Development of nitrogen directed C-H activation protocols for the synthesis of natural products, drugs and new scaffolds

Abstract

The thesis is mainly based on the development and application of nitrogen directed C‒H activation methodologies in the synthesis of natural products, new scaffolds, and drugs. We have successfully developed Pd‒catalyzed “olefin amidation/C‒H activation” protocol for the synthesis of (±)-8- oxocanadine and (±)-8-oxostylopine protoberberine alkaloids and formal synthesis of the drug tetrahydropalmatine. Quinazolinone directed C(sp2)‒arylation and C(sp3)‒acetoxylation protocols have also been developed for the synthesis of new quinazolinones using Pd-catalysis. Novel Ru‒catalyzed regioselective cascade annulation of acrylamides with 2-alkynoates via aza-Michael/C‒H activation sequence for the synthesis of various 6-oxo nicotinic acid esters has been developed. The regioselectivity is confirmed by silver mediated protodecarboxylation of the corresponding 6-oxo nicotinic acid to furnish 2- pyridone. The detection of ruthenacycle intermediate (HRMS) in the reaction mixture and the nonreactivity of the phenyl and t-butyl substituted 2-alkynoates under the developed protocol suggests a plausible mechanism and involvement of allene intermediates.