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

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.