New Synthetic Strategies for the Synthesis of Diverse Organic Compounds Using Cyclic Diazo Compounds

Abstract

Diazo compounds have emerged as one of the most versatile and useful reagents in modern synthetic organic chemistry. Specially, applications of this diazo chemistry to the preparation of biologically interesting and active compounds are increasing day by day. Natural products bearing β-substituted α-haloenones, furopyrimidinediones, furopyranones and indene skeletons are widely found in nature. They have shown to possess a variety of biological activities such as antiproliferative, cytotoxic agents, antimicrobial, antimalarial, antitumor, anticancer, antibacterial, and fungicidal properties. Due to the importance of their biological activities and properties, this thesis aims at XIV developing novel and efficient synthetic methodologies for the construction of biologically interesting diverse organic compounds such as β-substituted α-haloenones, furo[2,3-d]pyrimidinediones and thioxofuro[2,3-d]pyrimidineones, furo[2,3-b]pyran-6-ones and functionalized indene derivatives using cyclic diazo compounds as starting materials. First, efficient synthesis of α-chloroenones bearing β-carbonates or β-carbamates was achieved by rhodium(II)-catalyzed reaction of cyclic diazodicarbonyl compounds with a variety of chloroformates or carbamyl chlorides in 42-84% yield. These reactions provided a useful and rapid entry to β-substituted α-haloenones. These reactions are mild and solvent free. Second, the rhodium(II)-catalyzed reactions of cyclic diazo compounds derived from barbituric acid or thiobarbituric acid with arylacetylenes and styrenes were examined. These reactions provided a rapid synthetic route to the preparation of a variety of novel and diverse furo[2,3-d]pyrimidine-2,4-diones, 2-thioxodihydrofuro[2,3-d]pyrimidin-4-ones, dihydrofuro [2,3-d]pyrimidine-2,4-diones, and 2-thioxotetrahydrofuro[2,3-d]pyrimidin-4-ones in 40-78% yield. Third, rhodium(II)-catalyzed reactions of diazo compound derived from Meldrum’s acid and a variety of ethynyl compounds were carried out. These reactions provided a rapid route for preparing a variety of furo[2,3-b]pyran-6-one derivatives in the range of 35-65% yield. This one-pot cascade reaction undergoes metal carbenoid reaction/ketene formation/[2+2]cycloaddition/ring expansion. This methodology has the advantages of mild reaction conditions, efficient catalytic ability, and simple experimentation requirements. Last, a sequential Wolff rearrangement of 1-diazonaphthalen-2(1H)-ones followed by trapping of the ketene intermediate with aliphatic and aromatic primary amines or alcohols and phenols in the presence of various aldehydes produced 1H-indene-3-carboxamides in 45-94% yield or 1H-indene-3-carboxylates in 39-65% yield. This strategy constitutes an unprecedented three-component coupling reaction that allows for the synthesis of functionalized indene derivatives under catalyst-free thermal conditions. This thermal cascade reactions of 1-diazonaphthalen-2(1H)-ones involves Wolff rearrangement/ketene addition/ aldol condensation.