Synthesis 2021; 53(01): 161-174
DOI: 10.1055/s-0040-1707274
paper

Stereoselective 1,4-Addition of Primary Alcohols to γ-Alkoxy-α,β-unsaturated Esters

Saki Inatomi
,
Yuta Takayanagi
,
Kento Watanabe
,
Akinori Toita
,
Hiroyuki Yamakoshi
Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan   Email: nakamura@phar.nagoya-cu.ac.jp
,
Seiichi Nakamura
› Author Affiliations
This research was supported in part by the Platform Project for Supporting in Drug Discovery and Life Science Research from Japan Agency for Medical Research and Development (AMED).


Abstract

The scope and limitations of the diastereoselective 1,4-addition reaction of primary alcohols to γ-alkoxy-α,β-unsaturated esters were investigated. We found that a variety of sodium alkoxides, generated from the corresponding primary alcohols with NaH, underwent 1,4-addition reactions with (E)-enoates in CH2Cl2 at –23 °C to give β-alkoxy esters in modest yields with good to excellent syn-selectivity, whereas stereoselectivity was not observed with the use of glycerol derivatives as nucleophiles. Cyclic acetal protection was found to play a pivotal role for the reaction to proceed.

Supporting Information



Publication History

Received: 03 July 2020

Accepted after revision: 07 August 2020

Publication Date:
22 September 2020 (online)

© 2020. Thieme. All rights reserved

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