69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide...
Transcript of 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide...
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Supporting Information
© Wiley-VCH 2007
69451 Weinheim, Germany
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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)
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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.
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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.
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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.
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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 %.
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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.
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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.
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S8
Preparation of S-hexyl (E)-allylic sulfides:
General procedure for the preparation of enantioenriched S-hexyl (E)-allylic
sulfides:
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 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]
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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
chromatography (petrol/EtOAc 40:1) yielded the title compound (139 mg, 70 %) as a
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,
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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
chromatography (petrol/EtOAc 40:1) yielded the title compound (92 mg, 61 %) as a
colourless oil, [α]24
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).
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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
chromatography (petrol/EtOAc 40:1) yielded the title compound (128 mg, 64 %) as a
colourless oil, [α]28
D -18.5 (c 0.6 CH2Cl2); νmax(film)/cm-1
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 %;
30 °C, chiral OD-H; detection at 254 nm gave ee of 88 %. Retention time 13.6 min
(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
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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
D -38.8 (c 3.0 CH2Cl2); νmax(film)/cm-1
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).
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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
colourless oil, [α]25
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]
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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
chromatography (petrol/EtOAc 20:1) yielded the title compound (69 mg, 79 %) as a
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,
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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).
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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
chromatography (petrol/EtOAc 20:1) yielded the title compound (93 mg, 87 %) as a
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;
hexane:IPA 1 %; 30 °C, chiral AD-H; detection at 215 nm gave ee of 89 %. Retention
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,
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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
(minor), 19.3 min (major).
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S18
Preparation of S-hexyl (Z)-allylic sulfides:
General procedure for the preparation of enantioenriched S-hexyl (Z)-allylic
sulfides:
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 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
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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;
30 °C, chiral OD-H; detection at 215 nm gave ee of 93 %. Retention time 31.5 min
(minor), 36.9 min (major).
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).
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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
chromatography (petrol/EtOAc 20:1) yielded the title compound (23.7 mg, 82 %) as a
colourless oil, [α]26
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
chromatography (petrol/EtOAc 20:1) yielded the title compound (53.0 mg, 82 %) as a
colourless oil, [α]29
D -10.7 (c 1.1 CH2Cl2). Chiral HPLC: Flow rate 1.0 mL/min;
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S21
hexane:IPA 1 %; 30 °C, chiral AD-H; detection at 215 nm gave ee of 92 %. Retention
time 5.7 min (major), 10.9 min (minor). (Other data correspond to that of racemic
sample).
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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]
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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-
enoate (20 mg, 0.052 mmol) upon chromatography (petrol/EtOAc 20:1) yielded the title
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.
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S24
Ethyl 2-[N-tert-Butoxycarbonyl]-5-phenylpent-3E-enoate (13e):
Bn CO2Et
HNBoc
Desulfurisation of ethyl 2-[N-tert-Butoxycarbonylhexylsulfenamide]-5-phenylpent-3E-
enoate (20 mg, 0.05 mmol) upon chromatography (petrol/EtOAc 30:1) yielded the title
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,
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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).
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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.
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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.
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S28
N
NN SHex
8b
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S29
N
NN SHex
8b
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S30
SHex
OH
10b
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S31
SHex
OH
10b
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S32
(+/-)10b-(S)-MTPA
SHex
O(S)-MTPA
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S33
10b-(S)-MTPA
SHex
O(S)-MTPA
