Directed functionalization of 2-oxazolines and dioxinones using mixed magnesium-lithium bases

Author(s)

João Henrique Carvalho Batista

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC)
• Defense date: 2015-08-28

Examining board members

Giuliano Cesar Clososki; Ivone Carvalho; Vladimir Constantino Gomes Heleno; Ricardo Vessecchi Lourenço; Mirela Ines de Sairre

• Advisor: Giuliano Cesar Clososki

Abstract

Since their discovery, organometallic reagents have been widely used in methodological studies aiming the preparation of new organic compounds and in the synthesis of bioactive molecules. In general, the choice by the use of certain organometallic reagent involves the knowledge of their chemical nature as well as their reactivity. Thus, the objective of this study was to investigate the reactivity of new mixed magnesium-lithium reagents in the functionalization of 2-oxazolines and dioxinones, which are important intermediates in the synthesis of bioactive substances. In the case of the 2-oxazolines, though the iodinemagnesium exchange reactions in iodinated substrates have not led to the expected results, an additional study involving the base TMPMgCl.LiCl led to the development of a new methodology for functionalization halophenyl-2- oxazolines. In this study, after the metalation step, the organometallic reagents could be reacted with various electrophiles, leading to the desired products in good yields. Furthermore, after a transmetalation step with zinc chloride, intermediates could be arylated via cross-coupling reactions. Similarly, the functionalization of a series of pyridine-oxazolines with TMPMgCl.LiCl was evaluated and led to the desired products in an interesting control chemo- and regioselectivity. In the final stage of the project, studies on the functionalization of dioxinones, that are important precursors in the synthesis of natural products, were conducted. In these studies, the mixed lithium-magnesium dibase TMP2MgCl.LiCl was used leading to the orhto-functionalized products with high selectivity. The success of this approach led us to perform preliminary investigations on the synthesis of an analogue of caramboxin, a natural product of great pharmacological interest (AU)

• FAPESP's process: 11/12589-3 - Application of New Organometallic Reagents in Synthesis of Bioactive Substance
• Grantee: João Henrique Carvalho Batista
• Support Opportunities: Scholarships in Brazil - Doctorate