Trapping reactive intermediates and their application towards catalysis

项目摘要 单加氧酶家族被用来执行氧化基转移催化以广泛驱动 两种功能之一：(1)代谢碳氢化合物组成成分(如类固醇、脂肪酸)以产生废物 细胞色素P450(CYPS)的管理或激素合成；(2)以甲烷为唯一的利用 碳和能源(即甲烷营养细菌)。这些氧化酶的共同特征是 电子调节其催化中心的能力，以实现氧转移到坚固的C-H键底物。 采用电子结构调整原理来设计新的合成、非生物催化剂 承诺(1)通过揭示什么反应序列来了解酶系统可能的功能 以及(2)开发模仿单加氧酶反应性的新催化反应。 本文介绍了新型金属-配体多键化合物的合成和表征。 金属稳定的自由基，模拟生物单加氧酶的功能。单加氧酶利用金属- 推动C-−氢键活化和C-−杂原子键形成的恶烯类配体，为如何 模仿这种反应性。选择性地将官能团结合到未活化的C-H键中的能力代表 在将廉价的化学原料(例如碳氢化合物)转化为附加值方面取得重大进展 功能分子(例如，药物前体)。为了实现这一目标，本提案概述了一项战略，以 合成具有恶烯官能团的金属-配体多键配合物并考察它们的反应 作为过渡金属和恶烯配体氧化还原状态的函数的化学。这项提议旨在解决 以下问题：(1)哪种过渡金属-氧键和伴随的电子结构可以促进C-H 键-羟基化化学？(2)单体铜能支持末端氧配体吗？ 建议用作颗粒甲烷单加氧酶中的活性氧化剂？(4)官能团如何 氧化态(即氧、氧、氧)对官能团转移催化的影响？(5)金属稳定的配体 自由基一般被开发来实现新的C-H键官能化催化？ 用二吡咯配体平台作为细胞色素中的卟啉平台的截断模型 单加氧酶，这项建议概述了一种合成和表征金属-配体多键的策略 在铁、钴、镍和铜上。空间位阻的联吡咯被认为是合成的理想化合物， 类似于电位的铜的末端恶烯加合物的结晶和全光谱表征 颗粒甲烷单加氧酶中的末端铜(O)加合物。建议的科学影响更广泛 研究内容可以概括为：本研究将提高对该领域影响因素的认识 有助于促进生产性C-H键的活化和官能化，进一步开发新的 催化剂，通过清洁的反应路线，以最少的废物合成附加值的商品化学品。

Project Summary The family of monooxygenase enzymes are utilized to perform oxidative group transfer catalysis to broadly drive one of two functions: (1) metabolize hydrocarbon building blocks (e.g., steroids, fatty acids) for waste management or hormone synthesis in cytrochrome P450 (CYPs); and (2) the utilization of methane as the sole carbon and energy source (i.e., methanotrophic bacteria). The common trait amongst the oxidizing enzymes is the ability to electronically tune their catalytic centers to achieve oxygen transfer to robust C–H bond substrates. Adapting the electronic structure tuning principles to devise new synthetic, abiological catalysts holds great promise to (1) understand how the enzymatic systems might function by uncovering what reaction sequences are possible, and (2) developing new catalytic reactions that mimic the reactivity of the monooxygenases. This proposal describes the synthesis and characterization of novel metal-ligand multiple-bonds and metal-stabilized radicals to mimic the function of biological monooxygenases. Monooxygenases utilize metal- oxenoid ligands to drive C−H bond activation and C−heteroatom bond formation, providing a blueprint on how to emulate this reactivity. The ability to selectively incorporate functionality into unactivated C–H bonds represents a significant advance in converting inexpensive chemical feed stocks (e.g. hydrocarbons) to value-added functional molecules (e.g., pharmaceutical precursors). To achieve this goal, this proposal outlines a strategy to generate metal-ligand multiply-bonded complexes featuring oxenoid functionalities and examine their reaction chemistry as a function of transition metal and oxenoid ligand redox state. This proposal seeks to address the following questions: (1) Which transition metal-oxo linkage and attendant electronic structure can facilitate C-H bond hydroxylation chemistry? (2) Can monomeric copper support a terminal oxo-like ligand as would be suggested for the reactive oxidant in particulate methane monooxygenases? (4) How do functional group oxidation states (i.e., oxo, oxyl, oxene) impact functional group transfer catalysis? (5) Can metal-stabilized ligand radicals in general be developed to enable new C-H bond functionalization catalysis? Using dipyrrin ligand platforms as truncated models of the porphyrin platform found in cytochrome monooxygenases, this proposal outlines a strategy to synthesize and characterize metal-ligand multiple bonds on iron, cobalt, nickel, and copper. A sterically encumbered dipyrrin is proposed to be ideal for the synthesis, crystallization, and full spectroscopic characterization of a terminal oxenoid adducts of Cu akin to the potential terminal Cu(O) adduct in particulate methane monooxygenase. The broader scientific impact of the proposed research can be summarized as the following: this study will improve the field’s understanding of factors contributing to the promotion of productive C–H bond activation and functionalization, further developing new catalysts to synthesize value-added, commodity chemicals via clean reaction routes with minimal waste product.