Asymmetric radical NHC organocatalysis-enabled highly enantioselective acylation of inert C(sp<sup>2</sup>)─C(sp<sup>3</sup>) bonds.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 42467759.
- Also identified by DOI 10.1126/sciadv.aeg0999.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
The pursuit of high enantioselectivity remains a central challenge in the burgeoning area of radical <i>N</i>-heterocyclic carbene (NHC) catalysis. Moreover, direct functionalizations of unstrained and unpolarized C─C bonds continue to pose a formidable obstacle in organocatalysis. Herein, we disclose an asymmetric NHC organocatalytic platform that achieves highly enantioselective radical acylation of inert C(sp<sup>2</sup>)─C(sp<sup>3</sup>) bonds. Central to this advance is the development of a previously unknown collection of chiral thiazolium catalysts integrating medium-ring backbones with <i>C</i><sub>2</sub>-symmetric chiral units, which facilitate the stereoselective acylation of C─C bonds through a Smiles-type rearrangement. This organocatalytic protocol affords more than 70 examples with outstanding yields (up to 99%) and excellent regioselectivity (up to 99:1 rr) and enantioselectivity (up to 99.5:0.5 er) under transition metal-free and light-free conditions. The practicality of this strategy is further underscored by stereo-controlled late-stage functionalization of complex bioactive molecules. Mechanistic insights from combined experimental and computational studies support a radical-mediated catalytic cycle and elucidate the origin of enantioselectivity.