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DOI: 10.1055/s-2008-1042743
Polycyclic Lactams via Cu(II)-Mediated Intramolecular Alkene Carboamination
Contributor(s):Victor Snieckus, Johnathan BoardUniversity at Buffalo, The State University of New York, USA
Copper(II) Carboxylate-Promoted Intramolecular Carboamination of Alkenes for the Synthesis of Polycyclic Lactams
Org. Lett. 2007, 9: 5477-5480
Publication History
Publication Date:
21 February 2008 (online)
Key words
lactams - amides - carboamination - copper
Significance
Reported is a copper-promoted synthesis of polycyclic lactams from readily prepared amides containing a terminal double bond. A series of indolizidines and pyrrolizidines are obtained by tuning the starting material and reaction conditions. In cases for which 6-endo- or 5-exo- reaction pathways exist, higher temperatures were shown to favor 5-exo products. A reaction mechanism is proposed involving syn aminocupration and C-Cu bond homolysis to give the lactam with a methylene radical tether (e.g. structure A above), which then undergoes cyclization to form the polycyclic structure. This mechanism is analogous to that previously reported for the formation of sultams (S. Chemler and co-workersJ. Org. Chem. 2007, 72, 3896).
Comment
This methodology is an extension of previous work by the authors into the carboamination of sulfonamides to form sultams. A modest catalyst screen was performed and copper salts, which are more soluble in organic media, were found to be better suited for the reaction. The range of analogues investigated is modest, reflecting the early stage of development of the methodology. However, due to the considerable scope in heterocyclic ring formation and the simple starting materials, this methodology has high potential for synthetic applications.