Simple, efficient chemoenzymatic synthesis of (s)-5-(tert-butyldimethylsilyloxy)-2-cyclohexenone and enantiomeric ketone intermediates of 19-nor-1α,25-dihydroxyvitamin D3

Full text of DOI:10.1021/jo016141g

J . Org. Chem. 2001, 66, 8277-8281
8277
and simpler method would be desirable. Recently, we
have demonstrated6 that the compound 3-hydroxy-5-(tert-
butyldimethylsilyoxy)-(1S,3R,5R)-cyclohexyl acetate (8,
ee >95%) is a key synthon for compactin lactone starting
from phloroglucitol. We planned to utilize this chiral
intermediate 8 for the synthesis of (S)-5-(tert-butyldi-
methylsilyloxy)-2-cylcopentenone (13) and both the enan-
tiomeric forms of chiral ketone 7 (Scheme 1). A recent
report7 on the utility of 13 toward a vitamin D3 analogue
prompts us to report our findings.
Sim p le, Efficien t Ch em oen zym a tic
Syn th esis of (S)-5-(ter t-
Bu tyld im eth ylsilyloxy)-2-cycloh exen on e
a n d En a n tiom er ic Keton e In ter m ed ia tes of
19-Nor -1r,25-d ih yd r oxyvita m in D3
Uttam R. Kalkote,* Sandeep R. Ghorpade,
Subhash P. Chavan, and T. Ravindranathan
Division of Organic Chemistry: Technology,
National Chemical Laboratory, Pune, India - 411 008
The key chiral intermediate 8 was synthesized as
shown in Scheme 2.8 While the SAM lipase-catalyzed
transesterification of 9 affords the diacetate 11 in good
yields (78%), the reaction is very lengthy (10 days, 35
°C).5 Thus, we sought to develop a much more convenient
method through enzymatic hydrolysis of triacetate 10,
which is easily made in quantitative yield from 9. Very
recently, the multiselective enzymatic hydrolysis of the
triacetate of trans-phloroglucitol was reported,9 but to the
best of our knowledge, there is no report on the selective
enzymatic hydrolysis of cis-triacetate 10 to 11. We
screened a few commercial enzymes for the hydrolysis
of 10 in phosphate buffer at pH 7 with PLE, and the most
efficient conversion was observed within 12 h to diacetate
11 (90%). The reaction was successfully scaled up to a
25 g scale (Scheme 2).
Diacetate 11 was protected as the TBDMS ether to give
meso-diacetate 12. Compound 12 was subjected to de-
symmetrization through enzymatic hydrolysis. Com-
pound 8 with [R]D ) -4 (c 1, CHCl3) could be obtained
using PPL, but the reaction was slow and was not
reproducible on a large scale. On the other hand, with
PLE as a catalyst, the reaction was quite rapid but
nonselective affording mainly completely hydrolyzed diol.
There are few reports where the enantioselectivity of
PLE-catalyzed reactions have been improved consider-
ably through optimization, i.e., optimization of reaction
media by adding organic cosolvents.10 The same approach
was applied for optimization of the hydrolysis of 12 using
PLE as the catalyst. After a few solvents at 10% v/v
concentration were screened, the best yield of 8 could be
obtained using tert-butyl alcohol as a cosolvent. The
enantiopurity of 8 was established by HPLC analysis of
its Mosher ester on an (R,R) Whelk-O1 (5 µm) chiral
column. In addition, the desymmetrization reaction was
standardized on an 8 g scale to afford product 8 with an
ee > 96% in 70% isolated yield at pH 8 using 8% v/v tert-
butyl alcohol as a cosolvent. The configuration of 8 at C5
was established to be R by converting it to enone 13 and
comparing the rotation with the reported value {com-
pound 13 [R]D ) +9.4 (c 1, CHCl3) (lit.11 [R]D ) +9.8 (c 1,
CHCl3) for (S)-13)}. Therefore, the absolute configuration
at centers C1 and C3 are automatically fixed as 1S and
kalkote@dalton.ncl.res.in
Received September 24, 2001
1R,25-Dihydroxyvitamin D3 (1), the bioactive metabo-
lite of vitamin D, and its various analogues have high
potential for application as drugs in a diverse range of
disease conditions.1 Among various A-ring modifications,
deletion of the 19-exomethylene function has been shown
to induce interesting biological activities. 19-Nor-1R,25-
dihydroxyvitamin D3 2 displays reduced calcemic effects
(<10%) while retaining good cell-differentiating proper-
ties.2 Several synthetic approaches toward the synthesis
of the hormone 1R,25-D3 and its various analogues have
been developed.3 Among all these approaches, the phos-
phine oxide coupling approach, first developed by
Lythgoe,4 is probably the most useful method for produc-
ing side-chain and other analogues, wherein the phos-
phine oxide 4 is directly coupled to a Grundmann’s ketone
derivative of type 3 producing the 1R,25-D3 skeleton
(Scheme 1). The shortcoming of this route is that the
synthesis of the A-ring fragment 4 is somewhat tedious.
While there are good syntheses of 4, more simple and
efficient syntheses are still required. Phosphine oxide
fragments 4a and 4b can be easily accessed from cyclo-
hexylidene esters 5a and 5b, respectively,2b,4c,f which in
turn are obtained from 3,5-trans-disubstituted cyclo-
hexanones 6 and 7, respectively, through Peterson’s
olefination in good yields.2b The quinic acid method
developed by De Luca et al.2b for the preparation of
cyclohexanone 7 is an efficient method but involves the
use of costlier DIBALH, Bu3SnH, etc. Also, the chemo-
enzymatic synthesis of 2 described by Vandewalle et al.
involves very lengthy chemoenzymatic procedures (5-
10 days) and, hence, is not practical.5 Therefore, a shorter
(1) Hamda, K.; Shinomiya, H. Drugs Future 1993, 16, 1057.
(2) (a) Perlman, K. L.; Sicinski, R. R.; Schnoes, H. K.; DeLuca, H.
F. Tetrahedron Lett. 1990, 31, 1823. (b) Perlman, K. L.; Swenson, R.
E.; Paaren, H. E.; Schnoes, H. K.; DeLuca, H. F. Tetrahedron Lett.
1991, 32, 7663. (c) Bouillon, R.; Sarandeses, A.; Allewaert, K.; Zhao,
J .; Mascarenas, J .; Mourino, A.; Vrielynck, S.; De Clerca, P.; Vande-
walle, M. J . Bone Miner. Res. 1993, 8, 1009.
(3) Zhu, G.-D.; Okamura, W. H. Chem. Rev. 1995, 95, 1877.
