JOC_MS pyrrole_rev_220118.pdf (1.09 MB)
Copper-promoted regioselective synthesis of polysubstituted pyrroles from aldehydes, amines and nitroalkenes via1,2-phenyl/alkyl migration
journal contribution
posted on 2023-06-09, 11:43 authored by Dimitrios Andreou, Michael G Kallitsakis, Edouardos Loukopoulos, Catherine Gabriel, George KostakisGeorge Kostakis, Ioannis N LykakisThe facile Copper-catalyzed synthesis of polysubstituted pyrroles from aldehydes, amines and ß-nitroalkenesis reported. Remarkably, the use of a-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 a-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 a-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.
History
Publication status
- Published
File Version
- Accepted version
Journal
Journal of Organic ChemistryISSN
0022-3263Publisher
American Chemical SocietyExternal DOI
Issue
4Volume
83Page range
2104-2113Department affiliated with
- Chemistry Publications
Research groups affiliated with
- Centre for Byzantine Cultural History Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2018-01-22First Open Access (FOA) Date
2019-01-22First Compliant Deposit (FCD) Date
2018-01-22Usage metrics
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