Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

Zara M Seibel; Jeffrey S Bandar; Tristan H Lambert

doi:10.3762/bjoc.17.134

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

Beilstein J Org Chem. 2021 Aug 17:17:2077-2084. doi: 10.3762/bjoc.17.134. eCollection 2021.

Authors

Zara M Seibel¹, Jeffrey S Bandar¹, Tristan H Lambert^{1

2}

Affiliations

¹ Department of Chemistry, Columbia University, New York, New York 10027, USA.
² Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.

Abstract

A procedure for the enantioselective synthesis of α-substituted glutamates and pyroglutamates via a cyclopropenimine-catalyzed Michael addition of amino ester imines is described. Enantioselectivities of up to 94% have been achieved, and a variety of functional groups were found to be compatible. The impact of the catalyst structure and imine substitution is discussed. Compared to other methods, this protocol allows for a broader and more enantioselective access to pyroglutamate derivatives.

Keywords: Brønsted base; Michael addition; cyclopropenimine; enantioselective catalysis; pyroglutamate.

Grants and funding

Financial support for this work was provided by NIHGMS (R01 GM102611). We are grateful for NSF (Z.M.S. and J.S.B.) and NDSEG (J.S.B.) graduate fellowships.