Synthesis of quaternary carbon stereogenic centers through enantioselective Cu-catalyzed allylic substitutions with vinylaluminum reagents.
Synthesis of quaternary carbon stereogenic centers through enantioselective Cu-catalyzed allylic substitutions with vinylaluminum reagents.
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DOI：
10.1021/ja106829k
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发表时间：
2010-10-13
影响因子：
15
通讯作者：
Hoveyda AH
中科院分区：
文献类型：
--
作者：
Gao F;McGrath KP;Lee Y;Hoveyda AH
公开了催化对映选择性烯丙基取代(EAS)反应，其涉及使用烷基或芳基取代的乙烯基铝试剂并提供在其C-3位点含有季碳立构中心的1,4-二烯。 0.5-2.5 mol% 的磺酸盐手性二齿 N-杂环卡宾 (NHC) 络合物促进 C-C 键形成转化，有效提供所需产物（分离产物产率 66-97%），并具有高位点（>98% SN2'）和对映选择性 [高达 99:1 对映体比率 (er)]。据我们所知，本报告首次提出了烯丙基取代反应的案例，该反应通过添加乙烯基单元而产生全碳四元立体中心。芳基和乙烯基取代的乙烯基铝试剂不能通过与氢化二异丁基铝直接反应高效制备，而是通过最近引入的相应末端炔烃与相同廉价金属氢化物试剂的镍催化反应来获得。连续的Ni催化的加氢金属化和Cu催化的C-C键形成反应允许高效且选择性地合成一系列对映体富集的EAS产物，这是通过先前公开的策略无法获得的（由于低效的乙烯基金属合成或与Si取代的衍生物的低反应性和/或选择性）。通过天然产物补骨脂酚的简明对映选择性合成证明了所开发方案的实用性。
Catalytic enantioselective allylic substitution (EAS) reactions, which involve the use of alkyl- or aryl-substituted vinylaluminum reagents and afford 1,4-dienes containing a quaternary carbon stereogenic center at their C-3 site, are disclosed. The C–C bond forming transformations are promoted by 0.5–2.5 mol % of sulfonate bearing chiral bidentate N-heterocyclic carbene (NHC) complexes, furnishing the desired products efficiently (66–97% yield of isolated products) and in high site- (>98% SN2′) and enantioselectivity [up to 99:1 enantiomer ratio (er)]. To the best of our knowledge, the present report puts forward the first cases of allylic substitution reactions that result in the generation of all-carbon quaternary stereogenic centers through the addition of a vinyl unit. The aryl- and vinyl-substituted vinylaluminum reagents, which cannot be prepared in high efficiency through direct reaction with diisobutylaluminum hydride, are accessed through a recently introduced Ni-catalyzed reaction of the corresponding terminal alkynes with the same inexpensive metal-hydride agent. Sequential Ni-catalyzed hydrometallations and Cu-catalyzed C–C bond forming reactions allow for efficient and selective synthesis of a range of enantiomerically enriched EAS products, which cannot cannot be accessed by previously disclosed strategies (due to inefficient vinylmetal synthesis or low reactivity and/or selectivity with Si-substituted derivatives). The utility of the protocols developed is demonstrated through a concise enantioselective synthesis of natural product bakuchiol.
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影响因子：
5.2
作者：
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通讯作者：
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通讯作者：
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通讯作者：
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