) and saturated aqueous NaHCO3 (5 mL) in CH2Cl2 (10 mL) to afford α-amino aldehyde 3f (146 mg, 0.585 mmol, 98%) as a beige powder. 1H NMR(300 MHz, CDCl3) δ 9.56 (s, 1H, H4), 7.30-7.04 (m, 5H, HAr), 4.95 (s, 1H, NH), 4.42-4.27 (m, 1H, H5), 3.04 (d, J6,5 = 6.0 Hz, 2H, H6), 1.36 (s, 9H, H3). 13C NMR (75 MHz, CDCl3) δ 199.36 (C1, C4), 129.45 (CAr), 128.89 (CAr), 127.21 (CAr), 60.92 (C5), 35.65 (C6), 28.39 (C3).

(S)-methyl 2-(N-methyl-4-nitrophenylsulfonamido)-3-phenylpropanoate Eg. A solution of Eb (0.73 g, 2.0 mmol) and Cs2CO3 (0.72 g, 2.2 mmol) in dry DMF (5 mL) was stirred for 10 min before addition of MeI (0.15 mL, 2.4 mmol). After stirring for 16 h at RT, the mixture was filtrated. After addition of water (15 mL), the aqueous phase was extracted

with AcOEt (3 x 20 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated

11 De Marco, R.; Di Gioia, M. L.; Leggio, A.; Liguori, A.; Viscomi, M. C. Eur. J. Org. Chem. 2009, 2009, 3795. 12 (a)Lasheen, D. S.; Ismail, M. A. H.; Abou El Ella, D. A.; Ismail, N. S. M.; Eid, S.; Vleck, S.; Glenn, J. S.; Watts, A. G.; Abouzid, K. A. M. Bioorg. Med. Chem. 2013, 21, 2742. (b) Boland, N. A.; Casey, M.; Hynes, S. J.; Matthews, J. W.; Smyth, M. P. J. Org. Chem. 2002, 67, 3919. 13 Kishore Kumar, G. D.; Baskaran, S. J. Org. Chem. 2005, 70, 4520.

NHAc

O

Ph

NHBoc

O

Ph

N

O

PhMeO

SO2

NO2

S11

under reduced pressure. The residue was purified by flash chromatography on silica gel (AcOEt/heptane 2:8 to 3:7) to afford ester Eg (0.61 g, 1.6 mmol, 80%) as a white powder. [α]D25 −5.8 (c 0.8, CHCl3).1H NMR (300 MHz, CDCl3) δ 8.17 (d, J = 9.0 Hz, 1H, HAr), 7.62 (d, J = 9.0 Hz, 1H, HAr), 7.31-7.23 (m, 3H, HAr), 7.21-7.13 (m, 3H, HAr), 4.99 (dd, J = 10.5 and 5.5 Hz, 1H, CHN), 3.66 (s, 3H, OCH3), 3.34 (dd, J = 14.5 and 5.5 Hz, 1H, CH2Ph), 2.97-2.85 (m, 3H, CH2Ph, NCH3). 13C NMR (75 MHz, CDCl3) δ 170.3 (CO2Me), 144.9 (CqAr), 136.1 (CqAr), 129.0 (CAr), 128.9 (CAr), 128.8 (CAr), 128.3 (CAr), 127.2 (CAr), 123.9 (CAr), 61.0 (CHN), 52.4 (OCH3), 35.4 (CH2Ph), 30.2 (NCH3). IR 1761, 1521, 1420, 1309, 1269, 1154, 997 cm-1. ESIMS m/z = 379.10 ([M+H]+, 70%), 442.10 ([M+CH3CN+Na]+, 100%), 779.17 ([2M +Na]+, 50%). ESIHRMS m/z = 379.0966 [M+H]+. C17H19N2O6S requires 379.0964.

(S)-N-(1-hydroxy-3-phenylpropan-2-yl)-N-methyl-4-nitrobenzenesulfonamide 4g. The General Procedure (B) was then followed using Eg (0.3 g, 0.79 mmol) and LiBH4 (88 mg, 4 mmol) in THF (4 mL). After purification (AcOEt/heptane 2:8 to 5:5), 4b (67 mg, 0.055 mmol, 24%) was obtained as white powder. [α]D25 −29.9 (c 1, CHCl3). 1H NMR (300 MHz, CDCl3) δ 8.07 (d, J = 9.0 Hz, 1H, HAr), 7.57 (d, J = 9.0 Hz, 1H, HAr), 7.21-7.10 (m, 3H, HAr), 7.08-6.98 (m, 2H, HAr), 4.40-4.29 (m, 1H, CHN), 3.75-3.59 (m, 2H, CH2OH), 2.86 (s, 3H, NCH3), 2.77 (dd, J = 14.0 and 6.0 Hz, 1H, CH2Ph), 2.59 (dd, J = 14.0 and 9.0 Hz, 1H, CH2Ph). 13C NMR (75 MHz, CDCl3) δ 145.4 (CqAr), 137.2 (CqAr), 128.9 (CAr), 128.8 (CAr), 128.7 (CAr), 128.1 (CAr), 126.9 (CAr), 124.0 (CAr), 62.3 (CH2OH), 61.2 (CHN), 35.1 (CH2Ph), 28.6

(NCH3). IR 1530, 1352, 1329, 1308, 1155, 1075, 922, 906, 691 cm-1. ESIHRMS m/z = 351.1017 [M+H]+. C16H19N2O5S requires 351.1015.

4-nitro-N-[(2S)-3-methyl-1-oxobutan-2- yl]benzenesulfonamide 3h. The General Procedure (A) was followed using L-valine methyl ester hydrochloride (0.46 g, 2.8 mmol), triethylamine (0.8 mL, 6.1 mmol) and para-nitrobenzenesulfonyl chloride (0.68 g, 3.1 mmol in CH2Cl2 (10 mL) to afford after work-up the crude product Eh (0.81 g, 2.6 mmol, 92%) (NMR data

consistent with those reported in the literature). The General Procedure (B) was then followed using Eh (0.66 g, 2.1 mmol) and LiBH4 (0.18 g, 8.3 mmol) in dry THF (15 mL). After purification (AcOEt/heptane 3:7 to 5:5), 4h (0.38 g, 1.3 mmol, 63%) was obtained (NMR data consistent with those reported in the literature).14 The General Procedure (C) was followed using 4h (130 mg, 0.45 mmol), TEMPO (4 mg, 0.02 mmol), KBr (54 mg, 0.45 mmol), NaOCl (1.8 mL, 0.9 mmol) and saturated aqueous NaHCO3 (5 mL) in CH2Cl2 (10 mL) to afford 3h (121 mg, 0.42 mmol, 94%) as a beige powder. 1H NMR (300 MHz, CDCl3) δ 9.39 (s, 1H, CHO), 8.61 (d, J = 9.0 Hz, 2H, HAr), 7.97 (d, J = 9.0 Hz, 2H, HAr), 5.50-5.31 (m, 1H, NH), 3.87 (dd, J = 8.0 and 4.0 Hz, 1H, CHNH), 2.30-2.14 (m, 1H, CH(CH3)2), 0.98 (d, J = 7.0 Hz, 3H, CH(CH3)2), 0.88 (d, J = 7.0 Hz, 3H, CH(CH3)2).

(S)-N-(1-hydroxy-4-methylpentan-2-yl)-4-nitrobenzenesulfonamide 4i. The General Procedure (A) was followed using L-leucine methyl ester hydrochloride (1.5 g, 8.3 mmol), triethylamine (2.5 mL, 18.2 mmol) and para-nitrobenzenesulfonyl chloride (2 g, 9 mmol in CH2Cl2 (40 mL) to afford after work-up the crude product Ei (2.7 g, 8.2 mmol, 99%). The General Procedure

(B) was then followed using Ei (1.5 g, 4.5 mmol) and LiBH4 (0.38 g, 17.3 mmol) in dry THF (20 mL). After purification by flash chromatography on silica gel (AcOEt/heptane 3:7 to 5:5), 4i (1 g, 3.5 mmol, 78%) was obtained. Mp = 86-87 °C. [α]D25 −15.3 (c 0.6, CHCl3). 1H NMR (300 MHz, CDCl3) δ 8.38 (d, J = 9.0 Hz, 2H, HAr), 8.11 (d, J = 9.0 Hz, 2H, HAr), 3.86-3.75 (m, 1H, CH2OH), 3.62 (dd, 1H, J = 11.0 and 3.5

14 Sylla-Iyarreta Veitía, M.; Brun, P. L.; Jorda, P.; Falguières, A.; Ferroud, C., Tetrahedron: Asymmetry 2009, 20 (18), 2077-2089.

