C O M M U N I C A T I O N S
Several stoichiometric8 and catalytic9 stereoselective acylations of
chiral alcohols are known; however, we do not have sufficient
understanding of the factors that govern the stereoselectivity of such
processes to propose a stereochemical model for our system.
In conclusion, we have described a new method for the kinetic
resolution of R-acetoxy N-acyl oxazolidinethiones using a readily
prepared catalyst. The reaction has a wide substrate scope and
provides material of high enantiomeric excess. Efforts to apply this
catalyst to the kinetic resolution of other substrate classes are in
progress.
Scheme 4. Methanolysis of N-Acyl Oxazolidinethione 10
Table 1. Solvent Effects on the Methanolysis of 10
Acknowledgment. We thank Jessica Hodges for experimental
assistance, and the NIH (GM48498) for financial support of this
work.
Note Added after ASAP Publication. Typographical errors
in the second paragraph and ref 3 were corrected after this paper
was published on the Internet on September 7, 2005.
time
entry
solvent
(h)
% conv
s-factor
1
2
3
4
5
6
toluene
5
24
2
19
8
55
46
53
55
48
37
12
12
9
5
11
8.5
Supporting Information Available: Experimental procedures for
the synthesis and characterization of all new compounds, as well as
1H and 13C spectra for selected compounds, and X-ray crystallography
data for compound 8. This material is available free of charge via the
toluene/EtOH (30 equiv)a
CH2Cl2
THF
t-amyl alcohol/CH2Cl2 (1:1)
EtOH/THF (2:1)a
7
a Methanol was omitted from this reaction, thereby providing the ethyl
ester.
References
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A.; De Clercq, P. J.; Declercq, J.-P. J. Org. Chem. 1998, 63, 2548. (d)
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1445. (e) Cram, D. J.; Katz, H. E. J. Am. Chem. Soc. 1983, 105, 135. (f)
Ghosh, M.; Conroy, J. L.; Seto, C. T. Angew. Chem., Int. Ed. 1999, 38,
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Diederich, F.; Schu¨rmann, G.; Chao, I. J. Org. Chem. 1988, 53, 2744.
(2) For the nonenzymatic kinetic resolution of chiral esters containing
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2870. (b) Seebach, D.; Jaeschke, G.; Gottwald, K.; Matsuda, K.;
Formisano, R.; Chaplin, D. A.; Breuning, M.; Bringmann, G. Tetrahedron
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S.-K.; Chen, Y.; Hang, J.; Tang, L.; McDaid, P.; Deng, L. Acc. Chem.
Res. 2004, 37, 621. For catalytic asymmetric cleavage of other active
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Soc., Perkin Trans. 1 1987, 1053. (e) Narasaka, K.; Kanai, F.; Okudo,
M.; Miyoshi, N. Chem. Lett. 1989, 1187. (f) Cleij, M. C.; Drenth, W.;
Nolte, R. J. M. J. Org. Chem. 1991, 56, 3883. (g) Aitken, R. A.; Gopal,
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T.; Fujita, E.; Terada, S.; Shiro, M. Tetrahedron 1984, 40, 1215.
(4) The price listed in the 2004-2005 Acros Organics catalogue for the D-(+)
and L-(-) enantiomers of 5 (each 99% ee) is $119.40 and $114 per 100
grams, respectively.
(5) This compound is also commercially available, but at higher cost (Acros
Organics price is $35 or $49/g for the (-)- and (+)-enantiomers,
respectively).
(6) Prakash, G. K. S.; Krishnamurtu, R.; Olah, G. A. J. Am. Chem. Soc. 1989,
111, 393.
(7) The selectivity factor is defined as k(fast reacting enantiomer)/k(slow
reacting enantiomer). For a discussion of kinetic resolutions, see: Kagan,
H. B.; Fiaud, J. C. Top. Stereochem. 1988, 18, 249.
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Chen, Y.; McDaid, P.; Deng, L. Chem. ReV. 2003, 103, 2965. Other
examples: (b) Rosen, T.; Heathcock, C. H. J. Am. Chem. Soc. 1985, 107,
3731. (c) Theisen, P. D.; Heathcock, C. H. J. Org. Chem. 1993, 58, 142.
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Table 2. Substrate Scope (average of two runs)
temp
C)
time
(h)
ee of
entry
R
(
°
% conv
recovered SM
s
1
2
3a
4
5
6
7
Ph (10)
Bn (11)
Bn (11)
PhCH2CH2 (12)
Bu (13)
0
67
55
120
93
116
168
168
58.5
58.8
58.9
58.5
56.4
58.3
54.6
94%
>99%
>99%
96%
96%
96%
17
31
32
20
27
20
22
0
0
0
0
rt
i-Pr (14)
allyl (15)
-25
91%
a This run was conducted with 5% catalyst loading.
conversion in 2 h (Table 1, entry 3). However, the s-factor in this
solvent is 9, lower than that in toluene. In THF, the reaction is
significantly slower, requiring 19 h to proceed to 55% conversion,
and provides an eroded s-factor of 5 (Table 1, entry 4). We wished
to study the use of hydroxylic solvents; however, the background
reaction is too great in methanol, and compound 10 is only sparingly
soluble in t-amyl alcohol or ethanol. It is soluble in a 1:1 mixture
of t-amyl alcohol and CH2Cl2 or a 2:1 mixture of ethanol and THF.
These solvent systems proved inferior to toluene, providing
diminished s-factors of 11 and 8.5, respectively, at about half the
rate (Table 1, entries 5 and 6).
Having established that toluene is the solvent of choice, we next
studied the scope of this reaction and found that a variety of sub-
strates are effectively resolved (Table 2). Thus, the benzyl- (11) and
dihydrocinnamyl (12)-derived substrates react with s-factors of 31
and 20, respectively (entries 2 and 4). Simple alkyl-derived sub-
strates, such as butyl (13) and isopropyl (14), also display good
s-factors (27 and 20, respectively, entries 5 and 6). Finally, the allyl-
derived substrate (15) reacted with an s-factor of 22 (entry 7).
While the turnover-limiting step of the catalytic cycle is likely
the deacylation of an acyl catalyst intermediate analogous to 3,1a
the stereochemistry-determining step is the acylation of the catalyst.
JA053743Z
9
J. AM. CHEM. SOC. VOL. 127, NO. 39, 2005 13503