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Mechanism of the Nucleophilic Substitution of Acyl Electrophiles using Lithium Organocuprates
Author(s) -
Yoshikai Naohiko,
Iida Ryoko,
Nakamura Eiichi
Publication year - 2008
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200800060
Subject(s) - chemistry , thioester , nucleophile , nucleophilic substitution , nucleophilic acyl substitution , electrophile , chloride , oxidative addition , medicinal chemistry , lithium (medication) , reagent , alkyl , reductive elimination , substitution reaction , transition state , acylation , organic chemistry , catalysis , medicine , enzyme , endocrinology
The mechanism of nucleophilic substitution reaction at an sp 2 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 CS 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. 13 C 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.