Iron-Based Olefin Metathesis Catalysts

描述(申请人提供)：治疗学的准备在很大程度上依赖于化学家构建各种有机分子的能力。由于许多药物含有复杂的碳骨架，选择性地偶联两个碳部分的工艺是至关重要的。最有效和最有选择性的碳-碳键形成方法之一是Ru催化的烯烃歧化反应。由于铁的价格低廉且毒性低，设计铁基烯烃歧化催化剂将是一项重大的技术进步。制备这类催化剂需要合成迄今未知的低配位亚铁。作为起点，将制备式为CI_2(L)Fe=C(H)R的中性铁(11)亚烷，其中L是环氨基卡宾配体。与典型的低自旋的Ru亚烷基化合物不同，铁的络合物Ci_2(L)Fe=C(H)R可能以高自旋态存在。由于过渡金属中心的所有d轨道上至少存在一个电子，高自旋的Cl2(L)Fe=C(H)R络合物可能会阻止烯烃的配位，从而延缓复分解反应的活性。这一潜在问题的解决方案是合成XCI(L)Fe=C(H)R和X2(L)Fe=C(H)R配合物，其中X是CN-或C6F5-基团。这些较强的场配体取代了CI_2(L)Fe=C(H)R的CI-基团，增加了体系中的配位场分裂参数，从而促进了更有利于烯烃配位的低自旋态。为底物结合提供可获得的配位位置的另一种方法是通过氯抽提使Cl2(L)Fe=C(H)R络合物阳离子。生成的XCi(L)Fe=C(H)R和X2(L)Fe=C(H)R，其中X是极不配位的反离子，如B(C6F5)4-或HBC11Cl11-，应在溶液中解离，形成形式上的12和10电子铁单并分别得到CI(L)Fe=C(H)R+和(L)Fe=C(H)R2+。另一种方法是制备中性铁(O)亚烷基化合物。可能显示歧化活性的理想铁(0)物种是(R3P)LFe=(H)R。这类配合物应该能够解离溶液中的膦配体，提供至少有两个空位配位的LFe=(H)R碎片，而与金属的自旋状态无关。这项研究计划的最终目标是为合成界提供廉价、环境友好、高活性和选择性的烯烃歧化催化剂。与公共健康的相关性拟议的研究计划打算使用铁化合物来提供方法，使药物能够以更环保和更具成本效益的方式生产。因此，这项工作最终可能提供清洁的方法来生产更便宜的药物。

DESCRIPTION (provided by applicant): The preparation of therapeutics relies largely on the ability of chemists to construct a wide range of organic molecules. Since many pharmaceuticals contain a sophisticated carbon skeleton, processes that selectively couple two carbon moieties are of paramount importance. One of the most efficient and selective carbon-carbon bond forming methods is the ruthenium-catalyzed olefin metathesis reaction. Since iron is inexpensive and has a low toxicity, a significant technological advance would be to design iron-based olefin metathesis catalysts. Preparing such catalysts will require the synthesis of hitherto unknown low-coordinate iron alkylidenes. As a starting point, neutral iron(ll) alkylidenes of the formula CI2(L)Fe=C(H)R, where L is a cyclic amino carbene ligand, will be prepared. In contrast to ruthenium alkylidenes that are typically low-spin, iron complexes CI2(L)Fe=C(H)R may exist in a high-spin state. Due to the presence of at least one electron in all of the d-orbitals of the transition metal center, high-spin CI2(L)Fe=C(H)R complexes may resist olefin coordination, consequently retarding metathesis activity. A solution to this potential problem would be to synthesize XCI(L)Fe=C(H)R and X2(L)Fe=C(H)R complexes, where X is a CN- or C6F5- group. Replacement of the CI- groups of CI2(L)Fe=C(H)R by these stronger field ligands will increase the ligand field splitting parameter in the system, which should promote a lower-spin state more favorable for olefin coordination. Another approach to providing accessible coordination sites for substrate binding would be to render CI2(L)Fe=C(H)R complexes cationic by chloride abstraction. The resultant XCI(L)Fe=C(H)R and X2(L)Fe=C(H)R, where X is an extremely non-coordinating counterion such as B(C6F5)4- or HBC11Cl11-, should dissociate in solution to form the formally 12 and 10 electron iron mono and dications CI(L)Fe=C(H)R+ and (L)Fe=C(H)R2+, respectively. A different approach would be to prepare neutral iron(O) alkylidenes. An ideal iron(0) species that may display metathesis activity would be (R3P)LFe=(H)R. Complexes of this class should be capable of dissociating the phosphine ligand in solution, to afford LFe=(H)R fragments with at least two vacant coordination sites, independent of the spin state of the metal. The ultimate goal of this research proposal is to provide the synthetic community with inexpensive, environmentally benign, highly active and selective olefin metathesis catalysts. PUBLIC HEALTH RELEVANCE The proposed research plan intends to use iron compounds to provide methods that allow pharmaceuticals to be produced in a more environmentally friendly and cost effective manner. Thus, this work may ultimately provide clean methods to produce cheaper medicines.