Diastereoselective Addition of Zincated Hydrazones to Alkenylboronates and Stereospecific Trapping of Boron/Zinc Bimetallic Intermediates by Carbon Electrophiles
Diastereoselective Addition of Zincated Hydrazones to Alkenylboronates and Stereospecific Trapping of Boron/Zinc Bimetallic Intermediates by Carbon Electrophiles
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DOI：
10.1021/ja806258v
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发表时间：
2008-11-19
影响因子：
15
通讯作者：
Nakamura, Eichi
中科院分区：
文献类型：
--
作者：
Hatakeyama, Takuji;Nakamura, Masaharu;Nakamura, Eichi
将在锌原子上具有叔丁基的锌化腙与（E）-或（Z）-烯基硼酸频哪醇酯加成以产生具有良好至优异的非对映选择性（ds）的α-烷基化-γ-硼基-γ-锌酰腙中间体。在腙基的γ位上具有硼原子和锌原子的1，1-有机双金属中间体与碳亲电试剂进一步进行C-C键形成，得到具有多个连续立体中心的γ-硼酰腙，其DS高达99%。（S）-1-氨基-2-甲氧基甲基吡咯烷腙在加成/捕获序列中显示出高水平的不对称诱导。对加成反应途径的密度泛函理论计算揭示了一种金属烯机制，该机制由锌化腙和乙烯基硼烷之间形成π络合物，然后由高度有序的船形构象过渡态的六中心键重组组成。计算表明，锌原子与亚胺或腙一起使用是羟醛缩合反应的烯烃变体成功的关键，该反应由于反应的吸热性而长期被认为不会发生，并且从未被化学家认真研究过。在高度有序的过渡结构中，由锌原子上的庞大叔丁基配体和乙烯基硼酸酯底物的频哪醇部分引起的空间排斥导致了本碳锌化反应中观察到的高ds。
Zincated hydrazones possessing a tert-butyl group on the zinc atom undergo addition to (E)- or (Z)-alkenylboronic acid pinacol esters to produce alpha-alkylated-gamma-boryl-gamma-zinciohydrazone intermediates with good to excellent diastereoselectivity (ds). The 1,1-organodimetallic intermediate possessing a boron atom and a zinc atom in the position gamma to the hydrazone group undergoes further C-C bond formation with a carbon electrophile to give a gamma-boryl hydrazone possessing several contiguous stereogenic centers with up to 99% ds. The (S)-1-amino-2-methoxymethylpyrrolidine hydrazone shows a high level of asymmetric induction in the addition/trapping sequence. Density functional theory calculations on the pathways of the addition reaction revealed a metallo-ene mechanism consisting of the formation of a pi complex between a zincated hydrazone and a vinylborane followed by a six-centered bond reorganization of a highly ordered boat conformation transition state. The calculations indicated that the use of the zinc atom together with the imine or hydrazone is the key for the success of the olefinic variant of the aldol reaction that has long been considered not to take place because of the endothermicity of the reaction and has never been examined with any seriousness by chemists. The steric repulsion caused by the bulky tert-butyl ligand on the zinc atom and the pinacol moiety of the vinylboronate substrates in the highly ordered transition structures gives rise to the observed high ds of the present carbozincation reaction.