Organokatalisi asimetrikoa: benzoazepinen sintesia

Abstract

[EU] Gradu Amaierako Lan hau Donostiako Kimika Fakultateko Kimika Organikoa I sailean garatu da, Mikel Oyarbide Garmendia irakaslearen eta Antonia Mielgo Vicente irakaslearen zuzendaritzapean. Proiektu honetan benzoazepinen sintesi enantioselektiboa bilatu da 2-aminobentzaldehido fenilhidrazonatik eta metil (E)-2-oxo-4-fenilbut-3-enoatoatik abiatuz, honetarako Brønsted base/hidrogeno lotura emaile motako katalisi bifuntzionala erabiliz. Lehenik bi lehengaiak prestatu dira deskribatutako metodoen egokitzapenak eginez, non hainbat zailtasun aurkitu diren. Ondoren, erreakzio katalitikoan zera aurkitu da; katalizatzaile basikoak eta Brønsted base/hidrogeno lotura emaile motako katalizatzaile bifuntzionalak ez direla gai erreakzioa abiarazteko, aldiz, Brønsted azido izaerako katalizatzaileak bai. Hala ere, azken hauekin ez da lortu aurrekarietan lortutako selektibotasun maila hobetzea. Azkenik, erreakzioaren beste aldaera bat aztertu da, non, α-zetoester β,γ-asegabea erreakzionarazi den orto-hidrazona fenol batekin. Kasu honetan, saiatu diren katalizatzaileetatik, bakarrik izaera azidoa edo bifuntzionala dutenek eman dute produkturen bat. Hala ere, lortutako produktu nagusiaren egitura zehatza ezin izan da oraingoz determinatu.

[EN] This research project has been developed in the Department of Organic Chemistry I at the Faculty of Chemistry in Donostia, under the guidance of professor Mikel Oyarbide Garmendia and professor Antonia Mielgo Vicente. In this project a new enantioselective synthesis of benzoazepines has been sought, starting from 2-aminobenzaldehyde phenylhydrazone and (E)-2-oxo-4-phenylbut-3-enoate, using Brønsted base/hydrogen bond donor type bifunctional catalyst. First, the two starting reactants have been prepared by using described methods and/or their variations, which we have found yet suboptimal. Then, in the catalytic reaction it has been found that Brønsted base catalysts and Brønsted base/hydrogen bond donor type bifunctional catalysts are incapable of promoting the reaction, while Brønsted acid catalysts are. Even though, none of these catalysts have been successful in improving the level of (enantio)selectivity achieved in previous work. Finally, another variant of the reaction has been examined, where the β,γ-unsaturated α-ketoester has been reacted to an ortho-hydrazone phenol counterpart. In this case, among the tested catalysts, only Brønsted acids or bifunctional catalysts have given some useful conversions. However, the exact structure of the main product obtained could not be determined so far.