Tin-free radical carbon-carbon bond forming reactions

Abstract

The organotin-mediated radical reactions have greatly advanced in synthetic organic chemistry, but have many limitations for industrial application due to inherent toxicity. To overcome these problems, we focused on the development of tin-free radical carbon-carbon bond forming reactions. Decarboxylative acylation of new thiohydroxamte esters, which is less reactive and more stable than Barton’s ester, was developed. This active esters were easily prepared from the coupling of various carboxylic acids with N-methylhydroxydithiocarbamate. Primary, secondary and tertiary moieties worked well, yielding corresponding oxime ethers derivatives in high yields under thermal or photochemical condition. Synthetically useful tin-free radical acylation, vinylation, allylation and cyanation reactions using alkyl allyl sulfones as radical precursors were investigated. Alkyl allyl sulfones were highly efficient and reliable radical precursors for the generation of primary alkyl radicals under tin-free conditions and could be successfully applied for carbon-carbon bond formations. The radical alkylation of carboxylic amides was studied with ketene O,N-acetal (56) as radical alkylating reagent and was achieved by the addition of an alkyl radical to a ketene O,N-acetal and the subsequent cleavage of N-O bond. Alkyl halides activated with an α-electron-withdrawing group and simple alkyl halides underwent cleanly alkylations under tin-free or tin-catalyzed conditions. In addition, radical-mediated γ-alkylation of α,β-unsaturated carboxylic amides under tin-free conditions was also achieved by the selective γ-addition of alkyl iodides and bromides bearing a-electron-withdrawing group to diene O,N-acetals (75a-d). This approach could be further extended to the g-functionalizations using hetero groups such as phenylsulfanyl and phenylsulfonyl. $Et_3B$-initiated radical alkylations of carbonyl compounds using O-acetyl (89) and O-tert-butyldiphenylsilylhydroxyenamines (93) as radical a...