C–H Activation and Sequential Addition to Dienes and Imines: Synthesis of Amines with β-Quaternary Centers and Mechanistic Studies on the Complex Interplay Between the Catalyst and Three Reactants

Abstract

A Rh(III)-catalyzed sequential C-H bond addition to dienes and in situ formed aldimines was developed, allowing for the preparation of otherwise challenging to access amines with quaternary centers at the beta-position. A broad range of dienes were effective inputs and installed a variety of aryl and alkyl substituents at the quaternary carbon site. Aryl and alkyl sulfonamide and carbamate nitrogen substituents were incorporated by using different formaldimine precursors. Moreover, the in situ formed N-Cbz aldimine from ethyl glyoxylate provided beta,beta-disubstituted alpha-amino esters with high diastereoselectivity. Two rhodacycle intermediates along the catalytic cycle were isolated and characterized by X-ray structural analysis, and the equilibria between the rhodacycle species in the presence of different reactants were determined. Deuterium labeling studies provided additional information to explain the uncommon 1,3-addition selectivity to the conjugated diene. Density functional theory calculations were consistent with the equilibria determined between the rhodacycle intermediates in the presence of different reactants and provided further insight on the transition state structures and energies for key steps in the catalytic cycle.

Publisher

American Chemical Society

Publication Date

11-22-2024

Publication Title

ACS Catalysis

Department

Chemistry and Biochemistry

Document Type

Article

DOI

https://doi.org/10.1021/acscatal.4c05866

Keywords

Homogeneous catalysis, C-H functionalization, C-C bond formation, Aminomethylation, Mechanism, Rhodacycle

Language

English

Format

text

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