stereoselective carbon carbon bond formation via...
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Indian Journal of Chemistry
Vol. 57B, March 2018, pp. 327-339
Stereoselective carbon–carbon bond formation via 1,2-asymmetric induction by a
β-substituent in the reaction of α-chloro sulfides with organozinc reagents
S Raghavan*a & L Raju Chowhana,b
a Natural Product Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India b School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
E-mail: [email protected]
Received 8 October 2016; accepted (revised) 8 May 2017
The stereoselectivity of C–C bond formation in the reaction of α-chlorosulfides with a variety of organozinc reagents has been investigated. The study reveals excellent 1,2-asymmetric induction by a β-siloxy substituent and moderate 1,2-induction by the β-methyl
substituent. The stereoselectivity is a function of the size of the organozinc reagents.
Keywords: α-Chlorosulfide, organozinc reagents, 1,2-asymmetric induction, chiral α-substituted sulfides
α-Chloro sulfides are versatile intermediates for the
stereocontrolled formation of C–C bonds. Normant1
reported the preparation of organomagnesium reagent
from α-chloro- sulfides for C–C bond formation.
Takai and co-workers reported on the reaction of
organochromium reagents2, derived from α-chloro
sulfides, with aldehydes. More recently, Mitzel and
co-workers have prepared organoindium reagents3 from
chloro sulfides and utilized them for the preparation
of epoxy alkynes. α-Chloro sulfides are valuable as
reactive electrophiles for the alkylation of aromatics4,
alkenes5, enolates6, and silyl ethers of aldehydes, ketones7,
esters and lactones8. Chiral α-substituted sulfides are
useful synthons for the preparation of epoxydiynes9,
α,β-unsaturated acids10, allylic alcohols11, and allylic
amino derivatives12. The stereoselective synthesis of
α-substituted sulfides therefore assumes importance.
Results and Discussion
The reaction of the simplest α-chloro sulfide with
phenylmagnesium bromide was reported as early as
1936 by Bohme13. The generality of the reaction was
demonstrated by introducing α-alkyl/aryl substituents
on simple cyclic and acyclic chloro sulfides. There
were no reports however, on the diastereoselective
preparation of α-substituted sulfides prior to our
preliminary report, utilizing organozinc reagents for
stereoselective C–C bond formation from β-siloxy
α-chloro sulfides, Scheme I (Ref 14). Herein, we
provide details of the steric influence of alkyl
substituents attached to the β-carbon of siloxy sulfides
3 in the reaction of the derived chloro sulfides, with
various organozinc reagents. Also the stereoselectivity
of C–C bond formation by 1,2-asymmetric induction
as a function of the size of the alkyl group in β-methyl
α-chloro sulfides derived from sulfides 5 is explored.
The siloxy substrates 3a-d were readily prepared
by reaction of phenythiomethyl lithium15 obtained
from 7 with commercially available aldehydes 8a-d,
followed by silylation (Scheme II).
The α-chloro sulfides, prepared from sulfides 3 by reaction with N-chlorosuccinimide, were reacted with octynylzinc bromide 10a, vinylzinc bromide 10b and butylzinc bromide 10c to furnish syn-siloxy sulfides 4 in synthetically useful yields and diastereoselectivity.
The results are collected in Table I. The structures were assigned to the products based on the J values of the methine protons of the diastereoisomers and by comparison with product 2 (Ref 9,14). The stereoselecitvity of the reaction was determined by integration of the peaks of the diastereomers in the
crude 1H NMR spectrum. An inspection of Table I reveals that sterically bulky sp2 (10b) and sp3 (10c) hybridized nucleophiles reacted with substrates 3a-d uniformly with high selectivity to furnish the syn-isomers as the sole product. With the less bulky sp hybridized reagent 10a, the influence of the β-alkyl
substituent could be discerned. The sulfide 3d with a bulky t-butyl substituent afforded propargylic sulfide 4da as the sole product. Moderate selectivity only was observed in the case of substrates 3b and 3c (dr = 3:1), which was poorer than that observed for sulfide 1 (dr = 9:1).
INDIAN J. CHEM., SEC B, MARCH 2018
328
The diastereoselectivity in the reaction of the
chloro sulfide derived from 3a with 10a could not be
determined by examination of the 1H NMR of crude
product mixture. Thus a branching at the α- or even at
the β-position of the alkyl group is sufficient to
furnish substituted sulfides in good to excellent
diastereoselectivity.
Synthesis and reactions of β-methyl sulfides 5
The substrate 5a was prepared from the known16
alcohol 11a, by reaction with diphenyl disulfide using
Hata's protocol17 (Scheme III). The sulfide 5b, 5c and
5d were prepared using Hata's protocol from the
known alcohols 11b, 11c and 11d (Ref 18). To
comprehend the influence of the β-methyl substituent
relative to the siloxy substituent in the 1,2-asymmetric
induction, sulfides 5a-d were reacted with reagents
10a-c and the results are collected in Table II.
A cursory examination of Table II reveals that
the asymmetric induction by the β-methyl group is
inferior compared to the siloxy group. While substrate
3d afforded 4da as the only product even in the
reaction with the least bulky of the nucleophiles
10a, the chloro sulfide derived from 5d afforded
6da as a 9:1 mixture of isomers. Likewise, while
sulfide 1 afforded products in the reaction with
organozinc reagents 10a-c in excellent selectivity,
5c furnished syn-propargylic sulfide 6ca in a 56:44
ratio. The allylic and alkyl sulfides 6cb and 6cc
were obtained as roughly 3:1 ratio of isomers.
Interestingly, relative to 5c, sulfide 5b possesing an
isopropyl substituent, afforded products with a
better stereoseectivity; allylic sulfide 6bb and alkyl
sulfide 6bc were obtained as sole products and
propargylic sulfide 6ba was obtained in a 3:1 ratio.
The superior induction by the OTBS group is evident
by comparing entry 2, Table I with entry 1, Table II;
the alkyl sulfide 6ac is obtained in a 7:3 ratio
while 6ac was obtained as the sole product. The
influence of the size of the alkyl substituent at the
Scheme I — Stereoselective synthesis of α-substituted sulfides by asymmetric induction
Scheme II — Synthesis of β-siloxy sulfides 3a-d
RAGHAVAN & CHOWHAN: ASYMMETRIC INDUCTION BY β-SUBSTITUENT
329
β-position is evident in the methyl series as in the
OTBS series. The branching at the α-position of
the alkyl substituent is required for efficient
chiral induction. As observed with substrates 3,
vinyl sulfides were obtained in the reaction of
chlorosulfides prepared from 5 with butylzinc reagent.
The ratio of alkylated to eliminated products was
lower due to lower reactivity. It can be concluded
that an alkyl group with α-branching (5b) is required
for obtaining substituted sulfides with good selectivity
in the β-Me series.
Assignment of structure
The observed stereoselectivity of products can be
rationalized by invoking a model depicted in
Scheme IV, wherein the nucleophile (R3M) attacks
the sulfenium ion from the face opposite to the larger
alkyl group (R1), R2 being OTBS/Me groups.
The relative stereochemistry of the compound 5ca
has been assigned as shown in Scheme V, on the
basis of preferred conformations. Acyclic compounds
having vicinal stereogenic centers, each bearing
one hydrogen, normally exist predominantly in the
Table I
Entry Substrate Propargylic sulfide, Yield (dr) Allylic sulfide, Yield (dr) Alkyl sulfide, Yield (dr)
1
86% (90:10)
80% (>95:<5)
64%a (>95:<5)
2
78% (70:30)
75% (>95:<5)
50%a (>95:<5)
3
80% (78:22)
85% (>95:<5)
50%a (>95:<5)
4
75% (75:25)
75% (>95:<5)
45%a (>95:<5)
5
65% (>95:<5)
73% (>95:<5)
48%a (>95:<5)
a: Vinyl sulfide side product also obtained resulting in poor yields.
