Catalytic Enantioselective Addition of Prochiral Radicals to Vinylpyridines.

Pyridine, one of the most important azaarenes, is ubiquitous in functional molecules. The electronic properties of pyridine have been exploited to trigger asymmetric transformations of prochiral species as a direct approach for accessing chiral pyridine derivatives. However, the full potential of this synthetic strategy for the construction of enantioenriched γ-functionalized pyridines remains untapped. Here, we describe the first enantioselective addition of prochiral radicals to vinylpyridines under cooperative photoredox and asymmetric catalysis mediated by visible light. The enantioselective reductive couplings of vinylpyridines with aldehydes, ketones, and imines were achieved by employing a chiral Brønsted acid to activate the reaction partners and provide stereocontrol via H-bonding interactions. Valuable chiral γ-secondary/tertiary hydroxyl- and amino-substituted pyridines were obtained in high yields with good to excellent enantioselectivities.

Conjugate Addition-Enantioselective Protonation of N-Aryl Glycines to α-Branched 2-Vinylazaarenes via Cooperative Photoredox and Asymmetric Catalysis.

An enantioselective protonation strategy has been successfully applied to the synthesis of chiral α-tertiary azaarenes. With a dual catalytic system involving a chiral phosphoric acid and a dicyanopyrazine-derived chromophore (DPZ) photosensitizer that is mediated by visible light, a variety of α-branched 2-vinylpyridines and 2-vinylquinolines with N-aryl glycines underwent a redox-neutral, radical conjugate addition-protonation process and provided valuable chiral 3-(2-pyridine/quinoline)-3-substituted amines in high yields with good to excellent enantioselectivities (up to >99% ee). An application of this methodology to a two-step synthesis of the enantiomerically pure medicinal compound pheniramine (Avil) is also presented.