1,3-Dipolar cycloaddition of 2-dialkylaminothioisomuenchnones with aliphatic aldehydes: Synthesis of β-lactams and thiiranes, structure elucidation, and rationale for chemoselective fragmentation of cycloadducts

Article abstract of DOI:10.1021/jo034188r

A series of highly funtionalized β-lactams and thiiranes can be generated on treatment of 1,3-thiazolium-4-olates (thioisomuenchnones) with aliphatic aldehydes. Although in some cases a variety of products have been obtained, the present paper now provides a mechanistic rationale to explain the product distribution based on stereoelectronic effects. Thus, ring fragmentation of the initial [3+2] cycloadduct is essentially dictated by the electronic character of the aryl substituent on the nitrogen atom of the parent thioisomuenchnone. However, further evolution of such cycloadducts into β-lactams or thiiranes is governed by steric effects to a large extent. Evidence for such interactions has been obtained by computing PM3-optimized diastereomeric transition structures in the reaction of a thioisomuenchnone with a chiral aliphatic aldehyde.