Asymmetric synthesis of CF₂-functionalized aziridines by combined strong Brønsted acid catalysis

Abstract

A diastereo- and enantioselective approach to access chiral CF2-functionalized aziridines from difluorodiazoethyl phenyl sulfone (PhSO2CF2CHN2) and in situ-formed aldimines is described. This multicomponent reaction is enabled by a combined strong Brønsted acid catalytic platform consisting of a chiral disulfonimide and 2-carboxyphenylboronic acid. The optical purity of the obtained CF2-substituted aziridines could be further improved by a practical dissolution–filtration procedure.

Synthetic Applications of Ambiphilic C‐acylimines in Organic Synthesis

“…A. Ma and colleagues described a stereoselective synthesis of chiral CF 2 ‐functionalized aziridines 80 from difluorodiazoethyl phenyl sulfone 80 using in situ‐formed aldimines 78 (Scheme 26). [30] The highlight of this work is a combination of strong Bronsted acids chiral disulfonimide and 2‐carboxyphenylboronic acid used to facilitate this multicomponent reaction.…”

Recent Progress on the Synthesis of Chiral Sulfones

“…In recent year, Zhang and co‐workers reported an enantioselective method to access chiral CF 2 ‐functionalized aziridines (Scheme 65). [79] The combined strong Brønsted acid catalytic system consisting of chiral disulfonimide OC 20 and 2‐carboxyphenylboronic acid could promote the asymmetric multi‐step reaction of aryl glyoxal monohydrates 144 , affording the desired chiral CF 2 ‐functionalized aziridines 145 in 38–70 % yields, >95 % dr, and 35–73 % ee. Scaled‐up experiments with model substrate also proved to be feasible and further synthesis and conversion into free aziridine, hydroxy‐substituted CF 2 ‐functionalized aziridine and CF 2 ‐functionalized α‐chloro‐β‐amino ketone.…”

Nickel‐Catalyzed Aminofluoroalkylation of Alkenes: Access to Difluoroalkylated N‐Containing Heterocyclic Compounds

“…Early in 2002, Uneyama's group [9] reported the synthesis of difluoromethylaziridines by the reaction of dimethylsulfonium methylide with difluoroenamines. Zhang and Ma [10] described a high stereoselective aza‐Darzen reaction between difluorodiazo reagent PhSO 2 CF 2 CHN 2 and in situ‐generated aldimines to generate a variety of difluromethylenated aziridines. More recently, a visible light promoted aminodifluoroalkylation of olefins with ethyl iododifluoroacetate was disclosed by He and Zhao to afford several difluoroacetate‐containing aziridines in moderated to good yields [11] .…”