Diastereoselective route to novel fused or bridged tricyclic β-lactams through intramolecular nitrone-alkene cycloaddition of 2-azetidinone-tethered alkenylaldehydes -: Synthetic applications to carbacephams and cyclic β-amino acid derivatives

A convenient, regio- and stereoselective direct route to optically pure unusually fused or bridged tricyclic beta-lactams has been developed by use of intramolecular nitrone-alkene cycloaddition (INAC) reactions of easily available monocyclic 2-azetidinone-tethered alkenylaldehydes as the key synthetic step. The regioselectivity of the cycloaddition can be tuned by moving the alkene substituent from N1 to C3 on the 2-azetidinone ring. In addition, some simple, interesting transformations were tested on representative examples of the different types of tricyclic systems prepared, in order to demonstrate their potential as intermediates in the preparation of differently polyfunctionalized compounds, including carbacepham derivatives and related unconventional bicyclic systems containing medium-sized rings fused to the beta-lactam nucleus, as well as several types of cyclic beta-amino acid derivatives. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005).