Copper-promoted regioselective synthesis of polysubstituted pyrroles from aldehydes, amines and nitroalkenes via1,2-phenyl/alkyl migration

Andreou, Dimitrios, Kallitsakis, Michael G, Loukopoulos, Edward, Gabriel, Catherine, Kostakis, George E and Lykakis, Ioannis N (2018) Copper-promoted regioselective synthesis of polysubstituted pyrroles from aldehydes, amines and nitroalkenes via1,2-phenyl/alkyl migration. Journal of Organic Chemistry. ISSN 0022-3263 (Accepted)

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Abstract

The facile Copper-catalyzed synthesis of polysubstituted pyrroles from aldehydes, amines and β-nitroalkenesis reported. Remarkably, the use of α-methyl substituted aldehydes provide efficient access to a series of tetra- and pentasubstituted pyrroles via an overwhelming 1,2-phenyl/alkyl migration. The present methodology is also accessible to non α-substituted aldehydes yielding the corresponding trisubstituted pyrroles. On the contrary, the use of ketones, in place of aldehydes, does not promote the organic transformation signifying the necessity of α-substituted aldehydes. The reaction proceeds under mild catalytic conditions with low catalyst loading (0.3 – 1 mol %), a broad scope, very good functional-group tolerance, high yields and can be easily scaled up to more than 3 mmol of product, thus highlighting a useful synthetic application of the present catalytic protocol. Based on formal kinetic studies, a possible radical pathway is proposed that involves the formation of an allylic nitrogen radical intermediate, which in turn reacts with the nitroalkene to yield the desired pyrrole framework via a radical 1,2-phenyl or alkyl migration.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
Research Centres and Groups: Centre for Byzantine Cultural History
Subjects: Q Science > QD Chemistry > QD0146 Inorganic chemistry
Depositing User: Georgios Kostakis
Date Deposited: 22 Jan 2018 17:18
Last Modified: 22 Jan 2018 17:18
URI: http://sro.sussex.ac.uk/id/eprint/73055

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