Development of organocatalytic asymmetric annulations synthesis of chiral drug like molecules

Abstract

Development of Organocatalytic Asymmetric newlineAnnulations: Synthesis of Chiral Drug-Like Molecules newline1. Abstract newlineChapter 1 describes about engineering of an enantioselective [3+3]-annulation reaction to furnish newlinemedicinally important 2,3-diazaspiro[4.5]deca-3,6-diene-1-ones by choosing specially designed newlinesubstrates with multi nucleophilic and multi-electrophilic centers. Here, we successfully newlineengineered the [3+3]-annulation of and#61537;-arylidene pyrazolinones with (E)-alkyl 2-oxo-4-aryl-but-3- newlineenoates to furnish the desired products 2,3-diazaspiro[4.5]deca-3,6-diene-1-ones with good newlinediasteroselectivity and excellent enantioselectivity under quinidine catalysis. The double sequence newlineof in situ isoaromatization and dearomatization of and#61537;-arylidene pyrazolinones was the driving force newlinefor the reaction to furnish the desired products. Here, we successfully synthesized 40 examples newlinewith up to 83% yields, 99:1 dr and 96% ee using the developed protocol. newlineChapter 2 deals with the development of a seven-step, one-pot regioselective protocol for the newlinesynthesis of biologically important 3-aryllawsones. Here, we designed the reaction in a seven-step newlinedouble cascade manner by combining Ramachary reductive coupling and the oxidative newlinedecarboxylation to furnish 3-aryllawsones. Owing to their structural importance, we successfully newlinesynthesized 41 differently functionalized 3-aryllawsones with up to 90% yields and gt99% newlineregioselectivity using commercially available starting materials. We have successfully investigated newlinethe substrate-controlled asymmetric aza-Michael/air-oxidation reaction on 2-arylnaphthalene-1,4- newlinediones with chiral amines (S)-(-)-tert-butylsulfinamide and (R)-(+)-tert-butylsulfinamide under newlinebasic medium without affecting the enantioselectivity. For the first time, we have provided the newlinecrystallographic proof for the alkyl migration via the X-ray crystal structures of both starting newlinematerial and the products. newlineChapter 3 deals with the development of a methodology for the regioselective C-alkylation of newlineconformationally flexible c