69451 weinheim, germany - wiley-vch · column chromatography on silica afforded the allylic sulfide...

Supporting Information

© Wiley-VCH 2007

69451 Weinheim, Germany

S1

Exploiting Organocatalysis: Enantioselective Synthesis of Vinyl Glycines via Allylic

Sulfimide [2,3]-Sigmatropic Rearrangement

Alan Armstrong,a* Lee Challinor,

a and Jennifer H. Moir

b

aDepartment of Chemistry, Imperial College London, South Kensington, London SW7

2AZ, UK

bOrganon Newhouse, Lanarkshire ML1 5SH, Scotland

E-mail: [email protected]; Fax: +44 (0) 20 75945804; Tel. +44 (0) 20

75945876

Supporting Information Contents:

Page Information (page number of spectra)

2 General Experimental Details

3 Preparation of sulfur electrophile (28-29)

4-5 Preparation and determination of ee of S-hexyl alcohol (30-33)

6-7 Optimisation of asymmetric αααα-sulfenylation/olefination

8-12 Preparation of S-hexyl (E)-allylic sulfides (34-59)

13-17 Preparation of (S)-tert-Butoxycarbonyl-N-hexylsulfenamides (60-81)

18-19 Preparation of S-hexyl (Z)-allylic sulfides (82-89)

20-21 Preparation of (R)-N-tert-Butoxycarbonyl-N-hexylsulfenamides (90-

91)

22-26 Preparation of N-Boc protected vinyl glycine derivatives (92-101)

27 References

28-101 Spectra (1H,

13C and

19F NMR spectra and Chiral HPLC traces)

S2

General Experimental Details:

Solvents were freshly distilled before use from sodium/benzophenone (diethyl ether,

THF, toluene) or CaH2 (dichloromethane). Liquid reagents were distilled prior to use,

while other commercial solids were used as supplied. Reactions were run under a positive

pressure of nitrogen. Reaction temperatures were recorded as bath temperatures. NMR

analyses were performed in CDCl3; chemical shifts are quoted in ppm relative to TMS (as

referenced to residual CHCl3 δH=7.26 or CDCl3 δC=77.0), with coupling constants quoted

in Hz. Infrared analyses of liquid compounds were recorded as a thin film, and of solid

compounds as a nujol mull, both on NaCl plates.

S3

Preparation of sulfur electrophile:

1-Hexylsulfanyl-[1,2,4] triazole was prepared according to a modification of the

procedure reported by Jorgensen.[1]

1-Hexylsulfanyl-[1,2,4] triazole (8b):

N

NN SHex

Sulfuryl chloride (0.80 ml, 10 mmol) was added dropwise to a solution of dihexyl

disulfide (2.34 g, 10 mmol) in dichloromethane (10 ml). The reaction was stirred at RT

for 15 minutes before adding it dropwise to a second solution of 1,2,4-triazole (1.73 g, 25

mmol) and triethylamine (3.07 ml, 22 mmol) in dichloromethane (10 ml). The reaction

was concentrated in vacuo and extracted with pentane (2 x 50 ml) followed by

pentane/dichloromethane (7:3, 50 ml) before the combined organics were concentrated in

vacuo. Fast chromatography (pentane/Et2O 2.3:1 – 4:6) to minimise decomposition

yielded the title compound (1.94 g, 52 %) as a colourless oil, νmax(film)/cm-1

2957, 2929,

2857, 1497, 1266, 1142, 1103, 985, 941, 674; δH (400 MHz, CDCl3) 8.22 (1H, s, CHNS),

8.05, (1H, s, CHNN), 3.03 (2H, t, J7.3, SCH2), 1.55 (2H, qu, J7.4, SCH2CH2), 1.45-1.20

(6H, m, CH2CH2CH2CH3), 0.87 (3H, t, CH3); δC (400 MHz, CDCl3) 154.0 (CH), 151.4

(CH), 41.0 (CH2), 31.2 (CH2), 27.9 (CH2), 27.8 (CH2), 22.4 (CH2), 13.9 (CH3); m/z (CI)

203 (MNH4+ 8 %), 186 (MH

+ 22 %); Found: MH

+, 186.1067. C8H16N3S requires:

186.1065.

S4

Preparation and determination of ee of S-hexyl alcohol (11b):

(S)-2-hexylthiobutanol (11b) was prepared by Jorgensen’s procedure but using the S-

hexyl-triazole electrophile.[1]

SHex

OH

Freshly prepared 1-hexylsulfanyl-[1,2,4] triazole (181 mg, 0.98 mmol) was added to a

solution of (S)-2-[Bis-(3,5-bistrifluoromethyl-phenyl)-trimethylsilanyloxy-methyl]-

pyrrolidine (89.6 mg, 0.15 mmol) and butanal (67.5 µl, 0.75 mmol) in toluene (1.5 ml)

and the reaction was stirred at RT for 3 hours. The reaction was diluted with MeOH (6

ml) and sodium borohydride (56 mg, 1.5 mmol) added. After 20 minutes the reaction was

quenched with 1 N KHSO4 (aq) (16 ml) and extracted with dichloromethane (3 x 20 ml)

before the combined organics were dried (MgSO4) and concentrated in vacuo.

Chromatography (petrol/EtOAc 20:1) yielded the title compound (108 mg, 76 %) as a

colourless oil, [α]20D -24.0 (c 2.0 CH2Cl2); νmax(film)/cm-1 3409, 2958, 2928, 2873, 2858,

1461, 1378, 1049, 1031, 726; δH (400 MHz, CDCl3) 3.67 (1H, m, CH2OH), 3.48 (1H, m,

CH2OH), 2.64 (1H, m, CHS), 2.48 (2H, m, SCH2), 2.29 (1H, br t, J6.1, OH), 1.70-1.45

(4H, m, SCH2CH2, SCHCH2), 1.43-1.20 (6H, m, CH3CH2CH2CH2), 1.04 (3H, t, J7.4,

CH3CH2CH2), 0.89 (3H, t, J6.7, CH3CH2CHS); δC (400 MHz, CDCl3) 63.4 (CH2), 51.4

(CH), 31.4 (CH2), 30.1 (CH2), 30.0 (CH2), 28.6 (CH2), 24.8 (CH2), 22.5 (CH2), 14.0

(CH3), 11.7 (CH3); m/z (CI) 208 (MNH4+ 100 %), 191 (MH

+ 78 %); Found: MH

+,

191.1471. C10H23OS requires: 191.1470.

S5

Preparation of Mosher’s ester of enantioenriched-11b

SHex

O(S)-MTPA

A solution of (S)-(+)-α-Methoxy-α-trifluoromethylphenylacetyl chloride (19 µl, 0.099

mmol), pyridine (170 µl), dichloromethane (170 µl), and 2-hexylthiobutanol (12.6 mg,

0.066 mmol) was stirred at RT for 1 hour. The reaction was quenched by the addition of

N,N-dimethyl-1,3-propanediamine (17 µl, 0.132 mmol). The reaction was diluted with

ether (1 ml), washed with cold 1 N HCl (0.5 ml), cold 1 N NaOH (0.5 ml), brine (2 x 0.5

ml), dried (MgSO4) and concentrated in vacuo to yield the title compound as a colourless

oil, δH (250 MHz, CDCl3) 7.57-7.45 (2H, m, Ph), 7.51-7.36 (3H, m, Ph), 4.52 (1H, dd,

J11.0, 5.0, CH2O), 4.22 (1H, dd, J11.0, 8.0, CH2O), 3.57 (3H, s, OCH3), 2.76 (1H, m,

SCH), 2.51 (2H, m, SCH2), 1.72-1.07 (10H, m, CH3CH2CH2CH2CH2, CH3CH2), 0.97-

0.77 (6H, m, CH3CH2, CH3CH2); δF (250 MHz, CDCl3) -75.84 (major), -75.80 (minor).

