Enantiospecific Trifluoromethyl-Radical-Induced Three-Component Coupling of Boronic Esters with Furans.

Yahui Wang,Adam Noble,Christopher Sandford,Varinder K Aggarwal

doi:10.1002/anie.201611058

Yahui Wang, Adam Noble + Show 2 more

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https://doi.org/10.1002/anie.201611058

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Abstract

In the presence of trifluoromethylsulfonium reagents, boronate complexes derived from 2‐lithio furan and non‐racemic secondary and tertiary alkyl or aryl boronic esters undergo deborylative three‐component coupling to give the corresponding 2,5‐disubstituted furans with excellent levels of enantiospecificity. The process proceeds via the reaction of boronate complexes with a trifluoromethyl radical, which triggers 1,2‐metallate rearrangement upon single‐electron oxidation. Alternative electrophiles can also be used in place of trifluoromethylsulfonium reagents to effect similar three‐component coupling reactions.

Highlights

Transition-metal-catalyzed stereoselective sp2-sp3 cross-coupling reactions of secondary alkyl organoboron reagents with aryl halides attract considerable interest owing to the importance of populating drug-discovery libraries with molecules containing 3D structural motifs.[1]
Several advances have been charted in this challenging area,[2] we recently developed a conceptually different, transition-metal-free cross-coupling reaction,[3] which enables the stereospecific coupling of non-racemic secondary and tertiary alkylboronic esters[4,5] with a wide range of aryl lithium reagents (Scheme 1 A)
Rearomatization-driven elimination of the halide and the boronic ester group generates the substituted aryl product. We reasoned that this useful methodology could be substantially expanded by using carbon-based electrophiles in place of halogenating agents, as the intermediate akin to boronic ester III would not undergo elimination, enabling not one, but two CÀC bonds to be formed in the process

Summary

Introduction

Transition-metal-catalyzed stereoselective sp2-sp3 cross-coupling reactions of secondary alkyl organoboron reagents with aryl halides attract considerable interest owing to the importance of populating drug-discovery libraries with molecules containing 3D structural motifs.[1]. Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under http://dx.doi.org/10. Electrophile-induced enantiospecific three-component coupling of boronic esters with furans.

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