Synthetic Methods based on Biphilic Phosphorus Catalysts

 描述(由申请人提供)：催化科学的进步使用于治疗人类疾病的药剂的制备成为可能。该项目的长期目标是开发一类广泛的廉价非金属催化剂，通过与后过渡金属催化剂大致相同的方式，通过正式的氧化态循环促进原子转移和键活化过程。在这一总体目标内，这项提案的主要重点是设计和评估在PIII⇌PV氧化还原对中发挥作用的磷基催化剂。虽然膦作为过渡金属催化的旁观者配体和亲核催化剂在催化中得到了很好的应用，但这项研究将研究新型组成和结构的磷基催化剂，探索通过可逆的PII�PV氧化态循环实现新的催化相关反应所需的结构和电子条件。第一个主要工作是发展膦催化的氧原子转移方法，导致羰基化合物的还原双官能化。第二个主要努力是发展由磷介导的键活化引发的胺官能化反应。这项拟议的研究有望为构建与药物相关的小分子提供新的实用催化方法，以满足可持续合成的挑战，并改善对p-嵌段结构和反应性之间相互作用的基础理解，这将为非金属在原子转移、键激活和催化方面的未来发展奠定基础。综上所述，这些成果将推动非金属催化领域的一种新的、强大的模式。

 DESCRIPTION (provided by applicant): The preparation of pharmaceutical agents used to treat human disease is enabled by advances in catalytic science. This project has the long-term goal of developing a broad class of inexpensive nonmetal catalysts that promote atom transfer and bond activation processes via formal oxidation state cycling in much the same way that late transition metal catalysts operate. Within this overarching goal, the primary focus of this proposal is the design and evaluation of phosphorus-based catalysts that function in the PIII⇌PV redox couple. While phosphines are well-established in catalysis as spectator ligands for transition metal catalysis and as nucleophilic catalysts, this research will investigate phosphorus-based catalysts of novel composition and structure that explore the structural and electronic conditions required to enable new catalytically-relevant reactivity via reversible PII�PV oxidation state cycling. The first major effort is the development of phosphine-catalyzed O-atom transfer methods that result in reductive difunctionalization of carbonyl compounds. The second major effort is the development of amine functionalization reactions that are initiated by phosphorus-mediated bond activation. The proposed research is expected to yield new practical catalytic 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 a new and powerful modality in nonmetal-based catalysis.