Integration of 19

F NMR gave ee of >95 %.

S6

Optimisation of asymmetric αααα-sulfenylation/olefination:

2-[Bis-(3,5-bistrifluoromethyl-phenyl)-trimethylsilanyloxy-methyl]-pyrrolidine (7)

was prepared according to the procedure reported by Jorgensen.[1]

CHO CHO

SHex SHex

CO2Et

96 11

Entry Method Base Solvent T [oC] Time [h] E/Z

[a] Yield [%]

[b] ee [%]

[c]

1 A NaH CH2Cl2 25 4 > 95:5 67 5

2 A NaH CH2Cl2 -78 6 > 95:5 56 43

3 B NaH CH2Cl2 -78 6 > 95:5 74 66

4 B NaH CH2Cl2 -78 1 > 95:5 73 83

5 B nBuLi CH2Cl2 -78 1 > 95:5 79 93

6 B nBuLi THF -78 1 9:1 76 89

[a] Determined by 1H NMR of crude reaction mixture. [b] Yield of (E)-alkene after flash

chromatography. [c] Determined by HPLC on a chiral stationary phase.

S7

Method A:

Freshly prepared 1-hexylsulfanyl-[1,2,4] triazole (1.3 eq) was added to a solution of (S)-

2-[Bis-(3,5-bistrifluoromethyl-phenyl)-trimethylsilanyloxy-methyl]-pyrrolidine (0.1 eq)

and butanol (1 eq) in solvent (1.5 M) and the mixture stirred at room temperature for 5

hours before cooling to temperature T. A solution of Base (1.5 eq) and

(Ethoxycarbonyl)methyl]triphenylphosphonium bromide (1.5 eq) in Solvent (0.3 M) at

temperature T was added to the sulfenylation reaction mixture. After stirring at -78 oC for

Time the solution was quenched with NH4Cl(sat), extracted (dichloromethane), dried

(MgSO4) and concentrated in vacuo. Column chromatography on silica afforded the

allylic sulfide products.

Method B:

The same as Method A except using triethylphosphonoacetate.

S8

Preparation of S-hexyl (E)-allylic sulfides:

General procedure for the preparation of enantioenriched S-hexyl (E)-allylic

sulfides:



and aldehyde (1 eq) in toluene (1.5 M) and the mixture stirred at room temperature for 5

hours before cooling to -78 oC. A pre-mixed solution of nBuLi (1.5 eq) and

triethylphosphonoacetate (1.5 eq) in dichloromethane (0.3 M) at -78 oC was added to the

sulfenylation reaction mixture. After stirring at -78 oC for 1 hour the solution was

quenched with NH4Cl(sat), extracted (dichloromethane), dried (MgSO4) and concentrated

in vacuo. Column chromatography on silica afforded the allylic sulfide products. Data for

the products are given below. Samples of racemic material for chiral HPLC comparison

were also prepared by modifications of literature routes.

Methyl (4S)-4-[hexylthio]-pent-2E-enoate (11a):

CO2Me

SHex

The organocatalysis/olefination of propionaldehyde (37.1 µl, 0.51 mmol) upon

chromatography (petrol/EtOAc 40:1) yielded the title compound (61 mg, 52 %) as a

colourless oil, [α] 23

D -110 (c 1.0, CHCl3); Chiral HPLC: Flow rate 1.0 mL/min; hexane;

30 °C, chiral OD-H; detection at 254 nm gave ee of 93 %. Retention time 15.0 min

(minor), 19.2 min (major). Data in agreement with literature values.[2]

S9

Ethyl (4S)-4-[hexylthio]-hex-2E-enoate (11b):

SHex

CO2Et

The organocatalysis/olefination of butanal (69.8 µl, 0.77 mmol) upon chromatography

(petrol/EtOAc 40:1) yielded the title compound (157 mg, 79 %) as a colourless oil, [α]24D

-86.0 (c 2.0 CH2Cl2). νmax(film)/cm-1 3027, 2967, 2932, 2870, 1722, 1645, 1455, 1264,

1234, 1162, 1041, 981, 861, 726; δH (500 MHz, CDCl3) 6.69, (1H, dd, J15.5, 9.8,

CHCHCO), 5.73 (1H, d, J15.5 CHCHCO), 4.22 (2H, q, J7.4, OCH2CH3), 3.15 (1H, m,

CHS), 2.38 (2H, m, SCH2), 1.68-1.50 (4H, m, CH2CH2S, CH3CH2CHS), 1.36-1.25 (9H,

m, CH3CH2CH2CH2, OCH2CH3), 0.98 (3H, t, J7.4, CH3CH2CHS), 0.88 (3H, t, J7.0,

CH3CH2); δC (500 MHz, CDCl3) 166.3 (C), 148.3 (CH), 120.7 (CH), 60.4 (CH2), 48.3

(CH), 31.4 (CH2), 30.6 (CH2), 29.4 (CH2), 28.6 (CH2), 26.9 (CH2), 22.5 (CH2), 14.2

(CH3), 14.0 (CH3), 11.9 (CH3); m/z (CI) 276 (MNH4+ 100 %), 259 (MH+ 72 %); Found:

MH+, 259.1735. C14H27O2S requires: 259.1732. Chiral HPLC: Flow rate 1.0 mL/min;

hexane; 30 °C, chiral OD-H; detection at 254 nm gave ee of 93 %. Retention time 13.8

min (minor), 16.4 min (major).

Ethyl (4S)-4-[hexylthio]-5-methylhex-2E-enoate (11c):

SHex

CO2Et

The organocatalysis/olefination of isovaleraldehyde (79 µl, 0.73 mmol) upon


colourless oil, [α]24

D -79.8 (c 1.78 CH2Cl2), νmax(film)/cm-1

2961, 2929, 2873, 1722,

1645, 1465, 1265, 1242, 1163, 983, 872, 775; δH (400 MHz, CDCl3) 6.77, (1H, dd, J15.5,

10.4, CHCHCO), 5.72 (1H, d, J15.5, CHCHCO), 4.22 (2H, q, J7.2, OCH2CH3), 3.03

(1H, dd, J10.4, 6.7, CHS), 2.37 (2H, t, J7.4, SCH2), 1.89 (1H, m, CH(CH3)2), 1.55 (2H,

S10

m, CH2CH2S), 1.45-1.22 (6H, m, CH3CH2CH2CH2), 1.31 (3H, t, J7.2, OCH2CH3), 1.04

(3H, d, J6.8, C(CH3)2), 1.00 (3H, d, J6.8, C(CH3)2), 0.90 (3H, t, J6.9, CH3CH2); δC (400

MHz, CDCl3) 166.3 (C), 146.9 (CH), 120.9 (CH), 60.4 (CH2), 54.3 (CH), 31.9 (CH), 31.4

(CH2), 31.0 (CH2), 29.3 (CH2), 28.6 (CH2), 22.5 (CH2), 20.6 (CH3), 20.1 (CH3), 14.2

(CH3), 14.0 (CH3); m/z (CI) 290 (MNH4+ 100 %), 273 (MH

+ 83 %); Found: MH

+,

273.1888. C15H29O2S requires: 273.1888. Chiral HPLC: Flow rate 0.2 mL/min;

hexane:IPA 1 %; 30 °C, chiral AD-H; detection at 254 nm gave ee of 91 %. Retention

time 24.5 min (minor), 46.0 min (major).

