Intermolecular Heck reactions with non-activated olefins. Substrate-directed processes and enantioselective formation of tertiary and quaternary stereocenters using nitrogen-containing ligands

Author(s)

Caio Costa Oliveira

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 2015-07-08

Examining board members

Carlos Roque Duarte Correia; Antonio Carlos Bender Burtoloso; Cristiano Raminelli; Ronaldo Aloise Pilli; Igor Dias Jurberg

• Advisor: Carlos Roque Duarte Correia

Abstract

Non-activated olefins are challenging substrates for the Heck reaction due the frequent isomerization of products and starting materials by Pd (II) complexes. However, owing to its synthetic potential, new efficient methods to circunvent these issues are highly desirable. In this scenario, in this Doctoral Thesis are presented synthetic efforts to implement the Heck-Matsuda reaction as an efficient and reliable alternative for the regio- and stereoselective arylation of cyclic and acyclic non-activated olefins. The first part of the results consists in the arylation of allylated-malonates and its synthetic applications. In this process, called "Substrate-directed Heck-Matsuda reaction" the observed regio-, chemo- and stereoselectivity were attributed to the chellation of cationic Pd (II) species to carbonyls groups present in the starting material. Moreover, a somewhat similar strategy was developed for the arylation of substituted cyclopentenes with high levels of facial differentiation. This method was applied in the synthesis of the immunosuppressive VPC01091 in 5 steps. Finally, efforts for the development of the first enantioselective Heck-Matsuda reaction is discussed by means of cyclic olefins desymmetization. Additionally, the improvement of this method, as well as, synthesis of new chiral ligands allowed its use to build tertiary and quaternary stereocenters from acyclic olefins in excellent levels of enantioselection. The synthetic potential of this transformation was demonstrated by the total synthesis of the calcium channel blocker (R)-verapamil (AU)

• FAPESP's process: 11/01162-9 - A methodological and mechanistic study of the Heck-Matsuda reaction controlled by the substrate and synthetic applications.
• Grantee: Caio Costa Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate