One-pot rhodium(I)-catalyzed hydroboration of alkenes: Radical conjugate addition

Article abstract of DOI:10.1021/jo034515v

B-Alkylcatecholboranes, prepared by rhodium-(I)-catalyzed hydroboration of alkenes, are suitable radical precursors for conjugate addition to activated olefins. This procedure proved to be particularly useful for the control of the regio- and chemoselectivity of such tandem processes. Enantioselective hydroboration has also been successfully coupled with radical chain reaction in a one-pot process.

Full text of DOI:10.1021/jo034515v

SCHEME 1. Regioselective Gen er a tion of Ra d ica ls
fr om TBDMS-P r otected Cycloh exen -3-ola
On e-P ot Rh od iu m (I)-Ca ta lyzed
Hyd r obor a tion of Alk en es: Ra d ica l
Con ju ga te Ad d ition
Philippe Renaud,*,† Cyril Ollivier,‡ and Vale´ry Weber‡
University of Berne, Department of Chemistry and
Biochemistry, CH-3000 Berne 9, Switzerland, and
University of Fribourg, Department of Chemistry, Pe´rolles,
CH-1700 Fribourg, Switzerland
philippe.renaud@ioc.unibe.ch
Received April 22, 2003
Abstr a ct: B-Alkylcatecholboranes, prepared by rhodium-
(I)-catalyzed hydroboration of alkenes, are suitable radical
precursors for conjugate addition to activated olefins. This
procedure proved to be particularly useful for the control of
the regio- and chemoselectivity of such tandem processes.
Enantioselective hydroboration has also been successfully
coupled with radical chain reaction in a one-pot process.
In 1967, organoboranes were recognized to participate
in free-radical processes.1 A few years ago, we started to
examine the possibility of using organoboranes, easily
available through hydroboration of alkenes, as radical
precursors in chain reactions. For instance, we have
shown that B-alkylcatecholboranes very easily undergo
radical substitution at boron and therefore are particu-
a
Key: (a) catecholborane, N,N-dimethylacetamide (10 mol %);
(b) catecholborane, [Rh(COD)Cl]2 (1 mol %) and PPh3 (4 mol %);
(c) CH2dCHCOOMe (5 equiv), PTOC-OMe (3 equiv) in benzene,
150 W lamp, 10 °C; (d) Zn, AcOH.
by radical conjugate addition to methyl acrylate afforded
2-S-pyridylthio-substituted ester 2 in low yield (Scheme
1). This product results from selective hydroboration at
position 2. Desulfurization with zinc in acetic acid5 gave
ester 3 in 86% yield as a trans/cis 2:1 mixture of isomers.
The low yield of the radical process is presumably caused
by fragmentation of the unstable 2-siloxycyclohexyl-
borane. Interestingly, by catalyzing the hydroboration
step with [Rh(COD)Cl]2 and PPh3, the regioisomeric
product 4 was isolated in 69% yield.6 Desulfurization gave
5 in 90% yield as a trans/cis 1:1 mixture of stereoisomers.
This first reaction proved that radical conjugate addition
of organoboranes can be performed in the presence of a
rhodium(I) catalyst and a phosphine without a detrimen-
tal effect on yield.
The chemoselectivity of hydroboration of a diene was
investigated next with commercially available (S)-(-)-
limonene 6 (Scheme 2). Under N,N-dimethylacetamide
catalysis, a nonseparable mixture of products resulting
from hydroboration of both double bonds was obtained.
Switching to rhodium(I)-catalyzed hydroboration changed
dramatically the course of the reaction, and only the
product 7 (as a 1:1:1:1 mixture of four diastereomers)
resulting from the hydroboration of the gem-disubstituted
alkene at the terminal position was isolated in 48-44%
and 43% yield using [Rh(COD)Cl]2 and Wilkinson cata-
lyst Rh(PPh3)3Cl, respectively.6 Small amounts (10-15%
yield) of the S-pyridyl derivative resulting from the direct
trapping of the radical with the PTOC-OMe chain-
larly good precursors for radical chain reactions.2
A
general and efficient method for intermolecular conjugate
addition to various activated olefins using a Barton
carbonate (N-methoxycarbonyloxypyridine-2-thione )
PTOC-OMe) as chain transfer reagent has been devel-
oped.3 The starting organoboranes were prepared in situ
by hydroboration of olefins with commercially available
catecholborane catalyzed by the N,N-dimethylacetamide
(10 mol %).4 This environmentally friendly method is very
efficient for simple systems. However, this approach is
not satisfactory for the control of regio- and chemoselec-
tivity. We report here that rhodium(I)-catalyzed hydro-
boration can be combined with radical reactions in one-
pot processes. This approach allows an enhanced control
of the regioselectivity and chemoselectivity of the reac-
tions. Successful enantioselective carbon-carbon bond
formation using this approach is also described.
