Hydrogen Bonding-Assisted and Nonheme Manganese-Catalyzed Remote Hydroxylation of C–H Bonds in Nitrogen-Containing Molecules
Jie Chen, Wenxun Song, Jinping Yao, WU Zhi-min, Yong‐Min Lee, Yong Wang, Wonwoo Nam, Bin Wang
Abstract
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 III –OOH precursor to generate Mn V (O)(OC(O)CH 2 Br) as an active oxidant but also to affect the stability and the activity of Mn V (O)(OC(O)CH 2 Br).