INDIAN J. CHEM., SEC B, MARCH 2018
330
conformation having the hydrogens anti to minimize
gauche interactions19. The preferred conformations
of 5ca and its anti-diastereomer is depicted in
Scheme V. The substituent gauche to the phenyl group
resonates upfield due to the net shielding effect of
the aromatic ring. The observed chemical shifts for
–CH2-C≡C- of 5ca is δ 2.10 (dt, J = 6.7, 2.2 Hz, 2H)
and for the minor anti-diastereomer the signal is
observed at δ 2.18 (dt, J = 6.7, 2.2 Hz, 2H). The
signals for the vinyl group in 5cb appeared at δ 5.56
(m, 1H), 4.80 (d, 1H), 4.68 (d, 1H) and for the anti-
isomer the signals were observed at δ 5.71 (m, 1H),
4.94 (d, 1H) and 4.76 (d, 1H). The chemical shift
values for the major isomer were upfield relative to
the minor isomer. Based on the above, the relative
orientation of the Me- and -SPh groups in the major
Scheme III — Synthesis of β-methyl sulfides 5a-d
Table II
Entry Substrate Propargylic sulfide, Yield (dr) Allylic sulfide, Yield (dr) Alkyl sulfide, Yield (dr)
1
82% (64:36)
73% (75:25)
40% a (68:32)
2
80% (75:25)
80% (>95:<5)
44%a (70:30)
3
80% (56:44)
78% (80:20)
40%a (70:30)
4
73% (90:10)
70% (>95:<5)
55%a (>95:<5)
a: Vinyl sulfide side product also obtained resulting in poor yields.
RAGHAVAN & CHOWHAN: ASYMMETRIC INDUCTION BY β-SUBSTITUENT
331
product 5ca-5cc were assigned as syn- and anti- in the
minor isomers. relation. The stereochemistry of other
compounds were assigned based on analogy.
Experimental Section
Unless otherwise indicated, all reactions were
carried out with magnetic stirring and if air or
moisture sensitive, in flame-dried glassware under
nitrogen. Syringes used to transfer reagents and
solvents were purged with nitrogen prior to use. 1H
and 13C NMR spectra were recorded at 200, 300, 400
and 50, 75, 100 MHz respectively in CDCl3. Reactions
were monitored by thin layer chromatography (TLC).
Before use, all the Grignard reagents were titrated
with salicylaldehyde phenylhydrazone indicator.
1-(Phenylthio)octan-2-ol, 9a
To a solution of the mixture of thioanisole 7
(1.2 mL, 10 mmol), DABCO (1.1 g, 10 mmol)
in anhydrous THF (16 mL) was added n-BuLi
(7.3 mL, 1.5 M in Hexanes, 11 mmol) at 0°C. The
mixture was gradually allowed to warm to RT and
stirred for 2 h. The reaction mixture was then
cooled to 0°C, a solution of heptaldehyde 8a (1.4 mL,
10 mmol) in anhydrous THF (10 mL) was added and
the mixture stirred at the same temperature for 1 h.
The reaction mixture was quenched with saturated aq.
NH4Cl, the layers were separated and the aqueous
layer was extracted with EtOAc (3×10 mL). The
combined organic layers were washed with brine
(10 mL), dried over anhyd. Na2SO4, concentrated under
reduced pressure and purified by column chromatography
using 10% EtOAc/Hexanes (v/v) as the eluent to
afford the alcohol 9a (2.0 g, 8.5 mmol) in 85% yield as
a colourless oil. TLC (SiO2): Rf = 0.32 (10% EtOAc/
Hexanes); IR (neat): 3426, 2923, 1582, 1480, 1443,
1301, 1085, 1055, 740, 696 cm−1; 1H NMR (CDCl3,
300 MHz): δ 7.32 (d, J = 7.1 Hz, 2H), 7.24 (t, J = 7.1
Hz, 2H), 7.16 (t, J = 7.1 Hz, 1H), 3.64-3.56 (m, 1H),
3.06 (dd, J = 13.5, 3.3 Hz, 1H), 2.80 (dd, J = 13.5, 8.6
Hz, 1H), 1.49-1.40 (m, 2H), 1.36-1.22 (m, 8H), 0.87
(t, J = 6.7 Hz, 3H); 13C NMR (CDCl3, 75 MHz): δ
135.8, 128.9, 128.3, 125.5, 69.2, 41.0, 35.7, 31.4,
28.9, 25.2, 22.2, 13.7; ESI-MS: m/z 238 [M]+.
4-Methyl-1-(phenylthio)pentan-2-ol, 9b: Following
the procedure detailed above, thioanisole 7 (1.2 mL,
10 mmol) and isovaleraldehde 8b (1.1 mL, 10 mmol)
furnished the alcohol 9b (1.79 g, 8.5 mmol) in 85%
yield as a liquid. TLC (SiO2): Rf = 0.39 (10% EtOAc/
Hexanes); IR (neat): 3448, 2926, 2855, 1630, 1462,
1254, 1217, 1060, 837, 767, 687 cm−1; 1H NMR
(CDCl3, 300 MHz): δ 7.34 (d, J = 7.9 Hz, 2H), 7.25
(t, J = 7.9 Hz, 2H), 7.16 (t, J = 7.9 Hz, 1H), 3.74-3.65
(m, 1H), 3.06 (dd, J = 13.4, 3.5 Hz, 1H), 2.80 (dd,
J = 13.4, 8.4 Hz, 1H), 2.32 (s, 1H), 1.85-1.72 (m, 1H),
1.31-1.24 (m, 2H) 0.95-0.85 (m, 6H); 13C NMR
Scheme IV — Model to rationalize stereoselectivity
Scheme V — Assignment of relative configuration
INDIAN J. CHEM., SEC B, MARCH 2018
332
(CDCl3, 75 MHz): δ 136.0, 129.6, 128.9, 126.2, 67.7,
45.3, 24.7, 23.4, 22.1, 14.2; ESI-MS: m/z 234 [M+Na]+.
3-Methyl-1-(phenylthio)butan-2-ol, 9c: Following
the procedure detailed above for the preparation 9a,
thioanisole 7 (1.2 mL, 10 mmol) and isobutanal 8c
(0.9 mL, 10 mmol) furnished sulfide 9c (1.5 g, 8.0
mmol) in 80% yield as a liquid. TLC (SiO2): Rf = 0.35
(10% EtOAc/Hexanes); IR (neat): 3426, 2923, 1582,
1480, 1443, 1301, 1085, 1055, 740, 696 cm−1; 1H NMR (CDCl3, 500 MHz): δ 7.34 (d, J = 7.8 Hz,
2H), 7.28 (t, J = 7.8 Hz, 2H), 7.18 (d, J = 7.8 Hz, 1H),
3.40-3.34 (m, 1H), 3.15 (dd, J = 13.6, 2.9 Hz, 1H),
2.80 (dd, J = 13.6, 5.8 Hz, 1H), 2.32 (s, 1H),
1.79-1.72 (m, 1H), 0.95 (d, J = 7.8 Hz, 3H), 0.94 (d,
J = 6.8 Hz, 3H); 13C NMR (CDCl3, 75 MHz): δ 135.5,
130.1, 129.2, 126.7, 73.9, 40.0, 34.0, 17.8, 17.2;
ESI-MS: m/z 234 [M+O+Na]+; ESI-HRMS: m/z
Calcd for C11H16O2SNa 235.0763. Found: 235.0756.
Note: The sulfide was oxidized to the sulfoxide while
recording the mass spectrum.
3,3-Dimethyl-1-(phenylthio)butan-2-ol, 9d: Following
the general procedure thioanisole 7 (1.2 mL, 10
mmol) and trimethylacetaldehyde 8d (1.1 mL, 10 mmol)
furnished the alcohol 9d (1.26 g, 6.0 mmol) in 60%
yield as a liquid. TLC (SiO2): Rf = 0.35 (10% EtOAc/
Hexanes); IR (neat); 3448, 2926, 2855, 1630, 1462,
1254, 1217, 1060, 837, 767, 697 cm−1; 1H NMR
(CDCl3, 500 MHz): δ 7.34 (d, J = 7.4 Hz, 2H), 7.26
(t, J = 7.4 Hz, 2H), 7.17 (t, J = 7.4 Hz, 1H), 3.25
(dd, J = 11.7, 1.9 Hz, 1H), 3.22 (dd, J = 13.6, 1.9 Hz,
1H), 2.70 (dd, J = 13.6, 11.7 Hz, 1H), 0.90 (bs, 9H); 13C NMR (CDCl3, 75 MHz): δ 135.3, 129.8, 129.0,
126.5, 76.3, 38.0, 34.7, 25.9; ESI-MS: m/z 249
[M+O+Na]+; ESI-HRMS: m/z Calcd for C12H18O2SNa
249.0919. Found: 249.0931. Note: The sulfide was oxidized
to the sulfoxide while recording the mass spectrum.
tert-Butyldimethyl(1-(phenylthio)octan-2-yloxy)
silane, 3a: To a solution of the alcohol 9a (2.0 g, 8.5
mmol) in anhydrous DCM (34 mL) cooled to 0°C was
added imidazole (867 mg, 12.7 mmol, 1.5 eq) followed
by TBS-Cl (1.4 g, 9.35 mmol, 1.1 eq). The mixture
was stirred at RT for a period of 2 h, then diluted
with DCM (30 mL), washed successively with
water (10 mL), brine (10 mL), dried over anhyd.
