Issue 11, 2021

Enantioselective modification of sulfonamides and sulfonamide-containing drugs via carbene organic catalysis

Abstract

A carbene-catalyzed method for highly enantioselective modification of sulfonamides is disclosed. The reaction proceeds under mild conditions with broad substrate scope, wide functional group tolerance, and good to excellent yields. When multiple sulfonamides or amines are present in the same molecule, the reaction occurs in a highly chemo-selective manner. Application of our method allows for selective modification of sulfonamide-containing drug molecules to form the corresponding phthalidyl derivatives as potential prodrugs. Experimental observations and DFT calculations suggest that the reaction proceeds via a stepwise addition pathway, assisted by Li+ ions or protons. Non-covalent interactions, such as cation–π interactions, play important roles in enhancing the reactivity and controlling the enantioselectivity of the reaction.

Graphical abstract: Enantioselective modification of sulfonamides and sulfonamide-containing drugs via carbene organic catalysis

Supplementary files

Article information

Article type
Research Article
Submitted
05 Gur 2021
Accepted
09 Bit 2021
First published
15 Bit 2021

Org. Chem. Front., 2021,8, 2413-2419

Enantioselective modification of sulfonamides and sulfonamide-containing drugs via carbene organic catalysis

R. Song, Y. Liu, P. K. Majhi, P. R. Ng, L. Hao, J. Xu, W. Tian, L. Zhang, H. Liu, X. Zhang and Y. R. Chi, Org. Chem. Front., 2021, 8, 2413 DOI: 10.1039/D1QO00212K

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