Enzymatic desymmetrization of meso-2,6-dimethyl-1,7-heptanediol. Enantioselective formal synthesis of the vitamin E side chain and the insect pheromone tribolure

Article abstract of DOI:10.1021/jo9516650

The chiral syn-1,5-dimethylalkyl subunit is found in many natural products with significant biological activities. Enzymatic esterification of meso-2,6-dimethyl-1,7-heptanediol with isopropenyl acetate in the presence of Pseudomonas cepacia lipase in organic medium provided the chiral nonracemic monoester in high enantiomeric excess (ee = 95%). This chiral building block was used in the formal syntheses of vitamin E side chain and the insect pheromone tribolure.

Full text of DOI:10.1021/jo9516650

J . Org. Chem. 1996, 61, 1219-1222
1219
En zym a tic Desym m etr iza tion of
m eso-2,6-Dim eth yl-1,7-h ep ta n ed iol. En a n tioselective F or m a l
Syn th esis of th e Vita m in E Sid e Ch a in a n d th e In sect P h er om on e
Tr ibolu r e
Robert Cheˆnevert* and Michel Desjardins
De´partement de chimie, Faculte´ des sciences et de ge´nie, Universite´ Laval,
Que´bec (Que´bec), Canada G1K 7P4
Received September 11, 1995 (Revised Manuscript Received December 8, 1995X)
The chiral syn-1,5-dimethylalkyl subunit is found in many natural products with significant
biological activities. Enzymatic esterification of meso-2,6-dimethyl-1,7-heptanediol with isopropenyl
acetate in the presence of Pseudomonas cepacia lipase in organic medium provided the chiral
nonracemic monoester in high enantiomeric excess (ee ) 95%). This chiral building block was
used in the formal syntheses of vitamin E side chain and the insect pheromone tribolure.
Ch a r t 1
In tr od u ction
The chiral syn-1,5-dimethylalkyl subunit 1 is found in
many natural products such as vitamin E1 (2), vitamin
K2 (3), phytol3 (4) (the side chain of chlorophyll), and
phytene-1,2-diol4 (a novel diterpene from Artemisia an-
nua) (Chart 1). This structural element is also found in
several insect pheromones5 such as 5 and 6, in some
marine natural products,6 and in membrane lipids (e.g.,
7) of archaebacteria,7 a type of microorganisms living
under extreme conditions such as high temperature, high
salt concentration, low pH, or absence of oxygen. We
report here the enzymatic desymmetrization of meso-2,6-
dimethyl-1,7-heptanediol and the use of the correspond-
ing enantiomerically enriched monoester in the synthesis
of vitamin E side chain and the insect pheromone
tribolure.
Resu lts a n d Discu ssion
meso-2,6-Dimethyl-1,7-heptanediol (9) was prepared by
hydroboration of 2,6-dimethylhepta-1,6-diene (8) with
thexyl borane according to the method reported by Still
et al.8 This reaction proceeds by formation of a borocycle
and gives the meso diol 9 with high 1,5-asymmetric
induction (meso:racemic ∼15:1).8 However, the separa-
tion of the minor racemic fraction cannot be achieved by
standard chromatography.
Initial experiments concerned screening hydrolases
(lipases, esterases, proteases) as catalysts in order to
determine which enzyme gives the best enantioselectivity
for the acylation of 9 or the hydrolysis of the correspond-
ing diacetate. Of the enzymes and conditions studied,
the esterification of 9 with isopropenyl acetate (IPA) in
the presence of Pseudomonas cepacia lipase (PCL) in
THF gave the best result and provided the chiral non-
racemic monoester 10 (Scheme 1). The enzymatic reac-
tion was performed on the meso/racemic (15:1) mixture.
This highly enantioselective lipase-catalyzed reaction can
separate all three stereoisomers in a mixture of meso and
racemic isomers.9 PCL favored the S stereocenter (vide
infra), so the meso (R,S)-isomer was monoacetylated, the
(S,S)-enantiomer was diacetylated, and the (R,R)-enan-
tiomer did not react. The monoacetate 10, the major
product, was easily separated from minor contaminants
by standard flash chromatography.
X Abstract published in Advance ACS Abstracts, February 1, 1996.
(1) Mercier, C.; Chabardes, P. Pure Appl. Chem. 1994, 66, 1509.
