The first highly enantioselective catalytic protocol for the reductive coupling of ketones and hydrazones is reported. These reactions proceed through neutral ketyl radical intermediates generated via a concerted proton-coupled electron transfer (PCET) event jointly mediated by a chiral phosphoric acid catalyst and the photoredox catalyst Ir(ppy)2(dtbpy)PF6. Remarkably, these neutral ketyl radicals appear to remain H-bonded to the chiral conjugate base of the Brønsted acid during the course of a subsequent C-C bond-forming step, furnishing syn 1,2-amino alcohol derivatives with excellent levels of diastereo- and enantioselectivity. This work provides the first demonstration of the feasibility and potential benefits of concerted PCET activation in asymmetric catalysis.

Enantioselective photoredox catalysis enabled by proton-coupled electron transfer

The remote radical migration strategy has gained considerable momentum. During the past three years, we have witnessed the rapid development of sustainable and practical C–C and C–H bond functionalization by means of long-distance 1,n-radical migration (n = 4, 5, 6) events. Its advent brings our chemical community a new platform to deal with the challenging migration transformations and thus complements the existing ionic-type migration protocols. In this review, the recent achievements in distal radical migration triggered C–C and C–H bond functionalization are summarized.

Distal radical migration strategy: an emerging synthetic means

Ultrasound-promoted Brønsted acid ionic liquid-catalyzed hydrothiocyanation of activated alkynes under minimal solvent conditions

Fluorinated ketones are widely prevalent in numerous biologically interesting molecules, and the development of novel transformations to access these structures is an important task in organic synthesis. Herein, we report the multicomponent radical acylfluoroalkylation of a variety of olefins in the presence of various commercially available aromatic aldehydes and fluoroalkyl reagents through N-heterocyclic carbene organocatalysis. With this protocol, over 120 examples of functionalized ketones with diverse fluorine substituents have been synthesized in up to 99 % yield with complete regioselectivity. The generality of this catalytic strategy was further highlighted by its successful application in the late-stage functionalization of pharmaceutical skeletons. Excellent diastereoselectivity could be achieved in the reactions forging multiple stereocenters. In addition, preliminary results have been achieved on the catalytic asymmetric variant of the olefin difunctionalization process.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.201915594

Radical Acylfluoroalkylation of Olefins through N‐Heterocyclic Carbene Organocatalysis

meta-Hydroxylated cores are ubiquitous in natural products. Herein, we disclose the first template assisted meta-hydroxylation reaction. Experimental and in silico studies helped us to gain valuable mechanistic insights, including the role of the hexafluoroisopropanol (HFIP) solvent, during C–H hydroxylation. The reactive intermediates, prior to the C–H activation, have been detected by spectroscopic techniques. Additionally, the C–O bond formation has been extended to meta-acetoxylation. The preparation of a phase II quinone reductase activity inducer and a resveratrol precursor illustrated the synthetic significance of the present strategy.

/pdf/directing-group-assisted-meta-hydroxylation-by-c-h-229lahg2h0.pdf

Directing group assisted meta-hydroxylation by C–H activation

A palladium-catalyzed three-component reaction between fluoroalkyl bromides, arylboronic acids, and alkenyl aldehydes has been developed and provides facile access to 5-, 6-, or 7-difluoroalkylated ketones under very mild reaction conditions. The resultant products can be smoothly converted into CF2 -containing tetrahydronaphthalenes by a novel silver-catalyzed intramolecular decarboxylative cyclization of 5-aryl-2,2-difluoropentanoic acids.

Palladium‐Catalyzed Remote Aryldifluoroalkylation of Alkenyl Aldehydes

Alkyl thiocyanates are prevalent in natural products, drugs, and biologically active compounds. We report here a novel, mild, and efficient Pd-catalyzed site-selective sp3 C-H bond thiocyanation of 2-aminofurans. Using Na2S2O8 as the oxidant and readily available NaSCN as the thiocyanation reagent, the kinetically favorable 2-amino-4-thiocyanatomethylfurans are selectively synthesized in promising yields with a broad substrate scope. This reaction represents the first example of transition-metal-catalyzed site-selective sp3 C-H bond thiocyanation, thus offering a novel strategy for the step- and atom-economic synthesis of alkyl thiocyanates.

Palladium-Catalyzed Site-Selective sp3 C–H Bond Thiocyanation of 2-Aminofurans

Copper-Catalyzed Trifluoromethylation of Alkenes with Redox-Neutral Remote Amidation of Aldehydes

Palladium-catalyzed cycloisomerization and aerobic oxidative cycloisomerization of homoallenyl amides: a facile and divergent approach to 2-aminofurans.

A fine-tunable transformation, including Pd-catalyzed acetoxylative, alkoxylative, and hydroxylative cycloisomerization of homoallenyl amides, has been realized with hypervalent iodine organic compounds as the oxidants, giving polysubstituted 2-aminofurans in promising yields at room temperature. The selective formation of three different types of products from the same starting materials makes this reaction particularly attractive and useful for organic synthesis.

Cungui Cheng

Papers

Palladium‐Catalyzed Remote Aryldifluoroalkylation of Alkenyl Aldehydes

Palladium-Catalyzed Site-Selective sp3 C–H Bond Thiocyanation of 2-Aminofurans

Copper-Catalyzed Trifluoromethylation of Alkenes with Redox-Neutral Remote Amidation of Aldehydes

Palladium-catalyzed cycloisomerization and aerobic oxidative cycloisomerization of homoallenyl amides: a facile and divergent approach to 2-aminofurans.

Divergent Synthesis of 2-Aminofurans via Palladium-Catalyzed Acetoxylative, Alkoxylative, and Hydroxylative Cycloisomerization of Homoallenyl Amides