Kinetic resolution of allylic alcohols using a chiral phosphine catalyst

Article abstract of DOI:10.1021/ol006923g

(Matrix presented) The kinetic resolution of racemic allylic alcohols 3, 6, and 12-17 has been explored using the PBO catalyst 7 for activation of isobutyric anhydride. Trisubstituted allylic alcohols (12-15; 17) are the best substrates and react with an enantioselectivity of s = 32-82 at -40°C.

Full text of DOI:10.1021/ol006923g

ORGANIC
LETTERS
2001
Vol. 3, No. 4
535-536
Kinetic Resolution of Allylic Alcohols
Using a Chiral Phosphine Catalyst
Edwin Vedejs* and James A. MacKay
Department of Chemistry, UniVersity of Michigan, Ann Arbor, Michigan 48109
edVed@umich.edu
Received November 25, 2000
ABSTRACT
The kinetic resolution of racemic allylic alcohols 3, 6, and 12−17 has been explored using the PBO catalyst 7 for activation of isobutyric
anhydride. Trisubstituted allylic alcohols (12−15; 17) are the best substrates and react with an enantioselectivity of s ) 32−82 at −40 °C.
Several groups have recently reported effective nonenzymatic
catalysts for the kinetic resolution of alcohols using chiral
amine1 or phosphine2 catalysts. Most of the initial efforts
were directed at aryl alkyl carbinols of general structure 1,
but considerable progress has been made with substrates
containing more versatile functionality (Scheme 1).1b,e,f
Methyl analogues of 5 (replace i-Pr by CH3), 6 (R ) H), or
cyclic allylic alcohols were not mentioned.
We have also explored the kinetic resolution of allylic
alcohols. As in our earlier study of aryl alkyl carbinols 1,
acylations were performed at -40 °C in toluene or heptane
with isobutyric anhydride and the di-tert-butylphenyl-PBO
catalyst 7, Scheme 2 (PBO ) phospha-bicyclo[3.3.0]octane
skeleton).2b In a preliminary survey,3 unsaturated alcohols 8
(n ) 1 or 2), containing the allylic double bond as well as
the hydroxyl group within a ring, were found to be less than
desirable substrates for the PBO catalysts (s < 1.5 at room
temperature). In the current study, both diastereomers of the
analogous cyclic allylic alcohol 9 were likewise acylated
without significant enantioselectivity. The allylic alcohol 10
having an exocyclic double bond was also a poor substrate
(s ) 1.6), suggesting that low enantioselectivities may be
associated with the presence of conformational constraints.
Scheme 1
(1) (a) Oriyama, T.; Hori, Y.; Imai, K.; Sasaki, R. Tetrahedron Lett.
1996, 37, 8543. Kawabata, T.; Nagato, M.; Takasu, K.; Fuji, K. J. Am.
Chem. Soc. 1997, 119, 3169. Spivey, A. C.; Fekner, T.; Spey, S. E. J. Org.
Chem. 2000, 65, 3154. Spivey, A. C.; Maddaford, A.; Fekner, T.; Redgrave,
A. J.; Frampton, C. S. J. Chem. Soc., Perkin Trans. 1 2000, 3460. (b) Sano,
T.; Miyata, H.; Oriyama, T. Enantiomer 2000, 5, 119. (c) Ruble, J. C.;
Tweddell, J.; Fu, G. C. J. Org. Chem. 1998, 63, 2794. (d) Ruble, J. C.;
Latham, H. A.; Fu, G. C. J. Am. Chem. Soc. 1997, 119, 1492. (e) Bellemin-
Laponnaz, S.; Tweddell, J.; Ruble, J. C.; Breitling, F. M.; Fu, G. C. Chem.
Commun. 2000, 1009. (f) Miller, S. J.; Copeland, G. T.; Papaioannou, N.;
Horstmann, T. E.; Ruel, E. M. J. Am. Chem. Soc. 1998, 120, 1629. Copeland,
G. T.; Jarvo, E. R.; Miller, S. J. J. Org. Chem. 1998, 63, 6784. Jarvo, E.
R.; Copeland, G. T.; Papaioannou, N.; Bonitatebus, P. J., Jr.; Miller, S. J.
J. Am. Chem. Soc. 1999, 121, 11638.
Oriyama et al. have demonstrated enantioselectivities above
100 for several bromohydrins 2 using a chiral diamine
catalyst,1b while Fu et al. have reported good results with
â-aryl-substituted substrates of general formula 3 using the
planar-chiral DMAP derivative 4 as the catalyst (for 3a and
3b, s ) 14 and s ) 22 in ether at room temperature, or s )
64 and s ) 80 in tert-amyl alcohol at 0 °C, respectively).1d,e
Lower selectivities were found for a number of other allylic
alcohols lacking the â-aryl group (s ) 4.7 to 29; 11
examples), including eight isopropyl alkenyl carbinols 5.
(2) (a) Vedejs, E.; Daugulis, O.; Diver, S. T. J. Org. Chem. 1996, 61,
430. (b) Vedejs, E.; Daugulis, O. J. Am. Chem. Soc. 1999, 121, 5813.
(3) Daugulis, O. Ph.D. Dissertation, University of Wisconsin, 1999.
10.1021/ol006923g CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/23/2001

