The Regio- and Stereoselective Synthesis of trans-2,3-Dihydropyridine N-oxides and Piperidines
The Regio- and Stereoselective Synthesis of trans-2,3-Dihydropyridine N-oxides and Piperidines
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DOI：
10.1002/anie.200900189
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发表时间：
2009-01-01
影响因子：
16.6
通讯作者：
Almqvist, Fredrik
中科院分区：
文献类型：
--
作者：
Andersson, Hans;Gustafsson, Magnits;Almqvist, Fredrik
一般已报道将格氏试剂加成到吡啶N-氧化物上以低收率得到开环的二烯醛肟[Eq.①]。[1]因此，吡啶N-氧化物不被认为是合成取代的哌啶的合适的结构单元。[2]在我们利用廉价易得的吡啶N-氧化物的冒险中，我们最近报道了用于合成取代吡啶的二烯醛肟的形成。[3]然而，由于多取代哌啶是突出的生物活性分子和它们的立体选择性合成仍然是一个挑战，我们的主要重点是针对这类化合物。[4]尽管已经进行了使用各种吡啶盐和亲核试剂而不阻断不期望的亲电位点（例如，4-位）的广泛研究，但是这些反应通常导致区域异构体混合物的形成。为了实现完全的区域选择性，使用N-亚氨基吡啶叶立德来规避吡啶N-氧化物的开环反应。[2]此外，这些反应有一个局限性，即，建立一个以上的立体中心的时间，特别是在立体选择性合成邻位反式异构体需要多步合成。[五]《中国日报》
The addition of Grignard reagents to pyridine N-oxides has in general been reported to give ring-opened dienal oximes in low yields [Eq.(1)].[1] As a consequence, pyridine N-oxides have not been considered as suitable building blocks for the synthesis of substituted piperidines.[2] In our venture to utilize inexpensive and readily available pyridine N-oxides, we recently reported the formation of dienal oximes for the synthesis of substituted pyridines.[3] However, since multisubstituted piperidines are prominent in bioactive molecules and their stereoselective synthesis remains a challenge, our main focus was directed toward this class of compounds.[4] Although extensive research using a variety of pyridinium salts and nucelophiles without blocking undesired electrophilic sites (eg, the 4-position) have been performed, these reactions generally result in the formation of regioisomeric mixtures. To achieve complete regioselectivity, N-iminopyridinium ylides were used to circumvent the ring-opened reactions of pyridine N-oxides.[2] Moreover, these reactions have a limitation; that is, establishing more than one stereogenic center at the time, especially in the stereoselective synthesis of vicinal trans isomers demands a multistep synthesis.[5]