Ethyl (4S)-4-[hexylthio]-5,5-dimethylhex-2E-enoate (11d):

SHex

CO2Et

The organocatalysis/olefination of 3,3-dimethylbutyraldehyde (66 µl, 0.52 mmol) upon



D -63.0 (c 1.21 CH2Cl2); νmax(film)/cm-1

2959, 2929, 2860, 1721,

1640, 1464, 1270, 1212, 1156, 1104, 983, 864, 779; δH (400 MHz, CDCl3) 6.83, (1H, dd,

J15.3, 10.9, CHCHCO), 5.64 (1H, d, J15.3, CHCHCO), 4.21 (2H, q, J7.2, OCH2CH3),

2.92 (1H, d, J10.9, CHS), 2.32 (2H, m, SCH2), 1.57-1.46 (2H, m, CH2CH2S), 1.40-1.22

(6H, m, CH3CH2CH2CH2), 1.30 (3H, t, J7.2, OCH2CH3), 1.01 (9H, s, C(CH3)3), 0.88

(3H, t, J6.9, CH3CH2); δC (400 MHz, CDCl3) 166.3 (C), 146.0 (CH), 120.4 (CH), 60.4

(CH2), 59.2 (CH), 34.1 (C), 31.4 (CH2), 31.2 (CH2), 29.2 (CH2), 28.5 (CH2), 27.8 (CH3),

22.5 (CH2), 14.3 (CH3), 14.0 (CH3); m/z (CI) 304 (MNH4+ 100 %), 287 (MH

+ 98 %);

Found: MH+, 287.2038. C16H31O2S requires: 287.2044. Chiral HPLC: Flow rate 1.0

mL/min; hexane:IPA 1.0 %; 30 °C, chiral AD-H; detection at 254 nm gave ee of 89 %.

Retention time 4.2 min (minor), 8.4 min (major).

S11

Ethyl (4S)-4-[hexylthio]-5-phenylpent-2E-enoate (11e):

Bn

SHex

CO2Et

The organocatalysis/olefination of 3-phenylpropinaldehyde (91.3 µl, 0.62 mmol) upon




3029, 2956, 2928, 2857, 1720,

1647, 1455, 1266, 1213, 1157, 1042, 981, 866, 727, 700; δH (400 MHz, CDCl3) 7.30-7.16

(5H, m, ArH), 6.76 (1H, dd, J15.4, 9.8, CHCHS), 5.63 (1H, d, J15.5, CHCO), 4.18 (2H,

q, J7.1, OCH2CH3), 3.50 (1H, q, J8.0, CHS), 2.93 (2H, m, CH2CHS), 2.38 (2H, m,

SCH2), 1.50 (2H, m, CH2CH2S), 1.36-1.20 (6H, m, CH3CH2CH2CH2), 1.28 (3H, t, J7.1,

OCH2CH3), 0.87 (3H, t, J6.9, CH3CH2); δC (400 MHz, CDCl3) 166.0 (C), 147.5 (CH),

137.9 (C),129.1 (CH), 128.4 (CH), 126.7 (CH), 121.0 (CH), 60.4 (CH2), 48.0 (CH), 40.3

(CH2), 31.4 (CH2), 30.9 (CH2), 29.2 (CH2), 28.5 (CH2), 22.5 (CH2), 14.2 (CH3), 14.0

(CH3); m/z (CI) 338 (MNH4+ 100 %), 321 (MH

+ 63 %); Found: MH

+, 321.1882.

C19H29O2S requires: 321.1888. Chiral HPLC: Flow rate 1.0 mL/min; hexane:IPA 2.0 %;


(minor), 16.5 min (major).

Ethyl (4S)-4-[hexylthio]-hept-2E-6-dienoate (11f):

SHex

CO2Et

The organocatalysis/olefination of 4-pentenal (73 µl, 0.74 mmol) upon chromatography

(petrol/EtOAc 40:1) yielded the title compound (146 mg, 73 %) as a colourless oil, [α]27

D

-62.0 (c 2.0 CH2Cl2); νmax(film)/cm-1

2956, 2927, 2857, 1721, 1648, 1465, 1267, 1220,

1159, 1042, 981, 918, 728; δH (400 MHz, CDCl3) 7.76 (1H, d, J15.5, CH=CH), 6.73,

(1H, dd, J15.5, 9.7, CHSCH), 5.80 (1H, m, CH2=CH), 5.14-5.09 (2H, m, CH=CH2), 4.22

(2H, q, J7.1, OCH2CH3), 3.33 (1H, m, CHS), 2.45-2.40 (4H, m, CH2CHS, SCH2), 1.55

S12

(2H, m, CH2CH2S), 1.45-1.20 (6H, m, CH3CH2CH2CH2), 1.32 (3H, t, J7.1, OCH2CH3),

0.90 (3H, t, J7.0, CH3CH2); δC (400 MHz, CDCl3) 166.2 (C), 147.6 (CH), 134.3 (CH),

120.9 (CH), 117.7 (CH2), 60.5 (CH2), 46.3 (CH), 38.1 (CH2), 31.4 (CH2), 30.7 (CH2),

29.3 (CH2), 28.6 (CH2), 22.5 (CH2), 14.2 (CH3), 14.0 (CH3). m/z (CI) 288 (MNH4+ 95

%), 271 (MH+ 100 %); Found: MH

+, 271.1733. C15H27O2S requires: 271.1732. Chiral

HPLC: Flow rate 0.6 mL/min; hexane:IPA 0.5 %; 30 °C, chiral AS-H; detection at 254

nm gave ee of 90 %. Retention time 13.0 min (minor), 15.7 min (major).

