Transition Metal-catalysed intramolecular carbenoid C-H insertion for pyrrolidine formation by decomposition of α-diazoesters

Abstract

The use of Pd‐, Rh(II)‐ and Ru(II)‐based catalysts has been explored in the transition metal‐catalysed intramolecular carbenoid C−H insertion of α‐diazoesters leading to pyrrolidines. Although the outcome of the reaction was highly substrate‐dependent, in general, it was possible to control the chemoselectivity of the process towards pyrrolidines by adequate catalyst selection. The Pd(0)‐catalysts were as efficient as [Rh(Ph3CCO2)2]2 in promoting the C(sp3)−H insertion of ortho‐substituted anilines. In contrast, for anilines bearing meta‐ and para‐substituents, the Rh(II)‐catalyst provided the best chemoselectivities and reaction yields. On the other hand, [Ru(p‐cymene)Cl2]2 was the most efficient catalyst for the insertion reaction of the N‐benzyl‐N‐phenyl and N,N‐dibenzyl α‐diazoesters, while the C(sp3)−H insertion of the N‐benzylsulfonamide substrate was only promoted by [Rh(Ph3CCO2)2]2. According to density functional theory (DFT) calculations, the mechanism involved in the Pd(0)‐ and Ru(II)‐catalysed C(sp3)−H insertions differs considerably from that typically proposed for the Rh(II)‐catalysed transformation. Whereas the Pd(0)‐catalysed reaction involves a Pd‐mediated 1,5‐H migration from the C(sp3)−H bond to the carbenoid carbon atom leading to the formal oxidation of the transition metal, a Ru(II)‐promoted Mannich type reaction involving a zwitterionic intermediate seems to be operative in the Ru(II)‐catalysed transformation. Keywords: carbenoid insertion; diazo compounds; pyrrolidines; palladium-catalysis; density functional theory calculations