The control of the regioselectivity of the hydroboration
was examined with silylated cyclohexen-3-ol 1. Hydro-
boration catalyzed by N,N-dimethylacetamide followed
† University of Berne.
‡ University of Fribourg.
(1) (a) Brown, H. C.; Midland, M. M. Angew. Chem., Int. Ed. 1972,
11, 692. (b) Ghosez, A.; Giese, B.; Zipse, H. In Methoden der Organis-
chen Chemie (Houben-Weyl), 4th ed.; Regitz, M., Giese, B., Eds; 1989;
Thieme: Stuttgart; Vol E19a, p 753. (c) Ollivier C.; Renaud P. Chem.
Rev. 2001, 101, 3415.
(2) (a) Ollivier, C.; Chuard, R.; Renaud, P. Synlett 1999, 807. (b)
Ollivier, C.; Renaud, P. Chem. Eur. J . 1999, 5, 1468. (c) Cadot, C.;
Dalko, P.; Cossy, J .; Ollivier, C.; Chuard, R.; Renaud, P. J . Org. Chem.
2002, 67, 7193.
(5) Barton, D. H. R.; Chern, C.-Y.; J aszberenyi, J . Cs. Tetrahedron
(3) (a) Ollivier, C.; Renaud, P. Angew. Chem., Int. Ed. 2000, 39, 925.
(b) Cadot, C.; Cossy, J .; Dalko, P. I. Chem. Commun. 2000, 1070.
(4) Garrett, C. E.; Fu, G. C. J . Org. Chem. 1996, 61, 3224.
1996, 52, 11503.
(6) Evans, D. A.; Fu, G. C., Hoveyda, A. H. J . Am. Chem. Soc. 1992,
114, 6671.
10.1021/jo034515v CCC: $25.00 © 2003 American Chemical Society
Published on Web 06/19/2003
J . Org. Chem. 2003, 68, 5769-5772
5769

SCHEME 2. Ch em oselective Gen er a tion of
14, respectively, with (S,S)-BDPP and (R,R)-DIOP. After
desulfurization, esters 13 and 15 were obtained in 68%
and 55% yield from the corresponding alkenes. In case
of the bicyclic system 13, an enantiomeric excess of 76%
was measured. The acyclic derivative 15 was obtained
with an ee of 41% by using (R,R)-DIOP. The correspond-
ing oxidative hydroboration was reported with an ee of
53%.7b
Ra d ica l fr om (S)-(-)-Lim on en ea
In conclusion, we have shown that rhodium(I)-cata-
lyzed hydroboration is perfectly compatible with our
recently developed tin free conjugate addition method.
This enhances considerably the scope of this reaction and
opens the way to cyclization reactions starting from
polyenes. The coupling of enantioselective hydroborations
with radical reactions offers also some promising op-
portunities for the synthesis of enantiomerically enriched
products.
a
Key: (a) catecholborane, [Rh(COD)Cl]2 (1 mol %) and PPh3 (4
mol %); (b) catecholborane, Rh(PPh3)3Cl (2 mol %); (c) CH2d
CHCOOMe (5 equiv), PTOC-OMe (3 equiv) in benzene, 150 W
lamp, 10 °C; (d) Zn, AcOH.
