Visible-Light-Activated Asymmetric Addition of Hydrocarbons to Pyridine-Based Ketones

Abstract

Enantioselective photoreduction of ketones with hydrocarbons is promising for the straightforward construction of chiral tertiary alcohols. But it is generally promoted by ultraviolet light via ketyl radical–alkyl radical coupling, which suffers from a competitive charge-transfer process and self/cross radical coupling reactions. An appropriate selection of a chiral catalyst that can alter the reaction pathway and deliver spatial selection is required. Accordingly, we disclosed a combined system involving Er­(III)-based chiral Lewis acid catalysis, Ir­(III)-based photoredox catalysis, and bromide-radical-mediated hydrogen atom transfer. The introduction of a bulky and nonredox chiral Lewis acid through the photoredox pathway enables the radical addition process and inhibits the above competitive reactions. The visible-light-promoted catalytic asymmetric alkylation of heteroaryl-based ketones with diverse hydrocarbons (mainly benzyl) delivered a variety of congested enantioenriched tertiary alcohols (up to 97% yield, 96% enantiomeric excess (ee)).

Enantioselective Radical Hydroacylation of α,β-Unsaturated Carbonyl Compounds with Aldehydes by Triplet Excited Anthraquinone

“…Our group recently achieved radical-involved asymmetric additions in the presence of chiral N , N ′-dioxide/metal complexes . Along this line, we speculated that a suitable HAT photocatalyst would trigger the acyl radical addition to enones, and in the presence of chiral N , N ′-dioxide/metal complexes, enantioselective HAT or protonation would deliver optically active 2-substituted 1,4-diketones (Scheme d).…”

Enantioselective Radical Addition to Ketones through Lewis Acid-Enabled Photoredox Catalysis

“…In the initial investigation, the addition product C1 from A1 and B1 catalyzed by Sc­(OTf) 3 (10 mol %) was obtained with a 19% yield at room temperature under 10 W LEDs (400 nm) irradiation in MeCN (Table , entry 1). The addition of chiral N , N ′-dioxide ligand − L 3 -RaPr 2 (10 mol %) significantly increased the yield of C1 to 82% with a 73:27 enantiomeric ratio (er) (Table , entry 2). Other Lewis acids were also tested, such as Mg­(OTf) 2 and Y­(OTf) 3 , giving poor yields and enantioselectivities (Table , entries 3–4; see the Supporting Information for details).…”

Photoinduced generation of ketyl radicals and application in C–C coupling withoutexternal photocatalyst

“…4 Recently, photoredox catalysis has been applied to bypass this challenge, providing an efficient way to generate ketyl radicals (Scheme 1B). 5 External photocatalysts such as metal complexes, 6 organic dyes, 7 or nanomaterials 8 are required in these reactions, which promote the generation of ketyl radicals via a two-step single electron transfer (SET) process from an electron donor such as tertiary amines. Despite these achievements, a photochemical strategy for ketyl radical generation without using an external photosensitizer is highly desired, as it would make the reaction simpler, more widely applicable, greener, and more economic.…”