Combining Ligand Deuteration with Ligand Bulkiness in Non-Heme Iron Oxidation Catalysis: Enhancing Catalyst Lifetime and Site-Selectivity

Abstract

Bulky tri-isopropyl silyl (TIPS) substituents and deuterium atoms in the ligand design have been shown to enhance the site-selective oxidation of aliphatic C−H bonds and the epoxidation of C=C bonds in non-heme iron oxidation catalysis. In this work, a series of non-heme iron complexes were developed by combining TIPS groups and deuterium atoms in the ligand. These bulky deuterated complexes show a significant increase in catalytic performance compared to their counterparts containing only TIPS groups or deuterium atoms. A broad range of substrates was oxidized with excellent yields, particularly, using [Fe(OTf)2((S,S)-TIPSBPBP-D4)] (1-TIPS-D4) (0.1 mol % to 1 mol %) via a fast or slow oxidant addition protocol, resulting in an overall improvement in catalytic performance. Notably, in the oxidation of the complex substrate trans-androsterone acetate, the use of a slow addition protocol and a lower catalyst loading of 1-TIPS-D4 resulted in significant increases in reaction efficiency. In addition, kinetic and catalytic studies showed that deuteration does not affect the catalytic activity and the secondary C−H site-selectivity but increases the catalysts’ lifetime resulting in higher conversion/yield. Accordingly, the yield of selectively oxidized secondary C−H products also increases with the overall yield by using the bulky deuterated iron complexes as catalysts. These catalytic improvements of the bulky deuterated complexes exemplify the enhanced design of ligands for homogeneous oxidation catalysis.