10320
J . Am. Chem. SOC.1994,116, 10320-10321
Deracemization of Cyclic Allyl Esters Barry M. T r o d and Michael G . Organ Department of Chemistry, Stanford University Stanford, California 94305-5080 Received July 25, 1994
Obtention of enantiomerically pure compounds has grown in importance by the focus on using pure enantiomers for biological purposes rather than racemates. Methods to achieve this aim utilizing abiological or biological catalysis wherein only a truly catalytic amount of an asymmetric agent is required represent the most desirable solutions. Among targets of practical significance stand allyl alcohols because of their importance as building blocks via numerous reactions exemplified by Claisen rearrangements,' cuprate coupling,2 epoxidations,3 and various cycloadditions.4 Asymmetric reduction of simple cycloalkenones has not been shown to be generally useful.5 Base-"catalyzed" opening of epoxides requires a stoichiometric amount of "catalyst" and also shows an important dependence on ring size.6 Kinetic resolutions of cycloalkenols by either transition metal7 or enzymatic catalysis* suffer from a theoretical yield of 50%. Amino alcohol catalyzed additions of stoichiometric organozinc compounds to aldehydes appear promising.9 We wish to record a new strategy for the preparation of cycloalkenols of high ee by the deracemization of the corresponding esters. The achievement of a catalytic deracemization of a racemic chiral allylic ester mandates its conversion to an achiral intermediate which will become chiral only in a chiral environment. A *-allyl metal complexconstitutes such an intermediate in which chirality is reintroduced by selective attack by an oxygen nucleophile at one of the allylic termini as shown in eq 1. The (1) Ziegler, F. E. Chem. Reo. 1988,88,1423. Wipf, R. In Comprehensiue OrganicSynthesis; Trost, B. M., Fleming, I., Paquette, L. A., Eds.; Pergamon Press: Oxford, 1991; Vol. 5, Chapter 7.2, pp 827-874. (2) Yamamoto, Y. Angew. Chem., Int. Ed. Engl. 1986,25,508. Lipshutz, B. H. Synthesis 1987,325. Klunder, J. M.; Posner, G. H.In Comprehensiue Organic Synthesis; Trost, B. M., Fleming, I., Pattenden, G., Eds.; Pergamon Press: Oxford, 1991; Vol. 3, Chapter 1.5, pp 220-223. (3) Rossiter, B. E. In AsymmetricSynthesis; Morrison, J. D., Ed.; Academic Press: Orlando, FL, 1985; Vol. 5, pp 193-246. Finn, M. G.; Sharpless, K. B. In Asymmetric Synthesis; Morrison, J. D., Ed.; Academic Press: Orlando, FL, 1985; Vol. 5, pp 247-308. Rao, A. In Comprehensiue OrganicSynthesis; Trost, B. M., Fleming, I., Ley, S. V., Eds.; Pergamon Press: Oxford, 1991; Vol. 7, Chapter 3.1, pp 364-371, 376-380. Johnson, R. A.; Sharpless, K. B. In Comprehensiue Organic Synthesis; Trost, B. M., Fleiming, I., Ley, S. V., Eds.; Pergamon Press: Oxford, 1991; Vol. 7, Chapter 3.2. (4) Simmons, H. E.; Cairns, T. L.; Vladuchick, S. A.; Hoiness, C. M. Org. React. (N.Y.) 1973, 20, 1. Brieger, G.; Bennett, J. N. Chem. Rev. 1980, 80, 63. Burke, S. D.; Grieco, P. A. Org. React. (N.Y.) 1979, 26, 361. Ciganek, E. Org. React. (N.Y.)1984, 32, 1. Roush, W. R. Adu. Cycloaddit. 1990, 2, 9 1. Carruthers, W. Cycloaddition Reactions in Organic Synthesis; Pergamon Press: Oxford, 1990. Helquist, P. In Comprehensiue OrganicSynthesis; Trost, B. M., Fleming, I., Semmelhack, M. F., Eds.; Pergamon Press: Oxford, 1991; Vol. 4, Chapter 4.6. (5) Sato, T.; Gotoh, Y.;Wakabayashi, Y . ;Fujisawa, T. TetrahedronLett. 1983,24, 4123. Kawasaki, M.; Suzuki, Y.; Terashima, S. Chem. Lett. 1984, 239. Brown, H. C.; Pai, G. G. J . Org. Chem. 1985,50, 1384. Corey, E. J.; Gavai, A. V. Tetrahedron Lett. 1988, 29, 3201. Corey, E. J.; Bakshu, R. K. Tetrahedron Lett. 1990, 31, 61 1. For preparation of cyclohex-1-en-3-01 uia asymmetric hydroboration, see: Brown, H. C.; Jadhav, P. K.; Bhat, K. S. J. Am. Chem. SOC.1985, 107, 2564. (6) Whitesell, J. K.; Felman, S. W. J . Org. Chem. 1980, 45, 755. Asami, M. Tetrahedron Lert. 1985, 26, 5083. Asami, M.; Kirihara, H. Chem. Lett. 1987,389. For a catalytic process which unfortunately proceeds with modest ee, see: Scheffold, R.; Su, H.; Walder, L.; da Zhang, Z. Helu. Chim. Acta 1988, 71, 1073. (7) Sharpless, K. B.; Behrens, C. H.; Katsuki, T.; Lee, A. W. M.; Martin, V. S.; Takatani, M.; Viti; Walker, F. J.; Wocdard, S. S. Pure Appl. Chem. 1983, 55, 589. (8) Ito, S.; Kasai, M.; Ziffer, H.; Silverton, J. V. Can. J . Chem. 1987,65, 574. (9) Oppolzer, W.; Radinov, R. N. Helu. Chim. Acta 1992, 75, 170.
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question of the appropriate oxygen nucleophile becomes critical. While a siloxidelo or a carboxylate" would be ideal because of their ease of subsequent manipulation, they have only served as nucleophiles in the Pd(0)-catalyzed reactions of vinyl epoxides, not in simplesubstitutions.l2 Of the two, thecarboxylate appeared preferable since the resultant esters are frequently the derivative of the allyl alcohol actually desired. The problem to be overcome is the differential rate of reaction of the starting ester compared to the product ester since, to the extent to which the product serves as a substrate, it ultimately will be equilibrated to the racemate. Thus, this approach envisions a kinetic trapping of the achiral r-allyl metal unit. The problem is more severe than it appears a t first glance since the chiral nonracemic ligand forms a matched and a mismatched pair with the racemic substrate but only a matched pair with the initial product. Thus, the rate of reaction of the mismatched pair of the substrate must be significantly greater than that of the matched pair of the product. We initially chose the methyl carbonate of cyclohexen-3-01 (la) and sodium pivalate with the notion that a bulky carboxylate would fix the conformation of the product wherein this substituent was pseudoequatorial thereby disfavoring its rate of ionization. Under our standard conditions of 2.5 mol % ?r-allylpalladium chloride dimer (2), 7.5 mol % chiral ligand 3,13 1.3 equiv of tetrahexylammonium bromide (THAB),14 and 1.3equiv of sodium pivalate (generated in situ from 1.3 equiv of N a H and 1.6 equiv of pivalic acid) in methylene chloride, the reaction of carbonate la gave a 94% yield of pivalate 4aI5of 91% ee, which increased very slightly to 92% ee at -20 OC (eq 2). The reaction was sluggish
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