(4) (a) Lythgoe, B.; Moran, T. A.; Namudiry, M. E. N.; Ruston, S.;
Tideswell, J .; Wright, P. W. Tetrahedron Lett. 1975, 3863. (b) Lythgoe,
B.; Namudiry, M. E. N.; Tideswell, J . Tetrahedron Lett. 1977, 3685.
(c) Lythgoe, B.; Moran, T. A.; Namudiry, M. E. N.; Ruston, S.;
Tideswell, J .; Wright, P. W. J . Chem. Soc., Perkin Trans. 1 1978, 590.
(d) Lythgoe, B.; Moran, T. A.; Namudiry, M. E. N.; Ruston, S. J . Chem.
Soc., Perkin Trans. 1 1976, 2386. (e) Lythgoe, B.; Manawaring, R.;
Milner, J . R.; Moran, T. A.; Namudiry, M. E. N.; Tideswell, J . J . Chem.
Soc., Perkin Trans. 1 1978, 387. (f) Froash, J . V.; Harrison, I. T.;
Lythgoe, B.; Saksena, A. K. J . Chem. Soc., Perkin Trans. 1 1974, 2005.
(5) Huang, P. Q.; Sabbe, K.; Pottie, M.; Vandewalle, M. Tetrahedron
Lett. 1995, 36, 8299.
(6) Ghorpade, S. R.; Kalkote, U. R.; Chavan, S. P.; Bhide, S. R.;
Ravindranathan, T.; Puranik, V. J . Org. Chem. 2001, 66, 6803.
(7) Hanazawa, T.; Inamori, H.; Masuda, S. O.; Sato, F. Org. Lett.
2001, 3, 2205.
(8) Strong, P. N.; Kena, J . F. W. J . Org. Chem. 1975, 40, 956.
(9) Wirta, B.; Iding, H.; Hilpert, H. Tetrahedron: Asymmetry 2000,
11, 4171.
(10) Bjorkling, F.; Boutelje, J .; Gatenbeck, S.; Hult, K.; Norin, T.
Tetrahedron Lett. 1985, 26, 4975.
(11) Hareau, G. P.-J .; Koiwa, M.; Hikichi, S.; Sato, F. J . Am. Chem.
Soc. 1999, 121, 3640.
10.1021/jo016141g CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/06/2001

8278 J . Org. Chem., Vol. 66, No. 24, 2001
Notes
Sch em e 1
Sch em e 2a
as critical steps to achieve the correct stereochemistry.
The symmetric nature of intermediate 8 offers an op-
portunity for selective manipulation of functional groups
to obtain both enantiomeric forms of the desired com-
pound. Since Mitsunobu inversion directly on compound
8 would further create problems due to hydrolysis of the
acetate group, compound 8 was protected as the THP
ether 14, which on solvolysis with methanol-K2CO3
afforded cyclohexanol derivative 15 in 96% yield (Scheme
3). Inversion of the cyclohexanol 15 was accomplished
quantitatively under Mitsunobu conditions (0 °C, DEAD,
benzoic acid) to affoard 16.12 Methanolysis of 16 with
methanol-K2CO3 afforded cyclohexanol 17 possessing
the required trans substitution pattern in 96% yield.
Compound 17 was protected as its TBDMS derivative
(TBDMSCl, Et3N, DMAP, 93%) followed by selective THP
deprotection using anhydrous MgBr2 in dry ether13 to
afford trans-3,5-disilyloxycyclo-hexanol 19 (95% yield).
Finally, PCC oxidation of 19 afforded the required ketone
7 (P ) TBDMS) in good yield (70%). Thus, an efficient
chiral synthesis of ketone 7 was achieved starting from
phloroglucitol (9) in 57% overall yield.
a
Key: (a) acetic anhydride, pyridine, 0 °C-RT, 8 h, 100%; (b)
PLE, pH 7, 12 h, 90%; (c) TBDMSCl, Et3N, DMAP, CH2Cl2, 0 °C-
RT, 90%; (d) PLE, pH 8, buffer with 8% tert-butyl alcohol, 30 °C,
48 h, 70%; (e) (i) PCC, CH2Cl2, RT, 2 h, 95%, (ii) DBU, CH2Cl2,
RT, 10 min, 90%.
Sch em e 3a
In a similar procedure, en t-7 (P ) THP) was obtained
from 17. In this case, free -OH in 17 was protected as
the THP ether 20 (DHP, PTSA, 0 °C, 90%) followed by
selective TBDMS deprotection using tetrabutylammo-
nium fluoride to afford compound 21 (99.5%) enantio-
merically related to 19. The compound 21 on PCC
oxidation afforded en t-7 (P ) THP) in 66% overall yield
from 9. Enantiomeric excess of en t-7 (P ) THP) was
determined to be 96% by HPLC analysis using a chiral
column [Lichrocart (R,R) Whelk- O 1 (5µm) column].
Since all the reactions were carried out under nonrace-
mizing conditions (even in the conversion of compound
21 to en t-7), the ee of 7 was also assumed to be nearly
96% similar to that of en t-7 (P ) THP).
In conclusion, we have demonstrated a simple and
efficient chemoenzymatic chiral synthesis of 2-cylco-
hexenone (13) and both enantiomeric forms of dipro-
tected trans-3,5-dihydroxy cyclohexanone (7) starting
from phloroglucitol (9), which are useful intermediates
of 19-nor-1R,25-dihydroxyvitamin D3 (2).
a
Key: (a) DHP, PTSA, 0 °C, 2 h; (b) K2CO3, methanol, RT, 2-12
h; (c) PPh3, benzoic acid, DEAD, 0 °C, 2 h; (d) TBDMSCl, Et3N,
DMAP, CH2Cl2, 0 °C-RT, 12 h; (e) MgBr2, etherate, dry ether,
RT, 3 h; (f) PCC, NaOAc, CH2Cl2, RT, 1 h; (g) TBAF, THF, 1 h.
3R as the compound is all cis, being derived from cis-
phloroglucitol (Scheme 2). This was further supported by
the recently published synthesis of en t-8 {Compound 8
[R]D ) -4.8 (c 1, CHCl3), en t-8 [R]D ) +5 (c 1, CHCl3)}.9
It is pertinent to note that, very recently, Sato7 has
demonstrated the utility of the same intermediate 13
toward the synthesis of Vitamin D3 intermediates.
Compound 8 (ee > 96%) was subjected to further
chemical transformations as shown in Scheme 3.
