High enantioselectivity is induced by a single monodentate phosphoramidite ligand in iridium-catalyzed asymmetric hydrogenation
High enantioselectivity is induced by a single monodentate phosphoramidite ligand in iridium-catalyzed asymmetric hydrogenation
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DOI：
10.1002/anie.200603930
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
de Vries, Johannes G.
中科院分区：
文献类型：
--
作者：
Giacomina, Francesca;Meetsma, Auke;de Vries, Johannes G.
双齿手性配体在金属催化的不对称氢化中是超过30年的规则[1]，因为螯合被认为是必要的，以赋予金属络合物必要的刚性，从而有效地转移手性。然而，最近，一些研究小组已经证明，单齿配体也可以诱导高的对映体选择性[2]，只要这些配体中的两个存在于活性物质中。在此，我们描述了由仅含有一个单齿配体的金属催化剂诱导的高度不对称氢化的第一个实例。[3]铱是加氢反应中的一种重要金属。Crabtree催化剂，[4]其对映选择性版本，由Pfaltz开发，基于手性P，N配体，[5]或著名的异丙甲草胺工艺催化剂[6]是基于Ir的氢化催化剂的主要实例（方案1）。我们感兴趣的是研究手性单齿亚磷酰胺铱配合物是否也可以作为有效的对映选择性氢化催化剂。虽然这种Ir配合物已经被报道[7]，这导致了新的环化物种的发现，这些物种在烯丙基取代中具有活性[8]，但没有报道它们在对映选择性氢化中的用途。我们最初的研究旨在制备阳离子铱络合物，其是含有亚磷酰胺配体L和与第二配体L 0相同的亚磷酰胺、膦或吡啶的Crabtree催化剂的类似物（方案1）。根据文献先例，[9]两当量的Monophos用[{Ir（cod）Cl} 2]处理，立即得到[Ir（cod）（L）Cl][7 b]，在另一当量的L存在下，氯化物提取后，应形成[Ir（cod）LLо]+类型的阳离子络合物。虽然我们筛选了几种亚磷酰胺与不同的辅助配体和抗衡阴离子的组合，但我们没有获得有效的氢化催化剂。该突破来自于以下观察结果：使用基于Binol的大体积亚磷酰胺获得活性但也具有对映选择性的催化剂，所述亚磷酰胺在3，3 〇位置具有取代基，而不提取氯化物配体，即，从每个金属仅含有一个亚磷酰胺配体的非阳离子催化剂前体[Ir（cod）（L）Cl]获得。[10]通过比较（Z）-2-乙酰氨基肉桂酸甲酯氢化过程中获得的氢吸收曲线，可以观察到配体二醇主链3，3 ′位取代的剧烈影响（图1）。图1清楚地表明，增加3、3 0位手性骨架的体积不仅导致活性的显著增加，而且导致对映体选择性的显著增加（对于R1= H、Me、Ph和R2= tBu，平均TOF分别为6、24、50和150 hF-1，ee值分别为28、67、93和98%;也参见方案1）。出于实际原因，即二醇前体是可商购的，具有tBu取代基的最大配体基于联苯酚，而其它配体基于联萘。[12]然而，通过改变亚磷酰胺的氨基结构来增加亚磷酰胺的体积并没有产生同样的效果，当二甲氨基被以未取代的联萘为骨架的双（α-甲基苄基）氨基取代时，配合物的催化性能仍然很差。这间接地加强了我们的假设，即在3，3о位置上的取代所起的主要作用。
Bidentate chiral ligands were the rule in metal-catalyzed asymmetric hydrogenation for more than 30years [1] as chelation was believed to be necessary to impart the necessary rigidity to the metal complex for an efficient transfer of chirality. Recently, however, a few groups have demonstrated that monodentate ligands can also induce high enantioselectivity [2] as long as two of these ligands are present in the active species. Herein, we describe the first example of a highly asymmetric hydrogenation that is induced by a metal catalyst containing only one monodentate ligand.[3] Iridium is an important metal in hydrogenation. The Crabtree catalyst,[4] its enantioselective version, developed by Pfaltz, based on chiral P, N ligands,[5] or the celebrated Metolachlor process catalyst [6] are prime examples of Irbased hydrogenation catalysts (Scheme 1). We were interested in investigating whether iridium complexes of chiral monodentate phosphoramidites could also act as efficient enantioselective hydrogenation catalysts. Although such Ir complexes have already been reported,[7] which has led to the discovery of new cyclometalated species that are active in allylic substitution,[8] there are no reports of their use in enantioselective hydrogenation. Our initial studies were aimed at the preparation of cationic iridium complexes that are analogues of the Crabtree catalyst containing a phosphoramidite ligand L, and either the same phosphoramidite, a phosphine, or pyridine as the secondary ligand Lо (Scheme 1). Based on literature precedents,[9] two equivalents of Monophos were treated with [{Ir (cod) Cl} 2] to immediately give [Ir (cod)(L) Cl][7b] which, upon chloride abstraction in the presence of another equivalent of L, should form a cationic complex of the type [Ir (cod) LLо]+. Although we screened several phosphoramidites in combination with different ancillary ligands and counteranions, we did not obtain an efficient hydrogenation catalyst. The breakthrough came with the observation that an active but also enantioselective catalyst is obtained with bulky phosphoramidites based on Binol with substituents in the 3, 3о positions without abstraction of the chloride ligand, that is, from the non-cationic catalyst precursor [Ir (cod)(L) Cl] containing only one phosphoramidite ligand per metal.[10] The drastic effect of the substitution in the 3, 3о positions of the diol backbone of the ligand can be visualized by comparing the hydrogen uptake curves obtained during the hydrogenation of methyl(Z)-2-acetamidocinnamate (Figure 1). Figure 1 clearly shows that increasing the bulkiness of the chiral backbone in the 3, 3о positions leads to a substantial increase not only in activity but also in enantioselectivity (average TOFs of 6, 24, 50, and 150 hÀ1 and ee values of 28, 67, 93, and 98% for R1= H, Me, Ph, and R2= tBu, respectively; see also Scheme 1). For practical reasons, namely that the diol precursor is commercially available, the bulkiest ligand with the tBu substituents is based on biphenol while the other ligands are based on binaphthol.[12] Increasing the bulkiness of the phosphoramidite by changing its amino moiety does not, however, produce the same effect, and the catalytic performance of the complex remained poor when the dimethylamino group was substituted by a bis (α-methylbenzyl) amino group with unsubstituted binaphthol as backbone. This indirectly reinforces our assumption about the major role played by substitution in the 3, 3о positions of the