Enantioselective synthesis of tetraarylmethanes through meta-hydroxyl-directed benzylic substitution

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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Detail(s)

Original languageEnglish
Pages (from-to)275-285
Number of pages11
Journal / PublicationNature Synthesis
Volume2
Issue number3
Online published16 Jan 2023
Publication statusPublished - Mar 2023

Abstract

Benzylic carbocations bearing an ortho- or para-hydroxyl group can be stabilized by forming quinone methides, which have been explored in enantioselective synthesis. However, those with a meta-hydroxyl group have remained almost unexplored in organic synthesis. The lack of resonance stabilization by a typical quinone methide form renders them not only difficult to generate, but also challenging to control for asymmetric bond formation. Here we report an efficient catalytic enantioselective reaction between meta-hydroxyl triarylmethanols and indoles, via triaryl carbocations, for the synthesis of tetraarylmethanes with excellent enantiocontrol. Control experiments reveal that the meta-hydroxyl group is essential for both reactivity and stereocontrol. Ortho-directing groups (alkoxyl, sulfenyl or fluoro) benefit enantiocontrol through secondary hydrogen-bonding interactions, but are not required for reactivity. The resulting tetraarylmethane products show anticancer activities, through a mechanism distinct from that of classical anticancer drugs. [Figure not available: see fulltext.]

© The Author(s), under exclusive licence to Springer Nature Limited2023