DABCO-Catalyzed Michael/Alkylation Cascade Reactions Involving α-Substituted Ammonium Ylides for the Construction of Spirocyclopropyl Oxindoles: Access to the Powerful Chemical Leads against HIV-1

Abstract

A novel Michael/alkylation cascade reaction of N-unprotected 3-bromooxindoles with α,β-unsaturated acyl phosphonates using DABCO as a robust catalyst followed by the derivatization of the acyl phosphonate intermediates in situ has been developed. This scenario enables rapid access to a diverse set of highly functionalized spirocyclopropyl oxindoles in moderate yields with good to excellent diastereoselectivities, which are analogues of a high active non-nucleoside reverse transcriptase inhibitor against HIV-1. The synthetic potential of this tactic has been highlighted by a gram-scale reaction and Suzuki cross-coupling reactions of the product. Moreover, the reaction mechanism has been tentatively elucidated by control experiments and dynamic high-resolution mass spectrometry studies, which indicates that the Michael/alkylation cascade reaction involves DABCO-derived α-substituted ammonium ylides.