Asymmetric Reformatsky Reaction of Aldehydes Catalyzed by Novel β-Amino Alcohols and Zinc Complexes

Abstract

A series of β-amino alcohols derived from (1R, 2S)-2-amino-1,2-diphenylethanol and substituted salicylaldehydes as novel chiral tridentate ligands has been applied to an asymmetric Reformatsky reaction of aldehydes with ethyl iodoacetate in the presence of ZnMe₂. This novel catalytic system produced the desired β-hydroxyl esters with moderate to good enantioselectivities (up to 81% ee) and yields for many aldehydes, including aromatic, heteroaromatic, conjugated, and aliphatic aldehydes.

GRAPHICAL ABSTRACT

Keywords:

• β-Amino alcohols
• aldehydes
• asymmetric Reformatsky
• chiral tridentate ligands

Notes

^a All reactions were carried out using 2 equiv ethyl iodoacetate and 2.25 equiv ZnMe₂ in Et₂O at RT for 1 hour with air.

^b Isolated yield.

^c The enantiomeric excess was determined by chiral HPLC analysis using a Chiralcel OD column.

^d Determined by LC-MS.

^e nd, not determined.

^a All reactions were carried out using 10 mol% 1d, 2 equiv ethyl iodoacetate, and 2.25 equiv ZnMe₂ in Et₂O at RT for 1 h with air.

^b Isolated yield.

^c The enantiomeric excess was determined by chiral HPLC analysis using Chiralcel OD column and Chiralpak AS column, or by chiral GC analysis using Chiralsil Dex CB column.

^d The absolute configuration of the product was assigned by comparison of HPLC retention time with values in the literature.^{[ 18 , 22 ]}