Diastereoselective synthesis of spirocyclic isoxazolo[5,4-c]pyrrolo[2,1-a]isoquinolines via cascade double [3 + 2]cycloadditions

Abstract

The one-pot base-promoted cascade double [3 + 2] cycloaddition reaction of N-cyanomethylisoquinolinium chloride with (E)-3-arylideneindolin-2-ones and (E)-N-hydroxybenzimidoyl chloride afforded novel polycyclic spiro[indoline-3,8′-isoxazolo[5,4-c]pyrrolo[2,1-a]isoquinolines] in good yields and with high diastereoselectivity. When 4-arylidenepyrazol-3-ones, 2-arylidene-1,3-indanediones and arylidenemalononitriles were employed in the reaction, the corresponding spiro[isoxazolo[5,4-c]pyrrolo[2,1-a]isoquinoline-8,4′-pyrazole], spiro[indene-2,8′-isoxazolo[5,4-c]pyrrolo[2,1-a]isoquinoline], and isoxazolo[5,4-c]pyrrolo[2,1-a]isoquinoline derivatives were also prepared in good yields and with high diastereoselectivty. The relative configurations of the polycyclic spiro compounds were clearly elucidated by determination of fifteen single crystal structures.