The synthesis of ketone 7 from 8 would require
Mitsunobu inversion12 and functional group interchange
Exp er im en ta l Section
P r ep a r a tion of cis,cis-3,5-Di(m eth ylca r bon yloxy)cyclo-
h exyl Aceta te (10). Phloroglucitol (9, dried at 110 °C to remove
water of crystallization, 6.6 g, 50 mmol) was mixed with pyridine
in a 100 mL two-necked round-bottom flask fitted with a
pressure-equalizing dropping funnel and a calcium chloride
guard tube. The mixture was cooled to 0 °C in an ice-salt
(12) (a) Mitsunobu, O. Synthesis 1981, 1. (b) Mitsunobu, O.; Yamada,
M.; Mukaiyama, T. Bull. Chem. Soc. J pn. 1967, 40, 935.
(13) Kim, S.; Park, J . H. Tetrahedron Lett. 1987, 28, 439.

Notes
J . Org. Chem., Vol. 66, No. 24, 2001 8279
mixture. To the cold, stirred mixture was added acetic anhydride
(17.34 g, 0.17 mol) dropwise while maintaining the temperature
below 0 °C. After the addition was over, the reaction mixture
was stirred at room temperature (RT) for 10 h. Then, it was
cooled to 0 °C in an ice-salt mixture, and the reaction was
quenched by slowly adding ice-cold, dilute HCl. The mixture was
taken up in a separating funnel and was extracted with ethyl
acetate (3 × 50 mL). Organic extracts were mixed and washed
several times with cold, dilute HCl until free from pyridine,
followed by an aqueous NaHCO3 wash and a final brine wash.
The organic layer was then dried on anhydrous sodium sulfate,
and solvent was evaporated under vacuum. Residue was crushed
and dried under high vacuum to afford pure, crystalline cis,cis-
3,5-di(methylcarbonyloxy)cyclohexyl acetate (10, yield 12.9 g,
reaction mixture was extracted with ethyl acetate (3 × 200 mL).
Organic layers were combined and washed with brine. They were
then dried on anhydrous sodium sulfate, and solvent was
removed under vacuum. The oily residue contained 3-hydroxy-
5-(tert-butyldimethylsilyloxy)-(1S,3R,5R)-cyclohexyl acetate 8
along with unreacted 12. These were separated by flash column
chromatography. cis,cis-3-(Methylcarbonyloxy)-5-(tert-butyldi-
methylsilyloxy) cyclohexyl acetate (12) was recovered: 2.04 g.
3-Hydroxy-5-(tert.butyldimethylsilyloxy)-(1S,3R,5R)-cyclohex-
yl acetate was recovered as a viscous liquid (8, yield 3.7 g, 70%
based on recovered starting material). 1H NMR (CDCl3): δ 0.06
(s, 9H), 0.87 (s, 6H), 1.35-1.60, (m, 3H), 2.05 (s, 3H), 2.15 (m,
3H), 3.74 (m, 2H), 4.77 (m, 1H). 13C NMR (CDCl3): -4.99, 17.68,
20.89, 25.49, 39.66, 40.11, 43.71, 64.80, 65.96, 67.83, 170.16. IR
(CHCl3): cm-1 758, 839, 1049, 1109, 1218, 1254, 1370, 1725,
2860, 2888, 2952, 3017. Mass: base m/e ) 75; other m/e ) 231,
171, 129, 117, 105, 97, 79, 75, 67, 59. Anal. Calcd for
C14H28O4Si: C, 58.33%; H, 9.72%. Found: C, 58.15%; H, 9.91%.
[R]D ) -4.8 (c 1, CHCl3). ee > 96% (determined by chiral HPLC
of corresponding Mosher ester. Column: (R,R) Whelk-O1 [4.0
mm Id x 25 cm] AT-256; λ ) 254 nm; flow rate ) 1 mL/min;
mobile phase ) hexane:2-propanol 98:02; retention time for
Mosher ester of 8 ) 4.59, for Mosher ester of en t-8 ) 4.34).
Syn t h esis of 3-Tet r a h yd r o-2H -2-p yr a n yloxy-5-(ter t-
bu tyldim eth ylsilyloxy)-(1S,3R,5R)-cycloh exyl Acetate (14).
3-Hydroxy-5-(tert-butyldimethylsilyloxy)-(1S,3R,5R)-cyclohex-
yl acetate (8, 2.9 g, 9.73 mmol) was dissolved in dry dichloro-
methane (30 mL). The solution was cooled to below 0 °C in an
ice-salt bath. To the stirred solution was added dihydropyran
(1 g, 12 mmol), and p-toluenesulfonic acid monohydrate (0.1 g)
was added as a catalyst. The reaction mixture was stirred at
-10 °C for 2 h. The reaction was quenched with aqueous sodium
bicarbonate solution. Both of the layers were separated. The
aqueous layer was extracted with dichloromethane (10 mL).
Organic layers were combined and washed with water followed
by brine. They were then dried on anhydrous sodium sulfate,
and solvent was removed under vacuum. The residue was
purified by flash column chromatography to yield 3-tetrahydro-
2H-2-pyranyloxy-5-(tert-butyldimethylsilyloxy)-(1S,3R,5R)-cyclo-
1
100%, mp 78 °C). H NMR (CDCl3): δ 1.33-1.51 (dd, 3H), 2.03
(s, 9H), 2.33 (m, 3H), 4.79 (m, 3H). 13C NMR (CDCl3): δ 21, 36,
67, 169. IR (KBr): cm-1 759, 1023, 1235, 1436, 1740, 2094, 2252,
2874, 2946. Mass: base m/e ) 139, 96; other m/e ) 238, 198,
156, 78, 67, 61. Anal. Calcd for C12H18O6 : C, 55.81%; H, 6.98%.
Found: C, 55.63%; H 7.01%.
P r ep a r a tion of cis,cis-3-Hyd r oxy-5-m eth ylca r bon yloxy-
cycloh exyl Aceta te (11). Finely powdered cis,cis-3,5-di(meth-
ylcarbonyloxy)cyclohexyl acetate (10, 6.5 g, 25.19 mmol) was
suspended in 0.1 M sodium phosphate buffer (pH 7) (135 mL)
and stirred vigorously. To the stirred suspension was added
Porcine Liver Esterase (0.110 g), and reaction mixture was
stirred vigorously at 30 °C for 12 h. The pH of the reaction
mixture was monitored every 2 h and was maintained at pH 7
using 1 N NaOH solution. After completion of the reaction (12
h), the mixture was extracted with ethyl acetate (3 × 150 mL).
