Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons

A terminal alkyne is one of the most useful reactants for the synthesis of alkyne and alkene derivatives. Because an alkyne undergoes addition reaction at a C-C triple bond or cross-coupling at a terminal C-H bond. Combining those reaction patterns could realize a new reaction methodology to synthesize complex molecules including C-C multiple bonds. In this report, we found that the reaction of 3 equivalents of terminal alkyne 1 (aryl substituted alkyne) and an alpha-bromocarbonyl compound 2 (tertiary alkyl radical precursor) undergoes tandem alkyl radical addition/Sonogashira coupling to produce 1,3-enyne compound 3 possessing a quaternary carbon in the presence of a copper catalyst. Moreover, the reaction of alpha-bromocarbonyl compound 2 and an alkyne 4 possessing a carboxamide moiety undergoes tandem alkyl radical addition/C-H coupling to produce indolinone derivative 5.