Site Selectivity in Pd-Catalyzed Reactions of α-Diazo-α-(methoxycarbonyl)acetamides: Effects of Catalysts and Substrate Substitution in the Synthesis of Oxindoles and β-Lactams

Abstract

The Pd-catalyzed intramolecular carbene C–H insertion of α-diazo-α-(methoxycarbonyl)acetamides to prepare oxindoles as well as β-lactams was studied. In order to identify what factors influence the selectivity of the processes, we explored how the reactions are affected by the catalyst type, using two oxidation states of Pd and a variety of ligands. It was found that, in the synthesis of oxindoles, ((IMes)Pd(NQ))2 can be used as an alternative to Pd2(dba)3 to catalyze the carbene CArsp2–H insertion, although it was less versatile. On the other hand, it was demonstrated that the Csp3–H insertion leading to β-lactams can be effectively promoted by both Pd(0) and Pd(II) catalysts, the latter being most efficient. Insight into the reaction mechanisms involved in these transformations was provided by DFT calculations.

Recent advances in transition-metal-catalyzed carbene insertion to C–H bonds

“…Notably, palladium catalysts have also been documented to enable intramolecular aryl C(sp 2 )-H functionalization by carbene insertion. 310,311 To suppress cyclopropanation as the side reaction the strategy is to diminish coordination of the CQC bond of an arene or alkene substrate to the catalytically active metal center. 4,216,293 Scheme 84 Ru(II)-catalyzed aryl C(sp 2 )-H functionalization by carbene insertion with diazo compounds.…”