Synthetic Methods based on Biphilic Phosphorus Catalysts

项目概要/摘要 催化科学和技术的进步使得能够制备用于 治疗人类疾病。该项目的长期目标是开发一系列廉价的 通过正式氧化态循环促进催化转化的非金属催化剂 类似于过渡金属催化。在这一总体目标中，该提案的主要重点是 在P(III)⇌P(V)氧化还原对中发挥作用的磷基催化剂的设计和应用。 虽然膦在催化领域已被广泛用作过渡金属催化的旁观配体， 作为亲核催化剂，这项研究描述了新型化合物的创新磷基催化剂 探索实现新催化剂所需的结构和电子条件的位置和结构 通过可逆的 P(III)⇌P(V) 氧化态循环实现与学相关的反应性。第一个主要努力是 发展膦催化的O原子转移方法，导致还原官能化 硝基芳烃化合物通过形成新的碳-氮键。第二个主要努力是 由膦完成的净氧化还原中性（环）脱水反应的发展 P(III)⇌P(V)氧化还原对的催化作用。拟议的研究预计将产生新的实用目录 用于构建应对挑战的药理学相关小分子的裂解方法 可持续合成，并提高对结构之间相互作用的基本理解 p 区的反应性将支撑原子转移、键合等非金属的未来发展 活化、催化。总而言之，这些成果将推动非金属氧化还原催化的发展 作为药物合成中一种新的、强大的方式。

PROJECT SUMMARY/ABSTRACT Advances in catalytic science and technology enable the preparation of pharmaceutical agents used to treat human disease. This project has the long-term goal of developing a broad class of inexpensive nonmetal catalysts that promote catalytic transformations via formal oxidation state cycling in qualitative analogy to transition metal catalysis. Within this overarching goal, the primary focus of this proposal is the design and application of phosphorus-based catalysts that function in the P(III)⇌P(V) redox couple. While phosphines are well-established in catalysis as spectator ligands for transition metal catalysis and as nucleophilic catalysts, this research describes innovative phosphorus-based catalysts of novel com- position and structure that explore the structural and electronic conditions required to enable new catalyt- ically-relevant reactivity via reversible P(III)⇌P(V) oxidation state cycling. The first major effort is the de- velopment of phosphine-catalyzed O-atom transfer methods that result in reductive functionalization of nitroarene compounds through the formation of new carbon-nitrogen bonds. The second major effort is the development of net redox-neutral (cyclo)dehydration reactions that are accomplished by phosphine catalysis in the P(III)⇌P(V) redox couple. The proposed research is expected to yield new practical cata- lytic methods for the construction of pharmacologically-relevant small molecules that meet the challenges of sustainable synthesis, and an improved fundamental understanding the interplay between structure and reactivity in the p-block that will underpin future development of nonmetals for atom transfer, bond activation, and catalysis. Taken together, these outcomes will advance nonmetal-based redox catalysis as a new and powerful modality in pharmaceutical synthesis.