20 November 2023

Mechanistic Insight into Palladium-Catalyzed Asymmetric Alkylation of Indoles with Diazoesters Employing Bipyridine-N,N’-dioxides as Chiral Controllers

Metal-catalyzed asymmetric alkylation of indoles with ?-diazoesters is well-known, however, the underlying mechanisms of this reaction, particularly the origin of stereoselectivity, remain uncertain. For the Pd catalysis, we address this cutting-edge challenge from two complementary viewpoints – i) the molecular level regarding a single catalytically active Pd center; and ii) nano-level Pd species investigating the factors favoring the appearance of the preferred catalytic centers. The formation of the active catalytic species was monitored by structural methods (NMR and ESI-MS), and metal particles were characterized with electron microscopy (SEM, EDX). On the molecular level, chiral bipyridine-N,N'-dioxides proved to be competent chiral controllers. The kinetic and DFT computational data revealed a crucial role of water in the rate and selectivity determining steps and showed that the enantioselectivity of the process is controlled by the protodepalladation step. On the nano-scale, the important effect of catalyst precursor on the overall reaction performance was shown.

Reference: Adv.Synth.Catal., 2024, 366, 121-133.

DOI: 10.1002/adsc.202300845