Riber D, Hazell R, Skrydstrup T
Department of Chemistry, University of Aarhus, Denmark.
J Org Chem. 2000 Aug 25;65(17):5382-90. doi: 10.1021/jo000538n.
The efficiency of the samarium(II) iodide induced pinacol-type coupling for the construction of seven-membered cyclic amino alcohols has been investigated. With the acyclic carbonylhydrazones 6 and 16, good yields of the hexahydroazepines 22 and 23 were obtained (56-57%) with high trans-selectivity (= 10:1), which compares well with similar reactions generating the corresponding five- and six-membered carbocycles (Fallis, A. G.; Sturino, C. F. J. Am. Chem. Soc. 1994, 116, 7447). It is essential for ring formation that the strongly electron-donating ligand, hexamethylphosphoramide, be present, as in its absense intermolecular pinacol coupling forming the diols 27-30 is the dominant reaction. Hence, the role for HMPA appears not only to increase the rate of electron transfer but also to modulate rate constants for the subsequent reactions (cyclization and pinacol coupling) of the intermediate ketyl. This ring forming reaction has been applied to the construction of the fully functionalized hexahydroazepine ring of the PKC inhibitor, balanol. Initial attempts to develop an asymmetric version of this reaction indicate the use of chiral ligands based on the structure of HMPA.
对碘化钐（II）诱导的用于构建七元环氨基醇的频哪醇型偶联反应的效率进行了研究。使用无环羰基腙6和16，以高反式选择性（=10:1）获得了良好产率（56 - 57%）的六氢氮杂卓22和23，这与生成相应五元及六元碳环的类似反应相比效果良好（法利斯，A.G.；斯图里诺，C.F.《美国化学会志》1994年，116卷，7447页）。对于环化反应来说，强供电子配体六甲基磷酰胺的存在至关重要，因为在其不存在时，形成二醇27 - 30的分子间频哪醇偶联反应是主要反应。因此，六甲基磷酰胺的作用似乎不仅在于提高电子转移速率，还在于调节中间体酮基后续反应（环化和频哪醇偶联）的速率常数。这种环化反应已应用于构建蛋白激酶C抑制剂巴拉诺尔的全功能化六氢氮杂卓环。对该反应不对称版本的初步开发尝试表明可使用基于六甲基磷酰胺结构的手性配体。
