Synthetic Methods based on Biphilic Phosphorus Catalysts

基于双亲磷催化剂的合成方法

基本信息

批准号：
10843564
负责人：
ALEXANDER T RADOSEVICH
金额：
$ 7.75万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-03-01 至 2024-02-29
项目状态：
已结题

项目摘要

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 new methods for activation of amides and stable oxoanions for direct functionalization via P(III)⇌P(V) redox reactivity. The second major effort is the development of phosphine-catalyzed O-atom transfer methods that result in reductive transformations of nitroarene compounds to furnish functional- ized anilines through the formation of new carbon-nitrogen bonds. The third major effort involves the de- velopment of P(III)⇌P(V)-catalyzed O-atom transfer methods that result in reductive N-functionalization of nitroalkanes, including new phosphacyclic structures that express biphilic P(III)⇌P(V) redox reactivity. The proposed research is expected to yield new practical catalytic methods for the construction of phar- macologically-relevant small molecules that meet the challenges of sustainable synthesis, and an im- proved 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 to- gether, these outcomes will advance nonmetal-based redox catalysis as a powerful modality in pharma- ceutical synthesis.

项目概要/摘要催化科学和技术的进步使得能够制备用于该项目的长期目标是开发一系列廉价的药物。通过正式氧化态循环促进催化转化的非金属催化剂与过渡金属催化类似，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认为是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启用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 ically 相关的反应性。开发用于活化酰胺和稳定含氧阴离子以直接官能化的新方法 P(III)⇌P(V) 氧化还原反应性的第二个主要成果是膦催化 O 原子的发展。导致硝基芳烃化合物还原转化以提供功能性的转移方法通过形成新的碳-氮键来实现苯胺化。 P(III)⇌P(V)催化O原子转移方法的发展导致还原N-官能化硝基烷烃，包括表达双亲 P(III)⇌P(V) 氧化还原反应性的新磷环结构。该研究预计将为构建药物提供新的实用催化方法。与宏观相关的小分子，可以应对可持续合成的挑战，并且是一个重要的证明了对 p 区结构和反应性之间相互作用的基本理解，这将支撑非金属在原子转移、键活化和催化方面的未来发展。总之，这些成果将推动非金属氧化还原催化成为制药领域的一种强大模式。细胞合成。