The organic layers were combined, washed with brine, dried on
anhydrous sodium sulfate, and concentrated under vacuum to
yield cis,cis-3-hydroxy-5-methylcarbonyloxycyclohexyl acetate
1
(11, yield 4.92 g, 90%) as a semisolid. H NMR (CDCl3): δ 1.43
(qn, 3H), 2.01 (s, 6H), 2.24 (m, 3H), 2.71 (bs, 1H), 3.72 (m, 1H),
4.72 (m, 2H). 13C NMR (CDCl3): δ 20.76, 35.99, 39.59, 64.83,
67.31, 170.04. IR (KBr): cm-1 755, 884, 1029, 1140, 1250, 1368,
1739, 2871, 2953, 3445. Mass: base m/e ) 96; other m/e ) 156,
138, 114, 73, 67, 67, 60, 55. Anal. Calcd for C10H16O5: C, 55.56%;
H, 7.40%. Found: C, 55.40%; H, 7.56%.
1
hexyl acetate (14, yield 3.7 g, 99.5%) as an oily liquid. H NMR
P r ep a r a t ion of cis,cis-3-(Met h ylca r b on yloxy)-5-(ter t-
bu t yld im et h ylsilyloxy)-cycloh exyl Acet a t e (12). cis,cis-3-
Hydroxy-5-methylcarbonyloxycyclohexyl acetate (11, 2 g, 9.26
mmol) and DMAP (0.113 g, 0.926 mmol) were placed in a 100
mL two-necked round-bottom flask equipped with a dropping
funnel and a two-way stopcock. The vessel was evacuated and
flushed with argon. Dry dichloromethane (10 mL) was added,
and the solution was cooled to -10 °C with stirring. A solution
of tert-butyldimethylsilyl chloride in dry dichloromethane (10
mL) was added dropwise while maintaining temperature below
0 °C. The reaction mixture was stirred for 15 min, and dry
triethylamine (2.02 g, 20 mmol) was added dropwise. The
reaction mixture was stirred at room temperature for 12 h. It
was then transferred to a separating funnel and washed suc-
cessively with cold, dilute HCl water, aqueous NaHCO3, and
then brine. The organic layer was dried on anhydrous sodium
sulfate, and solvent was removed under vacuum. The residue
was purified by flash column chromatography (eluent 2-4%
ethyl acetate in petroleum ether) to yield cis,cis-3-(methyl-
carbonyloxy)-5-(tert-butyldimethylsilyloxy)cyclohexyl acetate (12,
(CDCl3): δ 0.05 (s, 6H), 0.87 (s, 9H), 1.25-1.90 (m, 9H), 2.04 (s,
3H), 2.05-2.40 (m, 3H), 3.40-3.75 (m, 3H), 3.86 (m, 1H), 4.55-
4.80 (m, 2H). 13C NMR (CDCl3): δ -4.90, 18.00, 19.40, 19.50,
25.20, 25.80, 30.90, 36.80, 40.70, 41.00, 42.80, 62.00, 62.50, 66.00,
68.00, 69.70, 95.00, 96.80, 169.90. IR (CHCl3): cm-1 752, 768,
838, 1030, 1115, 1216, 1252, 1727, 2859, 2951, 3017. Mass: base
m/e ) 85; other m/e ) 231, 211, 171, 159, 129, 117, 105, 101, 85,
79, 75, 67, 55. Anal. Calcd for C19H36O5Si: C, 61.29%; H, 9.68%.
Found: C, 61.37%; H, 9.84%. [R]D ) +1.39 (c 1, CHCl3).
Syn t h esis of 3-Tet r a h yd r o-2H -2-p yr a n yloxy-5-(ter t-
b u t yld im et h ylsilyloxy)-(1S,3R,5S)-cycloh exa n -1-ol (15).
3-Tetrahydro-2H-2-pyranyloxy-5-(tert-butyldimethylsilyloxy)-
(1S,3R,5R)-cyclohexyl acetate (14, 3.5 g, 9.16 mmol) was dis-
solved in dry methanol (25 mL). To the solution was added
anhydrous potassium carbonate (0.828 g, 6 mmol), and the
mixture was stirred at room temperature for 2 h. Methanol was
removed under vacuum, and the residue was extracted with
dichloromethane (3 × 10 mL). Dichloromethane layers were
combined and washed with water followed by brine. They were
dried on anhydrous sodium sulfate. Solvent was removed under
vacuum, and the residue was purified by flash column chroma-
tography to yield 3-tetrahydro-2H-2-pyranyloxy-5-(tert-butyldi-
methylsilyloxy)-(1S,3R,5S)-cyclohexan-1-ol (15, yield 3 g, 96%)
as a viscous oil. 1H NMR (CDCl3): δ 0.06 (s, 6H), 0.87 (s, 9H),
1.35-1.90 (m, 10H), 2.05-2.35 (m, 3H), 3.40-3.75 (m, 4H),
3.80-3.98 (m, 1H), 4.73 (s, 1H). 13C NMR (CDCl3): δ -4.90,
18.00, 19.50, 25.20, 25.80, 30.90, 40.00, 40.70, 42.00, 42.30, 44.70,
62.00, 62.50, 65.80, 66.90, 69.50, 70.00, 96.40, 96.80. IR
(CHCl3): cm-1 753, 767, 838, 867, 1021, 1048, 1114, 1215, 1254,
2859, 2884, 2948, 3014, 3419. Mass: base m/e ) 75; other m/e
) 309, 189, 171, 129, 119, 101, 85, 79, 75, 67, 55. Anal. Calcd
for C17H34O4Si: C, 61.82%; H, 10.30%. Found: C, 61.83%; H,
10.74%. [R]D ) +0.93 (c 1, CHCl3).
1
yield 2.85 g, 90%) as an oily liquid. H NMR (CDCl3): δ 0.06 (s,
9H), 0.87 (s, 6H), 1.20-1.45 (m, 3H), 2.03 (s, 6H), 2.2 (m, 3H),
3.38 (m, 1H), 4.73 (m, 2H). 13C NMR (CDCl3): δ -5.07, 17.61,
20.73, 25.40, 36.17, 40.40, 65.43, 67.01, 169.64. IR (CHCl3): cm-1
759, 838, 1035, 1106, 1249, 1369, 1734, 2859, 2955. Mass: base
m/e ) 117; other m/e ) 273, 213, 171, 159, 129, 117, 97, 79, 75,
57. Anal. Calcd for C16H30O5Si: C, 58.18%; H, 9.10%. Found:
C, 58.19%; H, 9.29%.
