Synthesis of Pyrrolidinyl, Pyrazolidinyl, and Isoxazolidinyl Isoquinolines

Significance

An innovative cascade synthesis of complex heterocycles, involving a Pd-catalyzed allene coupling, heteroannulation and terminating with a 1,3-dipolar cycloaddition is reported. This sequence was postulated to proceed, for the reaction with amino esters, via intermediate B rather then A, providing pyrrolidinyl, pyrazolidinyl, and isoxazolidinyl isoquinolines, resulting in substantial increase in molecular complexity with the formation of five new bonds, two rings and two to four ste­reocenters with good regio- and stereoselectivity. Mechanistic considerations are proposed.