Synthesis of new immobilized ligands for the enantioselective arylation of aldehydes in batch and continuous for regime and development of a new metal-free methodology to synthesize functionalized indolines

Author(s)

José Augusto Forni

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 2017-08-31

Examining board members

Júlio Cezar Pastre; Ronaldo Aloise Pilli; Kleber Thiago de Oliveira

• Advisor: Júlio Cezar Pastre

Abstract

The objective of this work is to explore the inherent advantages of continuous flow processes in the enantioselective arilation of aldehydes using organozic reagents and chiral ligands. Different ligands were synthetised and evaluated in homogenous phase. The ligands that presented better yields and enantioselectivities were selected to be immobilized in polymeric resins and studied in batch and in a fixed-bed reactor. Immobilisation of the ligands had a negative impact in their performance once they were studied in batch. Conversely, in continuous flow regime, yields and enantioselectivities were comparable with those obtained in homogenous phase, but it was noticed a great increase in reaction kinetics: in batch the reaction is typically performed in 24 hours while in continuous flow regime efficient arylation was achieved in residence times as low as 1.5 minutes. Results obtained during this work also suggests that the current accepted mechanism for this reaction might be incomplete. Theoretical studies were conducted to propose a new mechanistic pathway. A second project was developed in the research group of Prf. Steven V. Ley, at the University of Cambridge. In this study, it was explored the reactivity of boronic acids towards diazomethane in the synthesis of functionalized indolines in a metal-free fashion. The protocol developed allowed the desired products to be synthesized with moderate to excellent yields and with excellent diasteroselectvity. In total, 24 compounds were synthesized, among which, 19 are novel compounds (AU)

• FAPESP's process: 14/26093-8 - Development of catalysts immobilized in carbon nanotubes and evaluation of their performance in continuous flow
• Grantee: José Augusto Forni
• Support Opportunities: Scholarships in Brazil - Master