P r epar ation of 3-Hydr oxy-5-(ter t-bu tyldim eth ylsilyloxy)-
(1S,3R,5R)-cycloh exyl Aceta te (8). cis,cis-3-(Methylcarbonyl-
oxy)-5-(tert-butyldimethylsilyloxy)cyclohexyl acetate (12, 8 g, 242
mmol) was dissolved in tert-butyl alcohol (32 mL). To the solution
was added 0.1 M sodium phosphate buffer (368 mL, pH 8), and
the mixture was stirred vigorously. To the stirred emulsion was
added Porcine Liver Esterase (0.30 g), and the mixture was
stirred vigorously at 30 °C for 48 h. During the reaction, the pH
was maintained at 8 using 1 N sodium hydroxide solution. The
Syn th esis of 1-P h en ylca r bon yloxy-3-tetr a h yd r o-2H-2-
p yr a n yloxy-5-(t er t -b u t yld im e t h ylsilyloxy)-(1R ,3R ,5R )-
cycloh exa n e (16). 3-Tetrahydro-2H-2-pyranyloxy-5-(tert-
butyldimethylsilyloxy)-(1S,3R,5S)-cyclohexan-1-ol (15, 1.2 g, 3.64

8280 J . Org. Chem., Vol. 66, No. 24, 2001
Notes
mmol), benzoic acid (0.61 g, 5 mmol), and triphenylphosphine
(1.31 g, 5 mmol) were placed in 50 mL two-necked round-
bottomed flask equipped with a two-way stopcock and a sidearm
addition funnel. The assembly was evacuated and flushed with
argon. Anhydrous THF (10 mL) was added, and the solution was
cooled to -10 °C in an ice-salt mixture with magnetic stirring.
To the cold, stirred solution was added diethylazodicarboxylate
(0.87 g, 5 mmol) in anhydrous THF (5 mL) dropwise over a period
of 30 min. while maintaining the temperature well below 0 °C.
The reaction mixture was stirred at 0 °C for 2 h. Then, it was
filtered through a silica gel bed and solvent was evaporated
under vacuum. The residue was purified on a silica gel column
(8% ethyl acetate in pet. ether) to afford 1-phenylcarbonyloxy-
3-tetrahydro-2H-2-pyranyloxy-5-(tert-butyldimethylsilyloxy)-
(1R,3R, 5R)-cyclohexane (16, yield 1.57 g, 100%) as a viscous
25.92, 31.11, 31.29, 38.74, 40.33, 41.94, 42.80, 43.65, 62.36, 62.79,
66.06, 67.12, 67.25, 69.81, 70.24, 96.85, 97.37. IR (CHCl3): cm-1
419, 450, 475, 668, 755, 769, 835, 1026, 1214, 2856, 2891, 2950,
3018. Mass: base m/e ) 85; other m/e ) 303, 285, 211, 185, 171,
159, 145, 129, 115, 101, 75. Anal. Calcd for C23H48O4Si2: C,
62.16%; H, 10.81%. Found: C, 62.29%; H, 11.01%. [R]D ) +3.98
(c 1, CHCl3).
Syn t h esis of 3,5-Di(ter t-b u t yld im et h ylsilyloxy)cyclo-
h exa n -1-ol (19). 2-[3,5-Di(tert-butyldimethylsilyloxy)cyclo-
hexyloxy]tetrahydro-2H-pyran (18, 0.3 g, 676 mmol) was dis-
solved in dry ether under an argon atmosphere. To the solution
was added magnesium bromide etherate (0.524 g, 2.03 mmol),
and the reaction mixture was stirred for 3 h at RT. The reaction
was quenched by adding cold, saturated ammonium chloride
solution. The ether layer was separated, and the aqueous layer
was extracted with ether (ether 3 × 5 mL). Organic extracts were
combined, washed with brine, and dried on anhydrous sodium
sulfate. Solvent was evaporated under vacuum, and the residue
was purified on a silica gel column (10% ethyl acetate in pet.
ether) to afford 3,5-di(tert-butyldimethylsilyloxy)cyclohexan-1-
1
liquid. H NMR (CDCl3): δ 0.06 (s, 6H), 0.88 (s, 9H), 1.20-1.95
(m, 9H), 2.05-2.60 (m, 3H), 3.51 (m, 1H), 4.00 (m, 2H), 4.69,
4.80 (2m, 1H), 5.52 (m, 1H), 7.40-7.65 (m, 3H), 8.00 (md, 2H).
13C NMR (CDCl3): δ -4.50, 18.18, 20.00, 25.80, 25.93, 31.00,
35.80, 37.00, 39.46, 41.70, 43.58, 62.32, 66.18, 69.50, 70.45, 96.54,
97.61, 128.49, 129.59, 130.80, 132.93, 165.58. IR (CHCl3): cm-1
418, 440, 470, 668, 748, 770, 1026, 1098, 1215, 1275, 1712, 2857,
1712, 2857, 2951, 3017. Mass: base m/e ) 105; other m/e ) 293,
179, 171, 159, 135, 129, 122, 105, 85, 67, 55. Anal. Calcd for
C24H38O5Si: C, 66.36%; H, 8.76%. Found: C, 66.24%; H, 8.91%.
[R]D ) +3.71 (c 1.3, CHCl3).
1
ol (19, yield 0.23 g, 95%) as an oily liquid. H NMR (CDCl3): δ
0.09 (s, 12H), 0.91 (s, 18H), 1.48-2.05 (m, 7H), 4.10 (m, 1H),
4.27 (m, 2H). 13C NMR (CDCl3): δ -4.93, -4.75, 17.96, 18.08,
25.77, 42.68, 64.50, 67.55, 68.89. IR (CHCl3): cm-1 436, 457, 753,
769, 834, 1039, 1060, 1092, 1117, 1215, 1254, 2859, 2892, 2934,
2950, 3014, 3482. Mass: base m/e ) 145; other m/e ) 303, 227,
211, 185, 171, 133, 129, 115, 101, 79, 72, 59. Anal. Calcd for
Syn t h esis of 3-Tet r a h yd r o-2H -2-p yr a n yloxy-5-(ter t-
bu tyld im eth ylsilyloxy)-(1R,3R,5S)-cycloh exa n -1-ol (17).
1-Phenylcarbonyloxy-3-tetrahydro-2H-2-pyranyloxy-5-(tert-
butyldimethylsilyloxy)-(1R,3R,5R)-cyclohexane (16,1.7 g, 3.92
mmol) was dissolved in dry methanol (15 mL). To the solution
was added anhydrous potassium carbonate (0.5 g, 3.6 mmol),
and the reaction mixture was stirred at RT for 12 h. Methanol
was removed under vacuum, and the residue was extracted with
ethyl acetate (3 × 10 mL). Organic extracts were combined,
washed with brine, and dried on anhydrous sodium sulfate.