Ethyl (4S)-4-[hexylthio]-6-[(tert-butyldimethylsilyl)oxy]-hex-2E-enoate (11g):

TBDMSO CO2Et

SHex

The organocatalysis/olefination of 4-[(tert-butyldimethylsilyl)oxy]butyraldehyde (226

mg, 1.12 mmol) upon chromatography (petrol/EtOAc 40:1) yielded the title compound

(269 mg, 62 %) as a colourless oil, [α]25


2961,

2931, 2860, 1713, 1650, 1470, 1262, 1228, 1165, 1097, 909, 734; δH (400 MHz, CDCl3)

6.75, (1H, dd, J15.5, 9.7, CHSCH), 5.75 (1H, d, J15.5, CH=CH), 4.22 (2H, q, J7.2,

OCH2CH3), 3.75 (2H, m, CH2OSi), 3.45 (1H, m, CHS), 2.45 (2H, m, SCH2), 1.82 (2H,

m, CH2CHS), 1.55 (2H, m, SCH2CH2), 1.45-1.21 (6H, m, CH3CH2CH2CH2), 1.32 (3H, t,

J7.2, OCH2CH3), 0.90 (12H, s, CH3CH2, C(CH3)3), 0.06 (6H, s, Si(CH3)2); δC (400 MHz,

CDCl3) 166.3 (C), 148.1 (C), 120.6 (CH), 60.4 (CH2), 60.0 (CH2), 43.0 (CH), 36.6 (CH2),

31.4 (CH2), 30.6 (CH2), 29.4 (CH2), 28.6 (CH2), 25.9 (CH3), 22.5 (CH2), 18.2 (C), 14.3

(CH3), 14.0 (CH3), -5.4 (CH3); m/z (CI) 406 (MNH4+ 100 %), 389 (MH 35 %); Found:

MH+, 389.2556. C20H41O3SSi requires: 389.2546. Chiral HPLC: Flow rate 0.2 mL/min;

hexane:IPA 1 %; 30 °C, chiral OD-H; detection at 254 nm gave ee of 93 %. Retention

time 15.6 min (minor), 18.3 min (minor).

S13

Preparation of (S)-tert-Butoxycarbonyl-N-hexylsulfenamides:

Oxaziridine was prepared according to the literature procedure.[3]

General procedure for the preparation of (S)-N-tert-Butoxycarbonyl-N-

hexylsulfenamides:

To a stirred solution of oxaziridine (1.05 eq) in CH2Cl2 (0.18 M) at – 78 oC was added

allylic sulfide (1.0 eq) in CH2Cl2 (0.16 M) dropwise. The resulting solution was allowed

to warm to room temperature over 30 min, after which time the solvent was removed

under reduced pressure. Column chromatography on silica afforded the sulfenamide

products. Data for the products are given below. Racemic material for chiral HPLC

comparison was also prepared by this route.

Methyl (2S)-[N-tert-Butoxycarbonylhexylsulfenamide]-pent-3E-enoate (12a):

CO2Me

NBocHexS

Rearrangement of methyl (4S)-4-[hexylthio]-pent-2E-enoate (26.7 mg, 0.12 mmol) upon

chromatography (petrol/EtOAc 20:1) yielded the title compound (31.6 mg, 79 %) as a


D -33.0 (c 2.0 CHCl3); δH (400 MHz, CDCl3) 5.77-5.72, (2H, m,

CH=CH), 4.84 (1H, br s, CHN), 4.17 (2H, q, J7.1, OCH2CH3), 2.81 (2H, m, SCH2), 2.12

(2H, m, CHCH2), 1.58 (2H, m, CH2CH2S), 1.46 (9H, s, C(CH3)3), 1.41-1.24 (6H, m,

CH3CH2CH2CH2), 1.26 (3H, t, J7.1, OCH2CH3), 1.02 (3H, t, J7.5, CH3CH2CH), 0.88

(3H, t, J6.8, CH3CH2). Chiral HPLC: Flow rate 1.0 mL/min; hexane; 30 °C, chiral AD-H;

detection at 215 nm gave ee of 93 %. Retention time 19.7 min (minor), 24.5 min (major).

Data in agreement with literature values.[2]

S14

Ethyl (2S)-[N-tert-Butoxycarbonylhexylsulfenamide]-hex-3E-enoate (12b):

CO2Et

NBocHexS

Rearrangement of ethyl (4S)-4-[hexylthio]-hex-2E-enoate (60 mg, 0.23 mmol) upon


colourless oil, [α]24D +10.7 (c 0.46 CH2Cl2); νmax(film)/cm-1 2977, 2965, 2935, 1746,

1698, 1459, 1367, 1292, 1253, 1161, 1028, 966, 772; δH (400 MHz, CDCl3) 5.77-5.72,

(2H, m, CH=CH), 4.84 (1H, br s, CHN), 4.17 (2H, q, J7.1, OCH2CH3), 2.81 (2H, m,

SCH2), 2.12 (2H, m, CHCH2), 1.58 (2H, m, CH2CH2S), 1.46 (9H, s, C(CH3)3), 1.41-1.24

(6H, m, CH3CH2CH2CH2), 1.26 (3H, t, J7.1, OCH2CH3), 1.02 (3H, t, J7.5, CH3CH2CH),

0.88 (3H, t, J6.8, CH3CH2); δC (400 MHz, CDCl3) 170.7 (C), 156.5 (C), 138.3 (CH),

123.0 (CH), 81.9 (C), 67.6 (CH), 61.2 (CH2), 38.7 (CH2), 31.5 (CH2), 28.6 (CH2), 28.1

(CH3), 27.3 (CH2), 25.5 (CH2), 22.5 (CH2), 14.1 (CH3), 14.0 (CH3), 13.1 (CH3); m/z (CI)

391 (MNH4+ 40 %), 374 (MH

+ 100 %); Found: MH

+, 374.2375. C19H36NO4S requires:

374.2370. Chiral HPLC: Flow rate 0.2 mL/min; hexane:IPA 1 %; 30 °C, chiral AD;

detection at 215 nm gave ee of 93%. Retention time 22.3 min (minor), 33.2 min (major).

Ethyl (2S)-[N-tert-Butoxycarbonylhexylsulfenamide]-5-methylhex-3E-enoate (12d):

CO2Et

NHexS Boc

Rearrangement of ethyl (4S)-4-[hexylthio]-5-methylhex-2E-enoate (17.8 mg, 0.07 mmol)

upon chromatography (petrol/EtOAc 20:1) yielded the title compound (20 mg, 81 %) as a

colourless oil, [α]24D +16.7 (c 0.36 CH2Cl2); νmax(film)/cm-1 2959, 2931, 2872, 1746,

1701, 1463, 1367, 1294, 1262, 1027, 970, 772; δH (400 MHz, CDCl3) 5.74-5.71, (2H, m,

CH=CH), 4.86 (1H, br s, CHN), 4.18 (2H, q, J7.1, OCH2CH3), 2.81 (2H, m, SCH2), 2.40

(1H, m, CH(CH3)2), 1.60 (2H, m, CH2CH2S), 1.48 (9H, s, C(CH3)3), 1.46-1.25 (6H, m,

S15

CH3CH2CH2CH2), 1.27 (3H, t, J7.1, OCH2CH3), 1.04 (6H, d, J6.7, CH(CH3)2), 0.90 (3H,

t, J6.8, CH3CH2); δC (400 MHz, CDCl3) 170.8 (C), 157.9 (C), 143.5 (CH), 121.2 (CH),

81.9 (C), 67.6 (CH), 61.2 (CH2), 39.3 (CH2), 31.5 (CH2), 31.0 (CH), 28.6 (CH2), 28.1

(CH3), 27.3 (CH2), 22.5 (CH2), 22.1 (CH3), 21.9 (CH3), 14.1 (CH3), 14.0 (CH3); m/z (CI)

388 (MH+ 48 %), 349 (MNH4

+ -tBu 100 %); Found: MH

+, 388.2521. C20H38NO4S

requires: 388.2522. Chiral HPLC: Flow rate 1.0 mL/min; hexane:IPA 1 %; 30 °C, chiral

AD-H; detection at 215 nm gave ee of 91 %. Retention time 5.6 min (minor), 8.6 min

(major).

