A Germanium Catalyst Accelerates the Photoredox α-C(sp³)-H Alkylation of Primary Amines

Kentaro Sakai, Kounosuke Oisaki* and Motomu Kanai*

*Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan, Email: oisakig.ecc.u-tokyo.ac.jp, motomukanaig.ecc.u-tokyo.ac.jp

K. Sakai, K. Oisaki, M. Kanai, Org. Lett., 2022, 24, 3325-3330.

DOI: 10.1021/acs.orglett.2c00871

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Abstract

The use of Ph₂GeCl₂ as a cocatalyst greatly improves the yield of α-C(sp³)-H alkylation of primary amines catalyzed by a PC-HAT hybrid system. The α-position of the amino group selectively reacted even when weaker C-H bonds existed in the substrates.

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proposed mechanism

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Details

The document discusses a study on the use of a germanium catalyst, specifically diphenyldichlorogermane (Ph₂GeCl2), to enhance the photoredox α-C(sp³)−H alkylation of primary amines. This process is significant for the synthesis of sp³-carbon-rich pharmaceuticals, which can improve clinical trial success rates. The study highlights the challenges of site-selectivity in C(sp³)−H functionalizations using photoredox catalysis (PC) and hydrogen atom transfer (HAT) catalysis. The germanium catalyst was found to significantly improve the yield of the desired product, achieving up to 82% yield compared to lower yields with other cocatalysts. The research involved optimizing various reaction conditions, including the use of different bases, solvents, and light irradiation. The study also explored the substrate scope, demonstrating the method's applicability to various amines and acceptors. The findings suggest that the germanium catalyst facilitates the reaction by forming aminogermane species, which lowers the bond dissociation energy of the α-C(sp³)−H bonds, making them more reactive. This research opens new avenues for the development of site-selective hybrid catalysis for complex compound synthesis, with potential applications in drug development and material science.

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Key Words

γ-lactams, photochemistry

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ID: J54-Y2022