Synthesis of Chiral Tetrasubstituted Azetidines from Donor-Acceptor Azetines via Asymmetric Copper(I)-Catalyzed Imido-Ylide [3+1]-Cycloaddition with Metallo-Enolcarbenes

Kostiantyn O Marichev; Kan Wang; Kuiyong Dong; Nicole Greco; Lynée A Massey; Yongming Deng; Hadi Arman; Michael P Doyle

doi:10.1002/anie.201909929

Synthesis of Chiral Tetrasubstituted Azetidines from Donor-Acceptor Azetines via Asymmetric Copper(I)-Catalyzed Imido-Ylide [3+1]-Cycloaddition with Metallo-Enolcarbenes

Angew Chem Int Ed Engl. 2019 Nov 4;58(45):16188-16192. doi: 10.1002/anie.201909929. Epub 2019 Sep 24.

Authors

Kostiantyn O Marichev¹, Kan Wang¹, Kuiyong Dong¹, Nicole Greco¹, Lynée A Massey¹, Yongming Deng¹, Hadi Arman¹, Michael P Doyle¹

Affiliation

¹ Department of Chemistry, The University of Texas at San Antonio One UTSA Circle, San Antonio, TX, 78249, USA.

Abstract

The all-cis stereoisomers of tetrasubstituted azetidine-2-carboxylic acids and derivatives that possess three chiral centers have been prepared in high yield and stereocontrol from silyl-protected Z-γ-substituted enoldiazoacetates and imido-sulfur ylides by asymmetric [3+1]-cycloaddition using chiral sabox copper(I) catalysis followed by Pd/C catalytic hydrogenation. Hydrogenation of the chiral p-methoxybenzyl azetine-2-carboxylates occurs with both hydrogen addition to the C=C bond and hydrogenolysis of the ester.

Keywords: azetidines; azetines; copper catalysis; cycloaddition; hydrogenation.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Abstract

Publication types

Grants and funding