Radical reaction of oxime ether derivatives

Abstract

Free radical-mediated acylation reactions using α-substituted oxime ethers have been studied. Our approach relies on addition of the alkyl radicals to C-N double bonds followed by β-fragmentation of the adduct to produce C-N double bonds such as oxime ethers. The efficiency of thiohydrazonate, oximoyl chloride, oximoyl cyanide, thioimidate, sulfinyl oxime ether and sulfonyl oxime ether as radical acceptors has been studied. Under photochemical condition with $(Bu_3Sn)_2$, the reactivity was shown in the order $PhSO_2$ > PhSO > Cl > PhS. This trend was in accordance with LUMO energy calculation by MOPAC with AM1 parametrization. Intramolelular addition of alkyl radicals to phenylsulfonyl oxime ethers with $(Bu_3Sn)_2 /hν$ (300nm) afforded 5- and 6-membered cyclic oximes in high yields. Tandem cyclization was also achieved by using the phenylsulfonyl oxime ether as a radical acceptor. In order to achieve intermolecular acylation reaction, O-benzyl-α-(phenylsulfonyl)-formaldoxime and O-benzyl-α-(phenylsulfonyl)-acetaldoxime were prepared from the corresponding oximes by three-step sequences in good yields. The intermolecular addition of primary, secondary and sterically hindered tertiary alkyl iodides to O-benzyl-α-(phenyl-sulfonyl)-formaldoxime and O-benzyl-α-(phenylsulfonyl)-acetaldoxime with $(Me_3Sn)_2 /hν(300nm)$ afforded the acylating compounds. All oxime ethers exist as an equilibrium mixture of cis and trans isomer and were easily hydrolyzed to the corresponding aldehyde or ketone under acidic condition. The approximate rate constants for intermolecular additions of alkyl radicals to phenylsulfonyl oxime ethers have been determined to be $k_a=9.6×10^5M^{-1}s^{-1}$ at 25℃ for O-benzyl-α-(phenylsulfonyl)-formaldoxime and $k_a=7.3×10^4M^{-1}s^{-1}$ at 60℃ for O-benzyl-α-(phenylsulfonyl)-acetaldoxime, indicating that additions are fast and highly efficient process.