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S34
SHex
CO2Me
(+/-)-11a
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S35
SHex
CO2Me
11a
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S36
11b
SHex
CO2Et
![Page 38: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/38.jpg)
S37
11b
SHex
CO2Et
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S38
(+/-) 11b
SHex
CO2Et
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S39
11b
SHex
CO2Et
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S40
SHex
11c
CO2Et
![Page 42: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/42.jpg)
S41
SHex
11c
CO2Et
![Page 43: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/43.jpg)
S42
SHex
(+/-)-11c
CO2Et
![Page 44: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/44.jpg)
S43
SHex
11c
CO2Et
![Page 45: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/45.jpg)
S44
HexS
11d
CO2Et
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S45
HexS
11d
CO2Et
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S46
HexS
(+/-)-11d
CO2Et
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S47
HexS
11d
CO2Et
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S48
HexS
Bn
11e
CO2Et
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S49
HexS
Bn
11e
CO2Et
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S50
HexS
Bn
(+/-)-11e
CO2Et
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S51
HexS
Bn
11e
CO2Et
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S52
HexS
11f
CO2Et
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S53
HexS
11f
CO2Et
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S54
HexS
(+/-)-11f
CO2Et
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S55
HexS
11f
CO2Et
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S56
TBDMSO
SHex
CO2Et
11g
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S57
TBDMSO
SHex
CO2Et
11g
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S58
TBDMSO
SHex
CO2Et
(+/-)-11g
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S59
TBDMSO
SHex
CO2Et
11g
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S60
CO2Me
NBocHexS
(+/-)-12a
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S61
CO2Me
NBocHexS
(R)-12a
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S62
(R)-12b
CO2Et
NBocHexS
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S63
(R)-12b
CO2Et
NBocHexS
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S64
(+/-)-12b
CO2Et
NBocHexS
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S65
(R)-12b
CO2Et
NBocHexS
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S66
(R)-12c
CO2Et
NHexS Boc
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S67
(R)-12c
CO2Et
NHexS Boc
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S68
(+/-)-12c
CO2Et
NHexS Boc
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S69
(R)-12c
CO2Et
NHexS Boc
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S70
NBoc
CO2Et
(R)-12e
HexS
Bn
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S71
NBoc
CO2Et
(R)-12e
HexS
Bn
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S72
NBoc
CO2Et
(+/-)-12e
HexS
Bn
![Page 74: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/74.jpg)
S73
NBoc
CO2Et
(R)-12e
HexS
Bn
![Page 75: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/75.jpg)
S74
NBoc
CO2Et
(R)-12f
HexS
![Page 76: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/76.jpg)
S75
NBoc
CO2Et
(R)-12f
HexS
![Page 77: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/77.jpg)
S76
NBoc
CO2Et
(+/-)-12f
HexS
![Page 78: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/78.jpg)
S77
NBoc
CO2Et
(R)-12f
HexS
![Page 79: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/79.jpg)
S78
CO2Et
NBocHexS
TBDMSO
12g
![Page 80: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/80.jpg)
S79
CO2Et
NBocHexS
TBDMSO
12g
![Page 81: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/81.jpg)
S80
CO2Et
NBocHexS
TBDMSO
(+/-)-12g
![Page 82: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/82.jpg)
S81
CO2Et
NBocHexS
TBDMSO
(R)-12g
![Page 83: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/83.jpg)
S82
(Z)-11b
HexS CO2Et
![Page 84: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/84.jpg)
S83
(Z)-11b
HexS CO2Et
![Page 85: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/85.jpg)
S84
(Z)-(+/-)-11b
HexS CO2Et
![Page 86: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/86.jpg)
S85
(Z)-11b
HexS CO2Et
![Page 87: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/87.jpg)
S86
HexS CO2Et
(Z)-12f
![Page 88: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/88.jpg)
S87
HexS CO2Et
(Z)-12f
![Page 89: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/89.jpg)
S88
HexS
(Z)-(+/-)-12f
CO2Et
![Page 90: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/90.jpg)
S89
HexS
(Z)-12f
CO2Et
![Page 91: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/91.jpg)
S90
NBoc
CO2Et
(R)-12b
HexS
![Page 92: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/92.jpg)
S91
NBoc
CO2Et
(R)-12f
HexS
![Page 93: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/93.jpg)
S92
CO2Et
HNBoc
13c
![Page 94: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/94.jpg)
S93
CO2Et
HNBoc
13c
![Page 95: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/95.jpg)
S94
Bn CO2Et
HNBoc
13e
![Page 96: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/96.jpg)
S95
Bn CO2Et
HNBoc
13e
![Page 97: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/97.jpg)
S96
CO2Et
HNBoc
13f
![Page 98: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/98.jpg)
S97
CO2Et
HNBoc
13f
![Page 99: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/99.jpg)
S98
(+/-)-13f
CO2Et
HNBoc
![Page 100: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/100.jpg)
S99
13f
CO2Et
HNBoc
![Page 101: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/101.jpg)
S100
CO2Et
HNBoc
TBDMSO
(+/-)-13g
![Page 102: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/102.jpg)
S101
CO2Et
HNBoc
TBDMSO
(+/-)-13g
![Page 103: 69451 Weinheim, Germany - Wiley-VCH · Column chromatography on silica afforded the allylic sulfide products. Data for the products are given below. Samples of racemic material for](https://reader035.fdocuments.in/reader035/viewer/2022063004/5f76b33e57708134412a989f/html5/thumbnails/103.jpg)
S102