Naslov
Dearomative two-component cascade for pyrrolo [3,4- b] indole preparation

Autori
Bašić, Ines ; Mikleušević, Ana ; Gredičak, Matija

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
28th Croatian Meeting of Chemists and Chemical Engineers and 6th Symposium Vladimir Prelog : Book of Abstracts / Rogošić, Marko - Zagreb : Hrvatsko društvo kemijskih inženjera i tehnologa (HDKI), 2023, 54-55

Skup
28th Croatian Meeting of Chemists and Chemical Engineers and and 6th Symposium Vladimir Prelog

Mjesto i datum
Rovinj, Hrvatska, 28.03.2023. - 31.03.2023

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
pyrrolo [3, 4-b] indoles ;
(pyrrolo [3, 4-b] indoles)

Sažetak
Polycyclic structure is convenient for developing multiple mechanism drugs as it can both serve as a moiety that may be added to improve the pharmacokinetic properties of drugs currently used in clinic trials, or drug candidates under development ; or as a scaffold for the basis of the drug. [1] Our research aims to develop catalytic dearomatization reactions as the economical approach for the synthesis of a range of polycyclic molecules with structural novelty. [2] Development of novel dearomatization reactions of aromatic compounds with highly reactive nucleophiles/electrophiles and the ability to suppress possible rearomatization of the products by creating new quaternary carbon centers is the general strategy of the project. In consideration of the recent significant breakthrough achieved independently by the groups of You [3] and Zhao [4] who used catalytic systems consisting of a cinchona-derived amino-phosphine and silver salts we considered metal free reactions. The aim of this work is the development of cascade dearomatization of indoles for the construction of pyrrolo [3, 4-b] indoles with three consecutive stereogenic centers. Our strategy is based on the interrupted formal Barton-Zard reaction (Figure 1). In a base catalyzed reaction, isocyanide 2 is deprotonated, and the Michael-type addition occurs at the C2 position of the indole derivative 1. The resultant indole anion intermediate 3 then undergoes diastereoselective 5-endo-dig cyclization onto the isocyanide. Optimal reaction conditions include indole derivative 1 (1.0 eq), isocyanide 2 (1.5 eq), Cs2CO3 (3 eq) as base, TBAB (10 mol%) as a phase-transfer catalyst in dicloroethane-water 1:1 at 60 °C. In general, the reaction is tolerant on a range of substituents on indoles and isocyanides, and products 4 are obtained in high yields. The asymmetric variant of this transformation is currently under way.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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