Ethyl (2S)-[N-tert-Butoxycarbonylhexylsulfenamide]-5-phenylpent-3E-enoate (12e):

Bn CO2Et

NBocHexS

Rearrangement of ethyl (4S)-4-[hexylthio]-5-phenylpent-2E-enoate (39.6 mg, 0.12 mmol)

upon chromatography (petrol/EtOAc 20:1) yielded the title compound (45.8 mg, 85 %) as

a colourless oil, [α]24

D +12.4 (c 1.13 CH2Cl2); νmax(film)/cm-1

2977, 2930, 2858, 1745,

1723, 1698, 1454, 1367, 1291, 1253, 1159, 968, 771; δH (400 MHz, CDCl3) 7.30-7.17

(5H, m, ArH), 5.92-5.82, (2H, m, CH=CH), 4.89 (1H, br s, CHN), 4.19 (2H, m,

OCH2CH3), 3.45 (2H, d, J4.5, CH2C), 2.76 (2H, m, SCH2), 1.59-1.25 (8H, m,

CH3CH2CH2CH2CH2), 1.45 (9H, s, C(CH3)3), 1.27 (3H, t, J7.1, OCH2CH3), 0.89 (3H, t,

J6.9, CH3CH2); δC (400 MHz, CDCl3) 170.5 (C), 139.5 (C), 134.9 (CH), 128.6 (CH),

128.5 (CH), 126.2 (CH), 125.6 (CH), 82.0 (C), 77.2 (CH), 61.4 (CH2), 39.3 (CH2), 38.8

(CH2), 31.5 (CH2), 28.6 (CH2), 28.1 (CH3), 27.3 (CH2), 22.6 (CH2), 14.2 (CH3), 14.1

(CH3) (one carbon missing); m/z (CI) 453 (MNH4+ 22 %), 397 (MNH4

+ -tBu 100 %), 336

(MH+ -Boc 42%); Found: MH+, 436.2519. C24H38NO4S requires: 436. 2522. Chiral

HPLC: Flow rate 1.0 mL/min; hexane:IPA 1 %; 30 °C, chiral AD-H; detection at 215 nm

gave ee of 87 %. Retention time 11.1 min (minor), 12.7 min (major).

S16

Ethyl (2S)-[N-tert-Butoxycarbonylhexylsulfenamide]-hept-3E,6-dienoate (12f):

CO2Et

NHexS Boc

Rearrangement of ethyl (4S)-4-[hexylthio]-hept-2E-6-dienoate (75 mg, 0.28 mmol) upon


colourless oil, [α]19D +6.9 (c 1.5 CH2Cl2); νmax(film)/cm-1 2979, 2959, 2930, 2859, 1746,

1701, 1457, 1368, 1293, 1254, 1162, 1027, 969, 771; δH (400 MHz, CDCl3) 5.89-5.76,

(3H, m, CH=CH, CH2=CH), 5.11-5.04 (2H, m, CH2=CH), 4.90 (1H, br s, CHN), 4.20

(2H, q, J7.1, OCH2CH3), 2.89-2.73 (4H, m, CHCH2CH, SCH2), 1.59 (2H, m, CH2CH2S),

1.48 (9H, s, C(CH3)3), 1.46-1.26 (6H, m, CH3CH2CH2CH2), 1.30 (3H, t, J7.1,

OCH2CH3), 0.90 (3H, t, J6.8, CH3CH2); δC (400 MHz, CDCl3) 170.5 (C), 156.0 (C),

135.8 (CH), 134.0 (CH), 125.2 (CH), 115.9 (CH2), 82.0 (C), 67.6 (CH), 61.3 (CH2), 39.3

(CH2), 36.4 (CH2), 31.5 (CH2), 28.6 (CH2), 28.1 (CH3), 27.3 (CH2), 22.5 (CH2), 14.1

(CH3), 14.0 (CH3); m/z (CI) 386 (MH+ 23 %), 347 (MNH4

+ -tBu 100 %); Found: MH

+,

386.2368. C20H36NO4S requires: 386.2365. Chiral HPLC: Flow rate 1.0 mL/min;


time 5.2 min (minor), 8.6 min (major).

Ethyl(2S)-[N-tert-Butoxycarbonylhexylsulfenamide]-6-[(tert-butyldimethylsilyl)oxy]-

hex-3E-enoate (12g):

CO2Et

NBocHexS

TBDMSO

Rearrangement of ethyl (4S)-4-[hexylthio]-6-[(tert-butyldimethylsilyl)oxy]-hex-2E-

enoate (59.8 mg, 154 mmol) upon chromatography (petrol/EtOAc 40:1) yielded the title

compound (62.8 mg, 81 %) as a colourless oil, [α]19

D +10.2 (c 2.2 CH2Cl2);

νmax(film)/cm-1

2978, 2929, 1746, 1698, 1462, 1384, 1369, 1281, 1257, 1157, 1098, 969,

S17

836, 778; δH (400 MHz, CDCl3) 5.90-5.73 (2H, m, CH=CH), 4.87 (1H, br d, J5.6, CHN),

4.20 (2H, q, J7.1, OCH2CH3), 3.70 (2H, t, J7.0, OCH2CH2), 2.85 (2H, m, SCH2), 2.36

(2H, m, OCH2CH2), 1.58 (2H, m, CH2CH2S), 1.52-1.26 (6H, m, CH3CH2CH2CH2), 1.49

(9H, s, C(CH3)3), 1.29 (3H, t, J7.1, OCH2CH3), 0.90 (12H, s, CH3CH2, C(CH3)3), 0.08

(6H, s, Si(CH3)2); δC (400 MHz, CDCl3) 170.5 (C), 157.1 (C), 133.1 (CH), 125.8 (CH),

81.9 (C), 67.8 (CH), 62.6 (CH2), 61.3 (CH2), 39.3 (CH2), 36.1 (CH2), 31.6 (CH2), 28.6

(CH2), 28.1 (CH3), 27.3 (CH2), 22.5 (CH2), 18.3 (C), 14.14 (CH3), 14.05 (CH3); m/z (CI)

521 (MNH4+ 73 %), 465 (MNH4

+ -tBu 100 %); Found: MNH4

+, 521.3447.

