Metallaphotoredox catalysis to access spirocyclicglucals via carbonylative coupling

• Grant number: 24/08743-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: November 01, 2024
• End date: June 30, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Helio Alexandre Stefani
• Grantee: Milene Macedo Hornink
• Supervisor: Gary Molander
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Université Paris-Saclay, France
• Associated to the scholarship: 23/07257-9 - Carbonylative Coupling Reactions Employing 1- and 2-Iodoglucal: Cyclization reactions, BP.PD

Abstract

Glycosides are renewable building blocks ubiquitous in nature and widely explored in organic synthesis and medicinal chemistry. C-Glycosides exhibit in their structures an aglycone moiety or another glycoside linked through a C-C bond, which confers enzymatic and chemical resistance to hydrolysis. There are pharmaceutically relevant glycosides that exhibit a spirocyclic structure. Spiro compounds display interesting frameworks, and extensive studies have been made targeting the synthesis of these compounds. Among numerous accessible methods, the direct generation of spirocyclic structures with a quaternary center is unquestionably the most efficient and appealing method. Our goal is to develop a dual metallaphotoredox process to enable the preparation of new spirocyclic glucals. This process will be based on a carbonylative coupling and a C-H activation to achieve the spirocyclization. Currently, most of the available methods to perform carbonylative couplings and C-H activations are based on precious metal catalysis in conjunction with excess metal oxidants and thermal heating. We aim to study earth abundant metals, such as Ni and Co, to catalyze both carbonylative coupling and C-H activation steps. The exploitation of photocatalysts is a way to avoid the use of stoichiometric reagents and elevated temperatures. The most challenging aspect of this research will be to perform the process in a one-pot fashion.