Mechanistically driven development of iridium catalysts for asymmetric allylic substitution.
Mechanistically driven development of iridium catalysts for asymmetric allylic substitution.
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DOI：
10.1021/ar100047x
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发表时间：
2010-12-21
影响因子：
18.3
通讯作者：
Stanley, Levi M.
中科院分区：
文献类型：
--
作者：
Hartwig, John F.;Stanley, Levi M.
对映选择性烯丙基取代反应是制备对映体富集材料的最常用的方法之一。这些反应通过产生碳-氮、碳-氧、碳-碳和碳-硫键形成含有多个官能团的产物。多年来，烯丙基取代反应催化剂的研究主要集中在钯配合物上。然而，对其他金属络合物的研究揭示了通常补充钯体系的选择性。最引人注目的是观察到与不对称烯丙型亲电试剂的反应通常在烯丙型亲电试剂的阻碍较小的位点上与钯催化剂发生，而在基于其他金属的催化剂的阻碍较大的位点上发生。在这个帐户中，我们描述了一个铱前体和一个亚磷酰胺配体，催化反应与一个特别广泛的亲核试剂。该铱催化剂的活性形式不是通过亚磷酰胺配体与金属前体的简单结合产生的。相反，初始亚磷酰胺和铱前体在碱存在下反应以形成作为活性催化剂的金属环物质。该物质通过与添加的碱反应原位或单独以分离形式产生。活性催化剂结构的鉴定导致了简化催化剂的开发以及现在可用的催化剂的最活性形式，其通过松散结合的乙烯来稳定。最近，这种结构被用来制备含有烯丙基配体的中间体，其结构为这里讨论的对映选择性提供了模型。我们实验室对铱催化的烯丙基取代反应的初步研究表明，伯胺和仲胺，包括烷基胺，苄基胺和烯丙基胺的反应，以及酚盐和醇盐的反应以高产率发生，具有高的支化线性比和高的对映选择性。平行的机理研究揭示了活性催化剂的金属环结构，随后的实验有目的地形成金属配合物显着增加了反应范围。芳族胺、唑、氨和酰胺和氨基甲酸酯作为氨当量均以高选择性和产率反应。此外，弱碱性烯醇化物（如甲硅烷基烯醇醚）和烯醇化物等价物（如烯胺）也反应，并且其他研究小组已经使用这种催化剂在不存在另外的碱的情况下进行稳定的碳亲核试剂的反应。这种铱体系催化的反应的一个特点是总是高的对映选择性，这反映了形成烯丙基中间体的高立体选择性。对映选择性通常超过95%，形成支化产物与线性产物的区域选择性通常接近20：1，产率通常超过75%，通常大于90%。因此，铱催化剂的发展对映选择性烯丙基取代反应机理的研究可以导致一个特别活跃的和显着的一般系统的对映选择性的过程。在这种情况下，一个容易获得的催化剂的影响烯丙基取代，具有高的对映体选择性和区域选择性互补的古老的钯系统。
Enantioselective allylic substitution reactions comprise some of the most versatile methods for preparing enantiomerically enriched materials. These reactions form products that contain multiple functionalities by creating carbon–nitrogen, carbon–oxygen, carbon–carbon, and carbon–sulfur bonds. For many years, the development of catalysts for allylic substitution focused on palladium complexes. However, studies of complexes of other metals have revealed selectivities that often complement those of palladium systems. Most striking is the observation that reactions with unsymmetrical allylic electrophiles that typically occur with palladium catalysts at the less hindered site of an allylic electrophile occur at the more hindered site with catalysts based on other metals. In this Account, we describe an iridium precursor and a phosphoramidite ligand that catalyze reactions with a particularly broad scope of nucleophiles. The active form of this iridium catalyst is not generated by the simple binding of the phosphoramidite ligand to the metal precursor. Instead, the initial phosphoramidite and iridium precursor react in the presence of base to form a metallacyclic species that is the active catalyst. This species is generated either in situ or separately in isolated form by reactions with added base. The identification of the structure of the active catalyst led to the development of simplified catalysts as well as the most active form of the catalyst now available, which is stabilized by a loosely bound ethylene. Most recently, this structure was used to prepare intermediates containing allyl ligands, the structures of which provide a model for the enantioselectivities discussed here. Initial studies from our laboratory on the scope of iridium-catalyzed allylic substitution showed that reactions of primary and secondary amines, including alkylamines, benzylamines, and allylamines, and reactions of phenoxides and alkoxides occurred in high yields, with high branched-to-linear ratios and high enantioselectivities. Parallel mechanistic studies had revealed the metallacyclic structure of the active catalyst, and subsequent experiments with the purposefully formed metallacycle increased the reaction scope dramatically. Aromatic amines, azoles, ammonia, and amides and carbamates as ammonia equivalents all reacted with high selectivities and yields. Moreover, weakly basic enolates (such as silyl enol ethers) and enolate equivalents (such as enamines) also reacted, and other research groups have used this catalyst to conduct reactions of stabilized carbon nucleophiles in the absence of additional base. One hallmark of the reactions catalyzed by this iridium system is the invariably high enantioselectivity, which reflects a high stereoselectivity for formation of the allyl intermediate. Enantioselectivity typically exceeds 95%, regioselectivity for formation of branched over linear products is usually near 20:1, and yields generally exceed 75% and are often greater than 90%. Thus, the development of iridium catalysts for enantioselective allylic substitution shows how studies of reaction mechanism can lead to a particularly active and a remarkably general system for an enantioselective process. In this case, a readily accessible catalyst effects allylic substitution, with high enantioselectivity and regioselectivity complementary to that of the venerable palladium systems.
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