NHNs

O

NH

OH

SO2

O2N

N

OH

Ph

SO2

NO2

S12

Hz, CH2OH), 3.51 (dd, 1H, J = 11.0 and 5.0 Hz, CH2OH), 3.48-3.39 (m, 1H, CHNH), 1.56-1.39 (m, 1H, CH2i-Pr), 1.37-1.25 (m, 3H, CH2i-Pr), 0.82 (d, J = 6.5 Hz, 1H, CH(CH3)2), 0.71 (J = 6.5 Hz, 1H, CH(CH3)2). 13C NMR (75 MHz, CDCl3) δ 150.0 (CqAr), 146.8 (CqAr), 128.3 (CAr), 124.3 (CAr), 64.9 (CH2OH), 54.2 (CHNH), 41.0 (CH2i-Pr), 24.4 (CH(CH3)2), 22.7 (CH3), 21.9 (CH3). IR 3527, 3281, 2957, 1527, 1348, 1306, 1160 cm-1. ESIMS m/z = 303.10 ([M+H]+, 50%), 344.12 ([M+CH3CN+H]+, 100%). ESIHRMS m/z = 303.1009 [M+H]+. C12H19N2O5S requires 303.1015.

(S)-N-(4-methyl-1-oxopentan-2-yl)-4-nitrobenzenesulfonamide 3i. The General Procedure (C) was followed using 4i (147 mg, 0.49 mmol), TEMPO (4 mg, 0.02 mmol), KBr (58 mg, 0.49 mmol), NaOCl (2 mL, 1 mmol) and saturated aqueous NaHCO3 (5 mL) in CH2Cl2 (10 mL) to afford 3i (132 mg, 0.44 mmol, 90%) as a beige powder. 1H NMR (300 MHz, CDCl3)

δ 9.35 (s, 1H, CHO), 8.28 (d, J = 9.0 Hz, 2H, HAr), 7.97 (d, J = 9.0 Hz, 2H, HAr), 5.40-5.10 (m, 1H, NH), 4.03-3.89 (m, 1H, CHNH), 2.30-2.14 (m, 1H, CH(CH3)2), 1.85-1.65 (m, 1H, CH2i-Pr), 1.64-1.41 (m, 2H, CH2i-Pr), 1.40-1.27 (m, 1H, CH2i-Pr), 0.87 (d, J = 7.0 Hz, 3H, CH(CH3)2), 0.84 (d, J = 7.0 Hz, 3H, CH(CH3)2).

(R)-N-(1-((tert-butyldimethylsilyl)oxy)-3-hydroxypropan-2-yl)-4-

nitrobenzenesulfonamide 4j. The General Procedure (A) was followed using L-serine methyl ester hydrochloride (1 g, 8.4 mmol), triethylamine (2.4 mL, 17.6 mmol) and para-nitrobenzenesulfonyl chloride (1.9 g, 8.8 mmol in CH2Cl2 (40 mL) to afford after work-up the crude product Ej (1.68 g, 5.5 mmol, 66%). The dried solid was dissolved in DMF (20 mL), combined with imidazole (0.45 g, 6.6 mmol, 2 equiv) as well as t-butyldimethylsilylchloride (0.74g, 4.9 mmol, 1.5 equiv) and stirred overnight at room temperature. The reaction was quenched by the addition of water and the

aqueous phase was extracted with EtOAc (3 x 20 mL). Organic layers were combined, washed with water (3 x 20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (AcOEt/heptane 1:9 to 3:7) to afford the corresponding ester Ej’.15 The General Procedure (B) was then followed using Ej’ (0.5 g, 1.2 mmol) and LiBH4 (99 mg, 4.5 mmol) in dry THF (10 mL). After purification by flash chromatography on silica gel (AcOEt/heptane 3:7 to 5:5), 4j (0.46 g, 1.18 mmol, 99%) was obtained. [α]D25 +17.0 (c 0.4, CHCl3). 1H NMR (300 MHz, CDCl3) δ 8.34 (d, J = 9.0 Hz, 2H, HAr), 8.07 (d, J = 9.0 Hz, 2H, HAr), 5.41 (d, J = 8.0 Hz, 1H, NH), 3.72 (dd, 1H, J = 11.5 and 4.5 Hz, CH2O), 3.70 (dd, 1H, J = 10.0 and 4.0 Hz, CH2O), 3.60 (dd, 1H, J = 10.0 and 5.0 Hz, CH2O), 3.53 (dd, 1H, J = 11.5 and 5.0 Hz, CH2O), 3.43-3.32 (m, 1H, CHNH), 0.83 (s, 9H, SiC(CH3)3), 0.01 (s, 3H, Si(CH3)), 0.00 (s, 3H, Si(CH3)). 13C NMR (75 MHz, CDCl3) δ 146.6 (CqAr), 128.3 (CAr), 124.4 (CAr), 63.7 (CH2O), 62.9 (CH2O), 55.8 (CHNH), 25.7 (SiC(CH3)3), 18.1 (SiC(CH3)3), -5.6 (Si(CH3)). IR 3527, 3292, 2929, 2857, 1529, 1347, 1162, 1090 cm-1. ESIMS m/z = 391.13 ([M+H]+, 100%), 803.24 ([2M+Na]+, 20%). ESIHRMS m/z = 391.1362 [M+H]+. C15H27N2O6SSi requires 391.1359.

(S)-N-(1-((tert-butyldimethylsilyl)oxy)-3-oxopropan-2-yl)-4-nitrobenzenesulfonamide 3j. The General Procedure (C) was followed using 4j (105 mg, 0.27 mmol), TEMPO (2 mg, 0.013 mmol), KBr (32 mg, 0.27 mmol), NaOCl (1.1 mL, 0.54 mmol) and saturated aqueous NaHCO3 (3 mL) in CH2Cl2 (6 mL) to afford 3i (101 mg, 0.26 mmol, 97%) as a beige powder. 1H NMR (300 MHz, CDCl3) δ 9.50 (s, 1H, CHO), 8.32 (d, J = 7.0 Hz, 2H, HAr), 8.02 (d, J = 9.0 Hz, 2H, HAr), 5.40-5.10 (m, 1H, NH), 5.57 (d, J = 7.5 Hz, 1H, NH), 4.15 (dd, 1H, J = 10.5 and 3.5 Hz, CH2OTBS), 4.01-3.92 (m, 1H, CHNH), 3.78 (dd, 1H, J = 10.5 and 4.5 Hz, CH2OTBS), 0.80 (s, 9H,

15 Du Preez, J. G. H.; Wentzel, M.; Knoetze, S. Patent: WO2012/153253 A2, 2012

NHNs

O

NH

OH

OTBS

O2S

NO2

NH

O

OTBS

O2S

NO2

S13

SiC(CH3)3), 0.01 (s, 3H, Si(CH3)), 0.00 (s, 3H, Si(CH3)).

(S)-2,2,2-trifluoro-N-(1-oxo-3-phenylpropan-2-yl)acetimidic acid 3k. The General Procedure (C) was followed using 4k (150 mg, 0.61 mmol), TEMPO (5 mg, 0.03 mmol), KBr (72 mg, 0.61 mmol), NaOCl (2.4 mL, 1.2 mmol) and saturated aqueous NaHCO3 (5 mL) in CH2Cl2 (10 mL) to afford 3k (91 mg, 0.37 mmol, 61%) as a beige powder. 1H NMR (300 MHz, CDCl3) δ 9.69

(s, 1H, CHO), 7.40-7.11 (m, 10H, HAr), 8.02 (d, J = 9.0 Hz, 2H, HAr), 7.00-6.80 (bs, 1H, NH), 5.57 (d, J = 7.5 Hz, 1H, NH), 4.93-4.80 (m, 1H, CHNH), 3.37 (dd, 1H, J = 14.0 and 5.5 Hz, CH2Ph), 3.24 (dd, 1H, J = 14.0 and 7.5 Hz, CH2Ph). B. Petasis reaction

General Procedure (D) for the Petasis reaction To a stirred solution of α-amino aldehyde (1.3 equiv) was added sequentially freshly activated molecular sieves 4Å (mass = 1.5-2 x mass of all the reactants), boronic acid (1.0 equiv), PhCF3 ([boronic acid] = 0,15M) and amine (1.25 equiv). The resultant mixture was stirred for 48 h at room temperature. Solvent was removed under reduced pressure and the residue was purified by preparative TLC to afford corresponding amine.

