Abstract
The alkylative carboxylation of allenamide catalyzed by an N-heterocyclic carbene (NHC)-copper(I) complex [(IPr)CuCl] with CO2 and dialkylzinc reagents was investigated. The reaction of allenamides with dialkylzinc reagents (1.5 equiv) and CO2 (1 atm.) proceeded smoothly in the presence of a catalytic quantity of[(IPr) CuCl] to afford (Z)-alpha,beta-dehydro-beta-amino acid esters in good yields. The reaction is regioselective, with the alkyl group introduced onto the less hindered gamma-carbon, and the carboxyl group introduced onto the beta-carbon atom of the allenamides. The first step of the reaction was alkylative zincation of the allenamides to give an alkenylzinc intermediate followed by nucleophilic addition to CO2. A variety of cyclic and acyclic allenamides were found to be applicable to this transformation. Dialkylzinc reagents bearing beta-hydrogen atoms, such as Et2Zn or Bu2Zn, also gave the corresponding alkylative carboxylation products without beta-hydride elimination. The present methodology provides an easy route to alkyl-substituted alpha,beta-dehydro-beta-amino acid ester derivatives under mild reaction conditions with high regio- and stereoselectivtiy.