Carbon-Carbon Bond Construction Based on Radical Addition to C=N Bond

Abstract

We have studied the carbon radical addition to imine derivatives as an effective carbon-carbon bond forming method for the synthesis of a variety of amines. The reaction of oxime ethers proceeded smoothly in the presence of BF3·OEt2 to give the alkylated products in high yields via the free radical-mediated carbon-carbon bond forming process. Intermolecular radical addition to oxime ethers was effectively improved by using alkyl iodides and triethylborane, which acts multiply as a Lewis acid, a radical initiator and a terminator. The asymmetric synthesis of α-amino acids based on a diastereoselective radical addition to glyoxylic imine derivatives was achieved. Highly diastereoselective alkyl radical addition to Oppolzer’s camphorsultam derivatives of oxime ether provided a convenient method for preparing the enantiomerically pure α,β-dialkyl-β-amino acids. We have demonstrated that imine derivatives such as oxime ethers, hydrazones, and nitrones are excellent radical acceptors for the radical reactions in aqueous medium. The radical addition to imine derivatives in aqueous medium was also studied by using indium or zinc as a single-electron transfer radical initiator. We have found that triethylborane can be applied to solid-phase radical reactions. The solid-phase tandem carbon-carbon bond forming reaction of oxime ethers connected with an α,β-unsaturated carbonyl group proceeded effectively to give the azacycles or chiral oxacycles after cleavage from the resin.