Synthesis of b-Oxygenatd g-amino Acids and g-Oxygenated g-Amino Acids from a-Amino Acids

Abstract

A diastereoselective synthesis of 2-amino alcohols toward a synthesis of P-oxygenated y-amino acids, y-oxygenated 6-amino acids, and related compounds was summarized.Contents 1. Introduction 2. Asymmetric Reduction of Amino Ketoesters 3. Diastereoselective Synthesis of 2-Amino Alcohols by Alkylation of Chiral a-Amino Aldehyde 3.1 Alkylation with Enolate, Grignard Reagent, and Allylmetal 3.2.Alkylation with Titanium Homoenolate 4. Double Diastereodifferentiation Strategies in an Alkylation of a-Amino Aldehyde 5. Synthetic Application of Oxazolidin-2-ones as a Synthon for 2-Amino Alcohol ' 02' 2 HO*'OH R2In the present paper, among synthetic procedures for an effective chiral synthesis of 1 and its N-protected esters and their related analogues, we wish to focus on a highly diastereoselective synthesis of 2-amino alcohols toward a diastereoselective synthesis of P-hydroxy-y-amino acids and y-hydroxy-&amino acid derivatives, mainly reported from our laboratory. Asvmmetric Reduction of Amino Keto EstersReduction of the y-amino P-keto ester (7).derived from N-Boc-(S)-leucine, would be one of the most significant method from the point of view of commercial production of HETEROCYCLES.V o l 33.No. 2. 1992 1053 1 and related compounds, since it would be suitable for scaling up to large quantities.However, stereochemical control of the reduction has been known to he difficult.7.8 Reduction of 7 with usual reducing reagents such as NaBH4, LiBH4, Zn(BH4)z afforded a mixture of 8a and Sb with only moderate erythro selectivity.8Chirally modified L ~B H ~~ and K-selectride9 were found to be effective for increasing the degree of diastereoselectivity.The diastereoselectivity was reversed when N-dibenzyl was used as the protected group for nitrogen instead of N-Boc.~e e t z l o reported that reduction of 9 with NaBH4 resulted in a formation of threo isomers (10) with high diastereoselectivity.We also observed high threo selectivity in reduction of 11 with NaBH4 to give