One carbon homologation novel one ot synthesis of sulfone and pyrimidinone derivatives

Abstract

Multicomponent reactions MCRs are one of the most important approaches for the synthesis of complex and structurally diverse products in organic chemistry Multicomponent reaction MCR is defined as a process in which three or more starting materials are allowed to react in onepot to form a new adduct that contains essentially almost all portions of starting materials eliminating almost all byproducts MCR provides an easy access to synthetically useful and medicinally important functionalized heterocyclic scaffolds with welldefined regio and stereoselectivity The onepot reactions offer flexibility and thus MCRs have become excellent tools for the rapid assemblage of libraries of small molecules having structural diversity and complexity The MCR is environmentally benign and offers many advantages such as simple implementation high atom efficiency readily accessible time and energysaving and diversityoriented synthesis newlineIn Chapter 1 a general introduction about multicomponent reaction and its application are described Detailed discussion about onecarbon homologation Mannich reaction Nef reaction and eutectic mixture also presented newlineIn Chapter 2 the development of new and general synthetic methodology based on onecarbon homologation for the synthesis of functionalized sulfone derivatives is described In Part A a novel and efficient Mannichtype onecarbon homologation reaction for the synthesis of ketosulfones under mild condition using TFABn2NH salt as a catalyst is presented In this onepot reaction aryl sulfonyl hydrazideformaldehyde reagent system serves as a novel CH2SO2 Ar transfer agent The utility of ketosulfone was further shown in the Fisher indole synthesis in low melting mixture In Part B a simple and onepot method for the synthesis of substituted iv allyl sulfone derivatives by employing TFABn2NH salt as a catalyst is described In this onecarbon homologation reaction unsaturated aldehydes nitroalkenes and electronrich enol ethers are directly converted to the corresponding allyl sulfones in good yields The efficiency of this onecarbon homologation further demonstrated in synthesis of benzyl sulfone derivatives using aryl sulfonyl hydrazideformaldehyde reagent system as a novel CH2SO2Ar transfer agent The synthesized compounds were characterized by IR 1HNMR 13CNMR and HRMS analyses The structure and relative stereochemistry of sulfone derivatives were unambiguously confirmed by single crystal Xray analysis newline newline