The indole core is ubiquitous in bioactive natural products and pharmaceutical compounds and the chemistry of the indole nucleus is the subject of intense investigations both for the synthesis of the indole core and the functionalization at both pyrrole and benzene moieties. One of the most employed building blocks is 2-vinylindole that pertains to the class of heterocyclic internal-external ring dienes, a useful class of molecules able to take part in cycloadditions with various dienophiles providing an easy access to poly(hetero)cycles. Another interesting compound, is 4H-furo[3,2-b]indoles presenting the peculiar structure of 4π-system embedded in the furan ring, leading to an increase of reactivity in comparison to 2-vinylindole congeners. Thus, potentially, 4H-furo[3,2-b]indoles could take part in different cycloaddition reactions as dienes when employed in [4+2] or (4+3) cyclizations or as dienophilic partners in [2+2] reactions with the C1-C2 double bond of the furan moiety. Furthermore, the C2 carbon of furan shows nucleophilic properties and can participate in simple functionalization reactions with different electrophiles. Moreover, as reported for simple furan derivatives, the addition of an electrophile at C2 can be followed by rearrangement processes that include a ring opening step. Thus the thesis is focused on the synthesis of different functionalized 4H-furo[3,2-b]indoles and on the study of their reactivity in the presence of different electrophilic partners. In detail, the obtained results belong to three main research topics: the first part was focused on the gold activation of different π systems for the synthesis of indole derivatives from 4H-furo[3,2-b]indoles. In particular, it reports the cationic gold(I) catalyzed cascade reactions of 4H-furo[3,2-b]indoles with allenamides for the synthesis of spiropseudo-indoxyls. Successively, the activation of propargyl esters by gold(I) catalysts led to the synthesis of 2-alkenylidene-3-oxoindoles in a process that included a furan ring rearrangement. The second part reports the behavior of 4H-furo[3,2-b]indoles in the presence of a different electrophile, a copper(I) carbene, obtained from the in situ decomposition of a diazo compound under copper catalysis. The reaction allowed for the formation of a homologous series of the previously cited 2-alkenylidene-3-oxoindoles presenting a less extended conjugate system. The last part is focused on the in situ generation of an oxyallyl cation in order to study the performance of 4H-furo[3,2-b]indoles in (4+3) cycloaddition reactions. In this case, the electrophile was obtained from a α-haloketone under basic condition and then reacted with both 2-vinylindoles and 4H-furo[3,2-b]. In addition, some preliminary results on the study of the reactivity of benzo[c]isoxazoles (anthranils) under basic condition for the synthesis of 2-hydrazineylisophthalaldehydes were conducted.
METAL-CATALYZED SYNTHESIS OF POLYCYCLIC INDOLES / E. Brambilla ; tutor: E. Rossi; coordinatore: G. Aldini. - Milano : Università degli studi di Milano. Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, 2021 Mar 12. ((33. ciclo, Anno Accademico 2020.
|Titolo:||METAL-CATALYZED SYNTHESIS OF POLYCYCLIC INDOLES|
|Supervisori e coordinatori interni:||ALDINI, GIANCARLO|
|Data di pubblicazione:||12-mar-2021|
|Parole Chiave:||indole; cyclizzation; catalysis|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
|Citazione:||METAL-CATALYZED SYNTHESIS OF POLYCYCLIC INDOLES / E. Brambilla ; tutor: E. Rossi; coordinatore: G. Aldini. - Milano : Università degli studi di Milano. Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, 2021 Mar 12. ((33. ciclo, Anno Accademico 2020.|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.13130/brambilla-elisa_phd2021-03-12|
|Appare nelle tipologie:||Tesi di dottorato|