with preformed (+)-allyldiisopinocampheylborane [(+)-
(Ipc)2BCH2CHdCH2]. O-Methylation with MeI in the pres-
ence of Ag2O in MeCN gave quantitatively the ether 10.
Application of the recently reported isomerization16 of
terminal double bonds to the 2-propenyl equivalent in the
presence of 10 mol % of the second generation Grubbs’
catalyst C and equimolar Et3N in refluxing methanol gave
11 as a cis/trans mixture in excellent yield even on a gram
scale.17 After reaction of 11 with MeMgBr, the resulting gem-
dimethyl tertiary alcohol was O-allylated to the diene 12 by
treatment with allyl iodide and NaH in THF/DMPU in
excellent yield for the two steps.18 A ring closing metathesis
reaction in the presence of 5 mol % of Grubbs’ second
generation catalyst19 gave the R,â-unsaturated dihydropyran
13 in good yield. The metathesis reaction could be routinely
run on multiples of 100 mg scale at substrate concentration
of 1 mM. Next, we subjected the cyclic ether 13 to an allylic
oxidation in the presence of pyridinium chlorochromate20 to
give the unsaturated lactone 8 in satisfactory yield.
With the unsaturated lactone 8 in hand, we were ready to
perform the final dihydroxylation/reduction sequence (Scheme
3). Surprisingly, direct dihydroxylation21 of lactone 8 under
various conditions22 resulted in low recovery of the diol, in
contrast to several reports dealing with the dihydroxylation
of related analogues.23 We therefore decided to postpone the
dihydroxylation reaction until after the reduction of 8 with
DIBALH to an anomeric mixture of lactol intermediates 14.
Scheme 3. Final Steps toward L-(+)-Noviose
78% yield (Scheme 1).9 Substoichiometric (50 mol %) or
catalytic (20 mol %) (S)-B-Me-CBS was ineffective, often
leading to non-reproducible enantioselectivity levels. Re-
cently, Corey and co-workers reported the desymmetrization
of diketone 1 with 10 mol % of (S)-B-nBu-CBS (B) in
combination with catecholborane and in the presence of N,N-
diethylaniline (DEA).10 In the presence of 20 mol % of
catalyst A, catecholborane, and diethylaniline, ketone 5 was
obtained in 70% yield and the same enantioselectivity as
reported by Corey (94%).11
Conversion to the methyl ether 612 was followed by a
Sc(OTf)3-promoted Baeyer-Villiger reaction13 to give the
lactone 7. A Saegusa oxidation14 on the preformed trimeth-
ylsilyl enol ketene intermediate in the presence of Pd(OAc)2
led the unsaturated lactone 8 in 63% yield for three steps.
We also describe an alternative method to the lactone 8
which relies on the venerable asymmetric Brown allylation
reaction15 (Scheme 2). Freshly distilled benzyl glyoxylate 9
was converted to the desired homoallylic alcohol intermediate
in 72% yield and >92% ee following the Brown procedure15
(15) (a) Racherla, U. S.; Brown, H. C. J. Org. Chem. 1991, 56, 401-
404 and references therein. (b) Srebnik, M.; Rachamandran, P. V.
Aldrichimica Acta 1987, 20, 9-24. (c) Roush, W. R. In ComprehensiVe
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: New
York, 1991; Vol. 2, pp 1-53.
(16) Hanessian, S.; Giroux, S.; Larsson, A. Org. Lett. 2006, 8, 5481-
5484.
(8) Enantioselectivity was determined by 1H NMR analysis of the Mosher
ester derivatives at 700 MHz.
(17) The concomitant formation of homocoupling side products was
completely suppressed in the presence of equimolar Et3N. See: Dinger,
M. B.; Mol, J. C. Organometallics 2003, 22, 1089-1095.
(18) An O-allylation/RCM/allylic oxidation sequence was chosen in order
to bypass the inefficient formation of acryl and crotonyl esters of the
intermediate tertiary carbinol. Besides, the acrylate proved to be a poor
substrate for the ring closing metathesis under various conditions and led
mostly to decomposition. See: (a) Carda, M.; Castillo, E.; Rodriguez, S.;
Uriel, S.; Marco, J. A. Synlett 1999, 1639-1641. (b) Fu¨rstner, A.;
Langemann, K. J. Am. Chem. Soc. 1997, 119, 9130-9136.
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Kobayashi, F. Tetrahedron: Asymmetry 2000, 11, 3883-3886. (b) Cho,
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(11) In the presence of 10 mol % of A, alcohol 5 was isolated in 82%
ee, while 40 mol % of A provided 5 in 98% ee. Interestingly, a remarkable
temperature effect was observed when the reduction was performed in a
temperature range of -55 to 45 °C in the presence of 10 mol % of A,
which afforded 5 in 94% ee (full details of the procedures are provided in
the Supporting Information). For the effect of temperature on the enanti-
oselectivity in CBS-catalyzed reduction, see: Xu, J.; Wei, T.; Zhang, Q. J.
Org. Chem. 2003, 68, 10146-10151 and references therein.
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of racemic 2,2-dimethyl-3-hydroxycyclopentanone with Ag2O and MeI in
DMF (Yoon, U. C.; Quillen, S. L.; Mariano, P. S.; Swanson, R.; Stavinoha,
J. L.; Bay, E. J. Am. Chem. Soc. 1983, 105, 1218-1220). We observed
that in the absence of DMF the reaction proceeded smoothly almost to
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