Novel Reagents and Catalysts for Organic Synthesis

化学空间的产生及其转化为新的功能是合成化学的主要目标之一。BN/CC电子等排性（即，用硼-氮键取代碳-碳键）已经成为增加与生物医学研究相关的化合物的化学空间的可行策略。该提案描述了一个面向开发芳烃BN电子等排体的计划，这些电子等排体可用作合成有机化学和化学生物学应用的有用构件、试剂和催化剂。 具体而言，我们力求： 1)建立了作为四碳（4C）+1氮（1 N）+1硼（1B）合成子的氮杂硼杂环，用于利用氮杂硼杂环的预先安装的功能密度的合成应用，即，氮原子、硼原子和1，3-丁二烯单元，以有效地产生用于多样性定向合成的新的氨基硼化化合物。 2)建立了氮杂硼杂环作为新的配体家族，其可以与过渡金属以不同的配位模式进行，以影响金属催化转化中的新的反应性和选择性。 3)利用BN-吲哚及其相应的氨基酸BN-色氨酸来产生新的BN-同种异体蛋白，并开发一种新的生物缀合平台，该平台是快速的、无催化剂的、化学选择性的，并且与现有的生物缀合方法正交。 所提出的目标的完成将产生新的基础知识，有关硼的背景下，合成有机和生物化学。它将产生新的合成方法和研究工具，用于生物过程的研究，并激发新的含硼分子的设计和开发，用于生物医学应用。

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.