SCHEME 3. En a n tioselective
Hyd r obor a tion -Ra d ica l Con ju ga te Ad d ition a
Exp er im en ta l Section
P r oced u r e A: N,N-Dim eth yla ceta m id e-Ca ta lyzed Hy-
d r obor a tion -In ter m olecu la r Con ju ga te Ad d ition .3a Cat-
echolborane (0.64 mL, 6.0 mmol) was added dropwise at 0 °C to
a solution of the olefin (3.0 mmol) and N,N-dimethylacetamide
(28.0 µL, 0.3 mmol) in CH2Cl2 (2 mL).4 The reaction mixture
was heated at reflux for 3 h. Methanol (0.15 mL, 3.6 mmol) was
added at 0 °C, and the solution was stirred for 15 min at rt. A
yellow solution of PTOC-OMe (9.0 mmol, 3 equiv), freshly
prepared by stirring a solution of N-hydroxypyridine-2-thione
sodium salt (1.41 g, 9.45 mmol) and methyl chloroformate (0.7
mL, 9.0 mmol) in benzene (15 mL) in the dark, was added to
the B-alkylcatecholborane in benzene (15 mL) followed by the
activated alkene, methyl acrylate (1.35 mL, 15 mmol), and
DMPU (0.36 mL, 3.0 mmol). The reaction mixture was irradiated
at 10 °C with a 150 W tungsten lamp overnight and treated with
1 N NaOH. The aqueous layer was extracted with CH2Cl2 (3×),
and the combined organic phases were washed with aq satd
NaCl, dried (MgSO4), filtered, and concentrated in vacuo. The
crude product was purified by FC (hexane/EtOAc).
P r oced u r e B: Rh od iu m (I)-Ca ta lyzed Hyd r obor a tion -
In ter m olecu la r Con ju ga te Ad d ition . Catecholborane (0.64
mL, 6.0 mmol) was added dropwise at -78 °C to a solution of
the olefin (3.0 mmol) and rhodium catalyst (2 mol %), prepared
according to the procedure reported by Burgess et al.7b from [Rh-
(COD)Cl]2 (15 mg, 0.03 mmol) and PPh3 (32 mg, 0.12 mmol) or
(R,R)-DIOP (30 mg, 0.06 mmol) or (S,S)-BDPP (27 mg, 0.06
mmol), in THF (12 mL). The reaction mixture was stirred for
30 min at -78 °C and stored overnight at -25 °C. Methanol
(0.15 mL, 3.6 mmol) was added at 0 °C, and the solution was
stirred for 15 min at at 0 °C. The solvent was removed under
vacuum. A yellow solution of PTOC-OMe (9.0 mmol), freshly
prepared by stirring a solution of N-hydroxypyridine-2-thione
sodium salt (1.41 g, 9.45 mmol) and methyl chloroformate (0.7
mL, 9.0 mmol) in benzene (15 mL) for 1 h in the dark, was added
at rt to the B-alkylcatecholborane in benzene (15 mL) followed
by the activated alkene, methyl acrylate (1.35 mL, 15 mmol),
and DMPU (0.36 mL, 3.0 mmol, 1 equiv). The reaction mixture
was irradiated at 10 °C with a 150 W tungsten lamp overnight
and treated with 1 N NaOH. The aqueous layer was extracted
with CH2Cl2 (3×), and the combined organic phases were washed
with satd NaCl, dried (MgSO4), filtered, and concentrated in
vacuo. The crude product was purified by FC (hexane/EtOAc).
P r oced u r e C.5 To a solution of R-thiopyridyl ester (1.0 mmol)
in acetic acid (4 mL) was added at rt zinc in powder (654 mg,
10.0 mmol), and the disappearance of starting material was
monitored by TLC. The reaction mixture was filtered through
Celite and washed with Et2O. The filtrate was washed with
a
Key: (a) catecholborane, [Rh(COD)Cl]2 (1 mol %), diphopshine
(2 mol %); (b) CH2dCHCOOMe (5 equiv), PTOC-OMe (3 equiv) in
benzene, 150 W lamp, 10 °C; (c) Zn, AcOH.
transfer reagent were also isolated since the reaction was
performed under one-pot conditions without slow addition
of the PTOC-OMe. Desulfurization of 7 afforded 8 as a
1:1 mixture of diastereomers in 91% yield.
It was also of interest to examine if the enantioselective
hydroboration of alkenes can be coupled with radical
reaction in a one-pot procedure without variation of yield
and enantiomeric excess. The first experiment was run
with norbornene 9 (Scheme 3) and methyl acrylate as
radical trap. As catalysts for the hydroboration, [Rh-
(COD)Cl]2 and the chiral diphosphines (R,R)-DIOP and
(S,S)-BDPP were tested. The reaction product 10 was
obtained in 76% and 68% yield, respectively. After
desulfurization with zinc in acetic acid, ester 11 was
analyzed by gas chromatography on a chiral column, and
ee’s of 53% with (R,R)-DIOP and 85% with (S,S)-BDPP
were measured. These values fit well with the observed
value after oxidative treatment of the organoborane
reported by Burgess (ee 54-60% and 80%, respectively).7
The reaction was further tested with substrates 12 and
(7) (a) Burgess, K.; Ohlmeyer, M. J . Chem. Rev. 1991, 91, 1179. (b)
Burgess, K.; Van der Donk, W. A.; Ohlmeyer, M. J . Tetrahedron:
Asymmetry 1991, 2, 613.
