School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, China.
Institute of Drug Discovery Technology, Ningbo University, Ningbo 315211, China.
J Am Chem Soc. 2023 Mar 8;145(9):5456-5466. doi: 10.1021/jacs.2c13832. Epub 2023 Feb 22.
The development of catalytic systems capable of oxygenating unactivated C-H bonds with excellent site-selectivity and functional group tolerance under mild conditions remains a challenge. Inspired by the secondary coordination sphere (SCS) hydrogen bonding in metallooxygenases, reported herein is an SCS solvent hydrogen bonding strategy that employs 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as a strong hydrogen bond donor solvent to enable remote C-H hydroxylation in the presence of basic aza-heteroaromatic rings with a low loading of a readily available and inexpensive manganese complex as a catalyst and hydrogen peroxide as a terminal oxidant. We demonstrate that this strategy represents a promising compliment to the current state-of-the-art protection approaches that rely on precomplexation with strong Lewis and/or Brønsted acids. Mechanistic studies with experimental and theoretical approaches reveal the existence of a strong hydrogen bonding between the nitrogen-containing substrate and HFIP, which prevents the catalyst deactivation by nitrogen binding and deactivates the basic nitrogen atom toward oxygen atom transfer and the α-C-H bonds adjacent to the nitrogen center toward H-atom abstraction. Moreover, the hydrogen bonding exerted by HFIP has also been demonstrated not only to facilitate the O-O bond heterolytic cleavage of a putative Mn-OOH precursor to generate Mn(O)(OC(O)CHBr) as an active oxidant but also to affect the stability and the activity of Mn(O)(OC(O)CHBr).
在温和条件下，开发能够对未活化的 C-H 键进行高效区域和官能团选择性氧合的催化体系仍然是一个挑战。受金属加氧酶中次级配位球（SCS）氢键的启发，本文报道了一种 SCS 溶剂氢键策略，该策略使用 1,1,1,3,3,3-六氟异丙醇（HFIP）作为强氢键供体溶剂，在碱性氮杂芳环存在下实现远程 C-H 羟化，催化剂负载量低，且使用易得且廉价的锰配合物作为催化剂，过氧化氢作为末端氧化剂。我们证明，该策略是对当前最先进的保护方法的一种有前途的补充，这些方法依赖于与强路易斯酸和/或布朗斯台德酸的预络合。通过实验和理论研究揭示了含氮底物与 HFIP 之间存在强氢键，这可以防止催化剂因氮结合而失活，并使碱性氮原子对氧原子转移和与氮中心相邻的α-C-H 键对 H 原子的攫取失活。此外，HFIP 施加的氢键不仅被证明有利于生成 Mn(O)(OC(O)CHBr)作为活性氧化剂的假定 Mn-OOH 前体的 O-O 键异裂，而且还影响 Mn(O)(OC(O)CHBr)的稳定性和活性。
