Lei Liang

Herein, we report a metal- and light-free C-4 alkylation of pyridines through a decarboxylative Minisci-type reaction between fumarate-derived pyridinium salts and aryliodine( iii ) dicarboxylates.

We have developed a novel strategy for decarboxylative radical addition reactions that employs ground-state reduced nicotinamide adenine dinucleotide (NADH) analogues under ambient and open-air conditions, facilitating the efficient formation of Csp³-Csp³ bonds in a variety of substrates. This protocol is distinguished by its operational simplicity, mild reaction conditions, high efficiency, and the use of cost-effective starting materials. Furthermore, experimental studies have provided valuable insights into the reaction mechanism, elucidating the light-independent pathways that promote these transformations.

Dehydrogenative coupling of arenes with fluoroaryl nucleophiles enables the efficient synthesis of fluoroaromatic compounds from readily available starting materials. Although considerable progress has been made in direct C(sp²)–H bond polyfluoroarylation, significant limitations in the regioselective functionalization of complex molecules and the scope of Ar^F groups still exist. We report here a highly selective method to address these long-standing limitations via a tandem activation/cross-coupling strategy. This method tolerates a wide range of arenes, pharmaceutically relevant aromatic compounds and polyfluoroaryl nucleophiles.

An electrochemical approach to promote the ortho-C-H alkylation of (hetero)arenes via rhodium catalysis under mild conditions is described. This approach features mild conditions with high levels of regio- and monoselectivity that tolerate a variety of aromatic and heteroaromatic groups and offers a widely applicable method for late-stage diversification of complex molecular architectures including tryptophan, estrone, diazepam, nucleosides, and nucleotides. Alkyl boronic acids and esters and alkyl trifluoroborates are demonstrated as suitable coupling partners. The isolation of key rhodium intermediates and mechanistic studies provided strong support for a rhodium(III/IV or V) regime.

We describe Cu-catalyzed intermolecular alkynylation and allylation of unactivated C(sp³)–H bonds with singly occupied molecular orbital-philes (SOMO-philes) via hydrogen atom transfer (HAT). Employing N-fluoro-sulfonamide as a HAT reagent, a set of substituted alkene and alkyne compounds were synthesized in high yields with good regioselectivity and functional-group compatibility. Late-stage functionalization of natural products and drug molecules is also demonstrated.

The classical Sonogashira reaction of aryl electrophiles in the presence of Pd catalysts has been well established as a potent method for arylalkyne synthesis. However, the site-selective C(sp²)–C(sp) cross-coupling strategy using a non-noble-metal catalyst is rare. An efficient alternative approach for the synthesis of arylalkynes via a Cu-catalyzed Sonogashira-type reaction promoted by visible light is described. This method enables site-selective alkynylation from aryl sulfonium salts derived from diverse arenes to a set of arylalkynes with high selectivity and high functional-group compatibility. Moreover, rapid alkynylation of drug molecules is demonstrated.

Intermolecular asymmetric dearomative 1,3-dipolar cycloaddition of 2-nitrobenzofurans with azomethine ylides was enabled by using a chiral Cu(I)/(S,S_p)-ⁱPr-Phosferrox catalyst. As a result, a series of highly stereoselective chiral [2,3]-fused hydrobenzofurans possessing four contiguous stereogenic centers were obtained with good to high yields, diastereoselectivities and enantioselectivities. The reaction has broad substrate scope tolerating various functional groups.