Na2SO4 and the solvent evaporated under reduced
pressure to yield the crude product which was purified
by column chromatography using hexanes to furnish
the product 3a (2.9 g, 8.2 mmol) in 97% yield as a
liquid. TLC (SiO2): Rf = 0.81 (Hexanes); IR (neat):
2953, 2927, 2855, 1582, 1470, 1252, 1094, 1008, 755,
737, 694 cm−1; 1H NMR (CDCl3, 500 MHz): δ 7.28 (d,
J = 7.8 Hz, 2H), 7.19 (t, J = 7.8 Hz, 2H), 7.08 (t,
J = 7.8 Hz, 1H), 3.77 (m, 1H), 2.95 (dd, J = 13.6, 5.8
Hz, 1H), 2.90 (dd, J = 13.6, 5.8 Hz, 1H), 1.71-1.62
(m, 1H), 1.51-1.44 (m, 1H), 1.32-1.24 (m, 8H),
0.91-0.86 (bs, 12H), 0.03 (s, 3H), 0.00 (s, 3H); 13C NMR (CDCl3, 75 MHz): δ 137.3, 129.3, 128.6,
125.7, 71.4, 40.9, 36.4, 31.9, 29.4, 25.9, 25.8, 22.8,
18.1, 14.2, -4.3, -4.5; ESI-MS: m/z 369 [M+O+H]+.
Note: The sulfide was oxidized to the sulfoxide while
recording the mass spectrum.
tert-Butyldimethyl(4-methyl-1-(phenylthio)pentan-
2-yloxy)silane, 3b: Following the procedure detailed
above for the preparation of sulfide 3a, the alcohol 9b
(1.79 g, 8.9 mmol) furnished sulfide 3b (2.6 g, 8.2
mmol) in 92% yield as a liquid. TLC (SiO2): Rf = 0.82
(Hexanes); IR (neat): 2955, 2925, 2857, 1580, 1472,
1250, 1090, 1012, 758, 735, 697 cm−1; 1H NMR
(CDCl3, 500 MHz): δ 7.31 (d, J = 7.9 Hz, 2H), 7.22
(t, J = 7.9 Hz, 2H), 7.12 (t, J = 7.9 Hz, 1H), 3.85-3.79
(m, 1H), 2.97 (dd, J = 12.8, 4.9, Hz, 1H), 2.89 (dd,
J = 12.8, 6.9, Hz, 1H), 1.75-1.65 (m, 1H), 1.55-1.48
(m, 2H) 0.95-0.82 (m, 15H), 0.04 (s, 3H), 0.03 (s,
3H); 13C NMR (CDCl3, 75 MHz): δ 137.2, 129.7,
128.8, 126.0, 69.9, 46.1, 27.4, 26.1, 24.5, 23.7, 22.5,
18.4, -4.0, -4.4; ESI-MS: m/z 341[M+O+H]+. Note:
The sulfide was oxidized to the sulfoxide while
recording the mass spectrum.
tert-Butyldimethyl(3-methyl-1-(phenylthio)butan-
2-yloxy)silane, 3c: Following the procedure detailed
for the preparation 3a, the alcohol 9c (1.5 g, 7.9 mmol)
furnished the product 3c (2.2 g, 7.3 mmol) in 92%
yield as a liquid. TLC (SiO2): Rf = 0.81 (Hexanes); IR
(neat): 2953, 2927, 2855, 1582, 1470, 1252, 1094,
1008, 755, 737, 694 cm−1; 1H NMR (CDCl3, 300
MHz): δ 7.24 (d, J = 7.5 Hz, 2H), 7.28 (t, J = 7.5 Hz,
2H), 7.18 (t, J = 7.5 Hz, 1H), 3.45-3.44 (m, 1H), 3.14
(dd, J = 9.2, 3.1 Hz, 1H), 2.80 (dd, J = 9.2, 3.1 Hz,
1H), 1.81-1.67 (m, 1H), 0.93 (d, J = 6.7 Hz, 3H), 0.9
(s, 9H), 0.79 (d, J = 6.7 Hz, 3H), 0.06 (s, 3H), 0.00 (s,
3H); 13C NMR (CDCl3, 75 MHz): δ 137.4, 129.2,
128.9, 125.9, 75.6, 38.1, 32.5 26.0, 25.8, 18.9, 16.4,
-4.0, -4.5; ESI-MS: m/z 362 [M+O2+NH4]+. Note: The
sulfide was oxidized to the sulfone while recording
the mass spectrum.
RAGHAVAN & CHOWHAN: ASYMMETRIC INDUCTION BY β-SUBSTITUENT
333
tert-Butyl(3,3-dimethyl-1-(phenylthio)butan-2-yloxy)
dimethylsilane, 3d: Following the procedure detailed
for the preparation of 3a, the alcohol 9d (1.18 g, 5.6
mmol) furnished the product 3d (1.55 g, 4.8 mmol) in
85% yield as a liquid. TLC (SiO2): Rf = 0.86
(Hexanes); IR (neat): 2953, 2927, 2855, 1582, 1470,
1252, 1094, 1008, 755, 737, 694 cm−1; 1H NMR
(CDCl3, 500 MHz): δ 7.38 (d, J = 7.5 Hz, 2H), 7.33
(t, J = 7.5 Hz, 2H), 7.22 (t, J = 7.5 Hz, 1H), 3.54
(dd, J = 6.5, 3.1 Hz, 1H), 3.31 (dd, J = 13.0, 3.1 Hz, 1H),
2.86 (dd, J = 13.0, 6.5 Hz, 1H), 1.01 (bs, 9H), 0.97
(bs, 9H), 0.12 (s, 6H); ESI-MS: m/z 325 [M+H]+.
tert-Butyldimethyl((7R,8RS)-8-(phenylthio)hexadec-
9-yn-7-yloxy)silane, 4aa
To a solution of 1-octyne (165 mg, 1.5 mmol) in
anhydrous THF (0.8 mL) cooled to −10°C was added
i-PrMgCl·LiCl (1 mL, 1.5 mmol, 1.5 M in THF) and
stirred for 30 min at the same temperature. To the
so generated Grignard reagent, ZnBr2 (1.1 mL, 1.65
mmol, 1.5 M in THF) was added at 0°C and stirred
for 30 min. To the above organozinc reagent cooled
to 0°C was added the solution of chloro sulfide
(0.5 mmol) in anhydrous benzene (5 mL), generated
from sulfide 3a (176 mg, 0.5 mmol). The reaction
mixture was stirred, gradually allowing it to attain
RT, and stirred further for a period of 7 h when TLC
examination indicated complete consumption of the
chlorosulfide. The reaction mixture was cooled to 0°C
and quenched by the addition of an aq. saturated
NH4Cl solution. It was allowed to warm to RT and
diluted with Et2O (5 mL), the layers were separated
and aqueous layer was extracted with Et2O (3×10 mL).
The combined organic layers were washed with brine
(5 mL), dried over anhyd. Na2SO4. The solvent was
evaporated under reduced pressure to afford a crude
compound which was purified by column chromatography
using hexanes as the eluent to afford the pure product
4aa (179 mg, 0.39 mmol) in 78% yield as a liquid.