(2) Dowd, P.; Hershline, R.; Ham, S. W.; Naganathan, S. Nat. Prod.
Rep. 1994, 11, 251.
(3) Connolly, J . D.; Hill, R. A. Dictionary of Terpenoids: Vol. 2, Di-
and higher terpenoids; Chapman and Hall: London, 1991.
(4) Brown, G. D. Phytochemistry 1994, 36, 1553.
(5) (a) Aldrich, J . R.; Oliver, J . E.; Lusby, W. R.; Kochansky, J . P.;
Borges, M. J . Chem. Ecol. 1994, 20, 1103. (b) Mori, K. Tetrahedron
1989, 45, 3233. (c) Mori, K. The Synthesis of Insect Pheromones. In
The Total Synthesis of Natural Products; ApSimon, Ed.; Wiley: 1992;
Vol. 9.
This compound was derivatized with several common
chiral agents (Mosher’s ester, amino acid derivatives), but
(6) Minale, L. Terpenoids from Marine Sponges. In Marine Natural
Products; Scheuer, P. J ., Ed.; Academic Press: 1978; Vol. 1, Chapter
4.
(7) Zhang, D.; Poulter, C. D. J . Am. Chem. Soc. 1993, 115, 1270.
(8) Still, W. C.; Darst, K. P. J . Am. Chem. Soc. 1980, 102, 7385.
(9) For other examples, see: 9 (a) Wallace, T. S.; Baldwin, G. W.;
Morrow, C. J . J . Org. Chem. 1992, 57, 5231. (b) Takemura, T.; Saito,
K.; Nakazawa, S.; Mori, N. Tetrahedron Lett. 1992, 33, 6335. (c) Caron,
G.; Kazlauskas, R. J . Tetrahedron: Asymmetry 1994, 5, 657.
0022-3263/96/1961-1219$12.00/0 © 1996 American Chemical Society

1220 J . Org. Chem., Vol. 61, No. 4, 1996
Cheˆnevert and Desjardins
Sch em e 3
Sch em e 1
hydrolysis can be correlated with 17 (Scheme 2). This
correlation proved that compound 10 has the 2R,6S
configuration and PCL selectively acetylated the S ste-
reocenter.
Tosylate 15 was also coupled with methylmagnesium
iodide in the presence of dilithium tetrachlorocuprate to
give 18 (Scheme 3). Desilylation of 18 provided alcohol
19. This sequence constitutes a formal synthesis of
tribolure 5 since the transformation of 19 into tribolure
has been reported.13 Tribolure, (4R,8R)-4,8-dimethylde-
canal, is the male-produced aggregation pheromone of
flour beetles Tribolium confusum and T. castaneum.14
Sch em e 2
Con clu sion
Enzymatic enantiogroup differentiation in meso com-
pounds (also called asymmetrization or desymmetriza-
tion) provides enantiomerically pure compounds with
multiple stereogenic centers. The enzymatic desymme-
trization of meso-2,6-dimethyl-1,7-heptanediol provides
a versatile chiral building block. Further studies, includ-
ing the asymmetric synthesis of natural products using
10 as starting material, are in progress in our laboratory.
Exp er im en ta l Section
Pseudomonas cepacia lipase (formerly called P. fluorescens)
was purchased from Amano (lipase PS30). Melting points are
(11) For syntheses of the C14 side chain: (a) Scott, J . W.; Bizzaro,
F. T.; Parrish, D. R.; Saucy, G. Helv. Chim. Acta 1976, 59, 290. (b)
Cohen, N.; Eichel, W. F.; Lopresh, R. J .; Neukom, C.; Saucy, G. J . Org.
Chem. 1976, 41, 3505. (c) Fuganti, C.; Grasselli, P. J . Chem. Soc.,
Chem. Commun. 1979, 995. (d) Heathcock, C. H.; J arvi, E. T.
Tetrahedron Lett. 1982, 23, 2825. (e) Helmchen, G.; Schmierer, R.
Tetrahedron Lett. 1983, 24, 1235. (f) Be´rube´, G.; Deslongchamps P.
Can. J . Chem. 1984, 62, 1558. (g) Be´rube´, G.; Deslongchamps, P. Bull.
