Highly stereocontrolled synthesis of the 1β-methylcarbapenem key intermediate by the reformatsky reaction of 3-(2-bromopropionyl)-2-oxazolidone derivatives with a 4-acetoxy-2-azetidinone

Yoshio Ito, Akira Sasaki, Kastumi Tamoto, Makoto Sunagawa, Shiro Terashima

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

The key synthetic intermediate (4) of 1β-methylcarbapenems (1-3) was efficiently synthesized by employing highly stereocontrolled Reformatsky reaction (C4-alkylation) of 3-(2-bromopropionyl)-2-oxazolidone derivatives (6) with (3R,4R)-4-acetoxy-3-[(R)-1-(t-butyldimethylsilyloxy)ethylJ-2-azetidinone (5) in the presence of zinc dust followed by removal of 2-oxazolidone moieties. The best diastereoselectivity (β:α=95:5) could be realized by uses of sterically crowded achiral 2-oxazolidone derivatives such as 4,4-dimethyl-, 4,4,5,5-tetramethyl, and 4,4-dibutyl-5,5-pentamethylene-2-oxazolidone and higher reaction temperatures (refluxing tetrahydrofuran). The remarkable diastereoselectivities observed for the Reformatsky reactions could be explained by means of the weakly chelating transition state models.

Original languageEnglish
Pages (from-to)2801-2820
Number of pages20
JournalTetrahedron
Volume47
Issue number16-17
DOIs
Publication statusPublished - Jan 1 1991
Externally publishedYes

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Oxazolidinones
Derivatives
Alkylation
Chelation
Dust
Zinc
Temperature
4-acetoxy-2-azetidinone
1 beta-methylcarbapenem

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

Highly stereocontrolled synthesis of the 1β-methylcarbapenem key intermediate by the reformatsky reaction of 3-(2-bromopropionyl)-2-oxazolidone derivatives with a 4-acetoxy-2-azetidinone. / Ito, Yoshio; Sasaki, Akira; Tamoto, Kastumi; Sunagawa, Makoto; Terashima, Shiro.

In: Tetrahedron, Vol. 47, No. 16-17, 01.01.1991, p. 2801-2820.

Research output: Contribution to journalArticle

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