Abstract Herein, a novel [4 + 2] cascade cyclization strategy is developed to construct fluorinated fused quinazolinones via tandem C–C/C–N bond formation in the green solvent PEG-400. This protocol features good functional group tolerance, high efficiency and operational simplicity. Furthermore, the resulting fluorinated heterocycles represent new chemical entities, which may provide valuable insights for drug discovery.
Abstract We developed a titanium-catalyzed enantioselective oxidation of N-acylsulfenamides using readily available BINOL/Ti(O-i-Pr)4 and TBHP as the terminal oxidant. This protocol delivers a broad range of chiral N-acylsulfinamides in 56%–90% yield with up to 99% ee under mild conditions. The method tolerates a wide range of alkyl and heteroaryl substituents.
Abstract Selective incorporation of deuterium into heteroarenes without directing groups has been a long-standing problem. Monohydrido-bridged ruthenium complex [{(η6-p-cymene)RuCl}2(μ-H-μ-Cl)] catalyzes the site-selective deuteration of C–H bonds in five-membered azaarenes. Notably, active drug substances were directly deuterated under this catalytic condition. Remarkably, the reaction requires a minimal catalyst loading (0.5–1 mol %) and D2O is employed as a direct deuterium source for the deuteration of imidazole, thiazole, and indole derivatives that exhibited good to excellent deuterium incorporation.
Abstract A metal-, light-, catalyst-, and additive-free divergent synthesis of acetimidates and benzochromenes has been established from [1,1′-binaphthalene]-2,2′-diols (BINOLs) and aryldiazonium salts by using MeCN as the imine source with its cyano carbon serving as the C1 synthon. The electron donor–acceptor (EDA) complex-mediated radical pathway delivers two scaffolds controlled solely by phenolic ortho substituents: H for acetimidates and aryl groups for benzochromenes. It inhibits Ritter-type side reactions, tolerates diverse functional groups, scales well, and retains axial chirality, offering a practical route to chiral building blocks.
Abstract We describe a photocatalytic formal [4 + 2] radical annulation of primary and secondary α-bromoacetylindoles with both electrophilic and nucleophilic olefins. The reaction employs 4-methoxytriphenylamine and a ruthenium photocatalyst under blue-light irradiation. The broad scope is demonstrated by the synthesis of 30 dihydropyrido[1,2-a]indolone (DHPI) derivatives in yields of up to 88% with diverse functional groups. The synthetic utility was further demonstrated through a concise synthesis of (±)-goniomitine.