Solvent was removed under vacuum, and the residue was
purified on a silica gel column (20% ethyl acetate in pet. ether)
to afford 3-tetrahydro-2H-2-pyranyloxy-5-(tert-butyldimethyl-
silyloxy)-(1R,3R,5S)-cyclohexan-1-ol (17, yield 1.24 g, 96%) as a
viscous liquid. 1H NMR (CDCl3): δ 0.05 (s, 6H), 0.86 (s, 9H),
1.20-2.35 (m, 13H), 3.49 (m, 1H), 3.90 (m, 1H), 4.00 (m, 2H),
4.26 (m, 1H), 4.69 (m, 1H). 13C NMR (CDCl3): δ -4.66, 16.00,
19.70, 25.40, 25.80, 31.14, 37.82, 39.78, 41.73, 41.91, 43.53, 62.55,
62.67, 65.75, 66.36, 69.41, 70.02, 96.82, 97.34. IR (CHCl3): cm-1
435, 471, 668, 751, 770, 835, 1025, 1099, 1124, 1214, 1252, 2857,
2892, 2948, 3013, 3450. Mass: base m/e ) 85; other m/e ) 309,
229, 213, 187, 171, 159, 145, 119, 97, 79, 75, 69, 55. Anal. Calcd
for C17H34O4Si: C, 61.82%; H, 10.30%. Found: C, 61.76%; H,
10.56%. [R]D ) +1.59 (c 1, CHCl3).
C
18H40O3Si2: C, 60.00%; H, 11.11%. Found: C, 60.12%; H,
11.34%. [R]D ) +2.98 (c 1.17, CHCl3).
Syn th esis of 3,5-Di(ter t-bu tyld im eth ylsilyloxy)-(3S,5S)-
cycloh exa n -1-on e (7, P ) TBDMS). 3,5-Di(tert-butyldimethyl-
silyloxy)cyclohexan-1-ol (19, 0.15 g, 0.41 mmol) was dissolved
in dichloromethane (3 mL). To the solution were added pyri-
dinium chlorochromate (0.153 g, 0.71 mmol) and anhydrous
sodium acetate (0.02 g), and the reaction was stirred for 1 h.
The reaction mixture was diluted with ether (5 mL), and solvent
was decanted. A sticky residue was extracted with ether (3 × 5
mL). Ether extracts were combined, washed successively with
brine-water and brine. The organic layer was dried on anhy-
drous sodium sulfate, and solvent was removed under vacuum.
The residue was purified on a silica gel column (1% ethyl acetate
in pet. ether) to afford 3,5-di(tert-butyldimethylsilyloxy)-(3S, 5S)-
cyclohexan-1-one (7, yield 0.10 g, 70%) as an oily liquid. 1H NMR
(CDCl3): δ 0.05 (s, 12H), 0.86 (s, 18H), 1.94 (t, 2H, J ) 9), 2.38
(dd, 2H, J ) 12), 2.55 (dd, 2H, J ) 6), 4.34 (qn, 2H, J ) 6). 13C
NMR (CDCl3): δ -4.94, -4.88, 17.94, 25.71, 42.13, 50.25, 66.83,
207.84. IR (CHCl3): cm-1 411, 434, 452, 461, 478, 767, 806, 837,
868, 902, 1035, 1064, 1100, 1216, 1255, 1719, 2858, 2955, 3019.
Mass: base m/e ) 143; other m/e ) 301, 101. Anal. Calcd for
C
18H38O3Si2: C, 60.33%; H, 10.61%. Found: C, 60.21%; H,
Syn th esis of 2-[3,5-Di(ter t-bu tyld im eth ylsilyloxy)cyclo-
h exyloxy]tetr h yd r o-2H-p yr a n (18). 3-Tetrahydro-2H-2-pyr-
anyloxy-5-(tert-butyldimethylsilyloxy)-(1R,3R,5S)-cyclohexan-1-ol
(17, 0.5 g, 1.5 mmol) was dissolved in dry dichloromethane (5
mL) and dry HMPA (0.5 mL) under an argon atmosphere. The
solution was cooled to 0 °C in an ice-salt mixture. To the cold,
stirred solution was added tert-butyldimethylsilyl chloride (0.35
g, 2.3 mmol), and DMAP (0.02 g, 0.16 mmol) dissolved in dry
dichloromethane (2 mL) was added dropwise while maintaining
a temperature below 0 °C. The reaction mixture was stirred for
5 min. To the cold reaction mixture was added triethylamine
(0.3 g, 2.97 mmol, 0.41 mL) dropwise while maintaining a
temperature below 0 °C. After the addition was over, the reaction
mixture was stirred at RT for 12 h. The reaction was quenched
by adding ice-cold, dilute hydrochloric acid. The organic layer
was separated. The aqueous layer was extracted with dichloro-
methane. Organic layers were combined and washed with dilute
hydrochloric acid, brine-water, 10% sodium bicarbonate solu-
tion, and finally with brine. The organic layer was dried on
anhydrous sodium sulfate, and solvent was evaporated under
vacuum. The residue was purified on a silica gel column (2%
ethyl acetate in pet. ether) to afford pure 2-[3,5-di(tert-butyldi-
methylsilyloxy)cyclohexyloxy]tetrhydro-2H-pyran (18, yield 0.625
g, 93%) as an oily liquid. 1H NMR (CDCl3): δ 0.05, 0.06 (2s, 12H),
0.88 (s, 18H), 1.20-2.35 (m, 12H), 3.51 (m, 1H), 4.01 (m, 3H),
4.19(m, 1H), 4.26 (m, 1H), 4.65,4.73 (2m, 1H). 13C NMR
(CDCl3): δ -5.02, -4.66, 17.96, 18.20, 19.82, 20.06, 25.53, 25.71,
10.82%. [R]D ) -14.62 (c 1.1, CHCl3).
