First diastereoselective synthesis of perfluoroalkylated cis-spiropyrido[2,1-a]isoquinoline-1,5’-pyrimidines

The 1,4-dipoles derived from isoquinolines and methyl perfluoroalk-2-ynoates reacted readily with arylidene-substituted N,N-dimethylbarbituric acids resulting in the first diastereoselective synthesis of perfluoroalkylated cis-spiropyrido[2,1-a]isoquinoline-1,5’-pyrimidine derivatives in good to excellent yields under mild conditions. The reaction mechanism was proposed to illustrate the formation of the diastereoisomers and proton-promoted transformation of trans-spiropyrido[2,1-a]isoquinoline-1,5’-pyrimidines to the more thermodynamically stable cis-isomers. The DFT calculation demonstrated the diastereoselectivity of the reaction.