The Development of Efficient Synthetic Methods for C-C Bond Formation

新的有机合成方法的发展有可能影响对制药和材料工业具有重要意义的新分子的发现。这对于产生C-C键的方法尤其如此，因为它们固有地导致更复杂的产物。尽管在合成化学领域取得了巨大的进步，但复杂目标的合成通常会受到起始材料的可用性的限制，或者受到需要苛刻条件并且具有低原子经济性的低效方法的限制。因此，广泛适用的方法，而不是利用丰富的和成本有效的基板，或在温和的条件下操作是非常感兴趣的。我们的目标是开发新的强大的合成方法，专注于C-C键的构建。将追求两个主要途径：i）开发与用于C-C键形成方法的强配位配体结合的高活性均相过渡金属催化剂，以及ii）通过使用原位机理研究来理解和解决现有方法的局限性，以机理驱动的方式开发温和的C-C键形成反应。总之，这两种途径汇聚在发现温和，有效和广泛适用的合成方案，用于从丰富的前体制备具有挑战性的分子。这些项目的影响将是显著的，因为使用分子催化的方法被化学工业和学术界的研究人员广泛使用。特别是，研究成果将直接与制药行业相关，该行业代表了加拿大经济在全国各地众多初创企业和大型公司之间的主要增长部分。药物设计和发现中的许多具体研究依赖于对用于产生碳-碳键的稳健催化方法的需求。因此，该项目的发现将直接转化为加拿大日益增长的科学工业感兴趣的有机目标的制备。这项工作将进一步培训HQP，为研究生和本科生提供学习机会，通过发展他们在空气和湿度敏感合成以及有机和有机金属分子的纯化和表征方面的技能，为加拿大就业市场做好准备。我的研究团队将包括高度多样化的学生，我将指导他们撰写合成化学和机械化学的研究论文。

The development of new synthetic organic methods has the potential to influence the discovery of new molecules that are significant to the pharmaceuticals and materials industries. This is particularly true for methods which produce C-C bonds, as they inherently lead to products of greater complexity. Despite the tremendous progress made in the field of synthetic chemistry, the synthesis of complex targets can often be limited by the availability of starting materials, or by inefficient methods which require harsh conditions and suffer from low atom economy. Widely applicable methods which instead utilize abundant and cost effective substrates, or operate under mild conditions are therefore of great interest. Our Goal is to develop new robust synthetic methodology focusing on the construction of C-C bonds. Two main avenues will be pursued: i) the development of highly active homogeneous transition metal catalysts bound to strongly coordinating ligands for C-C bond forming methods and ii) the mechanistically driven development of mild C-C bond forming reactions by using in-situ mechanistic studies to understand and address limitations of existing methodology. Together, these two avenues converge on the discovery of mild, efficient and widely applicable synthetic protocols for the preparation of challenging molecules from abundant precursors. The impact of these projects will be significant as methods using molecular catalysis are widely used by researchers in chemical industry and academia. In particular, the research outcomes will be directly relevant to the pharmaceutical industry which represents a major growing part of the Canadian economy between the numerous start-ups and large scale companies located across the country. Much of the specific research in drug design and discovery relies on the need for robust catalytic methods for the generation of carbon-carbon bonds. As such, the discoveries resulting from this project will directly translate into the preparation of organic targets of interest to the growing scientific industries within Canada. This work will further train HQP providing learning opportunities for graduate and undergraduate students, preparing them for the Canadian job market by developing their skills in air and moisture sensitive synthesis, as well as in the purification and characterization of organic and organometallic molecules. My research team will include highly diverse students that I will mentor on research theses devoted to synthetic and mechanistic chemistry.