Development of New Anionic Hopping Cascade Routes to Synthesize Various Heterocycles

Abstract

Four new synthetic methods employing anion hopping strategy to synthesize various heterocylces are presented. In Chapter 1.A, a micro-review is presented which comprehensively cover reported reactions employing thio- and aminophosphate precursors for forming sulfur and nitrogen heterocycles. Whereas, in Chapter 1.B, a cationic and an anionic hopping cascades are reported to form 1,2,3,6-tetrahydropyridines. Origins, design, reaction, and optimizations are discussed. In Chapter 2, an asymmetric approach to assemble cis-vinyl aziridines is reported employing a strategically substituted dienolate, decorated with a γ-leaving group. Chapter 4 highlight efforts toward asymmetric total synthesis of (-)-kainic acid and (+)-α-allokainic acid. In Chapter 4A and Chapter 4B, lays the groundwork for a lithium-assisted asymmetric anion-accelerated amino-Cope rearrangement cascades in which nitrogen atom chiral auxiliary serves three critical roles, by (1) enabling in situ assembly of the chiral 3-amino-1,5-diene precursor, (2) facilitating the rearrangement via a lithium enolate chelate, and (3) imparting its influence on consecutive inter- or intramolecular C−C or C−X bond-forming events via resulting chiral enamide intermediates or imine products. Chapter 5 presents a comprehensive compilation and analysis of US FDA approved combination drugs, from the first approval in 1943 through 2018.