The "Staudinger ketene-imine reaction" between ketenes generated from natural O,N-protected trans-4-hydroxy-l-prolines and the N-benzyl-N-benzylideneamine led to mixtures of diastereoisomeric, enantiomerically pure pyrrolidine-derived spiro-beta-lactams with a relative cis configuration. These were transformed into the corresponding pyrroline-spiro-beta-lactams by means of treatment with a base and the new C=C double bond was submitted to a number of different reactions in order to evaluate its reactivity and obtain new polyheterocyclic enantiomerically pure spiro-beta-lactams.

On the occasion of the 85th birthday of Professor Rolf Huisgen Unsymmetric cyclic ketenes were generated from N-acyl-1,3-thiazolidine-2-carboxylic acids 1a ± c by means of Mukaiyamas reagent, and then reacted with imines 2a ± c to the new, isomeric spiro-b-lactams 3 and 4 via [2 2] cycloaddition (Staudinger ketene ± imine reaction; Scheme 1). The reactions were stereoselective ( Table 1) , make them potentially useful compounds for drug development. They can also act as bturn mimetics [10] and, particularly the 4-spiro-b-lactams, are synthetic precursors for cyclic a,a-disubstituted b-amino acids and peptide derivatives [11]. The synthesis of conformationally constrained amino acids is of special interest because the peptides derived from these modified amino acids may have valuable biological properties. As a consequence, the synthesis of 4-spiro-b-lactams has recently received particular attention [12].Further to our previous studies on the synthesis [13] and reactivity [14] of spiro-blactams, we now report the Staudinger ketene ± imine reaction between unsymmetrical cyclic ketenes generated from N-acyl-1,3-thiazolidine-2-carboxylic acids 1 and imines 2 for the synthesis of the new 1,3-thiazolidine derived 4-spiro-b-lactams 3 and 4 (Scheme 1). Our interest in these compounds is based on the spiro-fused thiazolidine ring, which could be opened to obtain a-keto-b-lactams.In our early work on cycloaddition reactions between mesoionic compounds (generated from cyclic N-acyl-a-amino acids via

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