Synthesis of 4- and 5-aryl prolines via Heck-Matsuda reaction and their use as organocatalysts in aldol reaction and multicomponent Mannich

Author(s)

Marla Narciso Godoi

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 0000-00-00

Examining board members

Carlos Roque Duarte Correia; Aloir Antonio Merlo; Silvio do Desterro Cunha; Paulo Cesar Muniz de Lacerda Miranda; Fernando Antonio Santos Coelho

• Advisor: Carlos Roque Duarte Correia

Abstract

This work aimed at the development of efficient routes for the synthesis of aryl prolines with the Heck-Matsuda reaction as key step. The potential of these arylated amino acids as organocatalysts was evaluated through aldol and multicomponent Mannich reactions. In the first chapter results will be presented concerning the synthesis of 5-aryl prolines. The stereoselective preparation of these compounds employed the Heck-Matsuda reaction as key step and involved an enecarbamate derived from piroglutamic acid. The organocatalytic behavior of these amino acids was evaluated and one noted that its performance was inferior to that of L-proline. Due to this observation, derivatives of prolines arylated in C-4 were synthesized and tested as organocatalysts. The second chapter begins with studies on the performance of the C-4- arylated aryl kainoid xx as organocatalyst. This amino acid was initially tested in aldol reactions and presented an organocatalytic performance slightly superior to that of L-proline itself. Hence, 4-arylprolines were synthesized, exploring the Heck-Matsuda reaction with L-dehydroprolines as olefins, and their potential as organocatalysts was also investigated. In this moment of the work, a methodologic study concerning the preparation of monoarylated enecarbamates was performed. Employ of microwaves-based heating on the arylation reactions allowed significant reduction of reaction times. From a stereoselective methanol elimination from 4-arylated 2-methoxy-prolines, employing silane hydrides and BF3.Et2O, one could obtain cis-4-aryl-prolines in only three steps. (AU)