Stereospecific Rearrangement of Optically Active Tertiary Allylic Epoxides To Give Optically Active Quaternary Aldehydes: Synthesis of a-Alkyl Amino Aldehydes and Acids


2-Methyl-2-vinyl-3-alkyloxiranes, readily obtained from Sharpless-Katsuki asymmetric epoxidation of allylic alcohols, undergo facile 1,2-alkyl migration with inversion of configuration leading to 2-methyl-2-vinylalkanals, thereby establishing an acyclic quatemary carbon in high yield and optical purity. The reaction conditions necessary for rearrangement are generally quite mild, e.g., BF3.OEt2 at -78 OC for 2 min, 5 M LiC104 in refluxing ether, anhydrous Zn(0Tf)z or ZnCl2, EtAlC12, silica gel, and sonication. As an application of this methodology, and to prove the stereochemical course of the process, the synthesis of (S)-( -)-a-methylphenylalanine [(+)-16a] is described. This methodology also permits access to optically active N-protected amino aldehydes [Le., (-)-15a and (-)-15b], compounds which are difficult to make by other routes. The key step in each case is the rearrangement of (-)-sa or (-)-8b to give the quatemary aldehydes (+)-9a or (+)-9b in good yield and optical purity. Background and Introduction Acid-catalyzed reactions of cyclic and acyclic oxiranes enjoy a long history3 from both synthetic and theoretical points of view.4 Recent reports demonstrate that optically active epoxides can serve as chiral carbonyl ~ y n t h o n s , ~ giving aldehydes and ketones in high yield with good enantioselectivity, including protected aldols. We now report that 2-methyl-2-vinyl-3alkyloxiranes, readily derived from Sharpless-Katsuki6 asymmetric epoxidation technology, undergo facile 1,2-alkyl migration, establishing a quatemary carbon in high yield and optical purity. As an application of this methodology, and to prove the stereochemistry course of the process, the synthesis of (9(-)-a-methylphenylalanine via the corresponding N-protected phenylalanal is described in detail. Results and Discussion In the course of a synthesis of the cytotoxic agent aplysiapyranoid A,I we required the dibromo olefin 3, which could be prepared from the readily available epoxy alcohol 1.8 Swem oxidation of 1 gave the corresponding aldehyde 2 in 96% yield. @Abstract published in Advance ACS Abstracts, July 1, 1995. (1) American Chemical Society Arthur C. Cope Scholar, 1995. (2) UCLA Department of Chemistry Prize for Excellence in Research (3) Parker, R. R.; Isaacs, N. S. Chem. Rev. 1959, 59, 757. (4) Rickbom, B. Acid Catalyzed Rearrangements of Epoxides. In Comprehensive Organic Synthesis; Trost, B . M., Ed.; Pergamon: Oxford, 1991; Vol. 3, Chapter 3.3, pp 733-775. ( 5 ) (a) Jung, M. E.; D'Amico, D. C. J. Am. Chem. SOC. 1993,115, 12208. (b) Maruoka, K.; Sato, J.; Yamamoto, H. Tetrahedron 1992, 48, 3749. (c) Maruoka, K.; Ooi, T.; Nagahara, S.; Yamamoto, H. Tetrahedron 1991, 47, 6983. (d) Maruoka, K.; Ooi, T.; Yamamoto, H. J. Am. Chem. SOC. 1989, 1 1 1 , 6431. (e) Shimazaki, M.; Hara, H.; Suzuki, K.; Tsuchihashi, G. Tetrahedron Lett. 1987,28,5891. (0 Suzuki, K.; Miyumi, M.; Tsuchihashi, G. Tetrahedron Lett. 1987, 28, 3515. (8) Maruoka, K.; Hagesawa, M.; Yamamoto, H.; Suzuki, K.; Shimazaki, M.; Tsuchihashi, G. J. Am. Chem. SOC. 1986, 108, 3827. (6) All asymmetric epoxidation reactions were catalytic in titanium. See: Hanson, R. M.; Sharpless, K. B. J. Org. Chem. 1986, 51, 1922. (7) Jung, M. E.; D'Amico, D. C.; Lew, W. Tetrahedron Lett. 1993, 34, 923. (8) Jung, M. E.; Lew, W. J. Org. Chem. 1991, 56, 1347. 1993-94; Dissertation Year Fellowship 1994-95. 0002-7863195115 17-7379$09.00/0 Attempted Corey -Fuchsg homologation of this aldehyde 2 under conditions using zinc metal with triphenylphosphine and carbon tetrabromide gave not the expected olefin 3, but rather the aldehyde 4 in good yield (60%). Presumably, the reaction proceeds via the intermediacy of the alkene 3, but the zinc bromide formed in the reaction is a strong enough Lewis acid to cause the rearrangement of 3 into 4, by coordination with the epoxide, assistance in the breakage of the tertiary C 0 bond, and internal migration of the alkyl group to the cationic center. This mechanism is supported by the following facts. When the triphenylphosphine was replaced with the more reactive hexamethylphosphorus triamide (HMPT) and the zinc metal was omitted, the normal Corey-Fuchs reaction occurred to afford the dibromoalkene 3 in nearly quantitative yield.'O Exposure of this alkene 3 to boron trifluoride etherate at -23 "C for 1 h then afforded the aldehyde 4 in 89% yield. Thus it is highly likely that 3 is an intermediate in the formation of 4 from 2 in the reaction using zinc metal. Thus one can obtain the optically active quatemary aldehyde in excellent yield in only two or three steps from the epoxy alcohol 1. OH (COCI)? , DMSO then TEA Me Me Wh (+I 1 HMPT, CHzC/ CBr, l z P h # 99% CBr4,60%


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