Enantioselective Heck reactions of endocyclic alkenes: use of attractive non-covalent interactions for the induction of diastereoselectivity

Author(s)

Ricardo Almir Angnes

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 2019-05-20

Examining board members

Carlos Roque Duarte Correia; Igor Dias Jurberg; Emilio Carlos de Lucca Júnior; Giuliano Cesar Clososki; Cristiano Raminelli

• Advisor: Carlos Roque Duarte Correia

Abstract

The palladium catalyzed arylation of alkenes is an efficient strategy for the construction of carbon-carbon bonds. The enantioselectivity in these reactions can usually be controlled by the use of a chiral bidentate ligand. Alternatively, one can control the diastereo or regioselectivity of such reactions by the judicious placing of a chelating group in the substrate that directs the reaction for the formation of a single isomer. In this work we employ simultaneously a chiral bidentate ligand to control the reaction enantioselectivity and a non-covalently binding directing group to induce diastereoselectivity, thus avoiding the need for pentacordinated Pd(II) species during the migratory insertion step. This strategy allowed for the direct access to highly functionalized products containing two or more defined stereocenters. The use of ionic promoters, cosolvents and the development of new ligands were strategies used for the optimization of reaction conditions. The scope and limitations of the reactions were evaluated and some of the structures synthesized were further derivatized to showcase their applicability. Mechanistic investigations were carried out through control experiments and theoretical calculations aiming at understanding the nature of the non-covalent interactions at play. The products had their relative and absolute stereochemistry attributed via chemical derivatization or monocrystal X-ray crystallography (AU)

• FAPESP's process: 13/25849-9 - Application of the enantioselective Heck-Matsuda reaction for substrate oriented regioselective desymmetrizations
• Grantee: Ricardo Almir Angnes
• Support Opportunities: Scholarships in Brazil - Doctorate