Radical-Mediated alkylation reactions

Abstract

Alkylations is one of the most important and fundamental reactions. However, radical-mediated alkylations have not been well studied. We studied the possibility of indirect radical-mediated aldol reactions using $\alpha$-acetoxy alkyl radicals along with reagent equivalents of the $\alpha$-ketone acceptor synthon, 2-acetoxy and 2-benzoyloxy substituted allyl sulfones. The combination of these allylating agents together with the $\alpha$-acetoxy alkyl radical precursors would provide $\alpha, \beta$ -unsaturated ketones in high yields after hydrolysis of the acetates and the following dehydration. Novel radical alkylation of organic nitro compounds via bis(silyloxy)enamines was studied and achieved by the radical addition of an alkyl radical onto bis(silyloxy)enamine $\textbf{26}$ and the subsequent homolytic cleavage of the N-O bond to yield oxime ether $\textbf{29}$. Alkyl halides activated with an $\alpha$-electron withdrawing group underwent cleanly alkylations under photo condition, yielding oxime ether compounds in high yields. Also, we could obtain the isoxazoline and isoxazole compounds via 1,3-dipolar cycloaddition reactions. Tin-free radical mediated $\gamma$ -alkylations of $\alpha, \beta$ -unsaturated carboxylic esters via O-$\textsl{tert}$-alkyl dienol ethers were studied. One of the key features in this approach is a facile $\beta$ -fragmentation of intermediate $\textbf{53}$ to yield alkylation product $\textbf{52}$ along with liberation of $\textsl{tert}$ -alkyl radical $\textbf{54}$ and to generate reactive primary alkyl radical $\textbf{55}$ by a radical cyclization of $\textsl{tert}$ -alkyl radical $\textbf{54}$ for an efficient iodine atom transfer. Radical-mediated $\gamma$ -alkylation of $\alpha, \beta$ -unsaturated carboxylic esters via silyl dienol ethers under tin-free conditions underwent cleanly, yielding $\gamma$ -alkylation products in high yields selectively. We studied the radical-mediated alkylation of carbonyl compounds v...