C25H53N2O5SSi requires: 521.3444. Chiral HPLC: Flow rate 0.2 mL/min; hexane:IPA 1

%; 30 °C, chiral OJ-H; detection at 254 nm gave ee of 91 %. Retention time 16.8 min


S18

Preparation of S-hexyl (Z)-allylic sulfides:

General procedure for the preparation of enantioenriched S-hexyl (Z)-allylic

sulfides:



and aldehyde (1 eq) in toluene (1.5 M) and stirred at room temperature for 5 hours before

cooling to -78 oC. A pre-mixed solution of nBuLi (1.5 eq) and ethyl

diphenylphosphonoacetate (1.5 eq) in dichloromethane (0.3 M) at -78 oC was added to

the organocatalytic reaction mixture. After stirring at -78 oC for 1 hour the solution was

quenched with NH4Cl(sat), extracted (dichloromethane), dried (MgSO4) and concentrated

in vacuo. Column chromatography on silica afforded the allylic sulfide products. Data for

the products are given below. Samples of racemic material for chiral HPLC comparison

were also prepared by modifications of literature routes

Ethyl (4S)-4-[hexylthio]-hex-2Z-enoate ((Z)-(11b)):

HexS CO2Et

The organocatalysis/olefination of butanal (39 µl, 0.43 mmol) upon chromatography

(petrol/EtOAc 40:1) yielded the title compound (71 mg, 64 %) as a colourless oil, [α]28D

+79.1 (c 1.0 CH2Cl2); νmax(film)/cm-1 2961, 2929, 2873, 2858, 1719, 1637, 1460, 1204,

1160, 1032, 832, 727; δH (400 MHz, CDCl3) 5.97, (1H, t, J11.2, CHCHCO), 5.82 (1H, d,

J11.2 CHCHCO), 4.69 (1H, m, CHS), 4.17 (2H, q, J7.1, OCH2CH3), 2.45 (2H, m, SCH2),

1.75-1.48 (4H, m, CH2CH2S, CH3CH2CHS), 1.44-1.20 (6H, m, CH3CH2CH2CH2) 1.31

(3H, t, J7.1, OCH2CH3), 1.00 (3H, t, J7.4, CH3CH2CHS), 0.89 (3H, t, J6.9, CH3CH2); δC

(400 MHz, CDCl3) 166.5 (C), 149.9 (CH), 118.9 (CH), 60.0 (CH2), 43.0 (CH), 31.4

(CH2), 30.8 (CH2), 29.7 (CH2), 28.7 (CH2), 27.5 (CH2), 22.6 (CH2), 14.2 (CH3), 14.0

S19

(CH3), 11.7 (CH3); m/z (CI) 276 (MNH4+ 90 %), 259 (MH

+ 98 %); Found: MH

+,

259.1737. C14H27O2S requires: 259.1732. Chiral HPLC: Flow rate 0.4 mL/min; hexane;



Ethyl (4S)-4-[hexylthio]-hept-2Z-6-dienoate ((Z)-(11f)):

HexS CO2Et

The organocatalysis/olefination of 4-pentenal (50 µl, 0.50 mmol) upon chromatography

(petrol/EtOAc 40:1) yielded the title compound (98.7 mg, 73 %) as a colourless oil,

[α]27D +123.6 (c 2.3 CH2Cl2); νmax(film)/cm-1 2957, 2929, 2858, 1720, 1640, 1465, 1412,

1260, 1205, 1177, 1031, 917, 829; δH (400 MHz, CDCl3) 5.98, (1H, t, J11.1, CHSCH),

5.85-5,78 (2H, m, CH2=CH, CH=CH), 5.13-5.08 (2H, m, CH2=CH), 4.83 (1H, m, CHS),

4.16 (2H, q, J7.1, OCH2CH3), 2.55-2.25 (4H, m, CH2CHS, SCH2), 1.56 (2H, m,

CH2CH2S), 1.40-1.23 (6H, m, CH3CH2CH2CH2), 1.30 (3H, t, J7.1, OCH2CH3), 0.89 (3H,

t, J6.9, CH3CH2); δC (400 MHz, CDCl3) 166.3 (C), 149.2 (CH), 134.5 (CH), 118.9 (CH),

117.2 (CH2), 60.1 (CH2), 40.9 (CH), 38.6 (CH2), 31.4 (CH2), 30.9 (CH2), 29.6 (CH2),

28.7 (CH2), 22.5 (CH2), 14.2 (CH3), 14.0 (CH3); m/z (CI) 288 (MNH4+ 100 %), 271 (MH

+

82 %); Found: MH+, 271.1733. C15H27O2S requires: 271.1732. Chiral HPLC: Flow rate

1.0 mL/min; hexane; 30 °C, chiral OD-H; detection at 254 nm gave ee of 92 %. Retention

time 10.3 min (major), 12.5 min (minor).

S20

Preparation of (R)-N-tert-Butoxycarbonyl-N-hexylsulfenamides:

General procedure for the preparation of (R)-N-tert-Butoxycarbonyl-N-

hexylsulfenamides (Same as described previously):

To a stirred solution of oxaziridine (1.05 eq) in CH2Cl2 (0.18 M) at – 78 oC was added

allylic sulfide (1.0 eq) in CH2Cl2 (0.16 M) dropwise. The resulting solution was allowed

to warm to room temperature over 30 min, after which time the solvent was removed

under reduced pressure. Column chromatography on silica afforded the sulfenamide

products. Data for the products are given below.

Ethyl (2R)-[N-tert-Butoxycarbonylhexylsulfenamide]-hex-3E-enoate (12b):

CO2Et

NBocHexS

Rearrangement of ethyl (4S)-4-[hexylthio]-hex-2Z-enoate (20 mg, 0.08 mmol) upon



D -11.9 (c 0.55 CH2Cl2); Chiral HPLC: Flow rate 0.2 mL/min;

hexane:IPA 1 %; 30 °C, chiral AD; detection at 215 nm gave ee of 93%. Retention time

19.8 min (major), 31.6 min (minor). (Other data correspond to that of racemic sample).

Ethyl (2R)-[N-tert-Butoxycarbonylhexylsulfenamide]-hept-3E,6-dienoate (12f):

CO2Et

NHexS Boc

Rearrangement of ethyl (4S)-4-[hexylthio]-hept-2Z-6-dienoate (45 mg, 0.168 mmol) upon



D -10.7 (c 1.1 CH2Cl2). Chiral HPLC: Flow rate 1.0 mL/min;

S21


time 5.7 min (major), 10.9 min (minor). (Other data correspond to that of racemic

sample).

S22

Preparation of N-Boc protected vinyl glycine derivatives:

General procedure for desulfurisation of N-tert-Butoxycarbonylhexylsulfenamides:

Triethylphosphite (1.5 eq) was added to N-tert-Butoxycarbonyl-N-hexylsulfenamide (1

eq) and triethylamine (5 eq) in dichloromethane (0.10 M) and the resulting solution was

stirred at room temperature for 1 hour, after which time the solvent was removed under

reduced pressure. Column chromatography on silica afforded the vinyl glycine

derivatives. Data for the products are given below.

General procedure for one-pot amination/rearrangement-desulfurisation of allylic

sulfides:

The allylic sulfide (1.0 eq) in CH2Cl2 (0.16 M) was added dropwise to a stirred solution

of oxaziridine (1.05 eq) in CH2Cl2 (0.18 M) at – 78 oC and allowed to warm to room

temperature over one hour. Triethylamine (5 eq) and triethylphosphite (1.5 eq) were

added and the solution was stirred at room temperature for 1 hour before the solvent was

removed under reduced pressure. Column chromatography on silica afforded the vinyl

glycine derivatives. Data for the products are given below.

