Catalysis of Organic..

Augustine, Tanielyan, Marin and Alvez 46351. Synthesis of Chiral 2-Amino-1-PhenylethanolAbstractRobert Augustine, Setrak Tanielyan, Norman Marin, Gabriela AlvezCenter for Applied Catalysis, Seton Hall University, South Orange, NJ 07079Two methods for the synthesis of chiral 2-amino-1-phenylethanol have beendeveloped. The first utilizes a chiral oxaborolidine catalyzed borane reduction ofphenacyl chloride to give the chiral chloro-alcohol in very good yield with an ee inthe 93%-97% range. Reaction with dilute ammonium hydroxide produced theamino-alcohol in very good yield with a high ee. The second approach involved firstconversion of the phenacyl chloride to the succinimide which was then hydrogenatedusing a chiral ruthenium complex in conjuction with a base and an optically activeamine (Noyori procedure) to give the optically active succinimido alcohol in verygood yield with an ee of 98%. Hydrolysis with dilute base produced the opticallyactive amino alcohol in very good yield and excellent enantioselectivity.IntroductionChiral β-amino alcohols such as (R) or (S) 2-amino-1-phenylethanol (1) areimportant intermediates in the synthesis of a variety of pharmaceutically importantcompounds. While there were some early procedures reported for the synthesis of1,(1,2) several years ago an evaluation of the more promising of these approaches ledto the conclusion that the most practical method for preparing 1 in larger quantitieswas by the resolution of the racemic material using di-O-toluoyltartaric acid (3) ordehydroabietic acid (4). In these resolutions, though, the chiral 1 was produced with99% ee but was obtained in only about a 25% yield. In recent years, however, someefficient methods for the enantioselective reduction of ketones have been developedand it was considered that application of some of these newer reactions could lead tothe efficient and enantioselective production of β-amino alcohols such as 1. The twoprocedures selected for investigation were the chiral oxazaborolidine catalyzedreduction of phenacyl chloride (2)(5-7) followed by amination of the chloro alcoholproduct (8) (Eqn. 1) and the Noyori hydrogenation (9) of an appropriately blocked β-aminoacetophenone followed by unblocking of the amine group (Eqn. 2).Results and DiscussionThe chiral reduction of phenacyl chloride (2) was run using either the methyl- ormethoxy- oxazaborolidine (3) as the catalyst. After optimization of the reaction