TLC (SiO2): Rf = 0.88 (Hexanes); IR (neat): 3063,
2954, 2928, 2857, 1586, 1463, 1384, 1253, 1094, 837,
777, 695 cm−1; 1H NMR (CDCl3, 300 MHz): δ 7.45 (d,
J = 6.9 Hz, 2H), 7.30-7.18 (m, 3H), 3.87 (dt, J = 4.5,
2.2 Hz, 1H), 3.75-3.73 (m, 1H), 2.16 (dt, J = 6.7, 2.2
Hz, 2H), 1.78-1.69 (m, 2H), 1.50-1.20 (m, 16H), 0.92-
0.87 (bs, 15H), 0.01 (s, 3H), 0.0 (s, 3H); 13C NMR
(CDCl3, 75 MHz): δ 135.3, 132.1, 128.7, 127.1, 86.1,
77.5, 74.0, 46.3, 33.6, 31.8, 31.3, 29.3, 28.6, 28.4,
25.8, 25.1, 22.6, 22.5, 18.9, 18.1, 14.1, 14.0, −4.5,
−4.6; ESI-MS: m/z 483 [M+Na]+.
tert-Butyldimethyl((3RS,4RS)-3-(phenylthio)dec-
1-en-4-yloxy)silane, 4ab: Following the general
procedure detailed above, the α-chlorosulfide derived
from sulfide 3a (176 mg, 0.5 mmol) was reacted with
vinylzinc bromide (1.5 mmol) at RT (6 h) to afford
the crude product which was purified by column
chromatography using hexanes as the eluent to furnish
the pure product 4ab (141 mg, 0.37 mmol) in 75%
yield as a liquid. TLC (SiO2): Rf = 0.84 (Hexanes); IR
(neat): 3067, 2930, 2856, 1468, 1254, 1094, 840, 776
cm−1; 1H NMR (CDCl3, 300 MHz): δ 7.40 (d, J = 6.9
Hz, 2H), 7.30-7.16 (m, 3H), 5.90 (ddd J = 17.0, 10.2,
8.5 Hz, 1H), 5.15-5.01 (m, 2H), 3.87-3.8 (m, 1H), 3.60
(dd, J = 8.5, 4.1 Hz, 1H), 1.82-1.60 (m, 2H), 1.40-1.20
(bs, 8H), 0.90 (bs, 12H), 0.06 (s, 3H), 0.05 (s, 3H); 13C NMR (CDCl3, 75 MHz): δ 135.7, 132.2, 129.5,
128.7, 126.8, 116.7, 74.5, 43.8, 33.6, 29.3, 25.9, 25.7,
25.6, 22.6, 18.2, 14.1, -3.6, -4.4; ESI-MS: m/z 417
[M+O+Na]+. Note: The sulfide was oxidized to the
sulfoxide while recording the mass spectrum.
tert-Butyldimethyl((5RS,6RS)-5-(phenylthio)dodecan-
6-yloxy)silane, 4ac: Following the general procedure,
the α-chloro sulfide derived from sulfide 3a (176 mg,
0.5 mmol) was reacted with n-butylzinc bromide
(1.5 mmol) at RT (6 h) to afford the crude product
which was purified by column chromatography
using hexanes as the eluent to furnish the pure product
4ac (101 mg, 0.25 mmol) in 50% yield as a liquid.
TLC (SiO2): Rf = 0.85 (Hexanes); IR (neat): 3063,
2954, 2930, 2857, 1468, 1253, 1089, 837 cm−1; 1H NMR (CDCl3, 500 MHz): δ 7.38 (d, J = 8.0 Hz,
2H), 7.24 (t, J = 8.0 Hz, 2H), 7.18 (t, J = 8.0 Hz, 1H),
3.69-3.64 (m, 1H), 3.12 (dt, J = 6.0, 3.0 Hz, 1H),
1.92-1.84 (m, 1H), 1.83-1.77 (m, 1H), 1.67-1.58 (m,
1H), 1.44-1.20 (m, 13H), 0.94-0.88 (m, 6H), 0.85 (s,
9H), -0.09 (s, 3H), -0.10 (s, 3H); 13C NMR (CDCl3,
75 MHz): δ 136.6, 132.0, 128.8, 126.7, 74.1, 55.7,
32.0, 31.5, 30.4, 29.8, 29.4, 28.7, 26.7, 26.0, 22.8,
18.0, 14.3, 14.2, -4.3, -4.4; ESI-MS: m/z 380 [M]+.
tert-Butyldimethyl((4RS,5RS)-2-methyl-5-(phenylthio)
tridec-6-yn-4-yloxy)silane, 4ba: Following the
general procedure, the α-chlorosulfide prepared from
sulfide 3b (162 mg, 0.5 mmol) was reacted with
1-octynylzinc bromide (1.5 mmol) at RT (6 h) to
afford the crude product which was purified by
column chromatography using hexanes as the eluent
to furnish the pure product 4ba (172 mg, 0.4 mmol) in
80% yield as a liquid. TLC (SiO2): Rf = 0.86
INDIAN J. CHEM., SEC B, MARCH 2018
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(Hexanes); IR (neat): 3063, 2954, 2928, 2857, 1586,
1463, 1384, 1253, 1094, 837, 777, 695 cm−1; 1H NMR
(CDCl3, 500 MHz): δ 7.49 (d, J = 6.7 Hz, 2H), 7.30-7.20
(m, 3H), 3.89 (dt, J = 4.5, 2.2 Hz, 1H), 3.78 (td, J = 7.5,
5.2 Hz, 1H), 2.15 (dt, J = 5.2, 2.2 Hz, 2H), 1.80-1.70
(m, 2H), 1.52-1.25 (m, 12H), 0.97-0.91 (bs, 15H),
0.02 (s, 6H); 13C NMR (CDCl3, 75 MHz): δ 135.5,
132.3, 128.8, 127.2, 86.3, 77.5, 74.2, 46.5, 33.8, 32.0,
31.5, 29.5, 28.8, 28.6, 26.0, 25.3, 22.8, 19.1, 18.3,
14.2, −4.3, −4.4; ESI-MS: m/z 455 [M+Na]+;
ESI-HRMS: m/z Calcd for C26H44OSSiNa 455.2779.
Found: 455.2765.
tert-Butyldimethyl((3RS,4RS)-6-methyl-3-(phenylthio)
hept-1-en-4-yloxy)silane, 4bb: Following the general
procedure, the α-chloro sulfide prepared from sulfide
3b (162 mg, 0.5 mmol) was reacted vinylzinc bromide
(1.5 mmol) at RT (6 h) to afford the crude product
which was purified by column chromatography using
hexanes as the eluent to furnish the pure product 4bb
(148 mg, 0.42 mmol) in 85% yield as a liquid. TLC
(SiO2): Rf = 0.85 (Hexanes); 1H NMR (CDCl3, 500
MHz): δ 7.36 (d, J = 7.0 Hz, 2H), 7.24 (t, J = 7.0 Hz,
2H), 7.19 (t, J = 7.0 Hz, 1H), 5.92 (ddd, J = 17.0, 10.0,
8.0 Hz, 1H), 5.10-5.01 (m, 2H), 3.91 (td, J = 8.0, 4.0
Hz, 1H), 3.65 (dd, J = 8.0, 4.0 Hz, 1H), 1.73-1.65
(m, 1H), 1.59-1.53 (m, 1H), 1.44-1.38 (m, 1H), 0.94
(d, J = 7.0 Hz, 6H), 0.89 (bs, 9H), 0.02 (s, 3H), 0.01
(s, 3H); 13C NMR (CDCl3, 75 MHz): δ 135.6, 135.5,
132.4, 128.8, 126.9, 117.0, 72.7, 58.7, 42.6, 26.1,
24.4, 23.8, 22.2, 18.3, −4.1, −4.3; ESI-MS: m/z 373
[M+Na]+; ESI-HRMS: m/z Calcd for C20H34OSSiNa
373.1997. Found: 373.1986.
tert-Butyldimethyl((4RS,5RS)-2-methyl-5-(phenylthio)
nonan-4-yloxy)silane, 4bc: Following the general
procedure, the α-chloro sulfide prepared from sulfide
3b (162 mg, 0.5 mmol) was reacted with n-butylzinc
bromide (1.5 mmol) at RT (6 h) to afford the crude product
which was purified by column chromatography using
hexanes as the eluent to furnish the pure product 4bc
(95 mg, 0.25 mmol) in 50% yield as a liquid. TLC
(SiO2): Rf = 0.85 (Hexanes); 1H NMR (CDCl3, 500
MHz): δ 7.52 (d, J = 7.5 Hz, 2H), 7.42-7.31 (m, 3H),
3.87 (td, J = 5.2, 3.0, Hz, 1H), 3.14 (td, J = 6.0, 3.0
Hz, 1H), 2.08-1.95 (m, 1H), 1.84-1.66 (m, 2H),
1.53-1.33 (m, 4H), 1.15-0.97 (m, 20H), 0.0 (s, 3H),
-0.01 (s, 3H); 13C NMR (CDCl3, 75 MHz): δ 132.5,
129.2, 129.0, 127.0, 71.9, 40.6, 30.6, 28.5, 26.0, 24.5,
24.2, 22.9, 21.8, 18.2, 14.3, -4.3, -4.5; ESI-MS: m/z
419 [M+O+Na]+. Note: The sulfide was oxidized to
the sulfoxide while recording the mass spectrum.