N-[(2S, 3R, 4E)-3-(diprop-2-en-1-ylamino)-1,5-diphenylpent-4-en-2-yl]-4-methylbenzenesulfonamide 5. The General Procedure (D) was followed using α-amino aldehyde 3a (59 mg, 0.193 mmol) diallylamine 2a (23 µL, 0.186 mmol), boronic acid 1a (22 mg, 0.149 mmol) and molecular sieve 4Å (100 mg) in PhCF3 (1

mL). After purification by preparative TLC (AcOEt/Heptane 2:8), 5 (39 mg, 0.08 mmol, 54%) was obtained as a yellow oil, ee = 93% determined by chiral HPLC (Chiralpak IC column, eluent: heptane+0.1% Et3N/ethanol+ 0.1% Et3N 97:3, rate = 1.0 mL/min, 254 nm, tminor = 17.66 min, tmajor = 21.29 min). [α]D25 + 4.7 (c 0.19, CHCl3). 1H NMR (300 MHz, CDCl3) δ 7.60 (d, J = 8.0 Hz, 2H, HAr), 7.37-7.14 (m, 10H, HAr), 7.12 (d, J = 8.0 Hz, 2H, HAr), 6.27 (d, J = 16.0 Hz, 1H, PhCH=CH), 5.85-5.67 (m, 3H, PhCH=CH, CH=CH2), 5.10-5.03 (m, 4H, CH=CH2), 4.67 (bs, 1H, NH), 3.82-3.68 (m, 1H, CHNH), 3.21 (dd, J = 14.5 and 5.5 Hz, 2H, NCH2), 3.10-3.02 (m, 2H, CH2Ph, CHNAll2), 2.96 (dd, J = 16 and 6.5 Hz, 1H, CH2Ph), 2.91 (dd, J = 14.5 and 7.5 Hz, 2H, NCH2), 2.37 (s, 3H, H5). 13C NMR (75 MHz, CDCl3) δ 143.0 (CqAr), 137.6 (CqAr), 137.2 (CqAr), 136.4 (CqAr), 135.9 (CH=CH2), 135.6 (PhCH=CH), 130.1 (CAr), 129.6 (CAr), 128.5 (CAr), 128.3 (CAr), 128.0 (CAr), 127.8 (CAr), 127.0 (CAr), 126.5 (CAr), 126.4 (CAr), 125.0 (PhCH=CH), 117.5 (CH=CH2), 64.6 (CHNAll2), 55.9 (CHNH), 53.4 (NCH2), 37.7 (CH2Ph), 21.6 (CH3). IR 3260, 2920, 1495, 1328, 1156, 1093 cm-1. ESIHRMS m/z = 487.2416 [M+H]+. C30H35N2O2S requires 487.2419.

N-[(2S, 3R, 4E)-3-(diprop-2-en-1-ylamino)-1,5-diphenylpent-4-en-2-yl]-4-nitrobenzenesulfonamide 8. The General Procedure (D) was followed using 3b (59 mg, 0.176 mmol), diallylamine 2a (21 µL, 0.169 mmol), boronic acid 1a (20 mg, 0.135 mmol) and molecular sieve 4Å (100 mg) in PhCF3 (0.85 mL). After

purification by preparative TLC (AcOEt/Heptane 2:8), 8 (51 mg, 0.098 mmol, 71%) was obtained as a yellow oil, ee = 93% determined by chiral HPLC (Chiralpak IC column, eluent: heptane+0.1% Et3N/ethanol+ 0.1% Et3N 95:5, rate = 1.0 mL/min, 254 nm, tminor = 11.19 min, tmajor = 15.05 min). [α]D25 +0.5 (c 0.19, CHCl3). 1H NMR (300 MHz, CDCl3) δ 7.93 (d, J = 8.0 Hz, 2H, HAr), 7.65 (d, J = 8.0 Hz, 2H, HAr),

NHTs

NAll2

PhPh

N

NHNsPh Ph

CF3COHN

O

S14

7.35-7.09 (m, 10H, HAr), 6.31 (d, J = 16.0 Hz, 1H, PhCH=CH), 5.96-5.76 (m, 3H, PhCH=CH, CH=CH2), 5.26-5.14 (m, 4H, CH=CH2), 3.91-3.80 (m, 1H, CHNH), 3.38 (ddt, J = 14.0, 5.0 and 2.0 Hz, 2H, NCH2), 3.24 (dd, J = 14.0 and 4.5 Hz, 1H, CH2Ph), 3.21 (t, J = 9.0 Hz, 1H, CHNAll2), 2.94 (dd, J = 14.0 and 8.0 Hz, 2H, NCH2), 2.79 (dd, J = 14.0 and 7 Hz, 1H, CH2Ph). 13C NMR (75 MHz, CDCl3) δ 149.2 (CqAr), 146.7 (CqAr), 137.3 (CqAr), 136.1 (CqAr), 136.0 (CH=CH2), 135.9 (PhCH=CH), 129.9 (CAr), 128.8 (CAr), 128.4 (CAr), 128.5 (CAr), 127.8 (CAr), 126.76 (CAr), 126.5 (CAr), 124.8 (PhCH=CH), 124.1 (CAr), 117.8 (CH=CH2), 65.8 (CHNAll2), 58.2 (CHNH), 53.9 (NCH2), 38.7 (CH2Ph). IR 3429, 3268, 2918, 1527, 1644, 1606 cm-1. ESIHRMS m/z = 518.2125 [M+H]+ (calculée pour C29H32N3O4S : 518.2114). On larger scale: The General Procedure (D) was followed using 3b (734 mg, 2.2 mmol), diallylamine 2a (0.26 mL, 2.1 mmol), boronic acid 1a (0.25 g, 1.69 mmol) and molecular sieve 4Å (3.5 g) in PhCF3 (10.8 mL). The mixture was stirred under argon for 48 h at room temperature and after solvent evaporation, the mixture was purified by flash chromatography on silica gel (AcOEt/heptane 1:9 to 3:7) to lead to 5 (0.633 g, 1.22 mmol, 72%, 91% ee). After dissolution in pentane/Et2O (5/1, 40 mL), the crystallisation of racemic crystal is obtained and after filtration and evaporation, 5 (590 mg) can be obtained in 99.5% ee.

N-[(2S,3R,4E)-3-(diprop-2-en-1-ylamino)-1,5-diphenylpent-4-en-2-yl]-2-(4-

methoxy-2,3,6- trimethyl)phenylsulfonamide 9. The General Procedure (D) was followed using α-amino aldehyde 3c (49 mg, 0.13 mmol) diallylamine 2a (15 µL, 0.13 mmol), boronic acid 1a (10 mg, 0.07 mmol) and molecular sieve 4Å (71 mg) in PhCF3 (0.7 mL). After purification by preparative TLC (AcOEt/Heptane 2:8), the diamine 9 (10 mg, 0.02 mmol, 28%) was obtained as a yellow oil, ee = 18% determined by chiral HPLC (Chiralpak IC column, eluent: heptane+0.1% Et3N/ethanol+ 0.1% Et3N 95:5, rate = 1.0 mL/min, 254 nm, tminor = 7.74 min, tmajor = 8.73 min). 1H NMR (300 MHz, CDCl3) δ 7.36-7.12 (m, 10H, HAr), 6.47 (s, 1H, HAr), 6.29 (d, J = 16.0 Hz, 1H, PhCH=CH), 5.92-5.71 (m, 3H, PhCH=CH,

CH=CH2), 5.15-5.10 (m, 4H, CH=CH2), 4.75 (bs, 1H, NH), 3.90-3.75 (m, 4H, CHNH, OCH3), 3.27 (dd, J

=14.0 and 4.5 Hz, 2H, NCH2), 3.13 (t, J = 9.0 Hz, 1H, CHNAll2), 3.09-2.89 (m, 4H, NCH2, CH2Ph), 2.65 (s, 3H, CH3), 2.40 (s, 3H, CH3), 1.93 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3) δ 138.9 (CqAr), 137.9 (CqAr), 135.9 (CH=CH2), 135.3 (PhCH=CH), 130.1 (CAr), 128.8 (CAr), 128.3 (CAr), 128.0 (CAr), 126.6 (CAr), 126.5 (CAr), 125.3 (PhCH=CH), 117.7 (CH=CH2), 111.9 (CAr), 64.8 (CHNAll2), 56.1 (CHNH), 55.6 (OCH3), 53.6 (NCH2), 37.9 (CH2Ph), 24.8 (CH3), 18.3 (CH3), 12.0 (CH3). IR 3306, 2925, 2853, 1642 cm-1. ESIHRMS m/z = 545.2883 [M+H]+. C33H41N2O3S requires 545.2838.

N-[(2S,3R,4E)-3-(diprop-2-en-1-ylamino)-1,5-diphenylpent-4-en-2-yl]-2-(trimethylsilyl)ethanesulfonamide 10. The General Procedure (D) was followed using α-amino aldehyde 3d (44 mg, 0.14 mmol) diallylamine 2a (17 µL, 0.13 mmol), boronic acid 1a (16 mg, 0.11 mmol) and molecular sieve 4Å (150 mg) in PhCF3 (0.7 mL). After purification by preparative TLC (AcOEt/Heptane 25:75), 10 (21 mg, 0.042 mmol, 39%) was obtained as an

yellow oil, ee = 71% determined by chiral HPLC (Chiralpak IC column, eluent: heptane+0.1% Et3N/ethanol+ 0.1% Et3N 95:5, rate = 1.0 mL/min, 254 nm, tminor = 11.01 min, tmajor = 12.29 min). [α]D25 −2.5 (c 0.8, CHCl3). 1H NMR (300 MHz, CDCl3) δ 7.45-7.20 (m, 10H, HAr), 6.43 (d, J = 16.0 Hz, 1H, PhCH=CH), 6.27 (dd, J = 16.0 and 9.5 Hz, 1H, PhCH=CH), 5.94-5.78 (m, 2H, CH=CH2), 5.28-5.13 (m, 4H, CH=CH2), 4.23 (bs, 1H, NH), 3.83-3.72 (m, 1H, CHNH), 3.49-3.39 (ddt, J = 14.5, 4.5 and 2.5 Hz, 2H, NCH2), 3.34 (dd, J = 13.5 and 4.0 Hz, 1H, CH2Ph), 3.26 (dd, J = 9.5 and 8.5 Hz, 1H, CHNAll2), 2.99 (dd, J = 14.5 and 8.0 Hz, 2H, NCH2), 2.62 (dd, J = 13.5 and 9.0 Hz, 1H, CH2Ph), 2.38-2.03 (m, 2H, CH2SO2), 0.87-