Soc. Chim. Fr. 1987, 103. (h) Takano, S.; Shimazaki, Y.; Iwabushi, Y.;
Ogasawara, K. Tetrahedron Lett. 1990, 31, 3619. (i) Naoshima, Y.;
Munakata, Y.; Yoshida, S.; Funai, A. J . Chem. Soc. Perkin Trans. 1
1991, 549. (j) Mori, K.; Harada, H.; Zagatti, P.; Cork, A.; Hall, D. R.
Liebigs Ann. Chem. 1991, 259. (k) Takabe, K.; Sawada, H.; Satani, T.;
Yamada, T.; Katagiri, T.; Yoda, H. Bioorg. Med. Chem. Lett. 1993, 3,
157. (l) Molander, G. A.; Shakya, S. R. J . Org. Chem. 1994, 59, 3445.
(12) For the syntheses of the C15 side chain: (a) Schmid, M.; Barner,
R. Helv. Chim. Acta 1979, 62, 464. (b) Zell, R. Helv. Chim. Acta 1979,
62, 474. (c) Cohen, N.; Lopresti, R. J .; Saucy, G. J . Am. Chem. Soc.
1979, 101, 6710. (d) Fujisawa, T.; Sato, T.; Kawara, T.; Ohashi, K.
Tetrahedron Lett. 1981, 22, 4823. (e) Trost, B. M.; Klum, T. P. J . Am.
Chem. Soc. 1981, 103, 1864. (f) Koreeda, M.; Brown, L. J . Org. Chem.
1983, 48, 2122. (g) Fujiwara, J .; Fukutani, Y.; Hasegawa, M.; Muruoka,
K.; Yamamoto, H. J . Am. Chem. Soc. 1984, 106, 5004. (h) Gramatica,
P.; Manitto, P.; Monti, D.; Speranza, G. Tetrahedron 1986, 24, 6687.
(i) Takaya, H.; Ohta, T.; Sayo, N.; Kumobayashi, A.; Akutagawa, S.;
Inoue, S.; Kasahara, I.; Noyori. R. J . Am. Chem. Soc. 1987, 109, 1596.
(j) Gould, T. J .; Balestra, M.; Wittman, M. D.; Gary, T. A.; Rossano, L.
T.; Kallmerten, J . J . Org. Chem. 1987, 52, 3889. (k) Hu¨bscher, J .;
Barner, R. Helv. Chim. Acta 1990, 73, 1068. (l) Heiser, B.; Broger, E.
A.; Crameri, Y. Tetrahedron Asymmetry 1991, 2, 51. (m) Takano, S.;
Sugihara, T.; Ogasawara, K. Synlett. 1991, 279. (n) Cohen, N.; Schaer,
G.; Scalone, M. J . Org. Chem. 1992, 57, 5783.
subsequent NMR or chromatographic analyses failed to
give distinct signals for diastereomeric products. As an
alternative, alcohol 10 was oxidized to the carboxylic acid
11 by ruthenium tetraoxide-periodate in a CCl4/H2O/
acetonitrile solvent system,10 and the latter was deriva-
tized to the amides with (S)-(-)-naphthylethylamine.
NMR (300 MHz) and HPLC analyses of this derivative
(12) showed an ee ) 95%.
Conversion of enantiomerically pure 10 to vitamin E
side chain was accomplished by the sequence illustrated
in Scheme 2. Monoalcohol 10 was converted into the
corresponding tert-butyldimethylsilyl ether 13 in high
yield by reaction with TBDMSCl in the presence of
tetramethylguanidine (TMG) in acetonitrile. Methanoly-
sis of 13 in the presence of K2CO3 provided alcohol 14.
Treatment of 14 with p-toluenesulfonyl chloride in py-
ridine led to tosylate 15. Condensation of tosylate 15
with excess isoamylmagnesium bromide in the presence
of dilithium tetrachlorocuprate as catalyst in THF pro-
duced 16. Desilylation of 16 with n-Bu4NF in THF
resulted in the formation of (2R,6R)-2,6,10-trimethyl-1-
undecanol (17), the vitamin E side chain.11,12 Since the
optical rotation and the absolute configuration of 17 are
known, the configuration of 10 obtained by enzymatic
(13) (a) Cheskis, B. A.; Lebedeva, K. V.; Moiseenkov, A. M. Izv. Akad.
