Synthesis of New Chiral β-Amino Alcohols Derived from Isomannide and Their Application to the Catalytic Enantioselective Addition of Diethylzinc to Aldehydes

Abstract

Enantioselective carbon-carbon bond formation is one of the most interesting challenges in organic synthesis. In recent years, the catalytic enantioselective addition of dialkylzincs to aldehydes has attracted much attention because of its potentials in the preparation of optically active secondary alcohols. Over the past decade, various types of chiral ligands using as catalysts for this reaction have been developed. Among the diverse chiral lignads, chiral amino alcohols are predominant. As other type of ligands, chiral amino thiols, amino thiocyanate, amino thioacetate, iminyl alcohols, oxazolinyl alcohols, amino amides, sulfonamides, phosphoramides, α-hydroxy carboxylic acid and diols such as TADDOLs and BINOLs have been published. Recently we reported the synthesis of various chiral βor γ-amino alcohols derived from inexpensive chiral pools, such as α-D-xylose, α-D-glucose and L-tartaric acid, and D-mannitol. As a continuation of our ongoing project on the development of new chiral ligands from an easy and inexpensive starting materials, we hereby report the synthesis of new β-amino alcohols 3a-f starting from isomannide 1 and their application for the catalytic ethylation to aldehydes. The ligands 3a-f were prepared in 87-98% yield by the treatment of 2 with 2.5 equiv. of dialkylamines under solvent-free conditions for 2-3 h at 45 C (Scheme 1). Subsequently we compared the enantioselectivities of these chiral ligands as catalyst for the enantioselctive addition of diethylzinc to benzaldehyde. Thus, the reaction was carried out by addition of 2 equiv. of diethylzinc in toluene to