Catalytic Intramolecular Hydroamination with a Bifunctional Iridium Pyrazolato Complex: Substrate Scope and Mechanistic Elucidation

Abstract

Catalytic intramolecular cyclization of nonactivated aminoalkene with functional group compatibility provides an atom-economical and concise route to valuable nitrogen-containing heterocycles yet remains a challenge. In this paper, we report the detailed substrate scope and mechanism of catalytic intramolecular hydroamination with a half-sandwich-type iridium pyrazolato complex we have recently developed. This metal–ligand bifunctional catalyst promoted the hydroamination of various primary and secondary aminoalkenes at mild temperatures (50–110 °C) without side reactions such as oxidative amination. Cyclization of secondary aminoalkenes containing ester, cyano, bromo, and hydroxy groups occurred with maintenance of these functional groups, while the reactions of aminoalkenes bearing allylic substituents proceeded with a perfect diastereoselectivity. Catalyst optimization revealed that the proton-responsive functional group at the position β to the metal is crucial to efficient catalytic turnover. Kinetic analysis indicated a highly ordered transition state associated with N–H bond cleavage in the rate-determining step. On the basis of these data along with the stoichiometric reactions and DFT calculations, we propose an unprecedented metal–ligand cooperating mechanism, in which cyclization occurs through syn addition of the amino group to the coordinated olefin bond with the aid of the Brønsted basic pyrazolato ligand.