N

HNPh Ph

SO2

OMe

N

NHPh Ph

SO2

Me3Si

S15

0.67 (m, 2H, CH2SiMe3), -0.14 (s, 9H, H3). 13C NMR (75 MHz, CDCl3) δ 138.9 (CqAr), 136.9 (CqAr), 136.5 (CH=CH2), 135.8 (PhCH=CH), 130.2 (CAr), 128.9 (CAr), 128.7 (CAr), 1278.0 (CAr), 127.0 (CAr), 126.7 (CAr), 125.5 (PhCH=CH), 117.6 (CH=CH2), 66.4 (CHNAll2), 58.4 (CHNH), 54.0 (NCH2), 50.6 (CH2SO2), 39.5 (CH2Ph), 10.1 (CH2SiMe3), -1.9 (Si(CH3)3). IR 3269, 2959, 1315, 1250, 1145 cm-1. ESIHRMS m/z = 497.2660 [M+H]+. C28H41N2O2SSi requires 497.2658.

N-[(2S,3R,4E)-3-(diprop-2-en-1-ylamino)-1,5- diphénylpent-4-en-2-yl]acétamide 11. The General Procedure (D) was followed using α-amino aldehyde 3d (22 mg, 0.11 mmol) diallylamine 2a (14 µL, 0.11 mmol), boronic acid 1a (8.1 mg, 0.055 mmol) and molecular sieve 4Å (80 mg) in PhCF3 (0.5 mL). After purification by

preparative TLC (AcOEt/Heptane 5:5), 11 (4.7 mg, 0.011 mmol, 23%) was obtained as an yellow oil, ee = 3.0% determined by chiral HPLC (Chiralpak IC column, eluent: heptane+0.1% Et3N/ethanol+ 0.1% Et3N 95:5, rate = 1.0 mL/min, 254 nm, tminor = 3.95 min, tmajor = 5.28 min). 1H NMR (300 MHz, CDCl3) δ 7.39-7.21 (m, 10H, HAr), 6.35 (d, J = 16.0 Hz, 1H, PhCH=CH), 6.15 (dd, J = 16.0 and 9.5 Hz, 1H, PhCH=CH), 5.94-5.81 (m, 2H, CH=CH2), 5.26-5.15 (m, 4H, CH=CH2), 4.58-4.48 (m, 1H, CHNH), 3.46 (ddt, J = 14.5, 4.5 and 2.5 Hz, 2H, NCH2), 3.28 (dd, J = 14.0 and 4.5 Hz, 1H, CH2Ph), 3.18 (t, J = 9.5 Hz, 1H, CHNAll2), 2.96 (dd, J = 14.5 and 8.0 Hz, 2H, NCH2), 2.81 (dd, J = 14.0 and 7.5 Hz, 1H, CH2Ph), 1.78 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3) δ 169.8 (CO), 138.5 (CqAr), 137.0 (CH=CH2), 134.9 (PhCH=CH), 129.8 (CAr), 128.8 (CAr), 128.5 (CAr), 127.8 (CAr), 126.6 (CAr), 126.5 (CAr), 125.7 (PhCH=CH), 117.3 (CH=CH2), 65.7 (CHNAll2), 53.6 (NCH2), 51.2 (CHNH), 37.8 (CH2Ph), 23.6 (CH3). IR 3330, 2924, 1649, 1545, 1495 cm-1. ESIHRMS m/z = 375.2435 [M+H]+. C25H31N2O requires 375.2436).

tert-Butyl[(2S,3R,4E)-3-(diprop-2-en-1-ylamino)-1,5- diphenylpent-4-en-2-yl]carbamate 12. The General Procedure (D) was followed using α-amino aldehyde 3e (70 mg, 0.28 mmol) diallylamine 2a (35 µL, 0.28 mmol), boronic acid 1a (20.7 mg, 0.14 mmol) and molecular sieve 4Å (118 mg) in PhCF3 (1.2 mL). After purification by preparative TLC (AcOEt/Heptane 2:8), 12 (12.7 mg, 0.029 mmol, 21%) was obtained as an yellow oil, ee = 18% determined by chiral HPLC (Chiralpak IC column, eluent: heptane+0.1% Et3N/ethanol+ 0.1% Et3N 98:2, rate =

1.0 mL/min, 254 nm, tminor = 4.62 min, tmajor = 5.17 min). 1H NMR (75 MHz, CDCl3) δ 7.42-7.19 (m, 10H, HAr), 6.37 (d, J = 16.0 Hz, 1H, PhCH=CH), 6.17 (dd, J = 16.0 and 9.5 Hz, 1H, PhCH=CH), 5.95-5.78 (m, 2H, CH=CH2), 5.24-5.05 (m, 4H, CH=CH2), 4.26 (d, J = 8.0 Hz, 1H, NH), 4.17-4.04 (m, 1H, CHNH), 3.41 (dd, J = 14.5 and 4.0 Hz, 1H, NCH2), 3.27 (dd, J4,4 = 14.0 Hz and 4.5 Hz, 1H, CH2Ph), 3.17 (t, J = 9.5 Hz, 1H, CHNAll2), 2.98 (dd, J = 14.5 and 8.0 Hz, 2H, NCH2), 2.78 (dd, J = 14.0 and 7.5 Hz, 1H, CH2Ph), 1.26 (s, 9H, CH3). 13C NMR (75 MHz, CDCl3) δ 155.7 (CO), 138.9 (CqAr), 137.1 (CH=CH2), 134.9 (PhCH=CH), 129.6 (CAr), 128.5 (CAr), 128.2 (CAr), 127.4 (CAr), 126.4 (CAr), 126.1 (CAr), 125.5 (PhCH=CH), 117.0 (CH=CH2), 79.0 (C(CH3)3), 65.9 (CHNAll2), 53.6 (NCH2), 52.6 (CHNH), 38.2 (CH2Ph), 28.4 (CH3). IR 3341, 2973, 1682, 1526, 1248, 1169 cm-1. ESIHRMS m/z = 433.2852 [M+H]+. C28H37N2O2 requires 433.2855.

N-((2S,3R,E)-3-(allyl(benzyl)amino)-1,5-diphenylpent-4-en-2-yl)-4-nitrobenzenesulfonamide 13. The General Procedure (D) was followed using 3b (59 mg, 0.176 mmol), amine 2b (26 µL, 0.169 mmol), boronic acid 1a (20 mg, 0.135 mmol) and molecular sieve 4Å (100 mg) in PhCF3 (0.85 mL). After purification by preparative TLC (AcOEt/Heptane 3:7), 13 (50 mg, 0.088 mmol, 65%) was obtained, ee = 98% determined by chiral HPLC (Chiralpak IC column, eluent: heptane+0.1% Et3N/ethanol+ 0.1% Et3N 90:10, rate = 1.0 mL/min, 254 nm, tminor = 7.13 min, tmajor = 8.90 min). [α]D25 −54.7 (c 0.6, CHCl3). 1H NMR (300 MHz, CDCl3) δ 7.82 (d, J =

N

NHAcPh Ph

N

HNPh Ph

O

O

N

HNPh

Ph

Ph

SO2

NO2

S16

9.0 Hz, 2H, HAr), 7.49 (d, J = 9.0 Hz, 2H, HAr), 7.31-7.14 (m, 10H, HAr), 7.05-6.97 (m, 3H, HAr), 6.91-6.84 (m, 2H, HAr), 6.25 (d, J = 16.0 Hz, 1H, PhCH=CH), 5.93 (dd, J = 16.0 and 10.0 Hz, 1H, PhCH=CH), 5.88-5.72 (m, 1H, CH=CH2), 5.20-5.05 (m, 2H, CH=CH2), 4.42 (bs, 1H, NH), 3.88 (d, J = 14.0 Hz, 1H, NCH2Ph), 3.84-3.72 (m, 1H, CHNH), 3.37-3.20 (m, 3H, NCH2Ph, NCH2CH=, CH2Ph), 3.09 (t, J = 10.0 Hz, 1H, CHNAllBn), 2.91 (dd, J = 14.0 and 8.0 Hz, 2H, NCH2), 2.57 (dd, J = 14.0 and 7.5 Hz, 1H, CH2Ph). 13C NMR (75 MHz, CDCl3) δ 149.2 (CqAr), 146.8 (CqAr), 139.2 (CqAr), 137.2 (CqAr), 136.2, 136.1 (CH=CH2, PhCH=CH), 129.9 (CAr), 128.6 (CAr), 128.5 (CAr), 128.4 (CAr), 128.2 (CAr), 127.5 (CAr), 127.2 (CAr), 126.5 (CAr), 126.4 (CAr), 124.6 (PhCH=CH), 123.9 (CAr), 117.9 (CH=CH2), 65.7 (CHNAllBn), 58.0 (CHNH), 54.7 (NCH2Ph), 54.7 (NCH2CH=), 38.7 (CH2Ph). IR 3265, 2918, 1604, 1524, 1346, 1158, 696 cm-1. ESIHRMS m/z = 568.2275 [M+H]+ (calculée pour C33H34N3O4S : 568.2270).

