NHC-Cu-Catalyzed Enantioselective Hydroboration of Acyclic and Exocyclic 1,1-Disubstituted Aryl Alkenes
NHC-Cu-Catalyzed Enantioselective Hydroboration of Acyclic and Exocyclic 1,1-Disubstituted Aryl Alkenes
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DOI：
10.1002/anie.201102398
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发表时间：
2011-01-01
影响因子：
16.6
通讯作者：
Hoveyda, Amir H.
中科院分区：
文献类型：
--
作者：
Corberan, Rosa;Mszar, Nicholas W.;Hoveyda, Amir H.
我们最近发现，1, 2-二取代芳基烯烃的硼氢化可以通过手性铜基二齿 N-杂环卡宾 (NHC)[1] 络合物催化。[2, 3] 反应仅产生均苄型 CÀB 键，[4] 这与烷基硼烷的转化或由更昂贵的 Rh 或 Ir 基络合物催化的转化相反，其中形成优先选择苄基 CÀB 键。[3]我们后来证明，NHCÀCu 催化的转化可以与 β-乙烯基硼酸酯有效地进行，以提供具有完全位点选择性的无环邻位二硼酸酯（< 2% 双子）。 [5]上述方案是对映选择性的，以 86:14–99:1 对映体比率 (er) 在仲碳原子处提供硼取代的立体中心。尽管取得了这些进展，并且其他研究小组也报告了开创性的发现，[3]但仍然存在一些缺陷。一个长期存在的问题涉及 1, 1-二取代烯烃的催化对映选择性硼氢化反应。[6]已经概述了在 1, 1-二取代烯烃反应中使用化学计量数量的手性硼烷；[7] 然而，只有当烯烃取代基之间存在显着的尺寸差异时，才能观察到高对映选择性 (er> 90: 10)。使用儿茶酚硼烷的 Rh 和 Ir 催化过程通常对 1, 1-二取代烯烃具有较低的对映选择性，并且在某些情况下，位点选择性的控制存在问题。 [8]最近，发现频哪醇硼烷的 I催化过程可提供完全的位点选择性，呃！两种 α 甲基苯乙烯衍生物为 90: 10（er= 66: 34–96: 4 的总体范围）。[9]在此，我们提出了一种 NHC-Cu 催化方法，用于 1, 1-二取代芳基烯烃的位点和对映选择性催化硼氢化（方案 1）；[10] 形成 α-烷基-β-频哪醇硼烷，位点选择性 > 98%，产率高达 > 98%，er= 96.5: 3.5。已经开发出涉及一系列无环1, 1-二取代芳基烯烃的反应，包括含有除通常使用的甲基单元之外的烷基取代基的那些。还包括环外烯烃的转化，据我们所知，此前尚未有报道。在考虑催化 1, 1-二取代烯烃硼氢化反应的机理时（方案 1），我们推测转化可能是由 [(NHC) Cu {B-(pin)}][11] i [由双 (频那醇) 二硼 (1) 与 NHC-Cu-醇盐反应形成] 引发的。随后添加 CuÀB 将得到 β-烷基硼烷 ii，其中包含季 Cu 取代的立体中心。 Cu-C 键的质子化，[12] 可能在构型保留的情况下发生，[4] 可以提供所需的产物并再生 iii，它与 1 反应形成 i。催化过程的一个不常见的特征是，最终的立体化学结果不仅仅取决于 CuÀB 加成的对映选择性：对映体富集的烷基铜与醇添加剂 (MeOH) 的分子间质子化的立体化学也至关重要。 [13]此外，含铜中间体可用于获取烷基硼烷以外的实体；[14]这与更传统的金属催化硼氢化方法相反，[3]其中C-B键是通过烷基-金属-硼还原消除形成的。在后一种情况下，将描述催化方法在合成多功能 2-取代烯丙基硼酸酯方面的应用。我们首先检查从对映体纯咪唑啉鎓盐 2-8 获得的 NHCÀCu 络合物（表 1）促进 α-甲基苯乙烯（9a；À158C，thf ...
We recently discovered that hydroboration of 1, 2-disubstituted aryl olefins can be catalyzed by chiral Cu-based bidentate N-heterocyclic carbene (NHC)[1] complexes.[2, 3] Reactions proceed to deliver homobenzylic CÀB bonds exclusively,[4] which is in contrast to transformations with alkylboranes or those catalyzed by the more costly Rh-or Irbased complexes, where formation of benzylic CÀB bonds is preferred.[3] We later showed that the NHCÀCu-catalyzed transformations proceed efficiently with β-vinylboronates to afford acyclic vicinal diboronates with complete site selectivity (< 2% geminal).[5] The above protocols are enantioselective, delivering boron-substituted stereogenic centers at secondary carbon atoms in 86: 14–99: 1 enantiomeric ratio (er). Despite such advances, as well as seminal findings reported by other research groups,[3] several shortcomings persist. One long-standing problem relates to catalytic enantioselective hydroborations of 1, 1-disubstituted alkenes.[6] The use of stoichiometric quantities of chiral boranes in reactions of 1, 1-disubstituted alkenes has been outlined;[7] however, high enantioselectivity (er> 90: 10) is only observed when there is a significant size difference between the olefin substituents. Rh-and Ir-catalyzed processes with catecholborane typically furnish low enantioselectivity with 1, 1-disubstituted alkenes and, in some cases, control of site selectivity is problematic.[8] Recently, an Ircatalyzed process with pinacolatoborane was found to afford complete site selectivity and er! 90: 10 in the case of two αmethylstyrene derivatives (overall range of er= 66: 34–96: 4).[9] Herein, we present an NHCÀCu-catalyzed process for the site-and enantioselective catalytic hydroboration of 1, 1-disubstituted aryl olefins (Scheme 1);[10] α-alkyl-β-pinacolatoboranes are formed with> 98% site selectivity, in up to> 98% yield and er= 96.5: 3.5. Reactions involving a range of acyclic 1, 1-disubstituted aryl olefins, including those that contain alkyl substituents other than the typically utilized methyl unit, have been developed. Also included are transformations of exocyclic alkenes, which, to the best of our knowledge, have not been previously reported. In considering the mechanism of catalytic 1, 1-disubstituted alkene hydroborations (Scheme 1), we surmised that transformations would likely be initiated by [(NHC) Cu {B-(pin)}][11] i [formed from reaction of bis (pinacolato) diboron (1) with an NHC-Cu-alkoxide]. Subsequent CuÀB addition would afford β-alkylborane ii, which contains a quaternary Cu-substituted stereogenic center. Protonation of the CuÀC bond,[12] likely occurring with retention of configuration,[4] can deliver the desired product and regenerate iii, which reacts with 1 to form i. An uncommon feature of the catalytic processes is that the eventual stereochemical outcome does not depend only on the enantioselectivity of the CuÀB addition: the stereochemistry of the intermolecular protonation of the enantiomerically enriched alkylcopper species with the alcohol additive (MeOH) is crucial as well.[13] Furthermore, the copper-containing intermediates might be utilized to access entities other than alkylboranes;[14] this is in contrast to the more traditional approach to metal-catalyzed hydroboration,[3] where the CÀB bond is formed through an alkyl-metal–boron reductive elimination. Within this latter context, application of the catalytic method towards the synthesis of versatile 2-substituted allylboronates will be described.We began by examining the ability of NHCÀCu complexes obtained from enantiomerically pure imidazolinium salts 2–8 (Table 1) to promote the enantioselective hydroboration of α-methylstyrene (9a; À158C, thf …