Mechanistic Investigation of the Ring Opening in the Staudinger Cycloaddition Involving Ketenes with Electron‐Withdrawing Substituents

Abstract

The cycloaddition of ketenes and imines (Staudinger cycloaddition) is a general method for the synthesis of various β‐lactams. However, reactions of imines and ketenes with electron‐withdrawing substituents produce α,β‐unsaturated alkenamides, ring‐opening products of the intermediates generated from imines and the ketenes, even as sole products, besides the desired β‐lactams. The mechanism of the formation of α,β‐unsaturated alkenamides was investigated. The results indicate that the α,β‐unsaturated alkenamides are generated via a base‐induced CC bond isomerization followed by electrocyclic ring opening of the formed azacyclobutenes (=1,2‐dihydroazetes; cf. Scheme 3).

Ketenes and Other Cumulenes as Reactive Intermediates

“…The only reaction observed upon treatment of 86 with various bases is some isomerization to the trans -isomer, and no evidence of ring-opening of cis -β-lactams substituted with electron-withdrawing groups is found (eq ) . The failure to obtain cis -β-lactams substituted with electron-withdrawing groups from ketene/imine cycloadditions therefore is not due to any instability of product cis -β-lactams. …”

Catalyst‐Free Synthesis of Diastereomerically Pure 3‐Cyanoazetidin‐2‐ones via Thermally Promoted Tandem Wolff Rearrangement–Staudinger [2+2] Cycloaddition

“…[13,14] An alternative, though practically less convenient and less general approach, is the thermal decomposition of various azides (Scheme 2b). [15][16][17][18] Finally, thermally promoted ring contraction of 4-azidopyrrolinones also provides a way to obtain 3-chloro-3-cyano-β-lactams (Scheme 2c). [16] And if the Staudinger [2 + 2] cycloadditions reported in the literature generally suffered from moderate yields, the latter two approaches (apparently limited in scope) required handling of potentially explosive azides.…”