Dual Functionalization of Organic Compounds via Oxidation of Halogen

Dual functionalization in organic synthesis is an elegant and powerful method for simultaneously introducing two different functional groups regio-selectively into a target molecule. We herein describe our recent work on retained dual functionalization and dehydrogenative dual functionalization via oxidation of halogen. For the dehydrogenative dual functionalization by oxidation of bromide ion, a catalytic dual functionalization of ethers through dealkylation-oxidation-bromination accompanied by C-O bond cleavage via aerobic oxidation of bromide was developed to obtain α-bromo ketones. Furthermore, a nitrite-catalyzed ring-contraction reaction of substituted tetrahydropyrans by oxidation of bromide under aerobic conditions was discovered to provide 2-acyltetrahydrofurans. We also succeeded a regio-selective Csp2-Csp2 bromo-amination of indole derivatives via the 1,3-migration of imides on indolyl(phenyl)iodonium imides and a remote Csp2-Csp3 iodo-amination of 2-methyl indole derivatives with iodinating reagents to furnish the corresponding halo-amino-indole derivatives via formation of indolyl(phenyl)iodonium imides from indole derivatives, bis(sulfonyl)imides, and (diacetoxy)iodobenzene as the retained dual functionalization using hypervalent iodine (III).