Organometallic Chemistry for Applications in Biomedical Sciences

描述（由申请人提供）：碳-氟键的形成是一种具有挑战性的化学转化，特别是当用于芳基氟化物的合成时。简单的分子可以用近100年来发展起来的氟化方法氟化，但更复杂的分子却不能。目前化学家无法通过后期的聚合反应有效地制造复杂的有机氟化物，这通常会阻碍药物开发和分子PET成像等不同领域的研究。拟议的研究解决了碳-氟键形成的化学挑战，以合成官能化的芳基氟化物。我们的碳-氟键形成策略是基于有机金属化学。我们提出了钯和银介导的芳基锡烷、芳基硼酸和芳基硅烷的取代反应.此外，我们建议开发过渡金属氟化物配合物，作为亲电试剂，使用阴离子氟化物作为最终的氟源。我们进一步建议使用我们的过渡金属介导的方法，通过后期的双金属化合成四个生物活性分子。我们研究的一个长期目标是将我们的正电子发射断层扫描反应应用于目前不可用的PET示踪剂的合成。在分子成像中应用质子交换膜反应超出了本资助计划的范围。

DESCRIPTION (provided by applicant): Carbon-fluorine bond formation is a challenging chemical transformation, especially when used for the synthesis of arylfluorides. Simple molecules can be fluorinated with fluorination methods developed during the last 100 years, molecules of greater complexity, however, cannot. The current inability of chemists to efficiently make complex organic fluorides by late-stage fluorination often prevents research in diverse areas, such as drug development and molecular PET imaging. The proposed research addresses the chemical challenges of carbon-fluorine bond formation to synthesize functionalized arylfluorides. Our strategy for carbon-fluorine bond formation is based on organometallic chemistry. We proposed Pd- and Ag- mediated fluorination reaction of arylstannanes, arylboronic acids, and arylsilanes. Additionally we propose to develop transition metal fluoride complexes that react as electrophilic fluorination reagents using anionic fluoride as ultimate fluorine source. We further propose to synthesize four biologically active molecules via late-stage fluorination using our transition-metal mediated approach. A long-term-goal of our research is the application of our fluorination reactions to the synthesis of currently unavailable PET tracers for molecular imaging using positron-emission tomography. The application of the fluorination reactions to molecular imaging is beyond the scope of this grant proposal.