Cyclizations of aniline N-oxides to give tetrahydroquinoline and related polycyclic scaffolds

Abstract

Chapter 1 outlines the properties of tetrahydroquinolines, their utility in various biologically-relevant contexts as well as other non-therapeutic contexts, and the synthetic strategies towards tetrahydroquinolines. Several natural products containing tetrahydroquinoline cores are examined as well as various reported syntheses. Many other non-natural pharmaceutical molecules are similarly explored as well as the synthetic approaches towards them. This chapter does include syntheses from prior to 2019; however, this chapter aims to highlight the synthetic progress towards tetrahydroquinolines since 2019. Chapter 2, the first project herein, describes the synthesis of 4-amino- and 4-sulfanyltetrahydroquinolines from aniline N-oxides and nitrogen- or sulfur-containing alkenes. This chapter also addresses the efforts toward the synthesis of indolines and 3,4-dihydroquinolines. Chapter 3 describes the efforts towards the demethylation of N-methyltetrahydroquinolines, a long-standing challenge for this research program. It focuses on various strategies employed to access the desired demethylated tetrahydroquinoline as well as the fortuitous synthesis of 2-aryl tetrahydroquinolines that came as a result of these experiments. This chapter also briefly addresses the efforts toward the synthesis of the natural products, Incargranine B and Seneciobipyrrolidine. Chapter 4 closes this document with the preliminary efforts and future directions toward the functionalization of diarylamines through the use of aniline N-oxides.