5770 J . Org. Chem., Vol. 68, No. 14, 2003

water (4×) and satd NaHCO3 (4×) and dried (MgSO4). After
concentration in vacuo, the crude product was purified by FC
(hexane/AcOEt).
(one dias), 29.8 (one dias), 27.8 (one dias), 27.4 (one dias), 25.7
(one dias), 23.8 (two dias), 23.16 (one dias), 23.14 (one dias), 16.5
(one dias), 16.1 (one dias); MS (CI, CH4) m/z 225 (MH+ (97), 193
(100). Anal. Calcd for C14H24O2 (224.34): C, 74.95; H, 10.78.
Found: C, 74.99; H, 10.80.
Meth yl 3-[(1R,2R,4R)-2-Nor bor n yl]-2-(2-p yr id ylsu lfa n yl)-
p r op a n oa te (10). Compound 10 was prepared according to
general procedure B from norbornene 9 (283 mg, 3.0 mmol) and
(R,R)-DIOP. FC (hexane/AcOEt 85:15) gave 10 (667 mg, 76%)
as a 1:1 mixture of two diastereomers and the direct trapping
S-pyridyl derivative (78 mg, 13%): yellow oil.
Compound 10 was prepared according to general procedure
B from 9 and (S,S)-BDPP. Hydroboration at -25 °C, overnight.
FC (hexane/EtOAc 95:5) gave 10 (596 mg, 68%) as a mixture of
two diastereomers (dr 1:1) and the direct trapping product (93
mg, 15%).
Meth yl 3-[3-(ter t-Bu tyld im eth ylsilyloxy)cycloh exyl]-2-
(2-p yr id ylsu lfa n yl)p r op a n oa te (4). Compound 4 was pre-
pared according to general procedure B from 1 (640 mg, 3.0
mmol). Hydroboration was achieved with [Rh(COD)Cl]2 and
PPh3 at rt overnight. FC (hexane/EtOAc 95:5) gave 4 (843 mg,
69%) as a 1:1:1:1 mixture of four diastereomers and 1-tert-
butyldimethylsilyloxy-3-(2-pyridylsulfanyl)cyclohexane (direct
trapping) (86 mg, 9%) as a 1:1 mixture of two diastereomers:
colorless oil.
Mixture of four diastereomers: IR (neat) ν 1740 cm-1; MS
(ESI) m/z 432.21 ([M + Na]+), 410.23 (MH+). Anal. Calcd for
C
21H35NO3SSi (409.66): C, 61.57; H, 8.61. Found: C, 61.69; H,
8.53.
Meth yl 3-[3-(ter t-Bu tyld im eth ylsilyloxy)cycloh exyl]p r o-
Compound 10 was prepared according to general procedure
A from 9 (283 mg, 3.0 mmol). FC (hexane/AcOEt 85:15) gave 10
(624 mg, 72%) as a mixture of two diastereomers (dr 1:1) and
p a n oa te (5). Compound 5 was prepared according to general
procedure C from 4 (225 mg, 0.55 mmol). FC (hexane/EtOAc 98:
2) gave 5 (149 mg, 90%) as a 1:1 mixture of two diastereomers:
colorless oil; GC (100 °C 10 min, 5 °C/min), column OPTIMA
1701, retention times: 38 min (49.5%) and 40 min (50.5%).
5 (less polar): 1H NMR (500 MHz, CDCl3) δ 4.03-4.00 (m,
1H), 3.66 (s, 3H), 2.30 (t, J ) 7.9, 2H), 1.77-1.61 (m, 4H), 1.60-
1.39 (m, 4H), 1.35 (ddd, J ) 2.6, 3.9, 12.5, 1H), 1.09 (ddd, J )
2.3, 11.1, 13.3, 1H), 0.95-0.88 (m, 1H), 0.88 (s, 9H), 0.02 (s, 6H);
13C NMR (500 MHz, CDCl3) δ 174.6, 66.9, 51.5, 40.1, 33.7, 32.3,
31.8, 31.1, 25.8, 20.0, 18.1, -4.8.
the direct trapping product (99 mg, 16%): IR (neat) ν 1738 cm-1
;
-
MS (CI, CH4) m/z 292 (MH+, 100), 260 (9). Anal. Calcd for C16H21
NO2S (291.41): C, 65.95; H, 7.26. Found: C, 65.92; H, 7.21.
