Asymmetric benzylic C(sp<sup>3</sup>)-H acylation via dual nickel and photoredox catalysis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34112783.
- Also identified by DOI 10.1038/s41467-021-23887-2 and PMC identifier 8192574.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Asymmetric C(sp<sup>3</sup>)-H functionalization is a persistent challenge in organic synthesis. Here, we report an asymmetric benzylic C-H acylation of alkylarenes employing carboxylic acids as acyl surrogates for the synthesis of α-aryl ketones via nickel and photoredox dual catalysis. This mild yet straightforward protocol transforms a diverse array of feedstock carboxylic acids and simple alkyl benzenes into highly valuable α-aryl ketones with high enantioselectivities. The utility of this method is showcased in the gram-scale synthesis and late-stage modification of medicinally relevant molecules. Mechanistic studies suggest a photocatalytically generated bromine radical can perform benzylic C-H cleavage to activate alkylarenes as nucleophilic coupling partners which can then engage in a nickel-catalyzed asymmetric acyl cross-coupling reaction. This bromine-radical-mediated C-H activation strategy can be also applied to the enantioselective coupling of alkylarenes with chloroformate for the synthesis of chiral α-aryl esters.