Chiral-induced Asymmetric Baylis-Hillman Reaction

The Baylis-Hillman reaction is a three-component interaction that can effectively construct carbon–carbon bonds,giving functionalized products that can be further converted.Thus the reaction is attracted interest in organic synthesis.In recent years,the development of a number of asymmetric induction system Baylis-Hillman reaction.And aiming at the problem that the reaction substrate has a narrow range of selection,long reaction time and low selectivity.We conducted asymmetric synthesis that was based on Baylis-Hillman reaction using achiral catalysts and/or achiral substrates.In order to obtain a new and efficient chiral induction system.1.Design,Synthesis and Application of Chiral SubstratesL-menthol,Tropicol,Dextrose,Crotonic acid,Cinnamic acid were used as raw materials.A total of five kinds of chiral substrates were designed and synthesized and applied to asymmetric Baylis-Hillman interaction.The effects of catalyst type and dosage,time,temperature and solvent system on activity and selectivity were investigated.When o-nitrobenzaldehyde and menthyl acrylate were adopted using DMF:H2O=9:1 as solvent,best performance(yield: 84%,de:91%)was observed at 20 oC for 36 h.In scope expension of aldehydes,excellent results(e.g.yield: 92%,de: 95%)were obtained under the optimized conditions for aldehydes with benzene ring containing an electron-withdrawing group,whereas poor results were observed for aromatic base containing an electron-donating group.Furthermore,good results were obtained when four kinds of chiral olefins(Tropicy acrylate,Borneol acrylate,Menthyl cinnamate and Menthyl crotonate)and nitrobenzaldehyde were subJ ect to Baylis-Hillman reaction.When the asymmetric products underwent ester hydrolysis,new chiral centers were obtained with good selectivity.2.Synthesis and Application of Chiral SolventsL-alanine,L-phenylalanine,L-proline and L-histidine were used as raw materials to synthesize twelve kinds of amino acid ionic liquids.The ionic liquids were used as chiral solvents to induce asymmetric synthesis in Baylis-Hillman reactions involving achiral catalysts and achiral substrates.The reactions wereoptimized in terms of type and amount of catalyst,chiral solvent,temperature,time and co-solvent.When the catalytic system was DABCO:2-nitrobenzaldehyde: methyl acrylate = 1:1:6,L-proline ethyl ester ionic liquid as chrial solvent,and at –10 oC for 36 h,the best result was 41% yield,46% ee.The applicability of substrates was investigated under the optimized conditions.In the Baylis-Hillman reaction of aromatic aldehydes with methyl acrylate,relatively good result was obtained in the case of nitrobenzaldehyde(51% yield,and 56%ee).Better results were obtained when the amino acid ionic liquid was used as chiral solvent for Baylis-Hillman reaction of different active olefins.Through a series of applications,it was demonstrated that the use of chiral amino acid ionic liquids as solvent results in asymmetric products as a consequence of chiral-induced Baylis-Hillman reaction.