Diastereo- and Enantiodifferentiation in Indium-Promoted Allylations of 2,3-Azetidinediones in Water. Definition of Long-Range Stereocontrol Elements on π-Facial Selectivity for β-Lactam Synthesis

Abstract

The stereochemical course of the reactions of N-benzyl-2,3-azetidinedione with six differently functionalized allylic bromides, as promoted by indium metal in 1:1 H2O−THF, were initially examined. Three of the examples that proved to be usefully stereoselective were subsequently reevaluated in azetidinediones which now carried (S)-α-methylbenzyl and (R)-α-(1-naphthyl)ethyl residues bonded to nitrogen. These enantiomerically pure building blocks afforded products that differed in the facial sense of organometallic addition to the ketonic carbonyl. Interestingly, the diastereofacial selectivity is directly linked to the R or S configuration of the exocyclic N-amido substituent. Stereochemical assignments to many of the products were based on X-ray crystallographic measurements. In other cases, spectral correlations were used. The global results clearly show that fundamental, yet previously unappreciated, long-range nonbonded steric interactions do control the extent to which competing cyclic transition states operate.