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种广泛的廉价 非金属催化剂，其通过定性的形式氧化态循环促进催化转化， 类似于过渡金属催化。在这一总体目标范围内，本提案的主要重点是 在P（III）→ P（V）氧化还原对中起作用的磷基催化剂的设计和应用。 虽然膦在催化中作为过渡金属催化的旁观配体是公认的， 作为亲核催化剂，这项研究描述了创新的磷基催化剂的新的com， 位置和结构，探索所需的结构和电子条件，使新的催化剂， 通过可逆的P（III）→ P（V）氧化态循环，第一个主要的努力是， 膦催化的O-原子转移方法的实施，其导致 硝基芳烃化合物通过形成新的碳氮键。第二个主要的努力是 由膦完成的净氧化还原中性（环）脱水反应的发展 P（III）→ P（V）氧化还原对中的催化作用。预计该研究将产生新的实用催化剂。 用于构建满足挑战的药理学相关小分子的裂解方法 可持续的综合，以及更好的基本理解结构之间的相互作用 和反应性的p-块，将巩固未来的发展，非金属原子转移，键 活化和催化。总之，这些成果将促进非金属基氧化还原催化 作为一种新的和强大的模式，在药物合成。

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.