Iron-Based Olefin Metathesis Catalysts

描述（由申请人提供）：治疗制剂的制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，因此选择性地偶联两个碳部分的过程至关重要。其中一种最有效和选择性的碳碳键形成方法是钌催化烯烃复分解反应。由于铁便宜且毒性低，设计铁基烯烃分解催化剂将是一项重大的技术进步。制备这种催化剂需要合成迄今为止未知的低配位铁烷基烷。作为起点，将制备中性铁（ll）烷基烯，分子式为CI2(L)Fe=C(H)R，其中L为环氨基羰基配体。与典型的低自旋的钌烷基烷相反，铁配合物CI2(L)Fe=C(H)R可能存在于高自旋态。由于在过渡金属中心的所有d轨道上至少存在一个电子，高自旋CI2(L)Fe=C(H)R配合物可能会抵抗烯烃配位，从而延缓复分解活性。解决这个潜在问题的方法是合成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。这些强场配体取代了CI2(L)Fe=C(H)R的CI-基团，增加了体系中配体场分裂参数，促进了更有利于烯烃配位的低自旋态。另一种为底物结合提供可接近的配位位点的方法是通过氯离子萃取使CI2(L)Fe=C(H)R配合物呈阳离子。得到的XCI(L)Fe=C(H)R和X2(L)Fe=C(H)R，其中X是B(C6F5)4-或HBC11Cl11-等极不配位的反离子，应该在溶液中解离，形成正式的12和10电子铁单体和指示CI(L)Fe=C(H)R+和(L)Fe=C(H)R2+。另一种方法是制备中性铁(O)烷基烷。一个理想的铁(0)种可能显示转化活性是（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片段，与金属的自旋状态无关。本研究的最终目标是为合成界提供廉价、环保、高活性和选择性的烯烃复分解催化剂。拟议的研究计划打算利用铁化合物提供方法，使药品能够以更环保和更具成本效益的方式生产。因此，这项工作可能最终为生产更便宜的药物提供清洁的方法。

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.