Carbon Dioxide-Promoted Palladium-Catalyzed Cyanomethylation Of Allylic Alcohols With Acetonitrile

Nitriles are useful intermediates in synthetic chemistry and materials science.Meanwhile,cyano groups also widely exist as active structural units in a variety of natural products and drug molecules.Compared to cyanation reaction,cyanomethylation reaction,which is easier to control and uses less toxic reagents,is an alternative for introducing cyano groups into organic molecules.Based on its inexpensive,available,and low-toxicity nature,the development of acetonitrile as an efficient,green,and atom-economical cyanomethylation reagent is a research hotspot in the field of the green chemical industry.However,the inherent chemical properties of acetonitrile pose challenges to the cyanomethylation reaction.The ability of nontoxic and renewable CO₂as a traceless activating reagent to promote the deprotonation of acetonitrile and stabilize the cyanomethyl anion provides a feasible way to develop acetonitrile as a cyanomethylation reagent.Herein,we have demonstrated CO₂-mediated cyanomethylation of allylic alcohols with acetonitrile.The cyanomethylation of cinnamyl alcohol was selected as the model reaction and the optimal reaction conditions were established as follow:allyl alcohol（1.0 equiv）,Pd（OAc）₂（5 mol%）,S-BINAP（5 mol%）,MTBD（2 equiv）,CO₂（1 atm）,80 ^oC in acetonitrile for 12 hours.It was found that the catalytic system is effective for both linear and branched allyl alcohols,both of which generate linear cyanomethylated products selectively.Under the optimal reaction conditions,35 kinds of straight-chain allyl alcohols and 8 kinds of branched-chain allyl alcohols can participate in the cyanomethylation reaction and obtainγ,δ-unsaturated nitrile compounds in 46%to 92%yields.The reaction could be scale-up to gram scale in slightly decreased yield.The bis-cyanomethylation reaction of bisallyl alcohol can also proceed smoothly,and the obtained dinitrile products were converted into two polyamide diacid monomers by hydrolysis,then seven kinds of polyamide materials were prepared.Through the control experiment and the capture experiment of the intermediate,it was found that CO₂,as a traceless activator,simultaneously activates allyl alcohol and acetonitrile to generate allyl alcohol carbonate and cyanoacetate intermediates respectively,therefore efficiently promotes the cyanomethylation.