Spotlights on Recent JACS Publications

摘要

The construction of acyclic all-carbon quaternary stereogenic centers is an ongoing challenge for synthetic chemists. One of the most common strategies is the chiral a-alkylation of carbonyl compounds, usually entailing coupling between electron-rich enolate or enamine-based intermediates and electrophiles, but this strategy has disadvantages that must be overcome. Now, Sanzhong Luo and co-authors report a creative modification to this approach by combining organocatalysis with radical addition, instead of conventional nucleophilic substitution (DOI:10.1021/ja508605a). The transformation proceeds via a tandem primary amine-photoredox catalytic process where photogenerated open-shell acyl radicals are added to β-ketocarbonyl-derived chiral enamine intermediates with high stereoselectivity. Even more impressively, spiro-γ-lactams with two well-defined nonadjacent quaternary stereo-centers can be synthesized from appropriate substrates in single operations. As a facile and powerful path to asymmetric α-alkylation, this method expands the tools available for the construction of chiral carbon centers. By facilitating access to molecular motifs that are otherwise intractable, it demonstrates potential utility in overcoming some of the challenges facing pharmaceutical and natural product chemistry.