The first example of ring expansion of N-tosylaziridines to 2-aroyl-N-tosylazetidines with nitrogen ylides in an aqueous medium

Abstract

Tertiary amine catalyzed ring expansion reaction of N-tosylaziridines to 2-aroyl-N-tosylazetidines, with nitrogen ylides formed in situ from phenacyl bromide derivatives in a silica gel-water system is reported. The reaction expeditiously affords functionalized azetidines in high yields and stereoselectivities in a one-pot process. Advantageously, the protocol precludes the preparation and isolation of nitrogen ylides and their precursors in a separate step as they are formed in situ.

Ammonium Ylide Mediated Cyclization Reactions

“…In continuation of their aziridination protocol (Scheme 19A), Yadav et al also reported that the addition of in situ generated ammonium ylides to simple aziridines 74 gave access to azetidines 75 in a formal [3+1] mode with high cis diastereoselectivities (Scheme 20). [49] We have tried without success to expand this method towards other ammonium ylides and epoxides, thereby confirming the earlier success is a rare example of such a reaction.…”

Ring Expansions of Activated Aziridines and Azetidines

“…Yadav and co-workers developed an efficient synthetic route towards 2-aroyl-Ntosylazetidines 31 via tertiary amine-catalyzed ring-expansion of N-tosylaziridines 8 with nitrogen ylides in aqueous media [49]. The highly stereoselective and organocatalytic reaction proceeds via the formation of an ammonium ylide intermediate 33 through 32 generated from 2-bromo-1-phenylethanone (30) and DABCO followed by ring opening of the aziridine 8 and a subsequent intramolecular cyclization of 34 (Scheme 11).…”

A Stereoselective [3+1] Ring Expansion for the Synthesis of Highly Substituted Methylene Azetidines

“…The [2+2] reactions have been well-explored 6 while the corresponding [3+1] reactions are less common, although N-atom transfer from an oxaziridine to a donor-acceptor cyclopropane was recently disclosed, as well as two examples of nucleophilic aziridine opening with sulfoxonium or nitrogen ylides. 7,8 Despite these advances, stereoselective access to highly substituted, densely functionalized azetidines remains difficult. We hypothesized that an umpolung [3+1] approach could address these challenges by engaging strained aziridines with electrophilic one-carbon sources to trigger a ring-opening, ring-closing cascade to yield the azetidines (Scheme 1C).…”