A highly effective phosphoramidite ligand for asymmetric allylic substitution
A highly effective phosphoramidite ligand for asymmetric allylic substitution
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DOI：
10.1002/anie.200353744
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发表时间：
2004-01-01
影响因子：
16.6
通讯作者：
Alexakis, A
中科院分区：
文献类型：
--
作者：
Tissot-Croset, K;Polet, D;Alexakis, A
与其他金属（例如Pd， Mo和Ir）相比，[2]铜允许使用更硬的亲核试剂，例如烷基。人们对铜中心与手性配体[3]配合的催化体系越来越感兴趣，例如与格氏[4]和有机锌试剂[5]配合本课题组的研究重点是开发用格氏试剂取代烯丙基氯化物的高效配体。在此之前，我们发现从四芳基- 1,3 -二氧唑烷- 4,5 -二甲醇（taddol）衍生的磷配体是与肉桂酰氯反应的高效手性试剂（g/a= 94/ 6,73% ee）。[4d]我们的第二代磷酸酰胺配体在此基础上得到了改进，ee值达到79%。它们还允许更广泛的适用范围。[4e]本文中，我们报道了新的磷酰胺配体，用于相同的应用，也与我们之前描述的一锅钌催化的复分解过程兼容。[4e]在大多数情况下，这些第三代配体的ee值高达96%，可用于ir催化的烯丙基取代。以双酚1a[6]和双萘酚基配体2a和3a[7]（见方案1）为起始化合物，在双酚（或双萘酚）或氨基官能团上进行结构修饰，制备相应的配体。配体1b-3b （Scheme1）在苯基环[8]上含有一个胺基和邻甲氧基取代基，极大地提高了产物的区域选择性和对映选择性。先前，[4e]我们表明，1a给出的ee值为79%，区域选择性为91:9，有利于将5a添加到4a的g产物（表1，条目1）。以双萘酚为基础的配体2a诱导了类似的对映体选择性，尽管区域选择性较差（条目2）。与配体3a的反应不具有区域选择性，但没有反转6的绝对构型（条目3）。在这种情况下，我们可以假设配体中的胺官能团决定了产物的绝对构型。这与这些配体在共轭加成中的行为相反与1a相比，修饰的配体1b具有更高的区域选择性（98/2）和相似的对映体选择性（条目4）。还制备了两种含双萘酚单位的非对映体2b和3b，以评价固定atropoisomerism的效果。
In contrast to other metals (Pd, Mo, and Ir, for example),[2] copper allows harder nucleophiles, such as alkyl groups, to be used. Increasing interest is being shown in catalytic systems where the copper center is coordinated to a chiral ligand,[3] such as with Grignard [4] and organozinc reagents.[5] The research in our group has focused on the development of efficient ligands for the substitution of allylic chlorides by Grignard reagents. Previously, we showed that phosphorus ligands derived from tetraaryl-1, 3-dioxolane-4, 5-dimethanol (taddol) were highly effective chiral reagents in the reaction with cinnamyl chloride (g/a= 94/6, 73% ee).[4d] Our second-generation phosphoramidite ligands improved on this result, with an ee value of 79% being observed. They also allowed a wider scope of applicability.[4e] Herein, we report new phosphoramidite ligands for the same application that are also compatible with our previously described one-pot Ru-catalyzed metathesis procedure.[4e] These third-generation ligands give ee values of up to 96% in most cases and can be applied to Ir-catalyzed allylic substitution. The biphenol 1a [6] and binaphthol-based ligands 2a and 3a [7](see Scheme 1) were used as the starting compounds, and related ligands were prepared by structural modifications, either at the biphenol (or binaphthol) or the amino functionality. Ligands 1b–3b (Scheme1) which contain an amine group as well as ortho-methoxy substituents on the phenyl rings [8] provided greatly improved results both in the regioselectivity and the enantioselectivity of the products. Previously,[4e] we showed that 1a gave an ee value of 79% and a regioselectivity of 91: 9 in favor of the g product resulting from the addition of 5a to 4a (Table 1, entry 1). The binaphtholbased ligand 2a induced a similar enantioselectivity although the regioselectivity was poorer (entry 2). The reaction with ligand 3a was not as regioselective, but did not invert the absolute configuration of 6 (entry 3). For this case we could hypothesize that the amine functionality in the ligand dictates the absolute configuration of the product. This is in contrast to the behavior of these ligands in conjugate addition.[6] The modified ligand 1b, in comparison with 1a, gave an increased regioselectivity (98/2) and a similar enantioselectivity (entry 4). Two diastereomeric ligands 2b and 3b containing binaphthol units were also prepared to evaluate the effect of a fixed atropoisomerism.