Free radical acylation reactions using sulfonyl oxime derivatives

Abstract

Free radical-mediated acylation reactions using sulfonyl substituted oxime ethers have been studied. Our approach relies on the addition of alkyl radicals to C-N double bonds followed by β-fragmentation of sulfonyl group in the adduct to produce C-N double bonds. Intermolecular radical acylation reaction of alkyl radicals with phenylsulfonyl methoxycarbonyl oxime ether and phenylsulfonyl acetyl oxime ether which were conveniently prepared via nitrosation reaction, afforded the oxime ether derivatives of α-keto esters and 1,2-diketones in high yield. These reactions were conducted with organotin compound [($Me_3Sn)_2$] under the photochemical condition [300 nm]. In order to achieve sequential intermolecular radical acylation, bis-methylsulfonyl-methanone-O-benzyl-oxime was prepared. Sequential intermolecular radical acylation of bis-methylsulfonyl-methanone-O-benzyl-oxime with two different alkyl iodides afforded the oxime ether derivatives of various ketone compounds, which were easily hydrolyzed to the corresponding ketones under acidic conditions. The synthesis of ketones was normally carried out by a three-step, one-pot procedure. This sequential radical acylation approach was successfully applied to syntheses of various cyclic ketones via intermolecular acylation, intramolecular cyclization, and intramolecular acylation. Atom-transfer-mediated radical acylation was investigated to avoid the use of tin-based reagents, because of high cost and inherent toxicity of organotin derivatives. O-Benzyl-α-(methylsulfonyl)-formaldoxime and methyl sulfonyl ethoxycarbonyl oxime ether were used as a radical acceptor and iodine atom transfer by methyl radical was used as a method for generation of alkyl radicals. Along with iodine atom transfer reaction, dithiocarbonate (xanthate) group transfer reaction was also applied. Nitromethylation of alkyl radicals was also studied using silyl nitronates as a radical acceptor. Though sood results were not obtained because of i...