Asymmetric synthesis of heterocycles via nucleopaladation reactions: Development, rational design of chiral ligands and mechanistic studies

• Grant number: 17/13306-1
• Support Opportunities: Scholarships abroad - Research
• Start date: February 01, 2018
• End date: January 31, 2019
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Marco Antonio Barbosa Ferreira
• Grantee: Marco Antonio Barbosa Ferreira
• Host Investigator: Matthew S Sigman
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Institution abroad: University of Utah (U), United States

Abstract

The main objective of this project is the application of stereoselective oxo-palladation reactions aiming the synthesis of heterocycles of biological interest, where the formation of the sigma-Pd (II) intermediate should be used in subsequently variations. To do so, two approaches will be applied. The first focuses on the synthesis of ”2-isoxazolinic, which, despite a high occurrence, few methodologies point to its stereoselective synthesis involving the C-O bond. Thus, the general objective of the first part of the work will be the developement of enantioselective methodologies involving the intermediate Wacker sigma, aiming at a synthesis of this compounds from oximes. Considering the great potential of methodological application of Heck reactions, in the second part of this project we envisage a stereoselective Wacker / "Heck-type" tandem conditions for a formal C(sp3)-C(sp3) coupling employing alkenols. For this purpose, a Redox-Relay strategy, which has precedents only for sp2 and sp carbons, will be employed.For all the successfully developed reactions, we intend to study from the mechanistic point of view the processes that govern its stereochemistry. We will employ computational techniques, where each proposed reactive intermediate and its transition states will be calculated. In addition, traditional organic physics-chemistry tools (kinetic velocity laws, KIE, etc.) will bring us evidence of limiting steps. We will also employ the approach involving multidimensional predictive models developed by Prof. Sigman for rationalization and development of ligands in metal catalysis.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SILVA, JORDAN DE JESUS; FERREIRA, MARCO A. B.; FEDOROV, ALEXEY; SIGMAN, MATTHEW S.; COPERET, CHRISTOPHE. Molecular-level insight in supported olefin metathesis catalysts by combining surface organometallic chemistry, high throughput experimentation, and data analysis. CHEMICAL SCIENCE, v. 11, n. 26, p. 6717-6723, JUL 14 2020. (17/13306-1, 14/50249-8, 15/08541-6)

FERREIRA, MARCO A. B.; SILVA, JORDAN DE JESUS; GROSSLIGHT, SAMANTHA; FEDOROV, ALEXEY; SIGMAN, MATTHEW S.; COPERET, CHRISTOPHE. Noncovalent Interactions Drive the Efficiency of Molybdenum Imido Alkylidene Catalysts for Olefin Metathesis. Journal of the American Chemical Society, v. 141, n. 27, p. 10788-10800, JUL 10 2019. (17/13306-1, 15/08541-6, 14/50249-8)