Heck-Matsuda arylation in trisubstituted olefins: methodological study and application in meso-hexestrol synthesis

Author(s)

Carlise Frota

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 2018-03-14

Examining board members

Carlos Roque Duarte Correia; Mauricio Moraes Victor; Kleber Thiago de Oliveira; Anita Jocelyne Marsaioli; Cátia Ornelas

• Advisor: Carlos Roque Duarte Correia

Abstract

The present work had as general objective the methodological study of the Heck-Matsuda reaction in trisubstituted olefins and its synthetic application. In the first chapter, a new methodology for the Heck-Matsuda arylation catalyzed by palladium was developed, employing trisubstituted alkenols with free hydroxyls or protected with silicon groups. The developed methodology used mild conditions and provided 'alpha',ß-disubstituted methyl ketones with moderate to high yields. The reaction was shown to be regioselective, providing only one arylation product, and highly diastereoselective, forming only the anti isomer. The new redox-relay arylation reaction for silyl ethers demonstrated that the presence of the free hydroxyl is not a unique condition for this process to occur. In addition, the synthetic potential of the method was demonstrated with a total synthesis of the meso-hexestrol in 4 steps and good yield. In the second chapter, efforts were made for the development of a enantioselective version of the Heck-Matsuda reaction employing trisubstituted alkenols. From the obtained results, the synthesis of seven new bidentate N',N' ligands with a phenyl group at the chiral portion was schematized. Compared with the ligands tested in other works, only one of the synthesized ligands gave a more satisfactory induction of chirality to the system. The 'alpha',ß-disubstituted methyl ketones were obtained in good to moderate yields and moderate enantiomeric ratios (AU)

• FAPESP's process: 13/10639-9 - Studies on the intermolecular enantioselective Heck-Matsuda reaction of complex acyclic olefins and synthetic applications.
• Grantee: Carlise Frota
• Support Opportunities: Scholarships in Brazil - Doctorate