Chiral Magnesium(II)-Catalyzed Asymmetric Hydroalkylation of Imine-Containing Vinylazaarenes through Conjugate
Dong Ye1, Mingyi Jiang1, Lichao Ning1
1Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, China.
Abstract:
The synthesis of chiral azaarenes is of great importance for pharmaceutical development. A direct and versatile approach to obtaining such compounds is the functionalization of imine-containing 2-vinylazaarenes. We have developed a chiral N,N'-dioxide/Mg(II) Lewis acid catalytic system to control nucleophilic β-cyclic or acyclic ketone amides/esters and overcome strong background reaction, enabling highly efficient enantioselective hydroalkylation of imine-containing 2-vinylazaarenes via conjugate addition. As a result, a library of chiral azaarenes bearing an all-carbon quaternary stereocenter can be obtained in high yields with good to excellent ee values. DFT calculations indicate assistances of azaarenes in hydrogen transfer, and the CH-π interaction between the substrate and the ligand's amide group in the enantioselective differentiation.
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