Benzylic C\u2212H acylation by cooperative NHC and photoredox catalysis

Qing-Yuan Meng,Lena Lezius,Armido Studer

doi:10.1038/s41467-021-22292-z

Qing-Yuan Meng, Lena Lezius + Show 1 more

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https://doi.org/10.1038/s41467-021-22292-z

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Journal: Nature Communications	Publication Date: Apr 6, 2021
Citations: 115	License type: open-access

Affiliation: University of Münster

Abstract

Methods that enable site selective acylation of sp3 C-H bonds in complex organic molecules are not well explored, particularly if compared with analogous transformations of aromatic and vinylic sp2 C-H bonds. We report herein a direct acylation of benzylic C-H bonds by merging N-heterocyclic carbene (NHC) and photoredox catalysis. The method allows the preparation of a diverse range of benzylic ketones with good functional group tolerance under mild conditions. The reaction can be used to install acyl groups on highly functionalized natural product derived compounds and the C-H functionalization works with excellent site selectivity. The combination of NHC and photoredox catalysis offers options in preparing benzyl aryl ketones.

Highlights

Methods that enable site selective acylation of sp[3] C-H bonds in complex organic molecules are not well explored, if compared with analogous transformations of aromatic and vinylic sp[2] C-H bonds
Alkyl acyl NiIII species were proposed as the key intermediates in these transformations and C–H activation was achieved via intermolecular hydrogen atom transfer (HAT; Fig. 1c)
Inspired by our previous work on radical acyltrifluoromethylation of alkenes via cooperative photoredox/N-heterocyclic carbene (NHC) catalysis[34] and recent NHC-catalyzed radical reactions[35,36,37,38,39,40,41,42,43,44,45], we wondered whether ketyl radical cross-coupling with benzylic radicals could be applied for acylation of benzylic C–H bonds

Summary

Introduction

Methods that enable site selective acylation of sp[3] C-H bonds in complex organic molecules are not well explored, if compared with analogous transformations of aromatic and vinylic sp[2] C-H bonds. Direct benzylic C–H bond acylation is not well explored. In 2012, the Rovis group introduced cooperative NHC (N-heterocyclic carbene) and photocatalysis for the asymmetric acylation of activated C–H bonds in N-aryl tetrahydroisoquinolines[28].

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Conclusion