Meth yl 3-[(1R,2R,4R)-2-Nor bor n yl]p r op a n oa te (11). Com-
pound 11 was prepared according to general procedure C from
10 (311 mg, 1.06 mmol). FC (hexane/EtOAc 95:5) gave 11 (176
mg, 91%, 53% ee): GC (85 °C) retention times: 123 min (76.4%)
and 127 min (23.6%). The absolute configuration of C2 was
assigned as 2R in accordance with the absolute configuration of
the alcohol resulting from the oxidation of the corresponding
5 (more polar): 1H NMR (500 MHz, CDCl3) δ 3.67 (s, 3H),
3.55-3.47 (m, 1H), 2.34-2.31 (m, 2H), 1.88-1.81 (m, 2H), 1.76-
1.68 (m, 1H), 1.64-1.59 (m, 1H), 1.59-1.54 (m, 1H), 1.33-1.24
(m, 2H), 1.23-1.12 (m, 2H), 1.00-0.89 (m, 1H), 0.88 (s, 9H),
0.82-0.73 (m, 1H), 0.05 (s, 6H); 13C NMR (500 MHz, CDCl3) δ
174.4, 71.3, 51.5, 42.6, 36.06, 36.04, 31.9, 31.66, 31.63, 25.9, 24.0,
18.2, -4.6.
B-alkylcatecholborane:7b [R]22 ) -13.8 (c ) 0.81, CHCl3).
D
Compound 11 was prepared according to general procedure
C from 10 (172 mg, 0.59 mmol). FC (hexane/EtOAc 98:2) gave
11 (97 mg, 90%, 85% ee): GC (isotherm 85 °C, â-cyclodextrine
25% acetoxy), retention times: 123 min (92.4%) and 127 min
1
(7.6%); [R]27 ) -20.3 (c ) 0.88, CHCl3); colorless oil; H NMR
D
Mixture of two diastereomers: IR (neat) ν 1740 cm-1; MS (CI,
(500 MHz, CDCl3) δ 3.66 (s, 3H), 2.27 (t, J ) 7.7 Hz, 2H), 2.19
CH4) m/z 301 (MH+, 10), 285 (22), 244 (11), 243 (66), 170 (100);
(s, 1H), 1.95 (s, 1H), 1.66-1.27 (m, 7H), 1.17-0.97 (m, 4H); 13
C
HRMS (CI, isobutane) for
301.2199, found 301.2194.
C
16H33O3Si (MH+) (300.5) calcd
NMR (125 MHz, CDCl3) δ 174.4, 51.4, 41.7, 40.8, 37.8, 36.5, 35.2,
32.6, 31.8, 29.9, 28.7; IR (neat) ν 1741 cm-1; MS (CI, CH4) m/z
183 (MH+, 100), 151 (55). Anal. Calcd for C11H18O2 (182.26): C,
72.49; H, 9.95. Found: C, 72.44; H, 9.94.
Meth yl 5-(4-Meth ylcycloh ex-3-en yl)-2-(2-pyr idylsu lfan yl)-
h exa n oa te (7). Compound 7 was prepared according to general
procedure B from (S)-(-)-limonene 6. Hydroboration was achieved
with [Rh(COD)Cl]2, PPh3, and catecholborane (0.35 mL, 3.3
mmol, or 0.64 mL, 6 mmol) at rt overnight. FC (hexane/EtOAc
95:5) gave 7 (441 mg, 44% or 479 mg, 48%, respectively) as a
1:1:1:1 mixture of four diastereomers (colorless oil) and 1-methyl-
4-(1-methyl-2-(2-pyridylsulfanyl)ethyl)cyclohex-1-ene (direct trap-
ping) (80 mg, 11% or 109 mg, 15%, respectively) as a 1:1 mixture
of two diastereomers.
