Presidential Young Investigator Award/Development of New Organometallic Reagents (Chemistry)

霍金斯博士是有机和大分子化学项目总统青年研究员奖的新研究员。在此基础上，将研究利用有机金属试剂开发新的有机合成方法。这将提高我们有效合成现代医学和农业中使用的复杂分子的能力。在第一个项目中，金属羰基将用含有相容亲核和亲电位点的有机底物处理。在配位一氧化碳的碳上加入亲核基团，会在亲电基团附近生成金属亲核基团。所得到的配合物将被建立为金属环，然后可以还原地消除所需的选择性羰基化有机产物。环氧醇，环氧胺，和磺酰基将被检查作为双功能有机底物。与环氧化物的预期反应对应于醛醇合成，其中起始环氧化物的几何形状控制了产物的相对立体化学。环氧胺可以生成具有立体化学控制的-内酰胺类化合物，为过渡金属烯酮配合物的合成提供了新的途径。第二个项目将涉及含pi-碱的手性二卤硼烷的合成、拆分和应用。同时具有路易斯碱和酸性位点的底物，如α、β不饱和酯，应通过同时协同的路易斯酸碱和-酸碱相互作用与这些催化剂结合。这种两点结合所施加的约束可能导致烯烃的一个面被选择性地阻塞。因此，另一个面将开放给试剂接近。Dienes将在这里接受测试；配位的-碱被进入的二烯置换可能导致不对称的Diels Alder反应。不再含有作为第二结合点的pi-酸，环己烯产物应该被两点结合起始材料从催化剂上取代。催化剂结构将会改变，以优化这种酶样的场景。双键的立体特异性相邻双甲基化方法将在第三个项目中探索。烯烃底物与杂双金属双甲基配合物的配位可导致插入到形成1,3-二金属环己烷的金属-碳键之一中。然后，该物质可还原消除金属环戊烷，该金属环戊烷可被质子化成所需的二甲基化产物。Mo-Co和Mo-Fe配合物将在该脉中进行研究。

Dr. Hawkins is a new investigator under the Presidential Young Investigator Award from the Organic and Macromolecular Chemistry Program. Under this will be studied the development of new organic synthetic methods using organometallic reagents. These will increase our capacity to synthesize efficiently the complex molecules used in modern medicine and agriculture. For the first project, metal carbonyls will be treated with organic substrates containing compatible nucleophilic and electrophilic sites. Addition of the nucleophilic moiety to the carbon of coordinated carbon monoxide should generate a metal nucleophile in proximity to the now pendant electrophilic moiety. The resulting complex will be set up for cyclization to a metallacycle, which may then reductively eliminate the desired selectively carbonylated organic product. Epoxy alcohols, epoxy amines, and sulphonium ylides will be examined as the bifunctional organic substrates. The anticipated reaction with epoxides corresponds to an aldol synthon where the starting epoxide's geometry controls the product's relative stereochemistry. Epoxy amines may accordingly give beta-lactams with stereochemical control The sulphonium ylide substrates may provide a new route to transition metal ketene complexes. The second project will involve the synthesis, resolution, and application of chiral dihaloboranes containing pi-bases. A substrate possessing both Lewis basic and pi-acidic sites such as an alpha, beta-unsaturated ester should bind to these catalysts via simulataneous synergistic Lewis acid-base and pi-acid base interactions. The constraints imposed by this two-point binding may cause one face of the olefin to be selectively blocked. Accordingly, the other face will be open to approach by reagents. Dienes will be tested here; displacement of the corrdinated pi-base by an incoming diene may result in an asymmetric Diels Alder reaction. No longer containing a pi-acid for a second binding point, the cyclohexene product should be displaced from the catalyst by the two-point binding starting material. The catalyst structures will be varied in order to optimize this enzyme-like scenario. Methods for the stereospecific vicinal bismethylation of a double bond will be explored in a third project. Coordination of an olefinic substrate to a heterobimetallic bis-mu-methylene complex may lead to insertion into one of the metal-carbon bonds forming a 1,3-dimetallacyclohexane. This species may then reductively eliminate a metallacyclopentane which can be protonolyzed to the desired bismethylated product. Mo-Co and Mo-Fe complexes will be studied in this vein.