Synthesis of Arylidene-β-lactams via exo-Selective Matsuda-Heck Arylation of Methylene-β-lactams

exo-Methylene-beta-lactams were synthesized in two steps from commercially available 3-bromo-2-(bromomethyl)-propionic acid and reacted with arene diazonium salts in a Heck-type arylation in the presence of catalytic amounts of Pd(OAc)(2) under ligand-free conditions. The products, arylidene-beta-lactams, were obtained in high yields as single isomers. The beta-hydride elimination step of the Pd-catalyzed coupling reaction proceeds with high exo-regioselectivity and E-stereoselectivity. With aryl iodides, triflates, or bromides, the coupling products were isolated only in low yields, due to extensive decomposition of the starting material at elevated temperatures. This underlines that arene diazonium salts can be superior arylating reagents in Heck-type reactions and yield coupling products in synthetically useful yields and selectivities when conventional conditions fail.

Automated summary

exo-Methylene-beta-lactams were synthesized in high yields as single isomers in a two-step reaction involving a Heck-type arylation with arene diazonium salts. The Pd-catalyzed coupling reaction showed high exo-regioselectivity and E-stereoselectivity in the beta-hydride elimination step. However, coupling products with aryl iodides, triflates, or bromides were obtained only in low yields due to extensive decomposition of the starting materials at elevated temperatures.