METHODS OF TRIFLUOROMETHYL CARBENE C-H INSERTION

Overview

Ir-catalyzed intramolecular α-CF3-α-alkyl carbene aliphatic C–H insertion to afford an array of di-, tri-, and tetra-substituted CF3-bearing cyclopentanes in a highly site- and diastereo-selective manner. An unprecedentedly high TON (up to 8,200,000) has been reached for accessing tri-substituted CF3-bearing cyclopentanes. Further application to the synthesis of tri-substituted CF3-bearing cyclopentane analogues of natural products, pharmaceuticals, sugars and peptides is demonstrated.

Technical name of innovation

Iridium-catalyzed Trifluoromethyl Carbene C-H Insertion

Commercialisation opportunities

technology licensing agreement

Problem addressed

TONs of catalytic functionalization of robust C–H bonds, especially for unactivated C(sp3)–H bonds, are typically <10,000 in the literatures. Therefore, improving turnover number of unactivated C–H bond functionalization to the same practical level as hydrogenation and cross-coupling is daunting.

Innovation

An unprecedentedly high TON (up to 8,200,000) has been reached for accessing tri-substituted CF3-bearing cyclopentanes by means of C-H activation
Developing a new approach to afford an array of di-, tri-, and tetra-substituted CF3-bearing cyclopentanes in a highly site- and diastereo-selective manner

Key impact

Identifying the importance of iridium catalyst for high product turnover number
Multi-substituted products with high site- and diastereo-selectivity and yield

Application

for synthesis of potentially pharmaceutically active molecules containing trifluoromethyl-bearing five-membered ring structures

Laboratory for Synthetic Chemistry and Chemical Biology (LSCCB) is an R&D centre funded by Health@InnoHK progamme of Innovation and Technology Commission of HKSAR. Established in 2020, LSCCB is operated with tripartite joint collaboration of The University of Hong Kong, Imperial College London and Peking University. LSCCB aims at integrating chemical and biomedical sciences to develop new molecular medicines and diagnostic tools for the treatment and analysis of human diseases, in particular, cancer. LSCCB currently assembles more than 20 principal investigators for 4 major research programmes including (a) Synthetic Chemistry; (b) Chemical Biology of Natural Products and Chinese Medicine; (c) Metal Anticancer Medicine, Diagnostics and Theranostics; and (d) Multi-Omics and Innovative Analytical Technologies for InnoHealth.

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