Multicomponent Reaction for Selective Synthesis of Spiro[indene‐2,7′‐isoquinoline] and 1,2,8,8 a‐Tetrahydroisoquinoline Derivatives

Abstract

The piperidine promoted three‐component reaction of N‐alkylpiperidin‐4‐ones, malononitrile and 2‐arylidene‐1,3‐indanediones in ethanol selectively resulted in the spiro[indene‐2,7′‐isoquinoline] and the ring‐opened cis‐ or trans‐1,2,8,8a‐tetrahydroisoquinoline derivatives at room temperature or at the elevated temperature. However, the four‐component reaction N‐alkylpiperidin‐4‐ones, malononitrile, aromatic aldehydes and 1,3‐indanedione in refluxing ethanol mainly afforded ring‐opened cis‐1,2,8,8a‐tetrahydroisoquinoline derivatives in good yields and with high diastereoselectivity. A plausible domino reaction mechanism was proposed for the formation of the different polycyclic products.

Comprehensive Strategies for the Synthesis of Isoquinolines: Progress Since 2008

“…[319] Cao et al have reported multicomponent reaction of N-alkylpiperidin-4-ones 552, 1,3-indanedione (553) and malononitrile (554) towards the selective synthesis of 1,2,8,8a-tetrahydroisoquinoline 556 and spiro [indene-2,7'-isoquinoline] derivatives 555 (Scheme 322). [320] Galvis et al reported the isoquinoline synthesis using Bischler-Napieralski reaction. The described protocol explored the instability of products formed during Bischler-Napieralski reaction and also authors have demonstrated the unusual in situ ionic interchange between [bmim]PF 6 ionic liquid and the dihydroisoquinoline core, which can stabilize the 1-styryl-3,4dihydroisoquinolines 558 (Scheme 323).…”

“…have reported multicomponent reaction of N ‐alkylpiperidin‐4‐ones 552 , 1,3‐indanedione ( 553 ) and malononitrile ( 554 ) towards the selective synthesis of 1,2,8,8 a ‐tetrahydroisoquinoline 556 and spiro [indene‐2,7’‐isoquinoline] derivatives 555 (Scheme 322). [320] …”