1,3-Dipolar cycloaddition of azinium ylides to alkynyl hetarenes: a synthetic route to indolizine and pyrrolo[2,1-a]isoquinoline based heterobiaryls

For the first time, pi-deficient alkynyl hetarenes were used as dipolarophiles in a 1,3-dipolar cycloaddition reaction with in situ generated azinium ylides. A three-component reaction of pyridine or isoquinoline, ethyl chloroacetate and alkynyl hetarene (pyrazine, quinoxaline, uracil, or lumazine derivative) in the presence of a base gave the corresponding indolizine or pyrrolo[2,1-a]isoquinoline based heter-obiaryl in good yields. The reactions proceeded with high regioselectivity; in all cases the most electron deficient carbon atom of the C equivalent to C bond of the starting alkynyl hetarene adds to the side-chain carbon of the azinium ylide. 1,3-Dipolar cycloaddition reactions of alkynyl hetarenes with azinium ylides or other 1,3-dipole reagents can be considered as an alternative synthetic approach to heterobiaryls. (C) 2016 Elsevier Ltd. All rights reserved.