Syn th esis of 2-[3-Tetr a h yd r o-2H-2-p yr a n yloxy-5-(ter t-
b u t yld im e t h ylsilyloxy)cycloh e xyloxy]-t e t r a h yd r o-2H -
p yr a n (20). 3-Tetrahydro-2H-2-pyranyloxy-5-(tert-butyldi-
methylsilyloxy)-(1R,3R,5S)-cyclohexan-1-ol (17, 0.30 g, 9.09
mmol) was dissolved in dry dichloromethane (5 mL) under a
nitrogen atmosphere. To the solution was added 3,4-dihydro-
pyran (0.115 g, 1.36 mmol). The solution was cooled to below 0
°C in an ice-salt mixture. To the cold, stirred solution was added
PTSA (0.01 g), and the mixture was stirred at 0 °C for 2 h. The
reaction was quenched by adding aqueous sodium bicarbonate
solution. The organic layer was separated, and the aqueous layer
was extracted with dichloromethane (2 × 3 mL). Combined
organic extracts were washed with brine-water and dried on
anhydrous sodium sulfate. Solvent was evaporated under vacuum,
and the residue was purified on a silica gel column (5% ethyl
acetate in pet. ether) to afford 2-[3-tetrahydro-2H-2-pyranyloxy-
5-(tert-butyldimethylsilyloxy)cyclohexyloxy]-tetrahydro-2H-py-
ran (20, yield 0.34 g, 90%) as an oily liquid. 1H NMR (CDCl3):
δ 0.06, 0.07 (2s, 6H), 0.89 (s, 9H), 1.15-2.38 (m, 18H), 3.5 (m,
2H), 3.8 (m, 4H), 4.14 (m, 1H), 4.72 (m, 2H). 13C NMR (CDCl3):
δ -4.84, 17.88, 19.31, 19.53, 25.30, 25.63, 30.93, 34.49, 35.82,
36.81, 38.00, 38.43, 40.52, 41.44, 43.31, 43.50, 62.10, 62.39, 65.70,
65.96, 69.45, 70.29, 70.70, 96.50, 97.05. IR (CHCl3): cm-1 437,
478, 747, 771, 1024, 1076, 1121, 1213, 1250, 2856, 2944, 3011.
Mass: base m/e ) 84; other m/e ) 272, 255, 210, 171, 128. Anal.

Notes
J . Org. Chem., Vol. 66, No. 24, 2001 8281
Calcd for C22H42O5Si: C, 63.77%; H, 10.14%. Found: C, 63.71%;
H, 10.31%. [R]D ) -0.55 (c 1.11, CHCl3).
3-Oxo-5-tert-butyldimethylsilyloxy-(1R,5S)-cyclohexyl acetate
(0.30 g, 1 mmol) was dissolved in dichloromethane (5 mL). To
the solution was added DBU (0.150 g, 1 mmol), and the reaction
mixture was stirred for 2 h. The reaction was quenched by
adding cold ammonium chloride solution. Both layers were
separated. The organic layer was washed with ammonium
chloride solution and was dried on anhydrous sodium sulfate.
Solvent was removed under vacuum, and the residue was
purified on a silica gel column to afford 5-tert-butyldimethyl-
silyloxy-(5S)-2-cyclohexanone (13, yield 0.224 g, 95%) as an oily
Syn t h esis of 3,5-Di(t et r a h yd r o-2H -2-p yr a yn yloxy)-1-
cycloh exa n ol (21). 2-[3-Tetrahydro-2H-2-pyranyloxy-5-tert-
butyldimethylsilyloxy)cyclohexyloxy]-tetrahydro-2H-pyran (20,
0.25 g, 0.60 mmol) was dissolved in THF (3 mL). To the solution
was added 1 M tetrabutylammonium fluoride solution (0.9 mL,
0.235 g, 0.9 mmol), and the reaction was stirred for 1 h. Solvent
was evaporated under vacuum, and the residue was purified on
a silica gel column (20% ethyl acetate in pet. ether) to afford
compound 3,5-di(tetrahydro-2H-2-pyraynyloxy)-1-cyclohexanol
(21, yield 0.18 g, 99.5%). 1H NMR (CDCl3): δ 1.4-2.15 (m, 19H),
3.52 (m, 2H), 3.90 (m, 2H), 4.13 (m, 3H), 4.72 (m, 2H). 13C NMR
(CDCl3): δ 19.23, 19.33, 19.50, 25.10, 30.76, 34.41, 35.98, 36.42,
38.04, 38.79, 40.02, 40.18, 62.06, 62.20, 62.32, 62.41, 65.51, 65.78,
69.18, 69.34, 69.60, 70.66, 71.01, 71.21, 96.51, 96.65, 96.80, 96.96.
IR (CHCl3): cm-1 667, 754, 1022, 1067, 1120, 1350, 1448, 2858,
2943, 3009, 3453. Mass: base m/e ) 85; other m/e ) 263, 215,
199, 185, 175, 115, 97. Anal. Calcd for C16H28O5: C, 64.00%; H,
9.33%. Found: C, 64.07%; H, 9.41%. [R]D ) +2.58 (c 1.18,
CHCl3).
1
liquid. H NMR (CDCl3): δ 0.07 (s, 6H), 0.87 (s, 9H), 2.25-2.75
(m, 4H), 4.23 (m, 1H), 6.05 (dm, 1H), 6.9 (m, 1H). 13C NMR
(CDCl3): δ -5.10, 17.62, 25.38, 35.23, 47.69, 67.32, 129.77,
146.27, 197.92. IR (CHCl3): cm-1 757, 834, 869, 1102, 1218,
1254, 1386, 1678, 2857, 2892, 2934, 2953, 3015. Mass: base m/e
) 74; other m/e ) 211, 169, 151, 127, 110, 94, 66, 58. Anal. Calcd
for C12H22O2Si: C, 63.72%; H, 9.73%. Found: C, 63.65%; H,
9.91%. [R]D ) +9.41 (c 1, CHCl3) (lit.11 [R]D ) +9.8 (c 1, CHCl3)).
P r ep a r a tion of Ra cem ic 3-Hyd r oxy-5-ter t-bu tyld im eth -
ylsilyloxycycloh exyl Acet a t e (+) 8. cis,cis-3-(Methylcar-
bonyloxy)-5-(tert-butyldimethylsilyloxy)cyclohexyl acetate (12,
1.0 g mmol) was dissolved in THF (30 mL). To the solution was
added methanol (5 mL) and K2CO3 (0.250 g), and the reaction
mixture was stirred at RT for 3 h. The reaction mixture was
concentrated under vacuum. The residue was extracted with
dichloromethane (3 × 5 mL). Organic extracts were combined,
washed with brine, and dried over anhydrous sodium sulfate.
They were concentrated under vacuum. The residue was chro-
matographed on a silica gel column to afford racemic 3-hydroxy-
5-tert-butyldimethylsilyloxy cyclohexyl acetate (+) 8, yielding
0.65 g (84.4%) on the basis of recovered starting material along
with unreacted starting material 12 (0.25 g). Spectral data for
racemic 8 was the same as that obtained for (-) 8.
