Diastereo‐ and Enantioselective Reductive Aldol Reaction with Trichlorosilane Using Chiral Lewis Bases as Organocatalysts

摘要: The catalytic enantioselective tandem reaction is an efficient synthetic methodology in which optically active compounds are assembled from simple prochiral substrates via two (or more) distinct processes taking place under the same conditions. efficiency enhanced by avoiding time-intensive and yield-reducing isolation purification of intermediates decreasing amounts chemicals solvents used. asymmetric reductive aldol transformation involving conjugate reduction a,b-unsaturated carbonyl followed enolate intermediate with aldehydes or ketones. Chiral transition-metal catalysts have been used to control stereochemistry these transformations. We recently reported that achiral phosphorus oxides function as Lewis base organocatalysts promote both enones trichlorosilane aldehydes. Herein we report catalysis this chiral bases provides good high diastereoand enantioselectivities. Scheme 1 outlines current method. Our previous study had shown catalyzed proceeds a six-membered transition state enone s-cis conformation give (Z)-trichlorosilyl exclusively. Therefore, syn selectivity expected for subsequent process, assuming through chair-like cyclic state. Moreover, enantioselectivity could also be achieved judicious selection (LB*). first examined various (Figure 1) chalcone (1a) benzaldehyde (2a) at 78 8C (Table 1). With (S)-BINAPO, dichloromethane gave adduct 3a respectable stereoselectivities 1, entry By simply changing solvent propionitrile, chemical yield dramatically improved 2). Other were then using entries 3–6). (R,R)-DIOPO showed comparable activity BINAPO afford similar slight loss diastereoselectivity 3). Although structurally BINAPO, (S)[a] Prof. Dr. M. Sugiura, N. Sato, Y. Sonoda, Nakajima Graduate School Pharmaceutical Sciences Kumamoto University 5-1 Oe-honmachi, 862-0973 (Japan) Fax: (+81)96-362-7692 E-mail : msugiura@kumamoto-u.ac.jp (M. Sugiura) nakajima@gpo.kumamoto-u.ac.jp Nakajima) [b] S. Kotani Priority Organization Innovation Excellence Supporting information article available on WWW http://dx.doi.org/10.1002/asia.200900450. 1. catalyst.