J. Am. Chem. Soc. 1997, 119, 9067-9068
9067
Scheme 1
Desymmetrization of meso-1,2-Diols via Chiral
Lewis Acid-Mediated Ring-Cleavage of
1,3-Dioxolane Derivatives
Motoharu Kinugasa, Toshiro Harada,* and Akira Oku
Department of Chemistry, Kyoto Institute of Technology
Matsugasaki, Sakyo-ku, Kyoto 606, Japan
ReceiVed January 28, 1997
Scheme 2
In transformations leading to enantiomerically pure products,
enantiotopic faces or groups of the starting materials have to
be differentiated. Chiral Lewis acids have been successfully
used in enantioface differentiation, where the enantiotopic faces
of a planar substrate are differentiated by conversion to
diastereotopic ones through coordination.1 Although being not
intensively studied,2,3 chiral Lewis acids can also be utilized in
enantiotopic group differentiation, or desymmetrization, of
nonplanar symmetrical bifunctional compounds (Scheme 1).4
The role of chiral Lewis acids (L-A*) is completely different
in this type of reaction. Diastereomeric complexes are formed
through coordination to the enantiotopic functional groups.5
Selective reaction from a specific diastereomer would lead to
the formation of enantiomerically pure product.
Lewis acid-mediated reaction of meso-acetal syn-1 with
nucleophiles affords enantiomeric products 2 or ent-2 depending
upon whether C-Opro-R or C-Opro-S undergoes bond cleavage
(Scheme 2).6,7 Herein, we wish to report that, in the presence
of chiral Lewis acid 3a, the cleavage reaction proceeds in an
enantiodifferentiating manner at the C-Opro-R to give the
desymmetrized product 2.
Scheme 3
Condensation of meso-2,3-butanediol with benzaldehyde
afforded syn-1a and anti-1a in a 1.6:1 ratio. Treatment of syn-
1a with Me2CdC(OTMS)OEt in the presence of N-tosyl
phenylalanine-derived phenylboron complex 3a8 (0.3 equiv) in
CH2Cl2 at -20 °C for 15 h gave ring-cleavage product 2a
diastereoselectively (>20:1) in 72% yield but with low ee (22%).
Under similar conditions, anti-1a was considerably less reactive
(1) Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York,
1993.
(2) (a) Seebach, D.; Jaeschke, G.; Wang, Y. M. Angew. Chem., Int. Ed.
Engl. 1995, 34, 2395. (b) Ramon, D. J.; Guillena, G.; Seebach, D. HelV.
Chim. Acta 1996, 79, 875.
(3) (a) Yamashita, H.; Mukaiyama, T. Chem. Lett. 1985, 1643. (b)
Yamashita, H. Bull. Chem. Soc. Jpn. 1988, 61, 1213. (c) Hayashi, M.;
Kohmura, K.; Oguni, N. Synlett 1991, 724. (d) Nugent, W. A. J. Am. Chem.
Soc. 1992, 114, 2768. (e) Hayashi, M. Ono, K.; Hoshimi, H.; Oguni, N. J.
Chem. Soc., Chem. Commun. 1994, 2699; Tetrahedron 1966, 52, 7817. (f)
Martinez, L. E.; Leighton, J. L.; Carsten, D. H.; Jacobsen, E. N. J. Am.
Chem. Soc. 1995, 117, 5897. (g) Hansen, K. B.; Leighton, J. L.; Jacobsen,
E. N. J. Am. Chem. Soc. 1995, 118, 10924. (h) Cole, B. M.; Shimizu, K.
D.; Krueger, C. A.; Harrity, J. P. A.; Snapper, M. L.; Hoveyda, H. Angew.
Chem., Int. Ed. Engl. 1996, 35, 1668.
affording the same product 2a in 10% yield with the recovery
of the starting dioxolane without isomerization to syn-1a.
In Lewis acid-acetal complex 4a, the R1 and R2 groups locate
respectively at the right- and left-hand sides of a chiral Lewis
acid, while the location of the groups is interchanged in
diastereomeric complex 4b (Scheme 3). According to this
simplified coordination model, the structural difference between
the R1 and R2 groups is an important factor for the differentiation
of the enantiotopic oxygen atoms. It was anticipated that the
sterically less demanding alkynyl group as R2 would improve
the enantioselectivity.
Indeed, higher selectivity was observed for 2-phenylethynyl
derivative syn-1b. Thus, transacetalization of 3,3-diethoxy-1-
phenylpropyne with meso-2,3-butanediol stereoselectively gave
a 86:14 mixture of syn- and anti-1b. Treatment of the mixture
with Me2CdC(OTMS)OEt and 0.3 equiv of 3a at -20 °C
afforded ring-cleavage product 2b (>20:1 diastereoselectivity)
(4) For nonenzymatic enantiotopic group-selective reactions, see: (a)
Ward, R. S. Chem. Soc. ReV. 1990, 19, 1. (b) Harada, T.; Oku, A. Synlett
1994, 95. (c) Gais, H.-J. Methods of Organic Chemistry (Houben-Weyl);
Helmchen, G., Hoffmann, R. W., Mulzer, J., Schumann, E., Eds.; Georg
Thieme Verlag: Stuttgart, 1995; Vol. E21a, p 589. (d) Vedejs, E.; Daugulis,
O.; Diver, S. T. J. Org. Chem. 1996, 61, 430 and references cited therein.
For enzymatic methods, see: (e) Wong, C. H.; Whitesides, G. H. Enzymes
in Synthetic Organic Chemistry; Baldwin, J. E., Magunus, P. D., Eds.;
Pergamon: Oxford, 1994; p 41.
(5) Reetz, M. T.; Rudolph J.; Mynott, R. J. Am. Chem. Soc. 1996, 118,
4494.
(6) For ring-cleavage of chiral cyclic acetals, see: (a) McNamara, J. M.;
Kishi, Y. J. Am. Chem. Soc. 1982, 104, 7371. (b) Sekizaki, H.; Jung, M.;
McNamara, J. M.; Kishi, Y. J. Am. Chem. Soc. 1982, 104, 7372. (c) Bartlett,
P. A.; Johnson, W. S.; Elliott, J. D. J. Am. Chem. Soc. 1983, 105, 2088.
For a recent review, see: (d) Alexakis, A.; Mangency, P. Tetrahedron
Asymmetry 1990, 1, 477. (e) Seebach, D.; Imwinkelreid, R.; Weber, T. In
Modern Synthetic Methods; Scheffold, R., Ed.; Springer Verlag: Berlin,
1986; Vol. 4, p 125. (f) Denmark, S. E.; Almstead, N. G. J. Am. Chem.
Soc. 1991, 113, 8089.
(8) For the use of amino acid-derived boron complexes as a catalyst for
the ring-cleavage of acetals, see: (a) Kinugasa, M.; Harada, T.; Fujita, K.;
Oku, A. Synlett 1996, 43. (b) Kinugasa, M.; Harada, T.; Egusa, T.; Fujita,
K.; Oku, A. Bull. Chem. Soc. Jpn. 1996, 69, 3639. (c) Kinugasa, M. Harada,
T.; Oku, A. J. Org. Chem. 1996, 61, 6772.
(7) (a) Harada, T.; Hayashiya, T.; Wada, I.; Iwa-ake, N.; Oku, A. J. Am.
Chem. Soc. 1987, 109, 527. (b) Review; Harada, T.; Oku, A. Synlett 1994,
95.
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