Methyl 2-[N-tert-Butoxycarbonyl]-pent-3E-enoate (13a):

CO2Me

HNBoc

Desulfurisation of methyl 2-[N-tert-Butoxycarbonylhexylsulfenamide]-pent-3E-enoate

(38 mg, 0.11 mmol) upon chromatography (petrol/EtOAc 20:1) yielded the title

compound (21.9 mg, 88 %) as a colourless oil, δH (400 MHz, CDCl3) 5.77 (1H, ddq,

J15.1, 6.5, 1.4, CH=CHCH), 5.44 (1H, br dd, J15.1, 5.3, CH=CHCH), 5.16 (1H, br s,

NH), 4.74 (1H, br s, CHNH), 3.74 (3H, s, OCH3), 1.69 (3H, ddd, J6.5, 1.5, 1.4,

CH3CH=CH), 1.42 (9H, s, C(CH3)3). Data in agreement with literature values.[2]

S23

One-pot amination/rearrangement-N-S bond cleavage of methyl 4-[hexylthio]-pent-2E-

enoate (47 mg, 0.20 mmol) upon chromatography (petrol/EtOAc 20:1) yielded the title

compound (39.8 mg, 85 %) as a colourless oil.

Ethyl 2-[N-tert-Butoxycarbonyl]-5-methylhex-3E-enoate (13c):

CO2Et

HNBoc

Desulfurisation of ethyl 2-[N-tert-Butoxycarbonylhexylsulfenamide]-5-methylhex-3E-


compound (13.2 mg, 94 %) as a colourless oil, νmax(film)/cm-1

3436, 3355, 2966, 2932,

2872, 1742, 1716, 1509, 1465, 1249, 1168, 1054, 1025, 971, 915, 730; δH (400 MHz,

CDCl3) 5.75 (1H, dd, J15.4, 8.0, CH=CHCHNH), 5.42 (1H, br dd, J15.4, 5.6,

CH=CHCHNH), 5.12 (1H, br s, NH), 4.73 (1H, br s, CH=CHCH), 4.21 (2H, q, J7.1,

OCH2CH3), 2.3 (1H, m, CH(CH3)2), 1.45 (9H, s, C(CH3)3), 1.27 (3H, t, J7.1, OCH2CH3),

0.99 (6H, d, J8.0, (CH3)2); δC (400 MHz, CDCl3) 171.9 (C), 154.1 (C), 141.6 (CH), 122.0

(CH), 80.1 (C), 61.8 (CH2), 55.7 (CH2), 31.2 (CH), 28.7 (CH3), 22.4 (CH3), 14.5 (CH3);

m/z (CI) 272 (MH+ 100 %); Found: MH

+, 272.1862. C14H26NO4 requires: 272.1862.

One-pot amination/rearrangement-N-S bond cleavage of ethyl 4-[hexylthio]-5-methylhex-

2E-enoate (35 mg, 0.128 mmol) upon chromatography (petrol/EtOAc 20:1) yielded the

title compound (27.2 mg, 78 %) as a colourless oil.

S24

Ethyl 2-[N-tert-Butoxycarbonyl]-5-phenylpent-3E-enoate (13e):

Bn CO2Et

HNBoc

Desulfurisation of ethyl 2-[N-tert-Butoxycarbonylhexylsulfenamide]-5-phenylpent-3E-


compound (13.8 mg, 94 %) as a colourless oil, νmax(film)/cm-1 3436, 3382, 2987, 2933,

2872, 1743, 1709, 1496, 1452, 1369, 1165, 1065, 1025, 911, 734; δH (400 MHz, CDCl3)

7.33-7.13 (5H, m, ArH), 5.93 (1H, dt, J15.4, 8.0, CH=CHCH), 5.55 (1H, br dd, J15.4,

5.6, CH=CHCH), 5.15 (1H, br s, NH), 4.81 (1H, br s, CH=CHCH), 4.21 (2H, q, J7.1,

OCH2CH3), 3.39 (2H, d, J8.0, CH2C), 1.43 (9H, s, C(CH3)3), 1.26 (3H, t, J7.1,

OCH2CH3); δC (400 MHz, CDCl3) 171.8 (C), 155.2 (C), 139.8 (C), 133.2 (CH), 129.0

(CH), 128.9 (CH), 126.7 (CH), 126.5 (CH), 80.5 (C), 62.0 (CH2), 55.7 (CH), 38.8 (CH2),

28.7 (CH3), 14.5 (CH3); m/z (CI) 320 (MH+ 100 %); Found: MH+, 320.1863. C18H26NO4

requires: 320.1862.

One-pot amination/rearrangement-N-S bond cleavage of ethyl 4-[hexylthio]-5-

phenylpent-2E-enoate (50 mg, 0.16 mmol) upon chromatography (petrol/EtOAc 30:1)

yielded the title compound (40.4 mg, 81 %) as a colourless oil.

Ethyl 2-[N-tert-Butoxycarbonyl]-hept-3E,6-dienoate (13f):

CO2Et

HNBoc

Desulfurisation of ethyl 2-[N-tert-Butoxycarbonylhexylsulfenamide]-hept-3E,6-dienoate

(25 mg, 0.06 mmol) upon chromatography (petrol/EtOAc 20:1) yielded the title

compound (16.0 mg, 92 %) as a colourless oil, νmax(film)/cm-1

3436, 3363, 2980, 2933,

1739, 1712, 1499, 1368, 1252, 1168, 1055, 914, 731; δH (400 MHz, CDCl3) 5.84-5.74,

S25

(2H, m, CH=CHCH, CH2=CH), 5.51 (1H, br dd, J15.6, 5.2, CH=CHCH), 5.14 (1H, br s,

NH), 5.07-4.99 (2H, m, CH2=CH), 4.79 (1H, br s, CHNH), 4.21 (2H, q, J7.1, OCH2CH3),

2.80 (2H, m, CHCH2CH), 1.45 (9H, s, C(CH3)3), 1.28 (3H, t, J7.1, OCH2CH3); δC (400

MHz, CDCl3) 171.6 (C), 155.4 (C), 136.1 (CH), 126.6 (CH), 125.7 (CH), 116.4 (CH2),

80.4 (C), 62.0 (CH2), 56.1 (CH), 37.0 (CH2), 28.7 (CH3), 14.5 (CH3); m/z (CI) 270 (MH+

100 %); Found: MH+, 270.1698. C14H24NO4 requires: 270.1705; Chiral HPLC: Flow rate

1.0 mL/min; hexane:IPA 1 %; 30 °C, chiral AD-H; detection at 215 nm. Retention time

17.0 min, 25.1 min. Integration of peaks indicated a racemic mixture.

One-pot amination/rearrangement-N-S bond cleavage of ethyl-4-[hexylthio]-hept-2E-6-

dienoate (40 mg, 0.15 mmol) upon chromatography (petrol/EtOAc 20:1) yielded the title

compound (32.3 mg, 81 %) as a colourless oil.

Ethyl (2S)-[N-tert-Butoxycarbonyl]-hept-3E,6-dienoate (13f):

CO2Et

HNBoc

One-pot amination/rearrangement-N-S bond cleavage of ethyl (4S)-4-[hexylthio]-hept-

2E-6-dienoate (38 mg, 0.14 mmol) upon chromatography (petrol/EtOAc 20:1) yielded the

title compound (31.0 mg, 82 %) as a colourless oil, [α]26

D +8.0 (c 0.5 CH2Cl2). Chiral

HPLC: Flow rate 1.0 mL/min; hexane:IPA 1 %; 30 °C, chiral AD-H; detection at 215 nm

gave ee of 93 %. Retention time 17.4 min (minor), 26.5 min (major). (Other data

correspond to that of racemic sample).