Nauk. SSSR, Ser. Khim. 1988, 4, 865. (b) Moiseenkov, A. M.; Cheskis,
B. A. Dokl. Akad. Nauk. SSSR 1986, 290, 1379.
(14) For other synthesis of tribolure, see: (a) Mori, K.; Kuwahara,
S.; Ueda, H. Tetrahedron 1983, 39, 2439. (b) Fuganti, C.; Grasselli,
P.; Servi, S.; Ho¨gberg, H. E. J . Chem. Soc., Perkin Trans. 1 1988, 3061.
(c) Mori, K.; Takikawa, H. Liebigs Ann. Chem. 1991, 497.
(10) Carlsen, P. H. J .; Katsuki, T.; Martin, V. S.; Sharpless, K. B.
J . Org. Chem. 1981, 46, 3936.

Formal Synthesis of Vitamin E Side Chain and Pheromone Tribolure
J . Org. Chem., Vol. 61, No. 4, 1996 1221
uncorrected. NMR spectra were recorded at 300 MHz (1H),
75.44 MHz (13C), and 282.23 MHz (19F).
raphy (ether-petroleum ether, 3:7) afforded alcohol 14 (521
25 30
mg, 96%): [R]D -3.6 (c 1.13, CHCl3); lit.11g [R]D -3.65 (c
3.45, CHCl3); IR (neat) 3100-3550, 2950, 2920, 2850, 1460,
1250, 1090, 830, 770 cm-1; 1H NMR (CDCl3) 0.03 (s, 6H), 0.86
(d, J ) 6.6 Hz, 3H), 0.89 (s, 9H), 0.91 (d, J ) 6.9 Hz, 3H),
1.01-1.43 (m, 6H), 1.59 (m, 2H), 3.32-3.54 (m, 4H); 13C NMR
(CDCl3) -5.35, 16.61, 16.79, 18.38, 24.36, 25.96, 33.50, 35.76,
68.38.
En zym a tic Ester ifica tion of m eso-2,6-Dim eth yl-1,7-
h ep ta n ed iol (9). P r ep a r a tion of (2R,6S)-7-Acetoxy-2,6-
d im eth yl-1-h ep ta n ol (10). To a solution of diol 9 (0.663 g,
4.14 mmol) and isopropenyl acetate (1.2 mL, 10.9 mmol) in
anhydrous THF was added P. cepacia lipase (300 mg). The
reaction mixture was stirred at room temperature, and the
reaction was monitored by TLC (53 h). The enzyme was
filtered and washed with THF, and the solvent was concen-
trated in vacuo. Flash chromatography (ether-petroleum
ether, 55:45) afforded monoester 10 (451 mg, 54%) along with
(2S,6R)-1-(Tosyloxy)-7-[(ter t-b u t yld im et h ylsilyl)oxy]-
2,6-d im eth ylh ep ta n e (15). Alcohol 14 (518 mg, 1.88 mmol),
p-toluenesulfonyl chloride (532 mg, 2.79 mmol), and DMAP
(61 mg) were dissolved in dry pyridine (20 mL). The solution
was stirred at room temperature under a dry atmosphere for
48 h. The solution was poured into ether, and the organic
layer was washed with aqueous 1 N HCl, saturated NaHCO3,
and water. The organic phase was dried (MgSO4) and con-
centrated in vacuo. Flash chromatography (ether-petroleum
ether, 5:95) provided 15 as an oil (661 mg, 82%): [R]D +3.8 (c
1.19, CHCl3); lit.11g [R]D25 +3.84 (c 3.31, CHCl3); IR (neat) 2950,
2920, 2840, 1590, 1460, 1360, 1185, 1170, 1090, 830 cm-1; 1H
NMR (CDCl3) 0.02 (s, 6H), 0.81 (d, J ) 6.4 Hz, 3H), 0.86 (d, J
) 6.4 Hz, 3H), 0.87 (s, 9H), 0.94-1.30 (m, 6H), 1.50 (m, 1H),
1.76 (m, 1H), 2.44 (s, 3H), 3.32 (dd, J 1 ) 6.4 Hz, J 2 ) 9.7 Hz,
1H), 3.39 (dd, J 1 ) 6.0 Hz, J 2 ) 9.7 Hz, 1H), 3.79 (dd, J 1 ) 6.6
Hz, J 2 ) 9.2 Hz, 1H), 3.87 (dd, J 1 ) 5.9 Hz, J 2 ) 9.2 Hz, 1H),
7.33 (m, 2H), 7.77 (m, 2H); 13C NMR (CDCl3) -5.51, 16.32,
16.54, 18.19, 21.46, 23.82, 25.81, 32.64, 32.86, 33.05, 35.49,
68.11, 74.95, 127.75, 129.63, 133.14, 144.43.
