Total synthesis of (-)goniotrionin: theoretical studies of stereoelectronic influence in the 1,5 selectivity of aldol reaction involving beta-alkoxy methylketones

Author(s)

Marco Antonio Barbosa Ferreira

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 2012-07-27

Examining board members

Gilson Rogério Zeni; Jose Daniel Figueroa Villar; Carlos Roque Duarte Correia; Cláudio Francisco Tormena

• Advisor: Luiz Carlos Dias

Abstract

TOTAL SYNTHESIS OF (-)-GONIOTRIONIN: We have accomplished the first total synthesis of the reported structure of goniotrionin (11) in 4% overall yield over a longest-linear sequence of 17 steps from glycidol (R)-109. Our synthetic route employed an epoxide-opening strategy, using chiral epoxides as building blocks. Key steps included a Mukaiyama aerobic oxidative cyclization and a 1,2-syn selective Mukaiyama aldol reaction. This synthesis employs highly flexible key couplings that allow for the preparation of analogs, including other diastereoisomers of goniotrionin (11). THEORETICAL STUDY OF THE STEREOELECTRONIC INFLUENCE IN 1,5 SELECTIVITY OF ALDOL REACTIONS INVOLVING b-ALKOXY METHYLKETONES: In the second part of this work was extended the knowledge about the origin of 1,5 selectivity in aldol reactions involving boron enolates of b-alkoxy methyl ketones, based on the calculation of electronic structures of the corresponding transition states. We investigated the influence of stereocenters at the a, b, y and s positions in aldol reactions, determining the key factors that govern the 1,5 induction. Additionally, we propose a theoretical model that racionalize the 1,5 selectivity depending on the stereoelectronic characteristics of b-bulky ketones (AU)

• FAPESP's process: 08/04432-4 - Total synthesis of goniotrionine and biological evaluation of promising candidates to treat cancer disease
• Grantee: Marco Antonio Barbosa Ferreira
• Support Opportunities: Scholarships in Brazil - Doctorate