Catalyst-Free (3 + 2) Annulation of Morita–Baylis–Hillman Carbonates With Isoquinolines to Access Functionalized Pyrrolo[2,1-a]Isoquinolines

Abstract

A divergent strategy has been developed for the reactions between Morita–Baylis–Hillman (MBH) carbonates and isoquinolines. When MBH carbonates, derived from o-acylamino-aryl aldehydes and acrylonitrile, were reacted with isoquinolines, the reaction proceeded via a (3 + 2) cycloaddition/aromatization pathway to afford a diverse array of completely aromatic pyrrolo[2,1-a]isoquinolines in moderate to good yields (51%–91%) with excellent chemo- and regioselectivity. In contrast, when the substrates were changed to MBH carbonates synthesized from o-acylamino-aryl aldehydes and methyl acrylate, and 3,4-dihydroisoquinolines were employed as reaction partners, the reaction underwent a formal (3 + 2) cycloaddition to provide pyrrolo[2,1-a]isoquinolines bearing two adjacent tertiary stereogenic centers in good yields (up to 93%) with excellent chemo-, regio-, and diastereoselectivity (all cases > 25:1 dr). Notably, these reactions proceeded under nearly identical reaction conditions, with no observable competitive side products.