25
diacetate (326 mg, 32%) and diol (31 mg, 5%): [R]D +8.8 (c
1.47, CHCl3); IR (neat) 3100-3650, 2820-2980, 1735, 1460,
1
1240, 1030 cm-1; H NMR (CDCl3) 0.89 (d, J ) 6.6 Hz, 3H),
0.90 (d, J ) 6.6 Hz, 3H), 1.02-1.46 (m, 6H), 1.56 (s, 1H), 1.58
(m, 1H), 1.76 (m, 1H), 2.03 (s, 3H), 3.39 (dd, J 1 ) 6.4 Hz, J 2
)
10.5 Hz, 1H), 3.49 (dd, J 1 ) 5.9 Hz, J 2 ) 10.5 Hz, 1H), 3.82
(dd, J 1 ) 6.9 Hz, J 2 ) 10.6 Hz, 1H), 3.98 (dd, J 1 ) 5.9 Hz, J 2
) 10.6 Hz, 1H); 13C NMR (CDCl3) 16.42, 16.73, 20.76, 23.99,
32.32, 33.15, 33.47, 35.52, 68.00, 69.23, 171.16. Anal. Calcd
for C11H22O3: C, 65.31; H, 10.96. Found: C, 65.57; H, 10.71.
Deter m in a tion of th e En a n tiom er ic Com p osition of
(2R,6S)-7-Acetoxy-2,6-d im eth yl-1-h ep ta n ol (10). Alcohol
10 (20 mg, 0.10 mmol) was dissolved into a mixture of
acetonitrile (0.2 mL), CCl4 (0.2 mL) and water (0.3 mL). RuCl3
(1 mg, 0.005 mmol) and NaIO4 (90 mg, 0.42 mmol) were
successively added. The mixture was stirred for 3 h at room
temperature. The mixture was poured into ether, and the acid
was extracted with saturated aqueous NaHCO3. The aqueous
phase was acidified to pH 2, and the acid was taken with ether.
This organic phase was dried (MgSO4) and concentrated in
vacuo. The yield of 11 was quantitative; 1H NMR (CDCl3) 0.90
(d, J ) 7.0 Hz, 3H), 1.17 (d, J ) 7.0 Hz, 3H) 1.1-1.8 (m, 7H),
2.04 (s, 3H), 2.44 (m, 1H), 3.88 (m, 2H); 13C NMR (CDCl3)
16.72, 16.89, 20.91, 24.38, 32.33, 33.61, 39.26, 69.39, 171.31,
182.72.
(2R ,6R )-1-[(t er t -Bu t yld im e t h ylsilyl)oxy]-2,6,10-t r i-
m eth ylu n d eca n e (16). To a solution of tosylate 15 (192 mg,
0.45 mmol) in anhydrous THF (0.7 mL) at -78 °C under a
dry atmosphere were added dropwise a solution of isoamyl-
magnesium bromide (0.6 M in THF, 1.6 mL) and then a
solution of Li2CuCl4 (0.1 M in THF, 32 µL). The mixture was
stirred at -78 °C for 20 min and at room temperature for 24
h. The mixture was poured into an aqueous saturated NH4Cl
solution. The aqueous phase was extracted several times with
petroleum ether, and the organic layer was dried (MgSO4) and
concentrated in vacuo. Flash chromatography (petroleum
ether) provided 16 as an oil (94 mg, 64%) and the starting
Acid 11 (20 mg, 0.09 mmol), 1-(3-(dimethylamino)propyl)-
3-ethylcarbodiimide hydrochloride (22 mg, 0.11 mmol), and
DMAP (2 mg, 0.02 mmol) were dissolved into CH2Cl2 (2 mL).
(S)-(-)-1-(1-Naphthyl)ethylamine (19 mg, 0.11 mmol) was
added, and the solution was stirred at room temperature for
16 h. The solution was poured into ether, and the organic
phase was washed with aqueous 1 M HCl and saturated
aqueous NaHCO3, dried (MgSO4), and evaporated. The dia-
stereomeric ratio of 12 was determined by proton NMR
spectroscopy (0.74 and 0.87 ppm, two doublets, CH3) and by
HPLC (column Supelcosil LC-SI; eluant ether/hexane, 35/65,
1.2 mL/min; detection UV at 225 nm; retention times 7.2 and
9.0 min).
