Construction of Spiropyrido[2,1-a]isoquinoline via Tandem Reactions of Huisgen's 1,4-Dipoles with Various Alkene Dipolarophiles

The three-component reaction of isoquinoline, dimethyl acetylenedicarboxylate and arylidene pivaloylacetonitrile in acetonitrile at room temperature afforded pyrido[2,1-a]isoquinolines 1a-1j in good yields and with high diastereoselectivity. When arylidene-substituted 1,3-indanediones, Meldrum acids, and N,N'-dimethylbarbituric acids were employed in the reaction, the novel functionalized spiro[indene-2,1-pyrido[2,1-a]isoquinolines] 2a-2j, spiro[pyrido[2,1-a]isoquinoline-1,5-[1,3]dioxanes] 3a-3h and spiro[pyrido[2,1-a]isoquinoline-1,5-pyrimidines] 4a-4e were also efficiently synthesized in satisfactory yields. The reaction mechanism included domino formation of Huisgen's 1,4-dipole, Michael addition and cyclization processes.