Synthetic application of Morita-Baylis-Hillman reaction: 1. Studies towards a new approach for the syntesis of the alkaloid (+ or -)-8-alfa-ethoxyprecriwelline. 2. Studies toward the asymmetric synthesis of indolizidinic alkaloids. 3. Probing the mechanism of formation of Troger's bases by ESI-(MS/MS)

Author(s)

Carlos Alberto Miranda Abella

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 2009-11-30

Examining board members

Fernando Antonio Santos Coelho; Hans Viertler; Antonio Euzebio Goulart Sant'Ana; José Augusto Rosário Rodrigues; Lucia Helena Brito Baptistella

• Advisor: Fernando Antonio Santos Coelho

Abstract

Chapter 1 describes the intermediates obtained towards the total synthesis of (±)-8-a-ethoxyprecriwelline. An intermediate with all required functionalities was obtained in order to achieve the target. Methylamine addition on silylated Morita-Baylis-Hillman adduct obtained from bromopiperonal gave mostly the syn diastereoisomer which was rationalized by the use of theoretical calculations. By means of changing the original synthetic proposal, it was possible to introduce a necessary secondary alcohol through an ozonolysis reaction followed by chemoselective reduction. Since there was no evidence of this kind of reaction on olefin of Morita-Baylis-Hillman adducts with aromatic ring in the literature, some test were done with adducts having different electronic requirements on the aromatic ring, and most were successfully obtained. Chapter 2 shows the application of a methodology developed in our research group envisaging the synthesis of indolizidinic alkaloids from polyfunctionalized bicyclic lactams. The latter were obtained in its racemic and chiral form. The chiral aldehyde synthesized didn' t racemize in the conditions used in the synthesis of Morita-Baylis-Hillman adduct, which was obtained as the anti as the major diastereomer. Both diastereomers were separated and the major one was cyclized to produce the bicyclic lactam. The first part of chapter 3 tells the tentative of use of Tröger' s bases as catalyst in the reaction of Morita-Baylis-Hillman, which didn' t prove useful. In the second part of the same chapter, the mechanism of formation of Tröger' s bases was studied by ESI-MS using formaldehyde as well as urotropine as the source of methylene. Key intermediates were characterized by ESI-MS/MS and it was found that the mechanism involves a sequence of electrophilic aromatic substitution reaction (AU)