N-((2S,3R,E)-3-(dibenzylamino)-1,5-diphenylpent-4-en-2-yl)-4-nitrobenzenesulfonamide 14. The General Procedure (D) was followed using 3b (53 mg, 0.158 mmol), amine 2c (30 µL, 0.152 mmol), boronic acid 1a (18 mg, 0.122 mmol) and molecular sieve 4Å (150 mg) in PhCF3 (0.80 mL). After purification by preparative TLC (AcOEt/Heptane 3:7), 14 (49 mg, 0.079 mmol, 65%) was obtained, ee = 98% determined by chiral HPLC (Chiralpak IC column, eluent: heptane+0.1% Et3N/ethanol+ 0.1% Et3N 90:10, rate = 1.0 mL/min, 254 nm, tminor = 7.76 min, tmajor = 9.60 min). [α]D25 −75.0 (c 0.6, CHCl3). 1H NMR (300 MHz, CDCl3) δ 7.91 (d, J = 9.0 Hz, 2H, HAr), 7.52 (d, J = 9.0 Hz, 2H, HAr), 7.48-7.25 (m, 15H, HAr), 7.13-6.98

(m, 3H, HAr), 6.78 (d, J = 7.0 Hz, 2H, HAr), 6.39 (d, J = 16.0 Hz, 1H, PhCH=CH), 6.16 (dd, J = 16.0 and 10.0 Hz, 1H, PhCH=CH), 4.24 (d, J = 9.5 Hz, 1H, NH), 3.51-3.39 (m, 3H, CHNH, NCH2Ph), 3.52-3.36 (m, 3H, NCH2Ph, CH2Ph), 3.15 (t, J = 10.0 Hz, 1H, CHNBn2), 2.51 (dd, J = 14.0 and 8.0 Hz, 1H, CH2Ph). 13C NMR (75 MHz, CDCl3) δ 149.2 (CqAr), 146.9 (CqAr), 139.2 (CqAr), 137.3 (CqAr), 136.5 (PhCH=CH), 136.4 (CqAr), 136.2 (CqAr), 129.7 (CAr), 129.1 (CAr), 128.7 (CAr), 128.6 (CAr), 128.4 (CAr), 128.2 (CAr), 127.4 (CAr), 127.3 (CAr), 126.5 (CAr), 126.4 (CAr), 124.6 (PhCH=CH), 123.9 (CAr), 65.7 (CHNBn2), 57.9 (CHNH), 54.9 (NCH2Ph), 38.9 (CH2Ph). IR 3336, 2924, 1605, 1525, 1347, 1160, 697 cm-1. ESIHRMS m/z = 618.2419 [M+H]+ (calculée pour C37H36N3O4S : 618.2427).

N-((2S,3R,E)-3-(benzyl(methyl)amino)-1,5-diphenylpent-4-en-2-yl)-4-

nitrobenzenesulfonamide 15. The General Procedure (D) was followed using 3b (62 mg, 0.184 mmol), amine 2d (23 µL, 0.177 mmol), boronic acid 1a (21 mg, 0.142 mmol) and molecular sieve 4Å (100 mg) in PhCF3 (0.85 mL). After purification by preparative TLC (AcOEt/Heptane 3:7), 15 (38 mg, 0.070 mmol, 49%) was obtained, ee = 74% determined by chiral HPLC (Chiralpak IC column, eluent: heptane+0.1% Et3N/ethanol+ 0.1% Et3N 90:10, rate = 1.0 mL/min, 254 nm, tminor = 8.30 min, tmajor = 10.10 min). [α]D25 −2.9 (c 0.6, CHCl3). 1H NMR (300 MHz, CDCl3) δ 7.96 (d, J =

9.0 Hz, 2H, HAr), 7.52 (d, J = 9.0 Hz, 2H, HAr), 7.38-7.145 (m, 15H, HAr), 6.31 (d, J = 16.0 Hz, 1H, PhCH=CH), 5.88 (dd, J = 16.0 and 10.0 Hz, 1H, PhCH=CH), 3.94 (td, J = 10.0 and 5.5 Hz, 1H, CHNH), 3.70 (d, J = 13.5 Hz, 1H, NCH2Ph), 3.46 (d, J = 13.5 Hz, 1H, NCH2Ph), 2.22-3.05 (m, 2H, CH2Ph), 2.95 (t, J

= 10.0 Hz, 1H, CHNMeBn), 2.22 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3) δ 146.7 (CqAr), 138.7 (CqAr), 136.7 (CqAr), 136.1 (PhCH=CH), 135.9 (CqAr), 130.2 (CAr), 128.7 (CAr), 128.6 (CAr), 128.5 (CAr), 128.4 (CAr), 128.2 (CAr), 127.7 (CAr), 127.3 (CAr), 126.7 (CAr), 126.3 (CAr), 124.1 (PhCH=CH), 124.0 (CAr), 68.2 (CHNMeBn), 58.4 (NCH2Ph), 57.0 (CHNH), 37.9 (CH2Ph), 37.8 (CH3). IR 3264, 2920, 1606, 1528, 1348, 1157, 1091, 683 cm-1. ESIHRMS m/z = 542.2124 [M+H]+ (calculée pour C31H32N3O4S : 542.2114).

N

HNPh

PhPh

Ph

SO2

NO2

N

HNPh

Ph

Ph

SO2

NO2

S17

N-((2S,3R,E)-5-cyclohexyl-3-(diallylamino)-1-phenylpent-4-en-2-yl)-4-nitrobenzenesulfonamide 16. The General Procedure (D) was followed using 3b (59 mg, 0.177 mmol), amine 2a (21 µL, 0.17 mmol), boronic acid 1b (21 mg, 0.136 mmol) and molecular sieve 4Å (100 mg) in PhCF3 (0.85 mL). After purification by preparative TLC (AcOEt/Heptane 3:7), 16 (35 mg, 0.067 mmol, 49%) was obtained, ee = 84% determined by chiral HPLC (Chiralpak IC column, eluent: heptane+0.1% Et3N/ethanol+ 0.1% Et3N 97:3, rate = 1.0 mL/min, 254 nm, tminor = 14.11 min, tmajor = 15.42 min). [α]D25 −21.8 (c 0.5, CHCl3).

1H NMR (300 MHz, CDCl3) δ 8.10 (d, J = 9.0 Hz, 2H, HAr), 7.69 (d, J = 9.0 Hz, 2H,

HAr), 7.14-6.85 (m, 5H, HAr), 5.88-5.71 (m, 2H, CH=CH2), 5.48 (dd, J = 15.5 and 6.5 Hz, 1H, CyCH=CH), 5.29 (dd, J = 15.5 and 9.0 Hz, 1H, CyCH=CH), 5.23-5.04 (m, 4H, CH=CH2), 3.81-3.67 (m, 1H, CHNH), 3.31 (dd, J = 14.0 and 4.5 Hz, 2H, NCH2), 3.14 (dd, J = 14.0 and 4.5 Hz, 1H, CH2Ph), 3.07 (t, J = 9.0 Hz, 1H, CHNAll2), 2.90 (dd, J = 14.0 and 7.5 Hz, 2H, NCH2), 2.60 (dd, J = 14.0 and 8.5 Hz, 1H, CH2Ph), 2.08-1.90 (m, 1H, CH), 1.92-1.56 (m, 5H, CH2), 1.40-1.03 (m, 5H, CH2). 13C NMR (75 MHz, CDCl3) δ 149.4 (CqAr), 147.1 (CqAr), 144.0 (CyCH=CH), 138.0 (CqAr), 136.0 (CH=CH2), 129.5 (CAr), 128.3 (CAr), 127.7 (CAr), 126.3 (CAr), 123.9 (CAr), 121.2 (CyCH=CH), 117.5 (CH=CH2), 65.7 (CHNAll2), 58.4 (CHNH), 53.6 (NCH2), 40.9 (CH), 38.5 (CH2Ph), 33.1 (CH2), 32.9 (CH2), 26.1 (CH2), 25.9 (CH2). IR 3339, 2923, 1526, 1346, 1160 cm-1. ESIHRMS m/z = 524.2573 [M+H]+ (calculée pour C29H38N3O4S : 524.2533).

