Umpolung (polarity reversal) strategies of aldehydes and imines have dramatically expanded the scope of carbonyl and iminyl chemistry by facilitating reactions with non-nucleophilic reagents. Herein, we report the first visible light photoredox-catalyzed β-selective reductive coupling of alkenylpyridines with carbonyl or iminyl derivatives with the aid of a Lewis acid co-catalyst. Our process tolerates complex molecular scaffolds (e.g. sugar, natural product, and peptide derivatives) and is applicable to the preparation of compounds containing a broad range of heterocyclic moieties. Mechanistic investigations indicate that the key step involves single electron transfer (SET) reduction of aldehydes or imines followed by the addition of resulting ketyl or α-aminoalkyl radicals to Lewis acid-activated alkenylpyridines.

Under the conditions of transfer hydrogenation employing an iridium catalyst generated in situ from [Ir(cod)Cl] 2 , the chiral phosphine ligands (R)-BINAP or (R)-Cl,MeO-BIPHEP and m-nitrobenzoic acid, allyl acetate couples to allylic alcohols 1a-1c, aliphatic alcohols 1d-1l and benzylic alcohols 1m-1u to furnish products of carbonyl allylation 3a-3u with exceptional levels of asymmetric induction. The very same set of optically enriched carbonyl allylation products 3a-3u are accessible from enals 2a-2c, aliphatic aldehydes 2d-2l and aryl aldehydes 2m-2u, using iridium catalysts ligated by (-)-TMBTP or (R)-Cl,MeO-BIPHEP under identical conditions, but employing isopropanol as a hydrogen donor. As corroborated by single crystal X-ray diffraction, the active catalyst is the cyclometallated complex V, which arises upon ortho-C-H insertion of iridium onto m-nitrobenzoic acid. The results of isotopic labeling are consistent with intervention of symmetric iridium π-allylationl intermediates or rapid interconversion of σ-allyl haptomers through the agency of a symmetric π-allyl. Competition experiments demonstrate rapid and reversible hydrogenationdehydrogenation of the carbonyl partner in advance of C-C coupling. The coupling products, which are homoallylic alcohols, experience very little erosion of optical purity by way of redox equilibration under the coupling conditions, although isopropanol, a secondary alcohol, may serve as terminal reductant. A plausible catalytic mechanism accounting for these observations is proposed, along with a stereochemical model that accounts for the observed sense of absolute stereoinduction. This protocol for asymmetric carbonyl allylation transcends the barriers imposed by oxidation level and the use of preformed allyl-metal reagents.

Hydrogenation of alkynes in the presence of carbonyl compounds and imines using cationic rhodium(I) and iridium(I) precatalysts enables the formation of allylic alcohols and allylic amines, respectively. Through the use of hydrogenation catalysts modified by chiral ligands, allylic alcohols and allylic amines may be generated in highly optically enriched forms. Hydrogenative fragment couplings of this type circumvent the use of preformed organometallic reagents and avoid the generation of stoichiometric byproducts.

An amine-N-oxide ligated palladium complex, in conjunction with a silver co-catalyst, catalyzes imidation of arenes by the reagent N-fluorobenzenesulfonimide. The reaction enables imidation of a variety of arenes at or below room temperature, requires no coordinating directing group on the substrate, and gives synthetically useful yields with only one equivalent of arene. Mechanistic data implicates an unusual mechanism devoid of commonly invoked organometallic intermediates; oxidation of the palladium catalyst occurs as the turnover-limiting step, while C–H bond functionalization occurs subsequently at a high oxidation state of the catalyst.

Aryl trifluoromethoxylation by a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxylamine derivatives and intramolecular OCF3  migration is presented. This protocol allows easy access to a wide range of synthetically useful ortho-OCF3 aniline derivatives. In addition, it utilizes bench-stable reagents, is operationally simple, shows high functional-group tolerance, and is amenable to gram-scale as well as one-pot synthesis. A reaction mechanism of a heterolytic cleavage of the NOCF3 bond followed by recombination of the resulting nitrenium ion and trifluoromethoxide is proposed for the OCF3 -migration reaction.