The Synergy of Microwave-Irradiation and Water Surface: A Fast Access to C-2 Functionalized Indolizines Via...

Herein, we report a sustainable, rapid, and cost-effective methodology for the synthesis of 2-functionalized indolizines from pyridine-2-carboxaldehydes by coupling with α,β-unsaturated compounds via the Baylis-Hillman pathway followed by cyclization in one-pot using DBU as the organocatalyst "on-water" under microwave irradiation. The water as the medium played a pivotal role in achieving quick conversion to the products in just 1 min in good to high yields (up to 78%). The method is further validated on several 2-acylpyridines; however, in these cases a longer time (up to 1 h) was required for complete conversion due to steric bulk at the reaction center and 1,2-functionalized indolizines are obtained in similar yields (up to 74%). The substituent variation in pyridine and α,β-unsaturated compounds show negligible electronic effect and a diverse functional group tolerance is observed. Furthermore, the scalability of the method is studied at the gram-scale with representative examples, which afford products in comparable yields to that of the small-scale reactions. The present method tick multiple sustainability matrices like metal-free synthesis, water as reaction medium, cost-effectiveness, and low E-factor.