Meth yl 3-(5,6-Isop r op ylid en ed ioxy-2-n or bor n yl)-2-(2-p y-
r id ylsu lfa n yl)p r op a n oa te. The compound was prepared ac-
cording to general procedure B from 128 and (S,S)-BDPP. FC
(hexane/EtOAc 95:5) gave methyl 3-(5,6-isopropylidenedioxy-2-
norbornyl)-2-(2-pyridylsulfanyl)propanoate (720 mg, 66%) as a
1:1 mixture of two diastereomers and exo-2,3-isopropylidene-
dioxy-exo-5-(2-pyridylsulfanyl)norbonane (direct trapping) (140
mg, 17%): colorless oil; IR (neat) ν 1730 cm-1; MS (CI, CH4)
m/z 365 ([M + 2]+, 7), 364 (MH+, 30), 306 (10), 170 (100). Anal.
Calcd for C19H25NO4S (363.47): C, 62.78; H, 6.93. Found: C,
62.86; H, 6.99.
Compound 7 was prepared according to general procedure B
from (S)-(-)-limonene 6. Hydroboration was achieved with the
Wilkinson catalyst [RhCl(PPh3)3] (56 mg, 0.06 mmol) and
catecholborane (0.35 mL, 3.3 mmol) at rt overnight. FC (hexane/
EtOAc 95:5) gave 7 (431 mg, 43%) as a 1:1:1:1 mixture of four
diastereomers (colorless oil) and 1-methyl-4-(1-methyl-2-(2-
pyridylsulfanyl)ethyl)cyclohex-1-ene) (direct trapping) (73 mg,
10%) as a 1:1 mixture of two diastereomers.
Meth yl
3-(5,6-Isop r op ylid en ed ioxy-2-n or bor n yl)p r o-
p a n oa te (13). Compound 13 was prepared according to general
procedure C from methyl methyl 3-[(1R,2R,4R,5S,6R)-5,6-iso-
propylidenedioxy-2-norbornyl]-2-(2-pyridylsulfanyl)propanoate
(206 mg, 0.57 mmol). FC (hexane/EtOAc 98:2) gave 13 (132 mg,
91%, 76% ee): GC (isotherm 115 °C, â-cyclodextrine 25%
acetoxy), retention times: 224 min (11.9%) and 229 min (88.1%).
The absolute configuration of 13 was not proved but tentitavely
assigned by assumed that the stereochemical outcome of the
7 (Mixture of four diastereomers): IR (neat) ν 1740 cm-1
.
Anal. Calcd for C19H27NO2S (333.49): C, 68.43; H, 8.16. Found:
C, 68.49; H, 8.16.
Meth yl 5-(4-Meth yl-cycloh ex-3-en yl)h exa n oa te (8). Com-
pound 8 was prepared according to the general procedure C from
7 (189 mg, 0.57 mmol). FC (hexane/EtOAc 98:2) gave 8 (116 mg,
91%, dr 1:1). The diastereomeric ratio was determined by
inverse-gated decoupling 13C NMR: colorless oil; IR (neat) ν
hydroboration of 12 was running similarly to 9: [R]27 ) -5.5
D
(c ) 0.86, CHCl3); white solid; mp 48 °C; IR (neat) ν 1740 cm-1
;
1H NMR (500 MHz, CDCl3) δ 3.96 (s, 2H), 3.67 (s, 3H), 2.30 (t,
J ) 7.7, 2H), 2.23 (d, J ) 4.5, 1H), 2.02 (s, 1H), 1.67 (dq, J )
7.6, 13.6, 1H), 1.62-1.59 (m, 1H), 1.55 (dq, J ) 7.7, 13.6, 1H),
1.43 (s, 3H), 1.28 (s, 3H), 1.24 (ddd, J ) 2.4, 8.4, 12.3, 1H), 1.20-
1.14 (m, 2H), 1.01 (dt, J ) 4.6, 17.1, 1H); 13C NMR (500 MHz,
CDCl3) δ 173.9, 108.8, 82.1, 81.8, 51.5, 44.5, 40.1, 35.5, 32.5, 31.1,
30.7, 28.7, 25.5, 24.0; MS (CI, CH4) m/z 255 (MH+, 100), 239
1740, 1440 cm-1 1H NMR (500 MHz, CDCl3) δ 5.39-5.35 (m,
;
2H, two dias), 3.67 (s, 6H, two dias), 2.34-2.24 (m, 4H, two dias),
2.04-1.86 (m, 6H, two dias), 1.81-1.62 (m, 6H, two dias), 1.63
(s, 6H, two dias), 1.61 (m, 2H, two dias), 1.45-1.10 (m, 10H,
two dias), 0.86 (d, J ) 6.9, 3H, one dias), 0.84 (d, J ) 6.6, 3H,
one dias); 13C NMR (500 MHz, CDCl3) δ 174.6 (two dias), 134.3
(two dias), 121.3 (one dias), 121.2 (one dias), 51.7 (two dias), 38.6
(one dias), 38.3 (one dias), 37.3 (one dias), 37.1 (one dias), 34.7
(two dias), 34.0 (one dias), 33.7 (one dias), 31.3 (one dias), 31.1
(8) Tanaka, M.; Yoshioka, M.; Sakai, K. Tetrahedron: Asymmetry
1993, 4, 981.