25
material (49 mg, 25%). 16: [R]D +2.0 (c 1.24, CHCl3); lit.11g
[R]D26 +2.13 (c 2.76, CHCl3); IR (neat) 2950, 2920, 2850, 1460,
1250, 1090, 830 cm-1 1H NMR (CDCl3) 0.04 (s, 6H), 0.83-
;
0.89 (m, 12H), 0.89 (s, 9H), 1.00-1.60 (m, 15H), 3.34 (dd, J 1
)
6.6 Hz, J 2 ) 9.8 Hz, 1H), 3.45 (dd, J 1 ) 5.8 Hz, J 2 ) 9.8 Hz,
1H); 13C NMR (CDCl3) -5.50, 16.67, 18.21, 19.59, 22.47, 22.56,
24.28, 24.64, 25.82, 27.84, 32.60, 33.40, 35.65, 37.14, 37.29,
39.24, 68.28.
(2R,6R)-2,6,10-Tr im eth yl-1-u n d eca n ol (17). A solution
of compound 16 (89 mg, 0.27 mmol) and tetra-n-butylammo-
nium fluoride (114 mg, 0.55 mmol) in THF (3 mL) was stirred
at room temperature for 24 h. Ether was added (100 mL),
and the organic phase was washed with brine. The aqueous
layer was extracted with petroleum ether. The organic layers
were combined, dried (MgSO4), and concentrated in vacuo.
Flash chromatography (ether-petroleum ether, 1:4) yielded
(2S,6R)-1-Acetoxy-7-[(ter t-bu tyld im eth ylsilyl)oxy]-2,6-
d im eth ylh ep ta n e (13). To a solution of alcohol 10 (432 mg,
2.13 mmol), triethylamine (0.36 mL, 2.6 mmol), and tetra-
methylguanidine (53 µL, 0.44 mmol) in anhydrous acetonitrile
(3.2 mL) was added TBDMSCl (360 mg, 2.4 mmol). The
solution was stirred at room temperature under a dry N2
atmosphere for 1 h. The solution was poured into ether (150
mL), and the organic layer was washed with aqueous NaHCO3,
and brine, dried (MgSO4), and concentrated in vacuo. Flash
chromatography (ether-petroleum ether, 3:97) provided 13
25
25
1711 (57 mg, 98%): [R]D +7.9 (c 1.15, hexane; lit.11k [R]D
25
+7.67 (c 1.02, hexane); lit.11g [R]D +8.6 (c 2.07, hexane); IR
(neat) 3060-3580, 2950, 2920, 2860, 1410, 1375, 1360, 1050
cm-1 1H NMR (CDCl3) 0.80-0.84 (m, 9H), 0.88 (d, J ) 6.6
;
25
(626 mg, 93%): [R]D +1.5 (c 1.06, CHCl3); IR (neat) 2950,
Hz, 3H), 1.01-1.51 (m, 14H), 1.57 (m, 1H), 3.38 (dd, J 1 ) 6.6
Hz, J 2 ) 10.4 Hz, 1H), 3.47 (dd, J 1 ) 5.7 Hz, J 2 ) 10.4 Hz,
1H); 13C NMR (CDCl3) 16.49, 19.57, 22.46, 22.55, 24.27, 24.63,
27.82, 32.61, 33.36, 35.67, 37.12, 37.23, 39.22, 68.23.
1
2920, 2850, 1740, 1460, 1240, 1090, 830, 770 cm-1; H NMR
(CDCl3) 0.01 (s, 6H), 0.84 (d, J ) 6.8 Hz, 3H), 0.87 (s, 9H),
0.90 (d, J ) 6.5 Hz, 3H), 1.00-1.42 (m, 6H), 1.55 (m, 1H), 1.75
(m, 1H), 2.02 (s, 3H), 3.34 (dd, J 1 ) 9.6 Hz, J 2 ) 6.4 Hz, 1H),
3.41 (dd, J 1 ) 9.6 Hz, J 2 ) 5.9 Hz, 1H), 3.82 (dd, J 1 ) 10.6 Hz,
(2R,6R)-1-[(ter t-Bu t yld im et h ylsilyl)oxy]-2,6-d im et h -
ylocta n e (18). To a solution of tosylate 15 (222 mg, 0.52
mmol) in anhydrous THF (2.0 mL) at -78 °C under a dry
atmosphere was added dropwise a solution of methylmagne-
sium iodide in ether (0.40 mL, 3.0 M) and then a solution of
Li2CuCl4 (0.1 M in THF, 37 µL). The mixture was stirred at
-78 °C for 30 min and at room temperature for 20 h. The
mixture was poured into an aqueous saturated NH4Cl solution.
