Highly Regio- and Enantioselective Copper-Catalyzed Hydroboration of Styrenes
Highly Regio- and Enantioselective Copper-Catalyzed Hydroboration of Styrenes
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DOI：
10.1002/anie.200902015
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发表时间：
2009-01-01
影响因子：
16.6
通讯作者：
Yun, Jaesook
中科院分区：
文献类型：
--
作者：
Noh, Dongwan;Chea, Heesung;Yun, Jaesook
过渡金属催化的烯烃硼氢化反应[1]因其独特的区域选择性和对映选择性而引起人们的广泛兴趣。特别是，苯乙烯衍生物的不对称硼氢化反应得到非外消旋的α-硼基化产物是一种有用的反应，因为所得的C3-B键可以在保持构型的情况下转化为C3-N、C3-O或C3-C键。[1b虽然许多催化体系，包括钌，[3a]镍，[3b]钐，[3c]和镧[3d]催化剂，已用于转化，高度区域和对映选择性硼氢化的发展仍然是一个挑战;到目前为止，只有铑配合物和儿茶酚硼烷（CatBH）在低温下的组合显示出所需的高区域和对映选择性。[4，5]考虑到儿茶酚硼烷和所得硼基化产物的不稳定性，有必要开发有效的区域选择性催化体系，其与更稳定（但反应性较低）的硼氢化试剂相容，与二取代烯烃反应，并且可以通过使用非外消旋配体容易地呈现对映选择性。本文中，我们报道了螯合膦配体与铜（I）配合物催化苯乙烯与频哪醇硼烷（PinBH）的区域选择性和对映选择性硼氢化反应，得到相应的α-硼酸化产物。在室温至408 ℃之间，在铜的手性配体存在下，反应以优于99：1的位点选择性和高对映体选择性进行。该过程还涉及在苄基碳原子处的第一个立体选择性铜到硼的金属转移。在我们研究基于添加氢化铜[6]和硼基铜试剂[7]的新的对映选择性催化过程的开发过程中，我们对如何利用在将铜物质添加到缺电子烯烃上时形成的Cu 2C键产生了兴趣，而不是通过简单的醇质子化来破坏键。[6，7]由于有人提出在频哪醇硼烷存在下原位生成氢化铜，[8]我们对与铜形成新的硼氢化循环的可能性感兴趣。虽然不存在Cu 2 O3 C（sp3）和PinBH之间的复分解的先例，并且已知Cu 2 O3 C和PinBH B之间的类似复分解反应是困难的[9]，但我们设想与适当配体配位的氢化铜（I）将经历区域选择性加成到苯乙烯，并促进所得Cu 2 O3 C键[11]与频哪醇硼烷的有效金属转移[10]，在探索了各种催化反应条件之后，[13]我们发现苯乙烯与频哪醇硼烷（1.2当量）在催化剂CuCl/KOtBu/dppbz（5摩尔%）存在下在甲苯中在室温下缓慢反应，在48小时内转化率达到96%。在60 ° C下的相同反应在7小时内达到完成，得到具有高区域选择性的所需异构体2 [Eq.①]。该反应是第一个高区域选择性的铜催化苯乙烯硼氢化反应。[14]苯乙烯在CuOH键上的区域选择性插入可以解释这种高的区域选择性; CuOH σ分子轨道和烯烃的π* 轨道（LUMO）之间的相互作用可能在插入步骤中起重要作用。苯基取代基通过使π电子密度从碳原子移动而使亚甲基碳原子更亲电（LUMO中亚甲基碳的轨道贡献更大）[15]，并将H2O加成指向亚甲基碳原子。
Transition-metal-catalyzed hydroboration reactions of alkenes [1] have attracted much interest, as they provide opportunities for unique regio-and enantioselectivity. In particular, the asymmetric hydroboration of styrene derivatives to afford nonracemic α-borylated products is a useful reaction, since the resulting CÀB bond can be transformed with retention of configuration into a CÀN, CÀO, or CÀC bond.[1b, 2] Although many catalytic systems, including ruthenium,[3a] nickel,[3b] samarium,[3c] and lanthanum [3d] catalysts, have been employed for the transformation, the development of a highly regio-and enantioselective hydroboration still remains as a challenge; so far, only combinations of rhodium complexes and catecholborane (CatBH) at low temperatures have shown the desirable high regio-and enantioselectivity.[4, 5] Given the instability of catecholborane and the resulting borylated product, it is necessary to develop efficient regioselective catalytic systems that are compatible with more stable (but less reactive) hydroboration reagents, react with disubstituted olefins, and can readily be rendered enantioselective by the use of nonracemic ligands. Herein, we report that copper (I) complexes coordinated with chelating phosphine ligands can catalyze the regio-and enantioselective hydroboration of styrenes with pinacolborane (PinBH) to afford the corresponding α-borated products. Reactions proceed with better than 99: 1 site selectivity and with high enantioselectivity in the presence of chiral ligands for copper between room temperature and 408C. This process also involves the first stereoselective copper-to-boron transmetalation at a benzylic carbon atom. During our studies on the development of new enantioselective catalytic processes based on the addition of copper hydride [6] and copper boryl reagents,[7] we became interested in how we could make use of the CuÀC bond that formed upon the addition of the copper species to electron-deficient alkenes, instead of destroying the bond by simple protonation with an alcohol.[6, 7] Since the in situ generation of copper hydride in the presence of pinacolborane has been suggested,[8] we were intrigued by the possibility of forming a new hydroboration cycle with copper. Although no precedent example of metathesis between CuÀC (sp3) and PinBH exists, and it is known that a similar metathesis reaction between CuÀC and BÀB is difficult,[9] we envisioned that a copper (I) hydride coordinated with an appropriate ligand would undergo regioselective addition to styrene and facilitate an efficient transmetalation [10] of the resulting CuÀC bond [11] with pinacolborane, rather than β-hydride elimination,[12] to afford the desired branched boronate ester (Scheme 1).After exploring a variety of catalytic reaction conditions,[13] we found that styrene reacted slowly with pinacolborane (1.2 equiv) in the presence of the catalyst CuCl/KOtBu/dppbz (5 mol%) in toluene at room temperature to 96% conversion in 48 h. The same reaction at 608C reached completion within 7 h to give the desired isomer 2 with high regioselectivity [Eq.(1)]. This reaction is the first highly regioselective copper-catalyzed hydroboration of styrene.[14] The observed high regioselectivity could be explained by the regioselective insertion of styrene into the CuÀH bond; the interaction of CuÀH σ molecular orbital and the π* orbital (LUMO) of the alkene is possibly important in the insertion step. The phenyl substituent makes the methylene carbon atom more electrophilic by shifttng π-electron density from the carbon atom (greater orbital contribution of the methylene carbon in the LUMO)[15] and directs the addition of HÀ toward the methylene …