Metal-Free Annulation of 2-Nitrobenzyl Alcohols and Tetrahydroisoquinolines toward the Divergent Synthesis of Quinazolinones and Quinazolinethiones.

A simple metal-free method for the synthesis of quinazolinones from commercially available 2-nitrobenzyl alcohols and tetrahydroisoquinolines is developed. The reaction conditions were tolerant of an array of functionalities such as halogen, tertiary amine, protected alcohol, and ester groups. Under nearly identical conditions, quinazolinethiones were obtained in the presence of elemental sulfur and suitable mediators.

Copper-catalyzed synthesis of pyrido-fused quinazolinones from 2-aminoarylmethanols and isoquinolines or tetrahydroisoquinolines.

Pyrido-fused quinazolinones were synthesized via copper-catalyzed cascade C(sp2)-H amination and annulation of 2-aminoarylmethanols with isoquinolines or pyridines. The transformation proceeded readily in the presence of a commercially available CuCl2 catalyst with molecular oxygen as a green oxidant. Moreover, the dehydrogenative cross-coupling of 2-aminoarylmethanols with tetrahydroisoquinolines was explored, in which CuBr exhibited higher catalytic activity than CuCl2.

Trisulfur-Radical-Anion-Triggered C(sp)-H Amination of Electron-Deficient Alkenes.

A trisulfur-radical-anion (Ṡ)-triggered C(sp)-H amination of α,β-unsaturated carbonyl derivatives with simple amines has been demonstrated. This protocol provides convenient access to a variety of synthetically valuable N-unprotected and secondary β-enaminones with absolute Z selectivity and tertiary β-enaminones with E selectivity. Mechanistic probe and electronic structure theory calculations suggest that Ṡ initiates the nucleophilic attacks via a thiirane intermediate.

Hydrogen peroxide-mediated synthesis of 2,4-substituted quinazolines one-pot three-component reactions under metal-free conditions.

An efficient metal-free synthesis of 2,4-substituted quinazolines a hydrogen peroxide-mediated one-pot three-component reaction of 2-aminoaryl ketones, aldehydes, and ammonium acetate has been developed. The transformation proceeded readily under mild conditions in the presence of commercially available hydrogen peroxide. The significant advantages of this approach are (1) the readily available atom-efficient and green hydrogen peroxide as oxidant; (2) no transition metal catalyst is required; (3) mild reaction conditions; and (4) wide substrate scope.

Functionalization of C-H bonds in acetophenone oximes with arylacetic acids and elemental sulfur.

Fused thieno[3,2-]thiazoles were synthesized a coupling of acetophenone ketoximes, arylacetic acids, and elemental sulfur in the presence of LiCO base. Functionalities including chloro, bromo, fluoro, trifluoromethyl, and pyridyl groups were compatible with reaction conditions. High yields and excellent regioselectivities were obtained even if -substituted ketoxime acetates were used.

Homo- and Heteroannulation of sp C-H Bonds in Acetophenones for Divergent Synthesis of Thienothiazoles.

A synthesis of fused thieno[3,2-]thiazoles via direct functionalization of C(sp)-H bonds in acetophenones was reported. The transformation is divergent to afford either 2-phenylbenzo[4,5]thieno[3,2-]thiazoles or benzo[4,5]thieno[3,2-]thiazol-2-yl(phenyl)methanones. Cross-coupling of acetophenones with C-H bonds in phenylacetic acids, methylazaarenes, and aldehydes was also feasible.