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

Saki Inatomi; Yuta Takayanagi; Kento Watanabe; Akinori Toita; Hiroyuki Yamakoshi; Seiichi Nakamura

doi:10.1055/s-0040-1707274

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

Saki Inatomi, Yuta Takayanagi, Kento Watanabe, Akinori Toita, Hiroyuki Yamakoshi, Seiichi Nakamura

Research output: Contribution to journal › Article › peer-review

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 CH ₂Cl ₂at -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.

Original language	English
Pages (from-to)	161-174
Number of pages	14
Journal	Synthesis (Germany)
Volume	53
Issue number	1
DOIs	https://doi.org/10.1055/s-0040-1707274
Publication status	Published - 2021 Jan 5
Externally published	Yes

Keywords

1,4-addition
cyclic acetals
primary alcohols
syn -selectivity
γ-alkoxy-α,β-unsaturated esters

ASJC Scopus subject areas

Catalysis
Organic Chemistry

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

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 CH 2Cl 2at -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.",

keywords = "1,4-addition, cyclic acetals, primary alcohols, syn -selectivity, γ-alkoxy-α,β-unsaturated esters",

author = "Saki Inatomi and Yuta Takayanagi and Kento Watanabe and Akinori Toita and Hiroyuki Yamakoshi and Seiichi Nakamura",

note = "Funding Information: 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).JapanAgencyforMedical ReeachandDevelopment) Funding Information: A.T. is grateful to JSPS for a graduate fellowship. The authors acknowledge the assistance of the Research Equipment Sharing Center at Nagoya City University. Publisher Copyright: {\textcopyright} 2021 Georg Thieme Verlag. All rights reserved.",

year = "2021",

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doi = "10.1055/s-0040-1707274",

language = "English",

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AU - Inatomi, Saki

AU - Takayanagi, Yuta

AU - Watanabe, Kento

AU - Toita, Akinori

AU - Yamakoshi, Hiroyuki

AU - Nakamura, Seiichi

N1 - Funding Information: 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).JapanAgencyforMedical ReeachandDevelopment) Funding Information: A.T. is grateful to JSPS for a graduate fellowship. The authors acknowledge the assistance of the Research Equipment Sharing Center at Nagoya City University. Publisher Copyright: © 2021 Georg Thieme Verlag. All rights reserved.

PY - 2021/1/5

Y1 - 2021/1/5

N2 - 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 CH 2Cl 2at -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.

AB - 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 CH 2Cl 2at -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.

KW - 1,4-addition

KW - cyclic acetals

KW - primary alcohols

KW - syn -selectivity

KW - γ-alkoxy-α,β-unsaturated esters

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

Abstract

Keywords

ASJC Scopus subject areas

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