A General Route to beta-Substituted Pyrroles by Transition-Metal Catalysis
2016 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 81, no 4, 1450-1460 p.Article in journal (Refereed) PublishedText
An atom-efficient route to pyrroles substituted in the beta-position has been achieved in four high yielding steps by a combination of Pd, Ru, and Fe catalysis with only water and ethene as side-products. The reaction is general and gives pyrroles substituted in the beta-position with linear and branched alkyl, benzyl, or aryl groups in overall good yields. The synthetic route includes a Pd-catalyzed monoallylation step of amines with substituted allylic alcohols that proceeds to yield the monoallylated products in moderate to excellent yields. In a second step, unsymmetrical diallylated aromatic amines are generated from the reaction of a second allylic alcohol with high selectivity in moderate to good yields by control of the reaction temperature. Ru-catalyzed ring-closing metathesis performed on the diallylated aromatic amines yields the pyrrolines substituted in the beta-position in excellent yields. By addition of ferric chloride to the reaction mixture, a selective aromatization to yield the corresponding pyrroles substituted in the beta-position was achieved. A reaction mechanism involving a palladium hydride, generated from insertion of palladium to O-H of an allyl alcohol, that is responsible for the C-O bond cleavage to generate the pi-allyl intermediate is proposed.
Place, publisher, year, edition, pages
2016. Vol. 81, no 4, 1450-1460 p.
IdentifiersURN: urn:nbn:se:uu:diva-282318DOI: 10.1021/acs.joc.5b02581ISI: 000370768000013PubMedID: 26789020OAI: oai:DiVA.org:uu-282318DiVA: diva2:916840
FunderSwedish Research Council FormasStiftelsen Olle Engkvist Byggmästare