or 1-naphthyl, respectively),2b while the enantioselectivity
for 11 had already been established in our earlier report.2b
All of these alcohols, as well as the analogous aryl carbinols
1 studied previously,2b reacted with a preference for the
R-enantiomer using the PBO catalyst 7. The more reactive
enantiomer for the remaining examples (14, 15)7 was
therefore assigned the same R-configuration by analogy.
Scheme 2
Good substrates for kinetic resolution via enantioselective
iso-butyroylation using the PBO catalyst 7 have a confor-
mationally flexible allylic hydroxyl-bearing carbon (Table
1). The best selectivities are obtained with alcohols 13-15.
The drop in selectivity from 11 to 12, from 11 to 16, or
from 13 to 12 suggests that the alkene substituent effect may
have a steric origin. One likely role of this effect would be
to keep the R-substituent in 13-15 turned away from the
plane of the double bond to minimize A1,2-strain. Lower
selectivities result when the size and number of alkene
substituents decreases or when the CdC-C-O subunit is
constrained, as in 8-10. The latter structures can be taken
to represent geometries that do not match catalyst preferences
for enantioselective isobutyroyl transfer.
In contrast to the results of Fu et al. using catalyst 4,1e
â-aryl substitution (as in 6c) does not enhance enantio-
selectivity in the PBO experiments. This was somewhat
unexpected because catalysts 4 and 7 have a qualitatively
similar selectivity profile with typical aryl carbinol substrates
1.1c,d,2b The reactive intermediates in phosphine-catalyzed or
DMAP-catalyzed acyl transfer are believed to be P-acyl
phosphonium or N-acylpyridinium carboxylates, respect-
ively.1c,d,2b However, important mechanistic features that
would play a role in determining transition state preferences
remain unknown in both series, including the location of the
crucial carboxylate anion that is probably involved as a
general base in the proton-transfer process. It would therefore
be premature to speculate further about transition state
geometries.
Evidently, these alcohols have restricted access to the
conformation required for enantiodiscrimination by the
reactive (P-butyroyl-phosphonium carboxylate) form of the
catalyst.
More flexible allylic alcohols 3 and 6 were investigated
(Table 1). Modest to good enantioselectivities were found,
Table 1. Kinetic Resolution of Allylic Alcohols with
Isobutyric Anhydride and 7 (Scheme 2)a
alcohol
time (h)
convn (%)
eeb
ee′c
s
3a
3b
6a
6b
6c
11
12
13
14
15
16
17
12
27
41
19
19
14
7
72
128
25
46
46
55.1
45.1
47.9
48.1
38.1
50.4
53.0
52.6
34
77.7
67.3
41.7
66.4
45.7
89.8
90.0
96.1
48.9
64.2
99.9
56.4
63.3
82.0
45.4
71.7
74.3
88.2
81.4
86.7
94.8
95.3
48.8
93.5
10
21
4
12
11
52d,e
34d
55
In summary, some promising structural types for kinetic
resolution of allylic alcohols have been identified. The dienyl
alcohol examples 12-15 represent a new category of good
substrates for chiral, nucleophilic acylation catalysts.
61
40.3
67.2
37.7
82d
25d
52
Acknowledgment. This work was supported by the
National Science Foundation.
a Reactions were performed at -40 °C using 0.1 M substrate, 2.5 equiv
of isobutyric anhydride, and 5 mol % of 7 in toluene unless noted.
b Unreacted alcohol ee. c Product ee′ (measured on alcohol obtained by ester
saponification). d Reaction in heptane solution. e Data from ref 2b.
Supporting Information Available: Assay and charac-
terization data; representative procedures. This material is
available free of charge via the Internet at http://pubs.acs.org.
and increased alkene substitution (3b vs 3a; 6b vs 6a)
resulted in better selectivity. Further improvements were
observed when the double bond was placed within a
carbocyclic ring (11-17), and the best selectivities were
found with substrates having larger alkene substituents.
The absolute configuration of the more reactive enanti-
omers of 3a and 3b was established by comparison with
literature data.1d,4 For 12 and 13,5 absolute configurations
were assigned after aromatization (Pd/C with norbornadiene
in refluxing toluene)6 to the corresponding 1 (Ar ) phenyl
OL006923G
(4) Brenna, E.; Caraccia, N.; Fuganti, C.; Fuganti, D.; Grasselli, P.
Tetrahedron: Asymmetry 1997, 8, 3801.
(5) Yoshii, E.; Takeuchi, Y.; Nomura, K.; Takeda, K.; Odake, S.; Sudani,
M.; Mori, C. Chem. Pharm. Bull. 1984, 32, 4767.
(6) Tabor, D. C.; White, F. H.; Collier, W. L. I.; Evans, S. A., Jr. J.
Org. Chem. 1983, 48, 1638.
(7) Prepared from the corresponding tetralone tosylhydrazone via the
alkenyllithium reagent and acetaldehyde, see: Cacchi, S.; Felici, M.; Rosini,
G. J. Chem. Soc., Perkin Trans. 1 1977, 1260. Celebi, S.; Leyva, S.;
Modarelli, D. A.; Platz, M. S. J. Am. Chem. Soc. 1993, 115, 8613.
536
Org. Lett., Vol. 3, No. 4, 2001