Tertiary carbon radicals have notable utility for uniting complex carbon fragments with concomitant formation of new quaternary carbons. This article explores the scope, limitations and certain mechanistic aspects of Okada’s method for forming tertiary carbon radicals from (N-acyloxy)phthalimides by visible-light photocatalysis. Optimized conditions for generating tertiary radicals from (N-acyloxy)phthalimide derivatives of tertiary carboxylic acids by visible-light irradiation in the presence of 1 mol% of commercially available Ru(bpy)3(PF6)2, diethyl 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate (8) and i-Pr2NEt, and their coupling in dichloromethane at room temperature with alkene acceptors were developed. Four representative tertiary (N-acyloxy)phthalimides and 15 alkene radical acceptors were examined. Both reductive couplings with electron-deficient alkenes and radical substitution reactions with allylic and vinylic bromides and chlorides were examined with many such reactions occurring in good yield using only a slight excess (typically 1.5 equiv) of the alkene. In general, the yields of these photocatalytic reactions were higher than the analogous transformations of the corresponding N-phthalimidoyl oxalates. Deuterium labeling and competition experiments reveal that the reductive radical coupling of tertiary (N-acyloxy)phthalimides with electron-deficient alkenes can be terminated by both hydrogen-atom transfer and single-electron reduction followed by protonation, and that this mechanistic duality is controlled by the presence or absence of i-Pr2NEt.

The coupling of tertiary carbon radicals with alkene acceptors is an underdeveloped strategy for uniting complex carbon fragments and forming new quaternary carbons. The scope and limitations of a new approach for generating nucleophilic tertiary radicals from tertiary alcohols and utilizing these intermediates in fragment coupling reactions is described. In this method, the tertiary alcohol is first acylated to give the tert-alkyl N-phthalimidoyl oxalate, which in the presence of visible-light, catalytic Ru(bpy)3(PF6)2, and a reductant fragments to form the corresponding tertiary carbon radical. In addition to reductive coupling with alkenes, substitution reactions of tertiary radicals with allylic and vinylic halides is described. A mechanism for the generation of tertiary carbon radicals from tert-alkyl N-phthalimidoyl oxalates is proposed that is based on earlier pioneering investigations of Okada and Barton. Deuterium labeling and competition experiments reveal that the reductive radical coupling of tert-alkyl N-phthalimidoyl oxalates with electron-deficient alkenes is terminated by hydrogen-atom transfer.

Radical arylations of para-substituted phenols and phenyl ethers proceeded with good regioselectivity at the ortho position with respect to the hydroxy or alkoxy group. The reactions were conducted with arenediazonium salts as the aryl radical source, titanium(III) chloride as the reductant, and diluted hydrochloric acid as the solvent. Substituted biaryls were obtained from hydroxy- and alkoxy-substituted benzylamines, phenethylamines, and aromatic amino acids. The methodology described offers a fast, efficient, and cost-effective new access to diversely functionalized biphenyl alcohols and ethers. Free phenolic hydroxy groups, aromatic and aliphatic amines, as well as amino acid substructures, are well tolerated. Two examples for the applicability of the methodology are the partial synthesis of a beta-secretase inhibitor and the synthesis of a calcium-channel modulator.

Simply aqueous sodium hydroxide is sufficient to exclude ionic side reactions and to prepare 2-aminobiphenyls from aryl diazotates and anilines through a new variant of the Gomberg-Bachmann reaction (see scheme). The metal-free reaction under basic conditions allows to exploit the highly radical-stabilizing effect of the aniline's free amino function for the first time, which leads to a so far unreached regioselectivity.

The reactivity of phenyldiazenes was studied intensively in the late 1960s, but not much is known about their behavior under acidic conditions. Based on the formation of phenyldiazenes from phenylazocarboxylates, we herein describe how reactions of phenyldiazenes can be directed into ionic or radical pathways. Cycloaddition reactions with furans leading to pyridazinium salts represent the first examples for the direct trapping of phenyldiazenes with conservation of the N=N moiety.