Interrupted SNAr-Alkylation Dearomatization

Bilal Altundas; John-Paul R Marrazzo; Tore Brinck; Christopher Absil; Fraser F Fleming

doi:10.1021/jacsau.3c00813

Interrupted S_NAr-Alkylation Dearomatization

JACS Au. 2024 Feb 19;4(3):1118-1124. doi: 10.1021/jacsau.3c00813. eCollection 2024 Mar 25.

Authors

Bilal Altundas¹, John-Paul R Marrazzo², Tore Brinck³, Christopher Absil⁴, Fraser F Fleming²

Affiliations

¹ Department of Chemistry, University of Illinois Urbana-Champagne, 505 South Mathews Avenue Urbana, Champaign, Illinois 61801, United States.
² Drexel University, Department of Chemistry, 3041 Chestnut Street, Philadelphia, Pennsylvania 19104, United States.
³ KTH Royal Institute of Technology, Department of Chemistry, Teknikringen 42, Stockholm SE-10044, Sweden.
⁴ Temple University, Department of Chemistry, 1901 N. 13th Street, Philadelphia, Pennsylvania 19122, United States.

Abstract

Dearomatizations provide powerful synthetic routes to rapidly assemble substituted carbocycles and heterocycles found in a plethora of bioactive molecules. Harnessing the advantages of dearomatization typically requires vigorous reagents because of the difficulty in disrupting the stable aromatic core. A relatively mild dearomatization strategy is described that employs lithiated nitriles or isocyanides in a simple S_NAr-type addition to form σ-complexes that are trapped by alkylation. The dearomatizations are diastereoselective and efficient and rapidly install two new carbon-carbon bonds, one of which is a quaternary center, as well as nitrile, isocyanide, and cyclohexadiene functionalities.