N-((2S,3R)-3-(diallylamino)-1-phenylpent-4-en-2-yl)-4-nitrobenzenesulfonamide 17. The General Procedure (D) was followed using 3b (54 mg, 0.162 mmol), amine 2a (15 µL, 0.125 mmol), boronic acid 1c (30 mg, 0.125 mmol) and molecular sieve 4Å (150 mg) in PhCF3 (0.80 mL). After purification by preparative TLC (AcOEt/Heptane 3:7), 17 (28 mg, 0.063 mmol, 51%) was obtained, ee = 86% determined by chiral HPLC (Chiralpak IC column, eluent: heptane+0.1% Et3N/ethanol+ 0.1% Et3N 90:10, rate = 1.0 mL/min, 254 nm, tminor = 7.83 min, tmajor = 9.02 min). [α]D25 −19.7 (c 0.6, CHCl3). 1H NMR (300 MHz, CDCl3) δ 8.04 (d, J = 9.0 Hz, 2H, HAr), 7.62 (d, J = 9.0 Hz, 2H, HAr), 7.08-6.88 (m, 5H, HAr), 5.86-5.65 (m, 3H, CHCH=CH2, CH2CH=CH2),

5.36 (dd, J = 10.5 and 2.0 Hz, 1H, CHCH=CH2), 5.21-5.04 (m, 5H, CHCH=CH2, CH2CH=CH2), 3.78-3.68 (m, 1H, CHNH), 3.31 (dd, J = 14.5 and 4.5 Hz, 2H, NCH2), 3.20-3.05 (m, 2H, CH2Ph, CHNAll2), 2.89 (dd, J

= 14.5 and 7.5 Hz, 2H, NCH2), 2.52 (dd, J = 14.0 and 8.5 Hz, 1H, CH2Ph). 13C NMR (75 MHz, CDCl3) δ 146.9 (CqAr), 137.8 (CqAr), 135.7 (CH2CH=CH2), 132.6 (CHCH=CH2), 129.5 (CAr), 128.4 (CAr), 127.7 (CAr), 126.4 (CAr), 123.9 (CAr), 121.4 (CHCH=CH2), 117.9 (CH2CH=CH2), 66.7 (CHNAll2), 58.3 (CHNH), 53.8 (NCH2), 38.4 (CH2Ph). IR 3255, 2920, 1531, 1349, 1156, 1091, 917 cm-1. ESIHRMS m/z = 442.1795 [M+H]+ (calculée pour C23H38N3O4S : 442.1801).

N-((1S,2S)-1-(dibenzylamino)-1-(furan-2-yl)-3-phenylpropan-2-yl)-4-nitrobenzenesulfonamide 18. The General Procedure (D) was followed using 3b (58 mg, 0.174 mmol), amine 2a (32 µL, 0.168 mmol), boronic acid 1d (15 mg, 0.134 mmol) and molecular sieve 4Å (150 mg) in PhCF3 (0.80 mL). After purification by preparative TLC (AcOEt/Heptane 3:7), 18 (49 mg, 0.084 mmol, 63%) was obtained, ee = 95% determined by chiral HPLC (Chiralpak IC column, eluent: heptane+0.1% Et3N/i-propanol+ 0.1% Et3N 80:20, rate = 1.0 mL/min, 254 nm, tminor = 20.58 min, tmajor

= 26.68 min). [α]D25 −50.8 (c 0.6, CHCl3). 1H NMR (300 MHz, CDCl3) δ 8.08 (d, J = 8.5 Hz, 2H, HAr), 7.60 (d, J = 8.5 Hz, 2H, HAr), 7.40-7.28 (m, 11H, HAr), 7.18-7.01

(m, 3H, HAr), 6.89-6.79 (m, 2H, HAr), 6.33-6.29 (m, 1H, HAr), 6.19 (d, J = 3.0 Hz, 1H, HAr), 4.44 (d, J = 9.5

N

HNPh

SO2

NO2

N

HNPh

SO2

NO2

N

HN

PhPh

PhO SO2

NO2

S18

Hz, 1H, NH), 4.37-4.20 (m, 1H, CHNH), 3.93 (d, J = 14.0 Hz, 2H, NCH2Ph), 3.74 (d, J = 8.5 Hz, 1H, CHNBn2), 3.25 (dd, J = 14.0 and 5.5 Hz, 1H, CH2Ph), 3.18 (d, J = 14.0 Hz, 2H, NCH2Ph), 2.85 (dd, J = 14.0 and 6.5 Hz, 1H, CH2Ph). 13C NMR (75 MHz, CDCl3) δ 150.3 (CqAr), 149.4 (CqAr), 147.1 (CqAr), 142.3 (CAr), 138.7 (CqAr), 136.6 (CqAr), 129.8 (CAr), 129.0 (CAr), 128.5 (CAr), 128.4 (CAr), 127.7 (CAr), 127.3 (CAr), 126.6 (CAr), 123.9 (CAr), 111.0 (CAr), 110.0 (CAr), 58.9 (CHNBn2), 57.1 (CHNH), 55.2 (NCH2Ph), 38.9 (CH2Ph). IR 3336, 2920, 1525, 1346, 1160 cm-1. ESIHRMS m/z = 582.2061 [M+H]+ (calculée pour C33H32N3O5S : 582.2063).

N-((1R,2S)-1-(diallylamino)-1-(4-methoxyphenyl)-3-phenylpropan-2-yl)-4-nitrobenzenesulfonamide 19. The General Procedure (D) was followed using 3b (29 mg, 0.086 mmol), amine 2a (10 µL, 0.082 mmol), boronic acid 1e (10 mg, 0.066 mmol) and molecular sieve 4Å (100 mg) in PhCF3 (0.40 mL). After purification by preparative TLC (AcOEt/Heptane 3:7), 19 (13 mg, 0.025 mmol, 38%) was obtained, ee = 82.5% determined by chiral HPLC (Chiralpak IC column, eluent: heptane+0.1% Et3N/ethanol+ 0.1% Et3N 90:10, rate = 1.0 mL/min, 254 nm, tminor = 9.53 min, tmajor = 18.83 min). [α]D25 +7.3 (c 0.7, CHCl3). 1H NMR (300 MHz, CDCl3) δ 8.06 (d, J = 9.0 Hz, 2H, HAr), 7.53 (d, J

= 9.0 Hz, 2H, HAr), 7.38-7.22 (m, 5H, HAr), 6.86 (d, J = 8.5 Hz, 1H, HAr), 6.60 (d, J = 8.5 Hz, 1H, HAr), 5.88-5.69 (m, 2H, CH=CH2), 5.19-5.08 (m, 4H, CH=CH2), 4.35-4.22 (m, 1H, CHNH), 3.74 (s, 3H, OCH3), 3.48 (d, J = 6.5 Hz, 1H, CHNAll2), 3.29 (dd, J = 14.0 and 4.0 Hz, 2H, NCH2), 3.20-3.03 (m, 2H, CH2Ph), 2.66 (dd, J = 14.0 and 8.0 Hz, 2H, NCH2). 13C NMR (75 MHz, CDCl3) δ 136.6 (CqAr), 135.7 (CH=CH2), 130.5 (CAr), 130.4 (CAr), 128.4 (CAr), 127.7 (CAr), 126.8 (CAr), 123.7 (CAr), 117.7 (CH=CH2), 113.3 (CAr), 65.4 (CHNAll2), 56.7 (CHNH), 55.0 (OCH3), 53.0 (NCH2), 38.4 (CH2Ph). IR 3302, 2922, 1607, 1526, 1511, 1347, 1250, 1157 cm-1. ESIHRMS m/z = 522.2061 [M+H]+ (calculée pour C28H32N3O5S : 522.2063).

N-((3S,4R,E)-4-(diallylamino)-2-methyl-6-phenylhex-5-en-3-yl)-4-nitrobenzenesulfonamide 20. The General Procedure (D) was followed using 3h (53 mg, 0.184 mmol), diallylamine 2a (22 µL, 0.177 mmol), boronic acid (1) (21 mg, 0.142 mmol) and molecular sieve 4Å (100 mg) in PhCF3 (0.85 mL). After purification by preparative TLC (AcOEt/Heptane 2:8), 20 (35 mg, 0.074 mmol, 53%) was obtained, ee = 87% determined by chiral HPLC (Chiralpak IC column, eluent: heptane+0.1% Et3N/ethanol+ 0.1% Et3N 97:3, rate = 1.0 mL/min, 254 nm, tminor = 17.40 min, tmajor = 22.80 min). Mp = 145-146 °C. [α]D25 −53.4 (c 0.5, CHCl3). 1H NMR (300 MHz, CDCl3) δ 7.92 (d, J = 9.0 Hz, 2H, HAr), 7.83 (d, J = 9.0 Hz, 2H, HAr), 7.26-7.17 (m, 3H, HAr), 7.08-6.97 (m, 2H, HAr), 6.14 (d, J = 16.0 Hz, 1H,

PhCH=CH), 5.85-5.66 (m, 2H, CH=CH2), 5.54 (dd, J = 16.0 and 10.0 Hz, 1H, PhCH=CH), 5.22-5.08 (m, 4H, CH=CH2), 4.45-4.23 (m, 1H, NH), 3.70-3.57 (m, 1H, CHNH), 3.33-3.21 (m, 2H, NCH2), 3.10 (t, J = 10.0, 1H, CHNAll2), 2.76 (dd, J = 14.0 and 8.5 Hz, 2H, NCH2), 2.54-2.37 (m, 1H, CH(CH3)2), 0.99 (d, J = 7.0 Hz, 3H, CH3), 0.84 (d, J = 7.0 Hz, 3H, CH3). 13C NMR (75 MHz, CDCl3) δ 147.5 (CqAr), 142.1 (CqAr), 136.4 (CH=CH2), 135.9 (CqAr), 135.6 (PhCH=CH), 128.5 (CAr), 128.3 (CAr), 127.5 (CAr), 126.1 (CAr), 125.0 (PhCH=CH), 124.0 (CAr), 117.5 (CH=CH2), 63.5 (CHNAll2), 61.4 (CHNH), 53.1 (NCH2), 27.3 (CH(CH3)2), 20.7 (CH3), 14.9 (CH3). IR 3276, 2963, 1526, 1347, 1644, 1162 cm-1. ESIHRMS m/z = 470.2115 [M+H]+ (calculée pour C25H32N3O4S : 470.2114).

