Mechanism of the nucleophilic substitution of acyl electrophiles using lithium organocuprates

Naohiko Yoshikai, Ryoko Iida, Eiichi Nakamura

Research output: Contribution to journalArticlepeer-review

Abstract

The mechanism of nucleophilic substitution reaction at an sp2 carbon center of a thioester or an acid chloride with a lithium organocuprate reagent has been investigated. Density functional calculations indicated that the thioester undergoes oxidative addition of the C-S bond to the copper(I) atom through a three-centered transition state to afford an organocopper(III) intermediate, which gives the product through reductive elimination of the alkyl and the acyl groups. On the other hand, the acid chloride loses a chloride anion very easily when it interacts with the cuprate, because the chloride anion is captured by a lithium(I) cation rather than a copper(I) atom. 13C kinetic isotope effect (KIE) experiments showed excellent agreement with computational predictions for the thioester reaction, but suggested that the nucleophilic displacement transition state of the acid chloride occurs much more advanced than the calculations predict.

Original languageEnglish
Pages (from-to)1063-1072
Number of pages10
JournalAdvanced Synthesis and Catalysis
Volume350
Issue number7-8
DOIs
Publication statusPublished - 2008 May 5
Externally publishedYes

Keywords

  • Cuprates
  • Density functional calculations
  • Isotope effects
  • Nucleophilic substitution
  • Reaction mechanisms

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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