Visible-light induced dearomative functionalization of aromatic indolizines

• Grant number: 24/01253-4
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: April 12, 2024
• End date: October 11, 2024
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Giuliano Cesar Clososki
• Grantee: Vitor Tassara de Moraes
• Supervisor: Georg Manolikakes
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University Of Kaiserslautern-Landau In Kaiserslautern, Germany
• Associated to the scholarship: 22/16916-3 - Development of an electrophilic amination methodology for aromatic indolizines, BP.MS

Abstract

Aromatic indolizines are important scaffolds in organic synthesis, with several applications on both medicinal and material chemistry. However, only the saturated indolizidine scaffold is found in nature, with diverse examples of alkaloids displaying remarkable biological activities. Therefore, various synthetic approaches to obtain the saturated version of this heterocycle, based on the de-novo synthesis of the bicyclic system, have been reported in the literature. Recently, visible-light induced dearomatization reactions have attracted great attention. One interesting strategy involves the dearomative functionalization of arenes employing arenophiles, such as triazolinediones (TADs), which can provide highly functionalized products from simple aromatic compounds. Despite the interest in alkaloid synthesis and the advance in the dearomative functionalization reactions, there are no reports using aromatic indolizines as substrates. Therefore, this research project aims to investigate the dearomative functionalization of aromatic indolizines. Within this project, we aim to develop a method for generating indolizine-TAD cycloaddition adducts and explore their reactivity to produce novel 3D-scaffolds. This approach holds the potential to synthesize a diverse array of highly functionalized alkaloid-like indolizine derivatives, featuring functionalities like amines and hydroxyl groups, among others. It is worth mentioning that the development of the present proposal in the Manolikakes' group will complement the Master studies about amination of aromatic indolizines developed in Brazil, adding saturated aminated indolizines to the portfolio of accessible molecules.