tert-Butyldimethyl((3RS,4RS)-2-methyl-4-(phenylthio)
dodec-5-yn-3-yloxy)silane, 4ca: Following the general
procedure, the α-chlorosulfide prepared from 3c (156
mg, 0.5 mmol) was reacted with the 1-octynylzinc
bromide at RT (6 h) to afford the crude product which
was purified by column chromatography using
hexanes as the eluent to furnish the pure product 4ca
(156 mg, 0.37 mmol) in 75% yield as a liquid. TLC
(SiO2): Rf = 0.85 (Hexanes); IR (neat): 3062, 2955,
2926, 2855, 1587, 1462, 1385, 1252, 1090, 835, 776,
693 cm−1; 1H NMR (CDCl3, 300 MHz): δ 7.46 (d,
J = 7.5 Hz, 2H), 7.30-7.10 (m, 3H), 3.89 (dt, J = 4.9,
2.4 Hz, 1H), 3.62 (dd, J = 4.7, 2.4 Hz, 1H), 2.20-2.0
(m, 2H), 1.40-1.20 (m, 8H), 0.91-0.72 (m, 19H), 0.10
(s, 3H), 0.01 (s, 3H); 13C NMR (CDCl3, 75 MHz): δ
136.1, 131.9, 128.8, 126.9, 86.3, 79.3, 78.9, 45.7,
32.2, 31.5, 29.8, 28.7, 26.3, 22.7, 20.8, 19.1, 18.6,
17.5, 14.2, -3.6, -4.0; ESI-MS: m/z 441 [M+Na]+.
tert-Butyldimethyl((3RS,4RS)-2-methyl-4-(phenylthio)
hex-5-en-3-yloxy)silane, 4cb: Following the general
procedure, the α-chlorosulfide prepared from 3c (156
mg, 0.5 mmol) was reacted with vinylzinc bromide
(1.5 mmol) at RT (6 h) to afford the crude product
which was purified by column chromatography using
hexanes as the eluent to furnish the pure product 4cb
(126 mg, 0.37 mmol) in 75% yield as a liquid. TLC
(SiO2): Rf = 0.82 (Hexanes); 1H NMR (CDCl3, 500
MHz): δ 7.34 (d, J = 6.8 Hz, 2H), 7.27-7.16 (m, 3H),
5.86 (ddd, J = 16.6, 9.7, 8.7 Hz, 1H), 4.94 (d, J = 9.7
Hz, 1H), 4.86 (d, J = 16.6 Hz, 1H), 3.65 (dd, J = 8.7,
4.8 Hz, 1H), 3.59 (t, J = 4.8 Hz, 1H), 2.04 (m, 1H),
0.99-0.93 (m, 15H). 0.10 (s, 3H), 0.05 (s, 3H); 13C NMR (CDCl3, 75 MHz): δ 136.9, 135.4, 132.3,
128.5, 126.7, 115.6, 79.5, 59.0, 32.1, 29.8, 26.3, 20.7,
17.9, −3.5, −3.8.
tert-Butyldimethyl((3RS,4RS)-2-methyl-4-(phenylthio)
octan-3-yloxy)silane, 4cc: Following the general procedure,
the α-chlorosulfide prepared from 3c (156 mg, 0.5
mmol) was reacted with n-butylzinc bromide (1.5 mmol)
at RT (6 h) to afford the crude product which was
purified by column chromatography using hexanes as
the eluent to furnish the pure product 4cc (81 mg,
0.23 mmol) in 45% yield as a liquid. TLC (SiO2):
Rf = 0.83 (Hexanes); 1H NMR (CDCl3, 500 MHz): δ
7.38 (d, J = 7.1 Hz, 2H), 7.30-7.18 (m, 3H), 3.56 (dd,
RAGHAVAN & CHOWHAN: ASYMMETRIC INDUCTION BY β-SUBSTITUENT
335
J = 4.9, 3.2 Hz, 1H), 3.12-3.06 (m, 1H), 1.90-1.80
(m, 1H), 1.40-1.20 (m, 2H), 1.02-0.85 (m, 22H),
−0.01 (s, 3H), −0.03 (s, 3H); 13C NMR (CDCl3, 75
MHz): δ 137.3, 131.2, 128.8, 126.2, 78.4, 55.4, 31.2,
30.4, 29.7, 26.0, 25.6, 22.6, 21.5, 19.0, 14.0, −4.1, −4.2.
tert-Butyl((3RS,4RS)-2,2-dimethyl-4-(phenylthio)dodec-
5-yn-3-yloxy)dimethylsilane, 4da: Following the
general procedure, the α-chlorosulfide prepared from
sulfide 3d (162 mg, 0.5 mmol) was reacted with
octynylzinc bromide (1.5 mmol) at RT (6 h) to afford
the crude product which was purified by column
chromatography using hexanes as the eluent to furnish
the pure product 4da (140 mg, 0.32 mmol) in 65%
yield as a liquid. TLC (SiO2): Rf = 0.88 (Hexanes); IR
(neat): 3064, 2952, 2928, 2857, 1586, 1463, 1384,
1253, 1094, 837, 777, 695 cm−1; 1H NMR (CDCl3, 500
MHz): δ 7.46 (d, J = 7.7 Hz, 2H), 7.25-7.15 (m, 3H),
4.02 (dt, J = 3.7, 2.2 Hz, 1H), 3.71 (d, J = 3.7 Hz,
1H), 2.16 (td, J = 6.0, 2.2 Hz, 2H), 1.49-1.42 (m, 2H),
1.32-1.23 (m, 6H), 1.02 (s, 9H), 1.00 (s, 9H), 0.90
(t, J = 6.7 Hz, 3H), 0.27 (s, 3H), 0.11 (s, 3H); 13C NMR (CDCl3, 75 MHz): δ 137.0, 131.4, 128.6,
126.4, 84.6, 83.3, 82.2, 43.4, 37.0, 31.6, 29.9, 28.7,
27.2, 26.5, 22.8, 19.1, 14.3, −2.9, −4.5; ESI-MS: m/z
455 [M+Na]+; ESI-HRMS: m/z Calcd for
C26H44OSSiNa 455.2779. Found: 455.2765.
tert-Butyl((3RS,4RS)-2,2-dimethyl-4-(phenylthio)
hex-5-en-3-yloxy)dimethylsilane, 4db: Following
the general procedure, the α-chlorosulfide prepared
from sulfide 3d (162 mg, 0.5 mmol) was reacted with
vinylzinc bromide (1.5 mmol) at RT (6 h) to afford
the crude product which was purified by column
chromatography using hexanes as the eluent to furnish
the pure product 4db (127 mg, 0.36 mmol) in 73%
yield as a liquid. TLC (SiO2): Rf = 0.83 (Hexanes); 1H NMR (CDCl3, 500 MHz): δ 7.35-7.11 (m, 5H),
5.95 (ddd, J = 17.3, 10.5, 9.0 Hz, 1H), 4.88 (d, J = 10.5
Hz, 1H), 4.72 (d, J = 17.3 Hz, 1H), 3.75 (dd, J = 9.0,
2.2 Hz, 1H), 3.52 (d, J = 2.2 Hz, 1H), 0.97 (s, 9H),
0.92 (s, 9H), 0.15 (s, 3H), 0.04 (s, 3H); 13C NMR
(CDCl3, 75 MHz): δ 139.8, 132.4, 129.1, 128.8, 126.7,
114.8, 82.8, 57.2, 37.5, 27.6, 26.7, 19.1, −2.7, −3.8.
tert-Butyl((3RS,4RS)-2,2-dimethyl-4-(phenylthio)
octan-3-yloxy)dimethylsilane, 4dc: Following the
general procedure, the α-chlorosulfide prepared from
sulfide 3d (162 mg, 0.5 mmol) was reacted with
n-butylzinc bromide (1.5 mmol) at RT (6 h) to afford
the crude product which was purified by column
chromatography using hexanes as the eluent to furnish
the pure product 4dc (92 mg, 0.28 mmol) in 48%
yield as a liquid. TLC (SiO2): Rf = 0.84 (Hexanes); 1H NMR (CDCl3, 500 MHz): δ 7.26 (d, J = 7.5 Hz,
2H), 7.19 (t, J = 7.5 Hz, 2H), 7.06 (t, J = 7.5 Hz, 1H),
3.49 (s, 1H), 3.20 (dd, J = 8.8, 5.4 Hz, 1H), 1.82-1.72
(m, 1H), 1.69-1.56 (m, 2H), 1.28-1.20 (m, 6H) 0.98
(s, 12H), 0.94 (s, 9H), 0.10 (s, 3H), 0.03 (s, 3H); 13C NMR (CDCl3, 75 MHz): δ 138.3, 130.4, 128.8,
125.7, 81.1, 51.8, 36.8, 35.8, 30.6, 27.8, 26.6, 22.7,
19.1, 14.2, −2.9, −3.8.
