One-pot synthesis of (hetero) chalcones via C-H functionalization: a transition metal-free methodology

• Grant number: 22/00600-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2022
• End date: February 28, 2023
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Giuliano Cesar Clososki
• Grantee: Isabela Wada Ferreira Pinto
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Chalcones are organic molecules commonly found in the molecular structure of natural and synthetic products of high added value, including clinically approved drugs, being considered privileged units in medicinal chemistry for presenting a wide spectrum of biological properties. These aspects make the development of synthetic methodologies relevant for the preparation of this class of compounds. In this sense, the literature has several synthetic protocols for the preparation of chalcones and their derivatives. Synthesis of chalcones mediated by transition metals, phosphines, and organocatalysts as well as various classical methods of preparation of chalcones are the means most frequently used to obtain this class of compounds. Although these methodologies generally provide (hetero)chalcones with high synthetic viability, they have as a prerequisite the use of functionalized starting materials. This limitation makes the development of synthetic alternatives for the preparation of (hetero)chalcones from non-functionalized materials attractive, with greater structural simplicity, thus eliminating the need for additional synthetic steps for the preparation of specific reagents or even the use of structurally starting materials. more complex. In this context, C-H-type chemical bond functionalizations have been used strategically to obtain chalcones recently. However, these methodologies are limited by the use of transition metals such as palladium, rhodium, and silver, in addition to the use of additives, phosphines, or halogenated solvents. Given this fact, our research group showed interest in the development of a new synthetic methodology that is more environmentally friendly, aiming at the preparation of chalcones and heterochalcones through functionalization of C-H type chemical bond in the absence of transition metals. For this, directed metallation reactions will be used as a starting point in the preparation of aldehydes in situ, from non-functionalized arenes and heteroarenes, through the reaction between a (hetero)arene and a formulating agent. After this step, the simple addition of an aryl ketone will be carried out in order to obtain the desired product after the aldol condensation step.(AU)