J . Org. Chem, Vol. 68, No. 14, 2003 5771

(58), 197 (71). Anal. Calcd for C14H22O4 (254.32): C, 66.12; H,
8.72. Found: C, 66.18; H, 8.62.
2.24 (m, 2H), 1.81-1.72 (m, 2H), 1.52-1.43 (m, 1H), 1.15-1.07
(m, 1H), 0.96-0.87 (m, 1H), 0.84 (s, 3H), 0.83 (s, 9H); 13C NMR
(500 MHz, CDCl3) δ 174.3, 51.4, 42.8, 34.4, 32.9, 31.2, 27.2, 24.0,
14.1; MS (CI, CH4) m/z 187 (MH+, 100), 171 (19); HRMS (CI,
isobutane) for C11H23O2 MH+ (186.29) calcd 187.1692, found
187.1691.
Met h yl (5S)-5,6,6-Tr im et h yl-2-(2-p yr id ylsu lfa n yl)h ep -
ta n oa te. The compound was prepared according to general
procedure B from 14 and (R,R)-DIOP. Hydroboration at rt
overnight. FC (hexane/EtOAc 95:5) gave methyl (5S)-5,6,6-
trimethyl-2-(2-pyridylsulfanyl)heptanoate (486 mg, 55%) as a 1:1
mixture of two diastereomers and (3R)-2,2,3-trimethyl-4-(2-
pyridylsulfanyl)butane (direct reduction) (100 mg, 16%): color-
Ack n ow led gm en t. This work was supported by the
Swiss National Science Foundation (Grant Nos. 21-
67106.01 and 7SUPJ 062348). We thank Callery Chemi-
cal Co. (Pittsburgh) and Z & S Handel AG (Kloten) for
the generous gift of catecholborane. We thank Prof. R.
Tabacchi and Dr. C. Saturnin from the University of
Neuchaˆtel as well as A. Saxer from the University of
Berne for their help in the determination of the enan-
tiomeric excesses by GC analysis.
less oil. Mixture of two diastereomers: IR (neat) ν 1840 cm-1
;
MS (CI, CH4) m/z 296 (MH+, 100), 280 (21), 261 (12). Anal. Calcd
for C16H25NO2S (295.44): C, 65.05; H, 8.53. Found: C, 65.10,
H, 8.50.
Meth yl (5S)-5,6,6-tr im eth yl-h ep ta n oa te (15). Compound
15 was prepared according to the general procedure C from
methyl (5S)-5,6,6-trimethyl-2-(2-pyridylsulfanyl)heptanoate (152
mg, 0.51 mmol). FC (hexane/ EtOAc 98:2) gave 15 (87 mg, 92%,
ee 41% ee (5S)): GC (isotherm 55 °C, â-cyclodextrine 25%
diacetoxy), retention times: 271 min, (70.3%) and 282 min-
(29.7%). The absolute configuration was assigned as 5S in
accordance with the absolute configuration of the alcohol result-
ing from the oxidation of the corresponding B-alkylcatechol-
borane:7b [R]27D ) -17.6 (c ) 0.96, CHCl3); colorless oil; IR (neat)
Su p p or tin g In for m a tion Ava ila ble: Detailed experi-
mental procedures and full characterization of all new com-
pounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
1
ν 1740 cm-1; H NMR (500 MHz, CDCl3) δ 3.67 (s, 3H), 2.36-
J O034515V
5772 J . Org. Chem., Vol. 68, No. 14, 2003