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Cu‐Catalyzed Alkylative Carboxylation of Ynamides with Dialkylzinc Reagents and Carbon Dioxide
Author(s) -
Takimoto Masanori,
Gholap Sandeep Suryabhan,
Hou Zhaomin
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201502774
Subject(s) - carboxylation , reagent , chemistry , catalysis , alkylation , stereoselectivity , nucleophile , organic chemistry , combinatorial chemistry , carbene , medicinal chemistry
Alkylative carboxylation of ynamides with CO 2 and dialkylzinc reagents using a N‐heterocyclic carbene (NHC)–copper catalyst has been developed. A variety of ynamides, both cyclic and acyclic, undergo this transformation under mild conditions to afford the corresponding α,β‐unsaturated carboxylic acids, which contain the α,β‐dehydroamino acid skeleton. The present alkylative carboxylation formally consists of Cu‐catalyzed carbozincation of ynamides with dialkylzinc reagents with the subsequent nucleophilic carboxylation of the resulting alkenylzinc species with CO 2 . Dialkylzinc reagents bearing a β‐hydrogen atom such as Et 2 Zn and Bu 2 Zn still afford the alkylated products despite the potential for β‐hydride elimination. This protocol would be a desirable method for the synthesis of highly substituted α,β‐ dehydroamino acid derivatives due to its high regio‐ and stereoselectivity, simple one‐pot procedure, and its use of CO 2 as a starting material.