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).


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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.

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Publication History

Received: 03 July 2020

Accepted after revision: 07 August 2020

Article published online:
22 September 2020

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