Synthesis of a library of 5,6-unsubstituted 1,4-dihydropyridines based on a one-pot 4CR/elimination process and their application to the generation of structurally diverse fused nitrogen heterocycles.
Synthesis of a library of 5,6-unsubstituted 1,4-dihydropyridines based on a one-pot 4CR/elimination process and their application to the generation of structurally diverse fused nitrogen heterocycles.
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DOI：
10.1021/cc100084b
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发表时间：
2010-07
影响因子：
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通讯作者：
S. Maiti;V. Sridharan;J. Menéndez
中科院分区：
文献类型：
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作者：
S. Maiti;V. Sridharan;J. Menéndez
三氯化铟是脂肪胺、β-酮酯、α，β-不饱和醛和乙醇之间连续四组分反应的有效催化剂，该反应生成6-乙氧基-1，4，5，6-四氢吡啶，在中性Al(2)O(3)存在下，通过乙醇消除原位转化为5，6-未取代的1，4-二氢吡啶，以非常有效的一锅法从易得的无环起始原料中生成两个C-Nσ键和一个C-Cπ键。由此产生的二氢吡啶文库的结构多样性通过其C-2位的碱基促进的γ-烷基化来扩展。通过Yb(OTf)(3)催化的亚氨基Diels-Alder(Povarov)反应，证明了这些1，4-二氢吡啶在合成分子多样性和复杂性方面的应用。这些反应非对映选择性地导致含有三个相邻立体中心的六氢苯并[h][1，6]-萘啶衍生物。采用四组分四氢吡啶合成/开环复分解/消除策略，合成了来自吡啶并[2，1-a]氮杂环己烷(高喹啉)骨架的稠合二氢吡啶。
Indium trichloride is an efficient catalyst for the sequential four-component reaction between aliphatic amines, β-ketoesters, α,β-unsaturated aldehydes, and ethanol to afford 6-ethoxy-1,4,5,6-tetrahydropyridines, which were converted in situ into 5,6-unsubstituted 1,4-dihydropyridines via ethanol elimination in the presence of neutral Al(2)O(3), in a very efficient, one-pot protocol from acyclic, readily available starting materials that involves the generation of two C-N σ and one C-C π bonds. The structural variety of the dihydropyridine library thus generated was extended by base-promoted γ-alkylation of their C-2 position. The application of these 1,4-dihydropyridines to the facile generation of molecular diversity and complexity was demonstrated by employing them as dienophiles for Yb(OTf)(3)-catalyzed imino Diels-Alder (Povarov) reactions leading diastereoselectively to hexahydrobenzo[h][1,6]-naphthyridine derivatives containing three adjacent stereocenters. The synthesis of fused dihydropyridines derived from the pyrido[2,1-a]azepine (homoquinolizine) frameworks was also achieved using a four-component tetrahydropyridine synthesis/ring-closing metathesis/elimination strategy.