Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

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buir.contributor.authorYağcı, Bilge Banu
buir.contributor.authorDönmez, Selin Özge
buir.contributor.authorTürkmen, Yunus Emre
buir.contributor.orcidYağcı, Bilge Banu|0000-0002-4641-6023
buir.contributor.orcidDönmez, Selin Özge|0000-0002-1377-2689
buir.contributor.orcidTürkmen, Yunus Emre|0000-0002-9797-2820
dc.citation.epage77en_US
dc.citation.spage66
dc.citation.volumeNumber19
dc.contributor.authorYağcı, Bilge Banu
dc.contributor.authorDönmez, Selin Özge
dc.contributor.authorŞahin, O.
dc.contributor.authorTürkmen, Yunus Emre
dc.date.accessioned2024-03-08T11:36:25Z
dc.date.available2024-03-08T11:36:25Z
dc.date.issued2023-07-17
dc.departmentDepartment of Chemistry
dc.departmentInstitute of Materials Science and Nanotechnology (UNAM)
dc.description.abstractWe have developed a catalytic aza-Nazarov reaction of N-acyliminium salts generated in situ from the reaction of a variety of cyclic and acyclic imines with α,β-unsaturated acyl chlorides to afford substituted α-methylene-γ-lactam heterocycles. The reactions proceed effectively in the presence of catalytic (20 mol %) amounts of AgOTf as an anion exchange agent or hydrogen-bond donors such as squaramides and thioureas as anion-binding organocatalysts. The aza-Nazarov cyclization of 3,4-dihydroisoquinolines with α,β-unsaturated acyl chlorides gives tricyclic lactam products 7 in up to 79% yield with full diastereocontrol (dr = >99:1). The use of acyclic imines in a similar catalytic aza-Nazarov reaction with 20 mol % of AgOTf results in the formation of α-methylene-γ-lactam heterocycles 19 in up to 76% yield and with good to high diastereoselectivities (4.3:1 to 16:1). We have demonstrated the scalability of the reaction with a gram-scale example. The relative stereochemistry of the α-methylene-γ-lactam products 19 has been determined via the single-crystal X-ray analysis of lactam 19l. In order to shed light on the details of the reaction mechanism, we have performed carefully designed mechanistic studies which consist of experiments on the effect of β-silicon stabilization, the alkene geometry of the α,β-unsaturated acyl chloride reactants, and adventitious water on the success of the catalytic aza-Nazarov reaction.
dc.identifier.doi10.3762/bjoc.19.6
dc.identifier.eissn1860-5397
dc.identifier.urihttps://hdl.handle.net/11693/114412
dc.language.isoEnglish
dc.publisherBeilstein-Institut Zur Forderung der Chemischen Wissenschaften
dc.relation.isversionofhttps://dx.doi.org/10.3762/bjoc.19.6
dc.source.titleBeilstein Journal of Organic Chemistry
dc.subjectα-methylene-γ-lactam
dc.subjectaza-Nazarov reaction
dc.subjectβ-silicon effect
dc.subjectHeterocycles
dc.subjectIntramolecular cyclization
dc.titleCatalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles
dc.typeArticle

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Department of Chemistry
Institute of Materials Science and Nanotechnology (UNAM)