Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles
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Tarih
2023
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Beilstein-Institut
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
We 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 alpha,13-unsaturated acyl chlorides to afford substituted alpha-methylene-gamma-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 alpha,13-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 alpha-methylene-gamma-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 alpha-methylene-gamma-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 13-silicon stabilization, the alkene geometry of the alpha,13-unsaturated acyl chloride reactants, and adventitious water on the success of the catalytic aza-Nazarov reaction.
Açıklama
Anahtar Kelimeler
?-methylene-?-lactam, aza-Nazarov reaction, ?-silicon effect, heterocycles, intramolecular cyclization
Kaynak
Beilstein Journal of Organic Chemistry
WoS Q Değeri
Q2
Scopus Q Değeri
Q2
Cilt
19
