Formal enantioconvergent substitution of alkyl halides via catalytic asymmetric photoredox radical coupling.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29934495.
- Also identified by DOI 10.1038/s41467-018-04885-3 and PMC identifier 6015005.
- 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
Classic nucleophilic substitution reactions (S<sub>N</sub>1 and S<sub>N</sub>2) are not generally amenable to the enantioselective variants that use simple and racemic alkyl halide electrophiles. The merging of transition metal catalysis and radical chemistry with organometallic nucleophiles is a versatile method for addressing this limitation. Here, we report that visible light-driven catalytic asymmetric photoredox radical coupling can act as a complementary and generic strategy for the enantioconvergent formal substitution of alkyl haldies with readily available and bench-stable organic molecules. Single-electron reductive debrominations of racemic α-bromoketones generate achiral alkyl radicals that can participate in asymmetric C<sub>sp3</sub>-C<sub>sp3</sub> bonds forming cross-coupling reactions with α-amino radicals derived from N-aryl amino acids. A wide range of valuable enantiomerically pure β<sup>2</sup>- and β<sup>2,2</sup>-amino ketones were obtained in satisfactory yields with good-to-excellent enantioselectivities by using chiral phosphoric acid catalysts to control the stereochemistry and chemoselectivity. Fluoro-hetero-quaternary and full-carbon quaternary stereocenters that are challenging to prepare were successfully constructed.