Modular Synthesis of Bicyclic and Tricyclic (Aza‐) Arenes from Nucleophilic (Aza‐)Arenes with Electrophilic Side Arms via [4+2] Annulation Reactions

Abstract

An efficient strategy for the synthesis of bicyclic and tricyclic (aza-)arenes from a nucleophilic (aza-)arene with an electrophilic side arm was developed. The (aza-)arene precursor has both nucleophilic and electrophilic sites, which were fixed at a 1,4-distance. The bicyclic and tricyclic (aza-)arene products were constructed via [4 + 2] annulation by using scandium(III) triflate as a catalyst and enolizable ketones or aldehydes as the counterpart reagents. A variety of six-membered carbocycles and heterocycles, such as indolizines, indoles, naphthalenes, carbazoles, and pyrido[1,2-α] indoles, were successfully synthesized. Some onepot sequential reactions were also developed, in which the 1,4-donor-acceptor precursors can be synthesized via oxidation of alcohols or a proper condensation reaction. Scheme 8. Synthesis of an indolizine derivative from 4 a and a 1,3-dicarbonyl compound. Scheme 9. Synthesis of indolizine 3 a h from an iminodiacetaldehyde bis(diethyl acetal), 4 b, and 2 a.UPDATES asc.wiley-vch.de

Synthesis of indoles and carbazoles from a lignin model compound α-hydroxyacetophenone

“…The reaction, if established, can offer a new way to access some functionalized indole derivatives. 23 Out of these considerations, we then investigated a three-component reaction of 1a, 2a and a 1,3-dicarbonyl compound. Gratifyingly, the combination of glycerol solvent and Sc(OTf ) 3 catalyst was proven to be effective for the this type of three-component reac- tions (see the ESI Table S2 and Fig.…”

“…1). 14 Out of all these considerations, in this study, pyrrole and indole were used as the arene-based counterpart nucleophiles of the α-hydroxyacetophenone derivative. Indeed, this endeavor enabled us to develop some hitherto unreported α-hydroxyacetophenone participated reactions, including pyrrole-to-indole and indole-to-carbazole transformations.…”

Synthetic Strategies for the Construction of Indolizines and Indolizine‐fused Compounds: Thienoindolizines and Indolizinoindoles

“…Annulation of substituted pyrroles 1 catalyzed by scandium triflate via a [4 + 2] reaction with 1,3-dicarbonyl derivatives 2 allowed to obtain substituted indolizines 3 a-r in moderate to high yields (Scheme 1). [11] To expand this approach, the authors developed a method for the formation of the indolizine ring from non-aromatic derivatives. Here, substituted pyrroles were generated in situ by the reaction of 2,2-diethoxyethylamine 4 with two molecules of a 1,3-dicarbonyl compound 5 in the presence of a catalytic amount of AlCl 3 in 1,4-dioxane.…”

“…Annulation of substituted pyrroles 1 catalyzed by scandium triflate via a [4+2] reaction with 1,3‐dicarbonyl derivatives 2 allowed to obtain substituted indolizines 3 a‐r in moderate to high yields (Scheme 1). [11] …”