(2-Methylpentyl)(phenyl)sulfane, 5a
To the mixture of the alcohol 11a (510 mg, 5
mmol) and diphenyl disulfide (1.2 g, 5.5 mmol) in
anhydrous THF (20 mL) cooled to 0°C was added
Bu3P (7.5 mL, 7.5 mmol, 1.5 M in EtOAc) drop-wise
and the mixture stirred for 4 h while allowing it to
warm to RT gradually. The reaction mixture was then
diluted with water (5 mL). The aqueous layer was
separated and extracted with EtOAc (3×15 mL). The
combined organic layer were washed with brine
(5 mL), dried over anhyd. Na2SO4 and concentrated
under reduced pressure to afford the crude sulfide
which was purified by column chromatography using
2% EtOAc/Hexanes (v/v) as the eluent to afford the
pure sulfide 5a as a viscous oil (824 mg, 4.25 mmol)
in 85% yield; TLC (SiO2): Rf = 0.81 (Hexanes); IR
(neat): 3445, 2955, 2927, 2855, 1580, 1470, 1252,
1094, 1006, 775, 694 cm−1; 1H NMR (CDCl3, 500
MHz): δ 7.26 (d, J = 7.4 Hz, 2H), 7.21 (t, J = 7.4 Hz,
2H), 7.09 (t, J = 7.4 Hz, 1H), 2.89 (dd, J = 12.8, 5.9
Hz, 1H), 2.74 (dd, J = 12.8, 7.9 Hz, 1H), 1.75-1.70
(m, 1H), 1.50-1.43 (m, 1H), 1.40-1.19 (m, 3H),
1.10 (d, J = 6.6 Hz, 3H), 0.89 (t, J = 7.1 Hz, 3H); 13C NMR (CDCl3, 75 MHz): δ 135.2, 128.9, 128.8,
125.6, 41.1, 38.6, 32.8, 20.1, 19.5, 14.4. ESI-MS: m/z
194 [M]+.
(2,3-Dimethylbutyl)(phenyl)sulfane, 5b: The
alcohol 11b (510 mg, 5 mmol) was converted into the
sulfide 5b by following the procedure detailed above.
The crude sulfide was purified by column
chromatography using 2% EtOAc/Hexanes (v/v) as
the eluent to afford the pure sulfide 5b as a viscous
oil (824 mg, 4.25 mmol) in 85% yield as a liquid.
TLC (SiO2): Rf = 0.84 (Hexanes); 3063, 2955, 2927,
2855, 1580, 1470, 1252, 1094, 1006, 775, 694 cm−1;
1H NMR (CDCl3, 500 MHz): δ 7.31 (d, J = 7.2 Hz,
2H), 7.25 (t, J = 7.2 Hz, 2H), 7.14 (t, J = 7.2 Hz, 1H),
3.01 (dd, J = 12.7, 5.4 Hz, 1H), 2.71 (dd, J = 12.7, 8.2
INDIAN J. CHEM., SEC B, MARCH 2018
336
Hz, 1H), 1.85-1.78 (m, 1H), 1.68-1.62 (m, 1H), 1.01
(d, J = 6.3 Hz, 3H) 0.95 (d, J = 7.2, Hz, 3H), 0.90
(d, J = 6.3 Hz, 3H); 13C NMR (CDCl3, 75 MHz): δ
137.8, 129.0, 128.8, 125.5, 39.0, 38.6, 31.6, 20.5,
18.0, 15.4; ESI-MS: m/z 194 [M]+.
Phenyl(2-phenylpropyl)sulfane, 5c: Sulfide 5c
was prepared by from alcohol 11c (680 mg, 5 mmol)
following the general procedure. The crude sulfide
was purified by column chromatography using
2% EtOAc/Hexanes (v/v) as the eluent to afford the
pure sulfide 5c as a viscous oil (969 mg, 4.25 mmol)
in 85% yield as a liquid. TLC (SiO2): Rf = 0.84
(Hexanes); 3063, 2955, 2927, 2855, 1580, 1470,
1252, 1094, 1006, 775, 694 cm−1; 1H NMR (CDCl3,
500 MHz): δ 7.28-7.09 (m, 10H), 3.18 (dd, J = 12.8,
5.4 Hz, 1H), 3.12-2.92 (m, 2H), 1.39 (d, J = 6.4 Hz,
3H); 13C NMR (CDCl3, 125 MHz): δ 145.3, 136.8,
128.8, 128.7, 128.3, 126.8, 126.4, 125.6, 41.8, 39.2,
20.8; ESI-MS: m/z 245 [M+O+H]+.
Phenyl(2,3,3-trimethylbutyl)sulfane, 5d: Sulfide
5d was prepared by from alcohol 11d (580 mg,
5 mmol) following the general procedure. The crude
sulfide was purified by column chromatography using
2% EtOAc/Hexanes (v/v) as the eluent to afford the
pure sulfide 5d as a viscous oil (884 mg, 4.25 mmol)
in 85% yield as a liquid. TLC (SiO2): Rf = 0.84
(Hexanes); 3065, 2955, 2927, 2855, 1580, 1470,
1252, 1094, 1006, 775, 694 cm−1; 1H NMR (CDCl3,
300 MHz): δ 7.30-7.17 (m, 4H), 7.10 (t, J = 6.9 Hz,
1H), 3.20 (d, J = 12.2 Hz, 1H), 2.40 (dd, J = 12.5, 1.8
Hz, 1H), 1.49-1.39 (m, 1H), 1.02 (d, J = 6.6 Hz, 3H),
0.91-0.88 (bs, 9H); 13C NMR (CDCl3, 75 MHz): δ
137.7, 128.8, 128.6, 125.4, 42.7, 36.9, 33.2, 27.3,
14.2; ESI-MS: m/z 208 [M]+.
((4SR,5RS)-4-Methyltridec-6-yn-5-yl)(phenyl)sulfane,
6aa: Following the general procedure, the α-
chlorosulfide prepared from sulfide 5a (97 mg, 0.5
mmol) was reacted with 1-octynylzinc bromide
(1.5 mmol) at RT (6 h) to afford the crude product
which was purified by column chromatography using
hexanes as the eluent to furnish the pure product 6aa
as a viscous oil (123 mg, 0.41 mmol) in 82% yield;
TLC (SiO2): Rf = 0.90 (Hexanes); IR (neat): 3063,
2954, 2928, 2857, 1586, 1463, 1384, 1253, 1094, 837,
777, 695 cm−1; 1H NMR (CDCl3, 500 MHz): δ 7.45
(d, J = 6.9 Hz, 4H), 7.25 (t, J = 7.9 Hz, 4H), 7.19
(t, J = 6.9 Hz, 4H), 3.84* (t, J = 1.9 Hz,1H), 3.75
(t, J = 1.9 Hz, 1H), 2.16 (dt, J = 6.9, 1.9 Hz, 4H),
1.82-1.76 (m, 2H), 1.72-1.66 (m, 2H), 1.50-1.42
(m, 6H), 1.38-1.22 (m, 16H), 1.09 (d, J = 5.9 Hz, 6H),
0.92 (t, J = 6.9, 6H), 0.89 (t, J = 6.9 Hz, 6H); 13C NMR (CDCl3, 75 MHz) 137.0, 136.4*, 132.0,
131.8*, 128.7*, 128.6, 127.1, 126.9*, 86.0*, 85.6,
78.8, 77.6*, 46.2, 45.2*, 37.6, 37.5*, 37.4, 36.9, 35.2,
31.4, 29.8, 28.8*, 28.5, 22.7, 20.5, 20.4*, 18.9, 14.4*,
14.2. Note: The signals for the minor diastereoisomer
are indicated by an asterisk mark.
