N-Heterocyclic carbene catalyzed base assisted C-C bond cleavage of cyclopropenones: an approach towards diastereoselective synthesis of azetidinones and benzoxazepines

N-Heterocyclic carbene catalyzed base assisted diastereoselective ring opening of diphenyl-cyclopropenone followed by ring-closing through [3 + 1] or [3 + 4] addition with o-aminophenol furnished biologically important scaffolds azetidinones or benzoxazepines, respectively. The unique feature of this reaction is that the key intermediate acylazolium species is generated through C-C bond cleavage of cyclopropenone rather than routine substrates such as conjugated enals, ynals and acyl halides. Interestingly, this reaction involves an alpha-aryl substituted acylazolium species, which has never been reported so far with respect to N-heterocyclic carbene catalysis. We have demonstrated a synthetic protocol to synthesize two different bio-active skeletons, that is, beta-lactam and benzoxazepine by using N-heterocyclic carbene as the catalyst. Herein, 3-membered strained cyclopropenone has been used as a 3C synthon.

Automated summary

In this study, biologically active scaffolds, azetidinones or benzoxazepines, were synthesized through a series of reactions catalyzed by N-heterocyclic carbene. The key intermediate acylazolium species in this reaction is generated through C-C bond cleavage of cyclopropenone, which is different from previous N-heterocyclic carbene catalysis. Two different bio-active skeletons, beta-lactam and benzoxazepine, were successfully synthesized using N-heterocyclic carbene as the catalyst.