S26

Ethyl 2-[N-tert-Butoxycarbonyl]-6-[(tert-butyldimethylsilyl)oxy]-hex-3E-enoate

(13g):

CO2Et

HNBoc

TBDMSO

Desulfurisation of ethyl 2-[N-tert-Butoxycarbonylhexylsulfenamide]-6-[(tert-

butyldimethylsilyl)oxy]-hex-3E-enoate (60 mg, 0.12 mmol) upon chromatography

(petrol/EtOAc 20:1) yielded the title compound (34.7 mg, 75 %) as a colourless oil,

νmax(film)/cm-1

3430, 3361, 2976, 2931, 1747, 1722, 1504, 1368, 1258, 1163, 1097, 970,

836, 778; δH (400 MHz, CDCl3) 5.79 (1H, dt, J15.4, 6.8, CH2CH=CH), 5.57 (1H, br dd,

J15.4, 5.2, CH=CHCH), 5.15 (1H, br d, J6.8, NH), 4.81 (1H, br s, CHNH), 4.23 (2H, m,

OCH2CH3), 3.66 (2H, t, J6.8, CH2OSi), 2.29 (2H, m, OCH2CH2), 1.47 (9H, s,

OC(CH3)3), 1.30 (3H, t, J7.0, OCH2CH3), 0.91 (9H, s, SiC(CH3)3), 0.06 (6H, s,

Si(CH3)2); δC (400 MHz, CDCl3) 171.3 (C), 155.0 (C), 130.7 (CH), 125.4 (CH), 79.9 (C),

62.4 (CH2), 61.5 (CH2), 55.3 (CH), 35.8 (CH2), 28.3 (CH3), 25.9 (CH3), 18.3 (C), 14.1

(CH3), -5.3 (CH3); m/z (CI) 405 (MNH4+ 72 %), 388 (MH+ 20 %), 349 (MNH4

+ -tBu 100

%); Found: MH+, 388.2527. C19H38NO5Si requires: 388.2519.

One-pot amination/rearrangement-N-S bond cleavage of 4-[hexylthio]-6-[(tert-

butyldimethylsilyl)oxy]-hex-2E-enoate (43 mg, 0.11 mmol) upon chromatography

(petrol/EtOAc 20:1) yielded the title compound (34.7 mg, 84 %) as a colourless oil.

S27

References:

[1] M. Marigo, T. C. Wabnitz, D. Fielenbach, K. A. Jorgensen, Angew. Chem. Int.

Ed. 2005, 44, 794.

[2] A. Armstrong, L. Challinor, R. S. Cooke, J. H. Moir, N. J. Treweeke, J. Org.

Chem. 2006, 71, 4028.

[3] A. Armstrong, L. H. Jones, J. D. Knight, R. D. Kelsey, Org. Lett. 2005, 7, 713.

S28

N

NN SHex

8b

S29

N

NN SHex

8b

S30

SHex

OH

10b

S31

SHex

OH

10b

S32

(+/-)10b-(S)-MTPA

SHex

O(S)-MTPA

S33

10b-(S)-MTPA

SHex

O(S)-MTPA

S34

SHex

CO2Me

(+/-)-11a

S35

SHex

CO2Me

11a

S36

11b

SHex

CO2Et

S37

11b

SHex

CO2Et

S38

(+/-) 11b

SHex

CO2Et

S39

11b

SHex

CO2Et

S40

SHex

11c

CO2Et

S41

SHex

11c

CO2Et

S42

SHex

(+/-)-11c

CO2Et

S43

SHex

11c

CO2Et

S44

HexS

11d

CO2Et

S45

HexS

11d

CO2Et

S46

HexS

(+/-)-11d

CO2Et

S47

HexS

11d

CO2Et

S48

HexS

Bn

11e

CO2Et

S49

HexS

Bn

11e

CO2Et

S50

HexS

Bn

(+/-)-11e

CO2Et

S51

HexS

Bn

11e

CO2Et

S52

HexS

11f

CO2Et

S53

HexS

11f

CO2Et

S54

HexS

(+/-)-11f

CO2Et

S55

HexS

11f

CO2Et

S56

TBDMSO

SHex

CO2Et

11g

S57

TBDMSO

SHex

CO2Et

11g

S58

TBDMSO

SHex

CO2Et

(+/-)-11g

S59

TBDMSO

SHex

CO2Et

11g

S60

CO2Me

NBocHexS

(+/-)-12a

S61

CO2Me

NBocHexS

(R)-12a

S62

(R)-12b

CO2Et

NBocHexS

S63

(R)-12b

CO2Et

NBocHexS

S64

(+/-)-12b

CO2Et

NBocHexS

S65

(R)-12b

CO2Et

NBocHexS

S66

(R)-12c

CO2Et

NHexS Boc

S67

(R)-12c

CO2Et

NHexS Boc

S68

(+/-)-12c

CO2Et

NHexS Boc

S69

(R)-12c

CO2Et

NHexS Boc

S70

NBoc

CO2Et

(R)-12e

HexS

Bn

S71

NBoc

CO2Et

(R)-12e

HexS

Bn

S72

NBoc

CO2Et

(+/-)-12e

HexS

Bn

S73

NBoc

CO2Et

(R)-12e

HexS

Bn

S74

NBoc

CO2Et

(R)-12f

HexS

S75

NBoc

CO2Et

(R)-12f

HexS

S76

NBoc

CO2Et

(+/-)-12f

HexS

S77

NBoc

CO2Et

(R)-12f

HexS

S78

CO2Et

NBocHexS

TBDMSO

12g

S79

CO2Et

NBocHexS

TBDMSO

12g

S80

CO2Et

NBocHexS

TBDMSO

(+/-)-12g

S81

CO2Et

NBocHexS

TBDMSO

(R)-12g

S82

(Z)-11b

HexS CO2Et

S83

(Z)-11b

HexS CO2Et

S84

(Z)-(+/-)-11b

HexS CO2Et

S85

(Z)-11b

HexS CO2Et

S86

HexS CO2Et

(Z)-12f

S87

HexS CO2Et

(Z)-12f

S88

HexS

(Z)-(+/-)-12f

CO2Et

S89

HexS

(Z)-12f

CO2Et

S90

NBoc

CO2Et

(R)-12b

HexS

S91

NBoc

CO2Et

(R)-12f

HexS

S92

CO2Et

HNBoc

13c

S93

CO2Et

HNBoc

13c

S94

Bn CO2Et

HNBoc

13e

S95

Bn CO2Et

HNBoc

13e

S96

CO2Et

HNBoc

13f

S97

CO2Et

HNBoc

13f

S98

(+/-)-13f

CO2Et

HNBoc

S99

13f

CO2Et

HNBoc

S100

CO2Et

HNBoc

TBDMSO

(+/-)-13g

S101

CO2Et

HNBoc

TBDMSO

(+/-)-13g

69451 weinheim, germany - wiley-vch · column chromatography on silica afforded the allylic sulfide...

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