The aqueous phase was extracted several times with pentane,
and the organic layer was dried (MgSO4) and concentrated in
vacuo. Flash chromatography (petroleum ether) provided 18
J 2 ) 6.9 Hz, 1H), 3.93 (dd, J 1 ) 10.6 Hz, J 2 ) 5.9 Hz, 1H); 13
C
NMR (CDCl3) -5.54, 16.59, 16.73, 18.17, 20.74, 24.03, 25.78,
32.34, 33.19, 33.54, 35.53, 68.12, 69.26, 170.99. Anal. Calcd
for C17H36OSi: C, 64.50; H, 11.46. Found: C, 64.67; H, 11.23.
(2S,6S)-7-[(ter t-Bu tyld im eth ylsilyl)oxy]-2,6-d im eth yl-
1-h ep ta n ol (14). A suspension of acetate 13 (625 mg, 1.97
mmol) and K2CO3 (1.090 g, 7.89 mmol) in MeOH (10 mL) was
stirred at room temperature for 1 h. The mixture was treated
with water and extracted with ether. The organic layer was
dried (Na2SO4) and concentrated in vacuo. Flash chromatog-
25
as an oil (75 mg, 53%): [R]D -2.1 (c 1.52, CHCl3); IR (neat)

1222 J . Org. Chem., Vol. 61, No. 4, 1996
Cheˆnevert and Desjardins
2950, 2920, 2850, 1455, 1250, 1090, 830, 770 cm-1; H NMR
(CDCl3) 0.04 (s, 6H), 0.84-0.88 (m, 9H), 0.90 (s, 9H), 0.98-
1.40 (m, 9H), 1.57 (m, 1H), 3.35 (dd, J 1 ) 6.6 Hz, J 2 ) 9.6 Hz,
1H), 3.45 (dd, J 1 ) 5.8 Hz, J 2 ) 9.6 Hz, 1H); 13C NMR (CDCl3)
-5.51, 11.22, 16.66, 18.20, 19.09, 24.58, 25.81, 29.31, 33.40,
34.25, 35.65, 36.82, 68.27. Anal. Calcd for C16H36OSi: C,
70.51; H, 13.31. Found: C, 70.24; H, 13.67.
1.15, CHCl3); lit.13 [R]D25 +6.9 (c 5.0, CHCl3); IR (neat) 3100-
1
3500, 2950, 2920, 2860, 1460, 1370, 1030 cm-1 1H NMR
;
(CDCl3) 0.84-0.93 (m, 9H), 1.03-1.40 (m, 9H), 1.62 (m, 1H),
3.41 (dd, J 1 ) 6.6 Hz, J 2 ) 10.4 Hz, 1H), 3.51 (dd, J 1 ) 5.8 Hz,
J 2 ) 10.4 Hz, 1H); 13C NMR (CDCl3) 11.21, 16.48, 19.08, 24.28,
29.28, 33.35, 34.23, 35.66, 36.75, 68.24.
(2R,6R)-2,6-Dim eth yl-1-octa n ol (19). A solution of com-
pound 18 (69 mg, 0.25 mmol), and tetra-n-butylammonium
fluoride (137 mg, 0.52 mmol) in THF (1.0 mL) was stirred at
room temperature for 20 h. The solution was diluted with
pentane-ether (4/1, 100 mL) and washed with brine. The
aqueous layer was extracted with pentane-ether and the
organic layers were combined, dried (MgSO4), and concen-
trated in vacuo. Flash chromatography (ether-petroleum
Ack n ow led gm en t. The authors would like to thank
the Natural Sciences and Engineering Research Council
of Canada (NSERC) for financial support as well as
NSERC and “le Fonds pour les chercheurs et l’aide a` la
recherche, Que´bec”, for postgraduate scholarships to
M.D.
25
ether, 1/3) afforded 19 as an oil (37 mg, 92%): [R]D +6.0 (c
J O9516650