((3SR,4SR)-4-Methylhept-1-en-3-yl)(phenyl)sulfane,
6ab: Following the general procedure, the α-chlorosulfide
prepared from sulfide 5a (97 mg, 0.5 mmol) was
reacted with vinylzinc bromide (1.5 mmol) at RT
(6 h) to afford the crude product which was purified
by column chromatography using hexanes as the
eluent to furnish the pure product 6ab as a viscous
oil (80 mg, 0.36 mmol) in 73% yield; TLC (SiO2): Rf
= 0.90 (Hexanes); IR (neat): 3067, 2930, 2856, 1468,
1254, 1094, 840, 776 cm−1; 1H NMR (CDCl3, 500
MHz): δ 7.29-7.21 (m, 10H), 5.78-5.70 (m, 2H), 4.94
(d, J = 9.0 Hz, 2H), 4.88 (d, J = 16.2 Hz, 1H), 4.84*
(d, J = 16.2 Hz, 1H), 3.55* (dd, J = 9.0, 5.0 1H), 3.51
(dd, J = 9.0, 5.0 Hz, 1H), 1.30-1.20 (m, 10H), 1.02
(d, J = 7.0 Hz, 3H), 1.00* (d, J = 7.0 Hz, 3H), 0.90
(t, J = 7.0, 6H); 13C NMR (CDCl3, 75 MHz): δ 137.4,
132.5*, 132.3, 129.0*, 128.6, 127.5, 127.1*, 126.8,
126.6*, 116.4*, 115.9, 59.4, 58.4*, 37.0, 35.9*, 29.7,
20.4, 20.2*, 17.2, 16.2*, 14.2. Note: The signals for
the minor diastereoisomer are indicated by an asterisk
mark.
((4SR,5SR)-4-Methylnonan-5-yl)(phenyl)sulfane,
6ac: Following the general procedure, the α-chlorosulfide
prepared from sulfide 5a (97 mg, 0.5 mmol) was
reacted with n-butylzinc bromide (1.5 mmol) at RT
(6 h) to afford the crude product which was purified
by column chromatography using hexanes as the
eluent to furnish the pure product 6ac as a viscous oil
(100 mg, 0.45 mmol) in 90% yield in 40:45 ratio of
sulfide 6ac and vinyl sulfide; TLC (SiO2): Rf = 0.90
(Hexanes); IR (neat): 3063, 2954, 2930, 2857, 1468,
1253, 1089, 837 cm−1; 1H NMR (CDCl3, 500 MHz): δ
7.39 (t, J= 7.7 Hz, 4H), 7.26 (t, J = 7.7 Hz, 4H), 7.28
(t, J = 7.7 Hz, 2H), 3.12-3.07 (m, 2H) 1.70-1.44
(m, 8H) 1.40-1.20 (m, 17H), 0.96 (d, J= 6.8 Hz, 6H),
0.89 (t, J= 6.8 Hz, 12H); 13C NMR (CDCl3, 75 MHz):
δ 137.5, 128.7, 128.6, 125.4, 41.0, 38.4, 32.6, 29.9,
20.0, 19.9, 19.3, 19.2, 14.3, 14.2.
RAGHAVAN & CHOWHAN: ASYMMETRIC INDUCTION BY β-SUBSTITUENT
337
((3SR,4RS)-2,3-Dimethyldodec-5-yn-4-yl)(phenyl)
sulfane, 6ba: Following the general procedure, the
α-chlorosulfide prepared from sulfide 5b (97 mg,
0.5 mmol) was reacted with 1-octynylzinc bromide
(1.5 mmol) at RT (6 h) to afford the crude product
which was purified by column chromatography using
hexanes as the eluent to furnish the pure product 6ba
as a viscous oil (113 mg, 0.37 mmol) in 80% yield;
TLC (SiO2): Rf = 0.90 (Hexanes); IR (neat): 3063,
2954, 2928, 2857, 1586, 1463, 1384, 1253, 1094, 837,
777, 695 cm−1; 1H NMR (CDCl3, 500 MHz): δ 7.4
(d, J = 7.1, 4H), 7.29-7.18 (m, 6H), 4.0-3.96* (m, 1H),
3.75-3.69 (m, 1H), 2.13 (td, J = 6.8, 2.2 Hz, 2H), 1.3-1.2
(m, 20H), 1.06 (d, J = 6.8 Hz, 6H), 0.95 (d, J = 6.7
Hz, 6H), 0.90 (t, J = 6.7 Hz, 6H), 0.85 (d, J = 6.7 Hz,
6H); 13C NMR (CDCl3, 75 MHz): δ 134.5, 132.3,
131.9*, 129.2, 128.6, 128.1*, 127.5*, 127.0, 85.5,
79.8, 44.9, 43.6, 43.4*, 31.6, 31.3*, 29.8, 28.7, 28.5,
22.6, 22.5*, 21.7, 21.1*, 19.3*, 18.9, 18.0*, 17.6,
14.5*, 14.1, 12.9*, 12.8; ESI-MS: m/z 302 [M]+.
Note: The signals for the minor diastereoisomer are
indicated by an asterisk mark.
((3SR,4SR)-4,5-Dimethylhex-1-en-3-yl)(phenyl)
sulfane, 6bb: Following the general procedure, the
α-chlorosulfide prepared from sulfide 5b (97 mg,
0.5 mmol) was reacted with vinylzinc bromide
(1.5 mmol) at RT (6 h) to afford the crude product
which was purified by column chromatography using
hexanes as the eluent to furnish the pure product 6bb
as a viscous oil (88 mg, 0.4 mmol) in 80% yield; TLC
(SiO2): Rf = 0.90 (Hexanes); IR (neat): 3064, 2932,
2858, 1468, 1256, 1094, 842, 774 cm−1; 1H NMR
(CDCl3, 500 MHz): δ 7.27 (d, J = 6.9 Hz, 2H), 7.20-7.10
(m, 3H), 5.63 (ddd, J = 17.0, 9.8, 9.4 Hz, 1H), 4.78
(d, J = 9.8 Hz, 1H), 4.66 (J = 17.0 Hz, 1H), 3.42 (dd,
J = 9.4, 8.3 Hz, 1H) 1.90-1.80 (m, 1H) 1.50-1.40 (m,
1H), 0.97 (d, J = 6.7 Hz, 3H), 0.9 (d, J = 6.7 Hz, 3H),
0.74 (d, J = 6.6 Hz, 3H); 13C NMR (CDCl3, 75 MHz):
δ 138.7, 133.0, 128.7, 128.6, 126.9, 115.1, 58.7, 43.1,
29.9, 22.0, 17.2, 12.4; ESI-MS: m/z 237 [M+O+H]+.
((3SR,4SR)-2,3-Dimethyloctan-4-yl)(phenyl)sulfane,
6bc: Following the general procedure, the α-chlorosulfide
prepared from sulfide 5b (97 mg, 0.5 mmol) was
reacted with n-butylzinc bromide (1.5 mmol) at RT
(6 h) to afford the crude product which was purified by
column chromatography using hexanes as the eluent to
furnish the pure product 6bc as a viscous oil (116 mg,
0.47 mmol) in 40% yield, TLC (SiO2): Rf = 0.90
(Hexanes); IR (neat): 3063, 2954, 2930, 2857, 1468,
1253, 1089, 837 cm−1; 1H NMR (CDCl3, 500 MHz): δ
7.30-7.10 (m, 5H), 3.25-3.10 (m, 1H), 1.70-1.40
(m, 8H), 1.10 (d, J = 6.7 Hz, 3H), 1.05 (d, J = 6.7 Hz,
3H), 0.99-0.85 (m, 6H).
Phenyl((2SR,3RS)-2-phenylundec-4-yn-3-yl)sulfane,
6ca: Following the general procedure, the α-chlorosulfide
from sulfide 5c (114 mg, 0.5 mmol) was reacted with
1-octynylzinc bromide (1.5 mmol) at RT (6 h) to
afford the crude product which was purified by
column chromatography using hexanes as the
eluent to furnish the pure product 6ca as a viscous oil
(134 mg, 0.4 mmol) in 80% yield; TLC (SiO2):
Rf = 0.91 (Hexanes); IR (neat): 3065, 2956, 2930,
2855, 1584, 1462, 1384, 1253, 1094, 837, 777, 695
cm−1; 1H NMR (CDCl3, 500 MHz): δ 7.43-7.36
(m, 8H), 7.29-7.15 (m, 12H), 4.01 (dt, J = 4.5, 2.2 Hz,
1H), 3.95* (dt, J = 4.5, 2.2 Hz, 1H), 3.07 (q, J = 6.7
Hz, 1H), 2.98* (m, 1H), 2.17 (td, J = 6.7, 2.2 Hz, 2H),
2.08* (dt, J = 6.7, 2.2 Hz, 2H), 1.48 (d, J = 6.7 Hz,
6H), 1.37-1.18 (m, 16H), 0.9 (t, J = 6.0 Hz, 3H),
0.80* (t, J = 6.7 Hz, 3H); 13C NMR (CDCl3, 75
MHz): δ 144.1*, 143.0, 135.2*, 134.6, 132.4, 132.2*,
129.4, 129.2*, 128.9, 128.8*, 128.4, 128.0*, 127.7,
127.3*, 127.1, 126.9, 87.2, 86.9*, 78.7, 77.4*, 46.7,
46.6*, 44.0, 43.4*, 31.5, 28.8*, 28.7, 28.6, 22.7, 19.7,
19.1, 19.0, 17.3, 14.3; ESI-MS: m/z 336[M]+. Note:
The signals for the minor diastereoisomer are indicated
by an asterisk mark.