N

HNPh

MeO SO2

NO2

HN

N

Ph

SO2

NO2

S19

N-((3R,4S,E)-3-(diallylamino)-6-methyl-1-phenylhept-1-en-4-yl)-4-

nitrobenzenesulfonamide 21. The General Procedure (D) was followed using 3i (55 mg, 0.142 mmol), diallylamine 2a (22 µL, 0.177 mmol), boronic acid 1 (21 mg, 0.142 mmol) and molecular sieve 4Å (100 mg) in PhCF3 (0.85 mL). After purification by preparative TLC (AcOEt/Heptane 3:7), 21 (40 mg, 0.083 mmol, 51%) was obtained, ee = 83% (96% after recrystallisation in Hept/EtOH 9/1) determined by chiral HPLC (Chiralpak IC column, eluent: heptane+0.1% Et3N/ethanol+ 0.1% Et3N 97:3, rate = 1.0 mL/min, 254 nm, tminor = 14.93 min, tmajor

= 17.34 min). Mp = 115-117 °C. [α]D25 −58.6 (c 0.5, CHCl3). 1H NMR (300 MHz, CDCl3) δ 7.99 (d, J = 9.0 Hz, 2H, HAr), 7.83 (d, J = 9.0 Hz, 2H, HAr), 7.23-7.13 (m, 3H, HAr), 7.10-7.01 (m, 2H, HAr), 6.15 (d, J = 16.0 Hz, 1H, PhCH=CH), 5.74-5.56 (m, 3H, CH=CH2, PhCH=CH), 5.11-5.01 (m, 4H, CH=CH2), 3.58 (td, J = 9.0 and 3.0 Hz, 1H, CHNH), 3.17 (dd, J = 14.0 and 4.5 Hz, 2H, NCH2), 3.02 (t, J = 9.0, 1H, CHNAll2), 2.76 (dd, J = 14.0 and 8.0 Hz, 2H, NCH2), 1.79-1.57 (m, 2H, CH2i-Pr, CH(CH3)2), 1.27-1.09 (m, 1H, CH2i-Pr), 0.84 (d, J = 6.0 Hz, 3H, CH3), 0.80 (d, J = 6.0 Hz, 3H, CH3). 13C NMR (75 MHz, CDCl3) δ 147.4 (CqAr), 136.0 (CqAr), 135.9 (CH=CH2), 135.5 (PhCH=CH), 128.6 (CAr), 128.2 (CAr), 127.8 (CAr), 126.2 (CAr), 124.8 (PhCH=CH), 124.0 (CAr), 117.6 (CH=CH2), 66.1 (CHNAll2), 55.0 (CHNH), 53.4 (NCH2), 42.6 (CH2i-Pr), 24.1 (CH(CH3)2), 23.7 (CH3), 21.7 (CH3). IR 3251, 2959, 1531, 1346, 1346, 1152, 1089 cm-1. ESIHRMS m/z = 484.2262 [M+H]+ (calculée pour C26H34N3O4S : 484.2270).

N-((2R,3R,E)-1-((tert-butyldimethylsilyl)oxy)-3-(dibenzylamino)-5-

phenylpent-4-en-2-yl)-4-nitrobenzenesulfonamide 22. The General Procedure (D) was followed using 3j (51 mg, 0.132 mmol), dibenzylamine 2c (25 µL, 0.127 mmol), boronic acid (1) (15 mg, 0.101 mmol) and molecular sieve 4Å (100 mg) in PhCF3 (0.65 mL). After purification by preparative TLC (AcOEt/Heptane 3:7), 22 (43 mg, 0.064 mmol, 63%) was obtained, ee = 82% (86% after recrystallisation in Hept/EtOH 9/1) determined by chiral HPLC (Chiralpak IC column, eluent: heptane+0.1% Et3N/ethanol+ 0.1% Et3N 97:3, rate = 1.0 mL/min,

254 nm, tminor = 10.50 min, tmajor = 17.83 min). Mp = 136-138 °C. [α]D25 −63.5 (c 0.6, CHCl3). 1H NMR (300 MHz, CDCl3) δ 8.04 (d, J = 9.0 Hz, 2H, HAr), 7.80 (d, J = 9.0 Hz, 2H, HAr), 7.40-7.22 (m, 15H, HAr), 6.28 (d, J = 16.0 Hz, 1H, PhCH=CH), 5.94 (dd, J = 16.0 and 10.0 Hz, 1H, PhCH=CH), 4.90 (d, J = 9.0 Hz, 1H, NH), 4.04 (dd, J = 9.5 and 2.5 Hz, 1H, CH2OTBS), 3.85 (d, J = 14.0 Hz, 2H, NCH2Ph), 3.68 (dd, J = 9.5 and 4.5 Hz, 1H, CH2OTBS), 3.55-3.65 (m, 1H, CHNH), 3.38 (d, J = 14.0 Hz, 1H, NCH2Ph), 3.02 (t, J = 9.5, 1H, CHNBn2), 0.86 (s, 9H, SiC(CH3)3), 0.03 (s, 3H, Si(CH3)), 0.00 (s, 3H, Si(CH3)). 13C NMR (75 MHz, CDCl3) δ 149.4 (CqAr), 147.0 (CqAr), 139.1 (CqAr), 136.1 (CqAr), 136.0 (PhCH=CH), 128.7 (CAr), 128.6 (CAr), 128.5 (CAr), 128.2 (CAr), 127.9 (CAr), 127.2 (CAr), 127.2 (CAr), 126.3 (CAr), 124.6 (PhCH=CH), 124.0 (CAr), 62.3 (CH2OTBS), 62.2 (CHNBn2), 56.7 (CHNH), 54.9 (NCH2), 29.7(SiC(CH3)3), 26.0 (SiC(CH3)3), -5.3 (s, 3H, Si(CH3)), -5.6 (s, 3H, Si(CH3)). IR 3342, 2928, 1528, 1346, 1162, 1091 cm-1. ESIHRMS m/z = 672.2928 [M+H]+ (calculée pour C37H46N3O5SiS : 672.2927).

N-((2S,3R,E)-3-(diallylamino)-1,5-diphenylpent-4-en-2-yl)-2,2,2-trifluoroacetamide 26. The General Procedure (D) was followed using α-amino aldehyde 3k (47 mg, 0.19 mmol) diallylamine 2a (23 µL, 0.18 mmol), boronic acid 1a (22 mg, 0.15 mmol) and molecular sieve 4Å (150 mg) in PhCF3 (0.9 mL). After

purification by preparative TLC (AcOEt/Heptane 7:3), 26 (27 mg, 0.06 mmol, 42%) was obtained as an yellow solid, ee = 4.0% determined by chiral HPLC (Chiralpak IA column, eluent: heptane+0.1%

HN

N

Ph

SO2

NO2

HN

NBn2

OTBSPh

SO2

NO2

N

NHTFAPh Ph

S20

Et3N/ethanol+ 0.1% Et3N 90:10, rate = 1.0 mL/min, 254 nm, tminor = 3.94 min, tmajor = 4.59 min). 1H NMR (300 MHz, CDCl3) δ 7.27-7.07 (m, 10H, HAr), 6.31 (d, J = 16.0 Hz, 1H, PhCH=CH), 6.06-5.90 (m, 2H, PhCH=CH, NH), 5.87-5.69 (m, 2H, CH=CH2), 5.22-5.06 (m, 4H, CH=CH2), 4.43-4.28 (m, 1H, CHNH), 3.43-3.32 (m, 2H, NCH2), 3.28 (dd, J = 14.0 and 4.5 Hz, 1H, CH2Ph), 3.22 (t, J = 9.5 Hz, 1H, CHNAll2), 2.89 (dd, J = 14.5 and 8.0 Hz, 2H, NCH2), 2.76 (dd, J = 14.0 and 8.0 Hz, 1H, CH2Ph). 13C NMR (75 MHz, CDCl3) δ 157.0 (CO), 137.2 (CqAr), 136.4 (CH=CH2), 136.3 (CqAr), 135.9 (PhCH=CH), 129.3 (CAr), 128.6 (CAr), 127.9 (CAr), 126.8 (CAr), 126.4 (CAr), 123.8 (PhCH=CH), 117.5 (CH=CH2), 65.2 (CHNAll2), 53.6 (NCH2), 52.5 (CHNH), 37.2 (CH2Ph. IR 3331, 2924, 1694, 1557, 1164 cm-1. ESIHRMS m/z = 429.2151 [M+H]+. C25H28F3N2O requires 429.2153).

