Novel Reagents and Catalysts for Organic Synthesis

生成化学空间并将其转化为新的功能是合成化学的主要目标之一。BN/CC等位异构体(即用碳-碳键取代硼-氮键)已成为增加与生物医学研究相关的化合物化学空间的可行策略。该提案描述了一项旨在开发芳烃的BN异构体作为合成有机化学和化学生物学应用的有用的构建块、试剂和催化剂的计划。 具体地说，我们力求： 1)将氮硼化合物建立为四碳(4C)+1氮(1N)+1硼(1B)合成子，用于利用氮原子、硼原子和1，3-丁二烯单元的预先安装的功能密度的合成应用，以有效地产生新的氨基硼化化合物，用于面向多样性的合成。 2)建立氮硼化合物作为一种新的配体家族，它们可以与过渡金属以不同的配位方式影响金属催化转化中的新反应活性和选择性。 3)利用BN-吲哚及其相应的氨基酸BN-色氨酸创造新的BN-同源蛋白，开发一种快速、无催化剂、化学选择性的、与现有生物标记方法正交的新的生物标记平台。 拟议目标的完成将产生与合成有机化学和生物化学中的硼有关的新的基础知识。它将产生新的合成方法和研究工具，用于研究生物过程，并启发设计和开发用于生物医学应用的新的含硼分子。

The generation of chemical space and its translation into new functions is one of the main goals of synthetic chemistry. The BN/CC isosterism (i.e., replacement of a carbon-carbon bond with a boron-nitrogen bond) has emerged as a viable strategy to increase the chemical space of compounds relevant to biomedical research. This proposal describes a program geared toward developing BN isosteres of arenes as useful building blocks, reagents, and catalysts for synthetic organic chemistry and chemical biology applications. Specifically, we seek to: 1) establish azaborines as four-carbon (4C) + 1 nitrogen (1N) + 1 boron (1B) synthon for synthetic applications that exploit the preinstalled functional density of an azaborine, i.e., a nitrogen atom, a boron atom, and a 1,3-butadiene unit to efficiently produce new aminoborylated compounds for diversity-oriented synthesis. 2) establish azaborines as a new family of ligands that can engage in distinct coordination modes with transition metals to affect new reactivity and selectivity in metal-catalyzed transformations. 3) utilize BN-indole and its corresponding amino acid BN-tryptophan to create novel BN-alloproteins and to develop a novel bioconjugation platform that is rapid, catalyst-free, chemoselective, and orthogonal to existing bioconjugation methods. Completion of the proposed aims will yield new fundamental knowledge related to boron in the context of synthetic organic and biological chemistry. It will generate new synthetic methods and research tools for the investigation of biological processes and inspire the design and development of new boron-containing molecules for biomedical applications.