Y. Kim et al. / Tetrahedron Letters 48 (2007) 2833–2835
2835
Stoltz, B. M. J. Am. Chem. Soc. 2004, 126, 4482; (c)
Radosevich, A. T.; Musich, C.; Toste, F. D. J. Am. Chem.
Soc. 2005, 127, 1090.
The high selectivity and high activity of this catalyst
enabled us to successfully perform a resolution of b-hydr-
oxy esters on a multigram scale. Additionally, to our
delight, the resolution of b-(E)-styryl substituted ester
11 gave a high level of selectivity (entry 7). At present,
R is limited to the aryl and styryl groups. When R
was an aliphatic group (R = PhCH2CH2), no dehydra-
tion occurred under the same reaction condition and
rac-12 was quantitatively recovered (entry 8).
4. Catalytic acylation: (a) Vedejs, E.; Daugulis, O. J. Am.
Chem. Soc. 2003, 125, 4166; (b) Tao, B.; Ruble, J. C.; Hoic,
D. A.; Fu, G. C. J. Am. Chem. Soc. 1999, 121, 5091; (c)
Miller, S. J.; Copeland, G. T.; Papaioannou, N.; Horst-
mann, T. E.; Ruel, E. M. J. Am. Chem. Soc. 1998, 120,
1629.
5. Shin, E.; Kim, H. J.; Kim, Y.; Kim, Y.; Park, Y. S.
Tetrahedron Lett. 2006, 47, 1933.
6. General procedure for asymmetric dehydration reactions:
Trimethylchlorosilane (0.3 equiv) was added to a suspen-
sion of zinc metal (8.0 equiv) in anhydrous THF (5 ml).
After the mixture was refluxed for 40 min, the heating was
stopped, and a solution of ligand (5 mol %), t-butyl
bromoacetate (8.0 equiv) and racemic b-hydroxy ester
(0.5 mmol, 1.0 equiv) and hexamethylbenzene (internal
standard, 0.5 equiv) in THF (5 ml) was slowly added. The
mixture was stirred at reflux for 1–1.5 h and then quenched
at 0 ꢁC with satd NH4Cl solution. The resulting mixture
was extracted with methylene chloride (3 · 5 ml) and the
combined extracts were washed with brine. The solvents
were removed under reduced pressure and the residue
purified by flash column chromatography to give 3 and 5–
11. The enantioselectivities were determined by HPLC
using Chiralcel OJ–H column for 3 and 5–7; Chiralcel OB–
H for 9 and 10; Chiralcel OD for 8 and 11 (0.5 ml/min, 2-
propanol/hexane).
In summary, we have developed the first efficient cata-
lytic method for the asymmetric dehydration of b-hy-
droxy esters via kinetic resolution. Asymmetric
synthesis of b-hydroxy ester by enantioselective dehy-
dration is conceptually novel and may ultimately lead
to new catalysts with higher selectivity and broad syn-
thetic utility. Efforts are currently underway to provide
detailed mechanistic insight into the catalytic cycle.
The methodology of the present work should also be
applicable to asymmetric syntheses of flavanone
derivatives.
Acknowledgment
This work was supported by a grant from Korea
Research Foundation (KRF-2006-005-J03402).
7. The selectivity factor (s) was estimated using the equation,
s = kS/kR = ln[(1 À C)(1 À ee)]/ln[(1 À C)(1 + ee)], where
ee is the enantiomeric excess of unconverted b-hydroxy
1
References and notes
ester 3 and the conversion (C) determined by H NMR of
reaction mixture using internal standard.
8. (a) Chang, J.; Shin, E.; Kim, H. J.; Kim, Y.; Park, Y. S.
Tetrahedron 2005, 61, 2743; (b) Nam, J.; Chang, J.; Shin,
E.; Kim, H. J.; Kim, Y.; Jang, S.; Park, Y. S. Tetrahedron
2004, 60, 6311; (c) Nam, J.; Chang, J.; Hahm, K.-S.; Park,
Y. S. Tetrahedron Lett. 2003, 44, 7727.
9. For recent rerferences on base-catalyzed elimination of b-
acetoxy and b-silyloxy esters, see: (a) Mohrig, J. R.; Carson,
H. K.; Coughlin, J. M.; Hofmeister, G. E.; McMartin, L.
A.; Rowley, E. G.; Trimmer, E. E.; Wild, A. J.; Schultz, S.
C. J. Org. Chem. 2007, 72, 793; (b) Nagano, Y.; Orita, A.;
Otera, J. Synlett. 2003, 684.
1. (a) Preparation of Alkenes: A Practical Approach; Williams,
J. M. J., Ed.; Oxford University Press: New York, 1996; (b)
Saunders, W. H., Jr.; Cockerill, A. F. Mechanism of
Elimination Reactions; Wiley & Sons: New York, 1973.
2. For a reference for enantioselective gas phase dehydration
of 2-butanol, see: Feast, S.; Rafiq, M.; Wells, R. P. K.;
Willock, D. J.; King, F.; Rochester, C. H.; Bethell, D.;
Page, P. C. B.; Hutchings, G. J. J. Catal. 1997, 167, 533.
3. For leading references on catalytic oxidation, see: (a)
Mueller, J. A.; Cowell, A.; Chandler, B. D.; Sigman, M.
S. J. Am. Chem. Soc. 2005, 127, 14817; (b) Trend, R. M.;