Catalytic enantioselective conjugate reduction of β,β-disubstituted nitroalkenes
Catalytic enantioselective conjugate reduction of β,β-disubstituted nitroalkenes
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DOI：
10.1002/anie.200352175
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发表时间：
2003-01-01
影响因子：
16.6
通讯作者：
Carreira, EM
中科院分区：
文献类型：
--
作者：
Czekelius, C;Carreira, EM
光学活性的硝基烷烃是精细化学合成中多种有用的结构单元的通用前体。然而，只有少数几种有效的制备方法可用。[1-3]尽管近年来二烷基锌试剂对a，b-不饱和硝基烯烃的加成反应取得了一些进展，但涉及金属催化对映选择性还原B，b-二取代硝基烯烃的补充方法还未见报道。[2]在本文中，我们记载了这样一种方法，其中双膦-Cu络合物（与tolbinap或josiphos [4]）催化B，b-二取代的硝基烯烃的对映选择性还原，以有用的产率和选择性得到光学活性的B，b二取代的硝基烷烃[Eq.①]。[5]另外的机制和实际重要性是我们已经观察到的卤化物的抑制作用;因此，在它们不存在的情况下，还原可以用低至0.1摩尔%的络合物进行，使得该过程成为共轭加成化学的更有效的方法之一。我们以前曾报道过，从tol-binap和CuOtBu制备的复合物有效地催化添加二烯醇化物到醛涉及金属烯醇化物中间体。[6]衍生自tol-binap、CuCl和NaOtBu的相关复合物介导α，不饱和酯和酮的对映选择性还原。[7，8]作为我们正在进行的用于不对称合成的铜-膦络合物研究的一部分，我们已经在还原B，b-二取代硝基烯烃中测试了此类系统，其不仅易于制备（即，将N2 O 4加成到烯烃中并随后消除[1，9]），而且其还原在小分子催化中是前所未有的。[10]在我们对用PMHS还原（E）-1-硝基-2-苯基-1-丙烯（1）的初步研究中，我们采用了公开的制备CuCl、tol-binap和NaOtBu之间形成的催化剂的方法。在这些条件下，反应进行得相当缓慢：5摩尔%的催化剂在258 ℃下22小时后导致18%的转化率。此外，观察到1异构化为B，g-不饱和硝基烯烃（14%）。然后，我们研究了由tol-binap和CuOtBu制备的催化剂，我们最初制定了用于羟醛加成化学中的机理研究。在5摩尔%的该催化剂存在下，观察到在室温下在18小时内1完全转化为2（65%产率，80%ee）[Eq.②]。[11]有趣的是，在该阶段，还原似乎相当普遍，因为2-甲基-3-硝基-丙-2-烯-1-醇以58%产率和56%ee提供相应的硝基烷烃。[12]这些结果沿着随后的研究使我们得出了重要的结论，即NaCl的存在抑制了Cu-膦络合物的活性，这一前提得到了以下发现的支持：（例如LiCl，NEt 4Cl，KCN）我们随后研究了反应中硅烷组分的变化，以努力增加周转频率，更低的催化剂负载。[13]我们发现在反应中使用二苯基硅烷或苯基硅烷导致反应速率增加，当使用PMHS（0.1当量）和苯基硅烷（1.2当量）的组合时观察到最高的加速。然而，在这些条件下，分离出大量的2-苯基-丙炔醇去肟（38%）。[14]然而，向反应混合物中加入1.2当量的水导致完全抑制这种过度还原。[15]这些条件的一个重要结果是，在tol-binap和josiphos的存在下，催化剂负载量可以...
Optically active nitroalkanes are versatile precursors for a wide range of useful building blocks for fine-chemical synthesis. However, only a few effective methods for their preparation are available.[1–3] Despite recent advances in the addition of dialkyl zinc reagents to a, b-unsaturated nitroolefins, the complementary method involving metal-catalyzed enantioselective reduction of b, b-disubstituted nitroalkenes has not been reported.[2] Herein we document such an approach in which bisphosphane–Cu complexes (with tolbinap or josiphos [4]) catalyze the enantioselective reduction of b, b-disubstituted nitroalkenes, giving optically active b, bdisubstituted nitroalkanes in useful yields and selectivities [Eq.(1)].[5] Of additional mechanistic and practical importance is the observation we have made regarding the inhibitory effect of halides; thus, in their absence the reductions can be carried out with as little as 0.1 mol% of complex, rendering the process among one of the more efficient methods for conjugate addition chemistry. We had previously reported that a complex prepared from tol-binap and CuOtBu effectively catalyzes the addition of dienolates to aldehydes involving a metalloenolate intermediate.[6] A related complex derived from tol-binap, CuCl, and NaOtBu mediates the enantioselective reduction of a, bunsaturated esters and ketones.[7, 8] As part of our ongoing investigations of copper–phosphane complexes for asymmetric synthesis, we have tested such systems in the reduction of b, b-disubstituted nitroalkenes, which are not only easily prepared (ie, addition of N2O4 to alkenes and subsequent elimination [1, 9]) but also whose reductions are unprecedented in small-molecule catalysis.[10] In our initial investigations on the reduction of (E)-1-nitro-2-phenyl-1-propene (1) with PMHS, we employed the published procedure for the preparation of the catalyst formed between CuCl, tol-binap, and NaOtBu. Under these conditions, the reaction proceeded rather sluggishly: 5 mol% of catalyst led to 18% conversion after 22h at 258C. Additionally, isomerization of 1 to the b, g-unsaturated nitroalkene (14%) was observed. We then investigated the catalyst prepared from tol-binap and CuOtBu which we had originally formulated for mechanistic studies in aldol addition chemistry. In the presence of 5 mol% of this catalyst, full conversion of 1 into 2 (65% yield, 80% ee) within 18h at room temperature was observed [Eq.(2)].[11] Interestingly, at this stage the reduction appeared to be quite general as 2-methyl-3-nitro-prop-2-en-1-ol provided the corresponding nitroalkane in 58% yield and 56% ee.[12] These results along with subsequent investigations led us to the significant conclusion that the presence of NaCl inhibits the activity of the Cu–phosphane complex, a premise which is supported by the finding that the addition of various inorganic salts (eg LiCl, NEt4Cl, KCN) always leads to diminished reaction rates.We subsequently looked to variation of the silane component in the reaction in an effort to increase turnover frequency and lower catalyst loading.[13] We found that the use of diphenylsilane or phenylsilane in the reaction resulted in increased reaction rates, with the highest acceleration observed when a combination of PMHS (0.1 equiv) and phenylsilane (1.2 equiv) was employed. Nevertheless, under these conditions, substantial amounts of 2-phenyl-propionaldehydeoxime (38%) were isolated.[14] However, the addition of 1.2 equivalents of water to the reaction mixture resulted in complete suppression of this overreduction.[15] An important consequence of these conditions is the fact that in the presence of tol-binap and josiphos, the catalyst loadings can …