Syn th esis of 3,5-Di(tetr a h yd r o-2H-2-p yr a yn yloxy)-(3R,
5R)-cycloh exa n -1-on e (en t-7, P ) THP ). 3,5-Di(tetrahydro-
2H-2-pyranyloxy)-1-cyclohexanol (21, 0.1 g, 0.33 mmol) was
dissolved in dichloromethane (2 mL). To the solution were added
sodium acetate (0.02 g) and pyridinium chlorochromate (0.108
g, 0.5 mmol) . The reaction mixture was stirred for 1 h and
diluted with ether (2 mL). Solvent was decanted, and the residue
was extracted with ether (3 × 2 mL). Organic extracts were
combined and washed with a 1:1 brine-water mixture followed
by brine. The organic layer was dried on anhydrous sodium
sulfate, and solvent was evaporated under vacuum. The residue
was purified on a silica gel column (10% ethyl acetate in pet.
ether) to afford 3,5-di(tetrahydro-2H-2-pyraynyloxy)-(3R,5R)-
cyclohexan-1-one (en t-7, P ) THP, yield ) 0.080, g 80%). ee )
96% {determined by HPLC on a chiral column: (R,R) Whelk-
O1 [4.0 mm Id x 25 cm] AT-256; λ )210 nm; flow rate ) 1 mL/
min; mobile phase ) hexane:2-propanol 97:03; retention time
for en t-7 ) 13.09 and 15.33 (diastereomeric pair), for enantiomer
of en t-7 ) 13.70 and 15.76 (diastereomeric pair)}. 1H NMR
(CDCl3): δ 1.35-1.95 (m, 12H), 2.00-2.33 (m, 2H), 2.38-2.85
(m, 4H), 3.50 (m, 2H), 3.85 (m, 2H), 4.30 (m, 2H), 4.68 (m, 2H).
13C NMR (CDCl3): δ 18.86, 19.12, 19.26, 25.04, 30.51, 34.33,
36.06, 37.72, 45.80, 46.06, 47.94, 48.16, 61.79, 61.94, 62.12, 62.42,
69.70, 70.03, 70.28, 70.61, 96.46, 96.97, 159.46, 206.95, 207.10,
207.32. IR (CHCl3): cm-1 436, 668, 756, 1214, 2947, 3018.
Mass: base m/e ) 85; other m/e ) 213, 197, 113, 101, 95, 67,
55. Anal. Calcd for C16H26O5: C, 64.43%; H, 8.72%. Found: C,
64.48%; H, 8.91%. [R]D ) +16.36 (c 1.12, CHCl3).
P r ep a r a tion of Ra cem ic Sa m p les for Keton e 7 (P )
TBDMS) a n d en t-7 (P ) THP ). Racemic ketones 7 (P )
TBDMS) and en t-7 (P ) THP) were prepared from racemic 8
following the same procedure described for optically pure
samples.
P r ep a r a tion of Mosh er Ester s of Ra cem ic 8 a n d Op ti-
ca lly En r ich ed 3-Hyd r oxy-5-ter t-bu tyld im eth ylsilyloxy-
cycloh exyl a cet a t e (-) 8. 3-Hydroxy-5-tert-butyldimethyl-
silyloxycyclohexyl acetate (8, 0.020 g, 0.0694 mmol) was dis-
solved in dry dichloromethane (1 mL). To the solution was added
pyridine (0.01 g, 0.126 mmol), and the solution was cooled to 0
°C in an ice-salt bath. To the cold solution was added a solution
of (S)-Mosher acid chloride (0.023 g, 0.09 mmol) in dry dichloro-
methane (0.5 mL). The reaction mixture was stirred at RT for 5
h. The reaction was quenched by adding cold, dilute hydrochloric
acid. The organic layer was separated and washed with dilute
hydrochloric acid followed by washing with brine-water, aque-
ous NaHCO3, and finally brine. The organic layer was dried on
anhydrous sodium sulfate, and solvent was removed under
vacuum to afford the Mosher ester of 171 (0.025 g). 1H NMR
(CDCl3): δ 0.09 (s, 6H), 0.88 (s, 9H), 1.43 (m, 3H), 2.05, 2.07
(2s, 3H), 2.25 (m, 3H), 3.54, 3.55 (2s, 3H), 3.73 (m, 1H), 4.77 (m,
1H), 5.00 (m, 1H), 7.45 (m, 5H).
P r ep a r a tion 5-ter t-Bu tyld im eth ylsilyloxy-(5S)-2-cyclo-
h exen on e (13). cis,cis-3-Hydroxy-5-tert-butyldimethylsilyloxy-
(1S,3R,5R)-cyclohexyl acetate (8, 1.40 g, 2.78 mmol) was dis-
solved in dichloromethane (5 mL). To the solution were added
sodium acetate (0.1 g) and pyridinium chlorochromate (1.57 g,
7.3 mmol). The mixture was stirred for 5 h at RT. The residue
was extracted with ether (3 × 10 mL). Organic extracts were
combined and filtered through Celite. The filtrate was washed
with 1:1 brine-water and finally with brine. The organic layer
was dried on anhydrous sodium sulfate and concentrated under
vacuum. The residue was filtered through a silica gel column to
afford 3-oxo-5-tert-butyldimethylsilyloxy-(1R,5S)-cyclohexyl ace-
Ack n ow led gm en t. S.R.G. is thankful to CSIR, New
Delhi, for financial support.
1
tate (1.30 g, 94%) as an oily liquid. H NMR (CDCl3): δ 0.07 (d,
6H), 0.88 (d, 9H), 2.06 (s, 3H), 2.41 (m, 4H), 2.65 (m, 2H), 4.01
(m, 1H), 5.00 (m, 1H). 13C NMR (CDCl3): δ -4.96, 17.80, 20.95,
25.56, 39.32, 45.91, 50.28, 65.96, 67.21, 169.85, 205.25. IR
(CHCl3): cm-1 442, 756, 1218, 1245, 1723, 2857, 2933, 2954,
3020. Mass: base m/e ) 163; other m/e ) 185, 169, 145, 127,
117, 111, 101, 95, 75, 59. Anal. Calcd for C14H26O4Si: C, 58.74%;
H, 9.09%. Found: C, 58.60%; H, 9.28%. [R]D ) -11.54 (c 1,
CHCl3).
Su p p or tin g In for m a tion Ava ila ble: Detailed spectral
data of all the compounds, some representative spectra, and
chiral HPLC charts. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O016141G