Phenyl((3SR,4SR)-4-phenylpent-1-en-3-yl)sulfane,
6cb: Following the general procedure the the
α-chlorosulfide prepared from sulfide 5c (114 mg,
0.5 mmol) was reacted with the organozinc reagent
prepared from vinylmagnesium bromide (1.5 mmol)
at RT (6 h) to afford the crude product which was
purified by column chromatography using hexanes as
the eluent to furnish the pure product 6cb as a viscous
oil (82 mg, 0.39 mmol) in 78% yield; TLC (SiO2): Rf
= 0.91 (Hexanes); IR (neat): 3064, 2932, 2856, 1468,
1254, 1094, 840, 776 cm−1; 1H NMR (CDCl3, 500
MHz): δ 7.42-7.21 (m, 20H), 5.75* (ddd, J = 16.9,
9.9, 9.0 Hz, 1H), 5.56 (ddd, J = 16.9, 9.9, 7.0 Hz, 1H),
4.95* (d, J = 9.9 Hz, 1H), 4.81 (d, J = 10.0 Hz, 1H),
4.77* (d, J = 16.9 Hz 1H), 4.68 (d, J = 16.9 Hz, 1H),
3.75* (dd, J = 6.7, 9.0 Hz, 1H), 3.71 (dd, J = 9.3, 7.0
Hz, 1H), 3.22* (q, J = 6.7 Hz, 1H), 3.01-3.11 (m, 1H),
1.48 (d, J = 6.7 Hz, 3H), 1.39* (d, J = 6.7 Hz, 3H); 13C NMR (CDCl3, 75 MHz): δ 137.2*, 136.7, 132.9,
132.8, 128.9, 128.8, 128.3*, 128.2, 127.9*, 127.86,
INDIAN J. CHEM., SEC B, MARCH 2018
338
127.1, 126.7, 116.9*, 116.3, 60.0, 59.8*, 43.9, 43.7*,
29.8; 19.8; ESI-MS: m/z 254 [M]+.
Phenyl((2SR,3SR)-2-phenylheptan-3-yl)sulfane, 6cc:
Following the general procedure the α-chlorosulfide
prepared from sulfide 5c (114 mg, 0.5 mmol) was
reacted with the organozinc reagent prepared from n-
butyl bromide (1.5 mmol) at RT (6 h) to afford the
crude product which was purified by column
chromatography using hexanes as the eluent to furnish
the pure product 6cc as a viscous oil (113 mg, 0.4
mmol) in 40% yield; TLC (SiO2): Rf = 0.90
(Hexanes); IR (neat): 30635, 2954, 2930, 2857, 1468,
1253, 1089, 837 cm−1; 1H NMR (CDCl3, 500 MHz): δ
7.5-7.2 (m, 20H), 3.39-3.34* (m, 1H), 3.14 (q, J = 6.7
Hz, 1H), 3.04* (q, J = 6.7 Hz, 1H), 2.95-2.85 (m, 1H),
1.65-1.60* (m, 1H), 1.55-1.47 (m, 1H), 1.42 (d, J = 6.7
Hz, 3H), 1.40 (d, J = 6.7 Hz, 3H), 1.25-1.15 (m, 12H),
0.97* (t, J = 6.7 Hz, 3H), 0.80 (t, J = 6.7 Hz, 3H);
13C NMR (CDCl3, 75 MHz): δ 131.7, 129.2, 129.0,
128.5, 128.2, 127.9, 127.6, 126.5, 57.6, 44.0, 42.5*,
33.2, 29.9*, 29.6, 25.3, 17.9*, 18.9, 14.1.
Phenyl((3SR,4RS)-2,2,3-trimethyldodec-5-yn-4-yl)
sulfane, 6da: Following the general procedure, the
α-chlorosulfide prepared from 5d (104 mg, 0.5 mmol)
was reacted with 1-octynylzinc bromide (1.5 mmol) at
RT (6 h) to afford the crude product which was
purified by column chromatography using hexanes as
the eluent to furnish the pure product 6da as a viscous
oil (115 mg, 0.36 mmol) in 73% yield; TLC (SiO2): Rf
= 0.93 (Hexanes); IR (neat): 3063, 2954, 2928, 2857,
1586, 1463, 1384, 1253, 1094, 837, 777, 695 cm−1; 1H NMR (CDCl3, 500 MHz): δ 7.44 (d, J = 7.2 Hz,
2H), 7.25-7.21 (m, 3H), 4.05 (d, J = 2.0 Hz, 1H), 2.10
(dt, J = 7.2, 2.0 Hz, 2H), 1.86-1.82 (m, 1H), 1.42-1.34
(m, 2H) 1.3-1.2 (m, 6H), 1.18 (d J = 7.2 Hz, 3H), 1.04
(bs, 9H), 0.88 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3,
75 MHz): δ 136.2, 131.9, 128.6, 126.8, 84.1, 81.9,
48.6, 43.0, 33.9, 31.5, 28.8, 28.8, 27.4, 22.7, 19.0,
14.2, 12.1; ESI-MS: m/z 316 [M]+.
Phenyl((3SR,4SR)-4,5,5-trimethylhex-1-en-3-yl)
sulfane, 6db: Following the general procedure, the
α-chlorosulfide prepared from 5d (104 mg, 0.5 mmol)
was reacted with vinylzinc bromide (1.5 mmol) at RT
(6 h) to afford the crude product which was purified
by column chromatography using hexanes as the
eluent to furnish the pure product 6db as a viscous
oil (82 mg, 0.35 mmol) in 70% yield; TLC (SiO2):
Rf = 0.92 (Hexanes); IR (neat): 3067, 2930, 2856,
1468, 1254, 1094, 840, 776 cm−1; 1H NMR (CDCl3,
500 MHz): δ 7.30-7.08 (m, 5H), 5.85 (ddd J = 15.8,
9.8, 8.3 Hz, 1H), 4.78 (m, 2H), 3.76 (dd, J = 8.3, 1.7
Hz, 1H), 1.66-1.56 (m, 1H), 1.10-1.04 (m, 12H); 13C NMR (CDCl3, 75 MHz): δ 140.0, 136.2, 132.1,
128.7, 126.6, 113.9, 55.5, 47.7, 29.2, 28.8, 27.5; ESI-
MS: m/z 234 [M]+.
Phenyl((3SR,4SR)-2,2,3-trimethyloctan-4-yl)sulfane,
6dc: Following the general procedure, the
α-chlorosulfide prepared from 5d (104 mg, 0.5 mmol)
was reacted with n-butylzinc bromide (1.5 mmol) at
RT (6 h) to afford the crude product which was
purified by column chromatography using hexanes as
the eluent to furnish the pure product 6dc as a viscous
oil (72 mg, 0.27 mmol) in 55% yield of sulfide 6dc;
TLC (SiO2): Rf = 0.91 (Hexanes); IR (neat): 3063,
2954, 2930, 2857, 1468, 1253, 1089, 837 cm−1; 1H NMR (CDCl3, 500 MHz) 7.33-7.10 (m, 5H), 3.37
(m, 1H), 1.65-1.55 (m, 7H), 1.13 (s, 9H), 1.01 (s, 3H),
1.0 (t, J = 6.6 Hz, 3H); 13C NMR (CDCl3, 75 MHz):
δ 137.5, 129.0, 128.9, 128.3, 44.9, 36.9, 30.0, 29.1,
28.5, 27.4, 22.7, 15.2, 14.1.
Conclusion
A general stereoselective route to α-substituted
sulfides has been developed taking advantage of
1,2-asymmetric induction. The asymmetric induction
by a β-siloxy substituent is better than the β-methyl
substituent. The products have useful handles for
further functionalization to synthetic intermediates.
Acknowledgements
LRC is thankful to CSIR, New Delhi for
fellowship. SR acknowledges funding from DST
(SR/S1/OC-5/2011) and CSIR, New Delhi as a part of
the XII five year plan programme under the title
ORIGIN (CSC-108).
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