Competitive mechanisms and origins of stereocontrol in the [2+2] thermal cycloaddition between imines and keteniminium cations. A complementary entryto 2-azetidinones (beta-lactams) and related compounds

The different reaction paths associated with the formal [2 + 2] thermal cyc loaddition between several keteniminium cations and imines has been studied computationally. It is found that the reaction takes place via stepwise me chanisms that involve the sequential formation of the N1-C2 and the C3-C4 b onds. In some cases, the second step of the reaction is subjected to torquo electronic effects and determines its stereochemical outcome. Under these c onditions, preferential or exclusive formation of cis cycloadducts is predi cted, in good agreement with part of the experimental evidence available. W hen chloroenamines are used as precursors of the keteniminium ions, the ste p in which the C3-C4 bond is formed can consist of an intramolecular S(N)2 reaction. Under these conditions, the stereocontrol of the reaction is sign ificantly lower and the trans isomer is preferentially formed. According to our results, generation of keteniminium cations from enamines having good leaving groups is recommended to improve the stereocontrol of the reaction.