Stereoselective 1,4-Addition of Primary Alcohols to γ-Alkoxy-α,β-unsaturated EstersThis 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).
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.
Key words1,4-addition - γ-alkoxy-α,β-unsaturated esters - primary alcohols - syn-selectivity - cyclic acetals
Received: 03 July 2020
Accepted after revision: 07 August 2020
22 September 2020 (online)
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