(2S,3R,E)-N3,N3-diallyl-1,5-diphenylpent-4-ene-2,3-diamine 23. To a stirred solution of 8 (38 mg, 0.073 mmol, 1.0 equiv) in dry DMF (0.6 mL) was added K2CO3 (51 mg, 0.367 mmol, 5 equiv) and PhSH (0.15 mL, 1.47 mmol, 20 equiv). The resulting mixture was stirred at 50 °C for 5 h. 15% NaOH (2 mL) was then added and the aqueous phase was extracted with Et2O (4 x 10 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (AcOEt/Heptane 9:1 to 1:0) to afford 23 (18 mg, 0.073 mmol, 74%). [α]D25 −88.4 (c

0.7, CHCl3).1H NMR (300 MHz, MeOD) δ 7.49-7.42 (m, 2H, HAr), 7.39-7.18 (m, 8H, HAr), 6.52 (d, J = 16.0 Hz, 1H, PhCH=CH), 6.26 (dd, J = 16.0 and 9.5 Hz, 1H, PhCH=CH), 5.97-5.80 (m, 2H, CH=CH2), 5.28-5.12 (m, 4H, CH=CH2), 3.44 (ddt, J = 14.5, 5.0 and 2.0 Hz, 2H, NCH2), 3.39-3.25 (m, 2H, CH2Ph, CHNH2), 3.14 (dd, J = 9.5 and 8.0 Hz, 1H, CHNAll2), 3.02 (dd, J = 14.5 and 7.5 Hz, 2H, NCH2), 2.38 (dd, J = 13.0 and 9.5 Hz, 1H, CH2Ph), 2.79 (dd, J = 14.0 and 7 Hz, 1H, CH2Ph). 13C NMR (75 MHz, MeOD) δ 141.1 (CqAr), 138.1 (CqAr), 137.9 (CH=CH2), 137.1 (PhCH=CH), 130.3 (CAr), 129.6 (CAr), 128.7 (CAr), 127.5 (CAr), 127.3 (CAr), 126.4 (PhCH=CH), 117.4 (CH=CH2), 68.6 (CHNAll2), 54.7 (CHNH), 54.6 (NCH2), 41.7 (CH2Ph). IR 3272, 2963, 1526, 1347, cm-1. ESIHRMS m/z = 333.2329 [M+H]+ (calculée pour C23H29N2 : 333.2331).

N-((2S,3R,E)-3-amino-1,5-diphenylpent-4-en-2-yl)-4-nitrobenzenesulfonamide

24. A solution of allylamine 8 (30 mg, 0.058 mmol, 1 equiv.) in dry degassed DCM (2 mL) was to tetrakis(triphenylphosphine)palladium (1 mg, 0.001 mmol, 0.02 equiv) and N,N’-dimethylbarbituric acid (54 mg, 0.78 mmol, 6 equiv) under argon.

The mixture was stirred at 35 °C for 6 hours and the solvent was removed under reduced pressure. A saturated solution of K2CO3 (10 mL) was then added and the aqueous phase was extracted with AcOEt (3 x 10 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (AcOEt/Heptane 7:3 to 1:0) to afford 24 (25 mg, 0.057 mmol, 98%). [α]D25 −12.0 (c 0.5, CHCl3).1H NMR (300 MHz, MeOD) δ 8.05 (d, J

= 9.0 Hz, 2H, HAr), 7.71 (d, J = 9.0 Hz, 2H, HAr), 7.37-7.20 (m, 3H, HAr), 7.01-6.91 (m, 5H, HAr), 6.60 (d, J

= 16.0 Hz, 1H, PhCH=CH), 6.27 (dd, J = 16.0 and 7.5 Hz, 1H, PhCH=CH), 3.70 (td, J = 9.5 and 4.0 Hz, 1H, CHNH), 3.59 (dd, J = 7.5 and 4.0 Hz, 1H, CHNH2), 2.81 (dd, J = 14.0 and 4.0 Hz, 2H, CH2Ph), 2.46 (dd, J = 14.0 and 9.5 Hz, 1H, CH2Ph). 13C NMR (75 MHz, MeOD) δ 151.0 (CqAr), 148.4 (CqAr), 139.3 (CqAr), 138.4 (CqAr), 133.8 (CAr, PhCH=CH), 130.5 (CAr), 130.0 (CAr), 129.9 (CAr, PhCH=CH), 129.5 (CAr), 129.0 (CAr), 128.8 (CAr), 127.7 (CAr), 127.3 (CAr), 125.3 (CAr), 62.8 (CHNH), 59.0 (CHNH2), 38.9 (CH2Ph). IR 3356, 3303, 3062, 3025, 2859, 2661, 1518, 1348, 1095 cm-1. ESIHRMS m/z = 438.1480 [M+H]+ (calculée pour C23H23N3O4S : 438.1488).

N

NH2Ph Ph

NH2

HNPh Ph

SO2

NO2

S21

(2S,3R,E)-1,5-diphenylpent-4-ene-2,3-diamine 25. To a stirred solution of 24 (19 mg, 0.043 mmol, 1.0 equiv) in dry DMF (0.5 mL) was added K2CO3 (60 mg, 0.434 mmol, 10 equiv) and PhSH (0.09 mL, 0.87 mmol, 20 equiv). The resulting mixture

was stirred at 50 °C for 5 h. 15% NaOH (2 mL) was then added and the aqueous phase was extracted with Et2O (10 x 10 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (AcOEt/iPrOH/H2O: 1:0:0 to 7:2:1 + 1% aq. NH3) to afford 25 (7 mg, 0.027 mmol, 64%). [α]D25 +24.3 (c 0.7, CHCl3).1H NMR (300 MHz, MeOD) δ 7.51-7.19 (m, 10H, HAr), 6.64 (d, J = 16.0 Hz, 1H, PhCH=CH), 6.26 (dd, J = 16.0 and 8.0 Hz, 1H, PhCH=CH), 3.53 (dd, J = 8.0 and 4.0 Hz, 1H, CHNH2), 3.18 (d dd, J = 9.0, 5.5 and 4.0 Hz, 1H, CHNH2), 2.91 (dd, J = 14.0 and 5.5 Hz, 1H, CH2Ph), 2.60 (dd, J = 14.0 and 9.0 Hz, 1H, CH2Ph). 13C NMR (75 MHz, MeOD) δ 140.0 (CqAr), 138.1 (CqAr), 134.6 (PhCH=CH), 130.3 (CAr), 129.7 (CAr), 129.6 (CAr), 129.5 (CAr), 128.7 (CAr), 128.7 (PhCH=CH), 127.6 (CAr), 58.6(CHNH2), 58.3 (CHNH2), 41.0 (CH2Ph). IR 2940, 1524, 1349, 1165, 835 cm-1. ESIHRMS m/z = 253.1706 [M+H]+ (calculée pour C17H21N2 : 253.1705).

NH2

NH2Ph Ph

S22

IV-HPLC-RMN

NHTs

NAll2

PhPh

5 (racemate)

NHTs

NAll2

PhPh

5

S23

N

HNPh Ph

SO2

NO2

8

N

HNPh Ph

SO2

NO28 (racemate)

S24

N

HNPh Ph

SO2

NO2

9 (after recrystallisation)

N

HNPh Ph

SO2

OMe9

S25

10 (32% ee)

N

NHPh Ph

SO2

Me3Si

N

NHPh Ph

SO2

Me3Si

10

S26

N

NHAcPh Ph

11

N

HNPh Ph

O

O

12

S27

N

HNPh

Ph

Ph

SO2

NO2

13

N

HNPh

Ph

Ph

SO2

NO213 (racemate)

S28

N

HNPh

PhPh

Ph

SO2

NO2

14 (racemate)

N

HNPh

PhPh

Ph

SO2

NO2

14

S29

N

HNPh

Ph

Ph

SO2

NO2

15

N

HNPh

Ph

Ph

SO2

NO2

15 (racemate)

S30

N

HNPh

SO2

NO2

16

N

HNPh

SO2

NO216 (racemate)

S31

N

HNPh

SO2

NO2

17

N

HNPh

SO2

NO217 (racemate)

S32

N

HN

PhPh

PhO SO2

NO218 (racemate)

N

HN

PhPh

PhO SO2

NO2

18

S33

N

HNPh

MeO SO2

NO2

19

N

HNPh

MeO SO2

NO2

19 (racemate)

S34

HN

N

Ph

SO2

NO220

HN

N

Ph

SO2

NO220 (30% ee)

S35

HN

N

Ph

SO2

NO2

21 (18% ee)

HN

N

Ph

SO2

NO2

21

S36

HN

NBn2

OTBSPh

SO2

NO2

22

N

NHTFAPh Ph

26

S37

3a

S38

S39

S40

S41

S42

S43

S44

S45

S46

S47

S48

S49

S50

S51

S52

S53

S54

S55

S56

S57

S58

S59

S60

S61

S62

S63

S64

S65

S66

S67

S68

S69