Ligand-to-metal ratio controls stereoselectivity: Highly functional-group-tolerant, iridium-based, (E)-selective alkyne transfer semihydrogenation

Abstract

Herein, we present ( E )-selective transfer semihydrogenation of alkynes based on an iridium complex in situ generated from [Ir(COD)Cl] 2 and an unsymmetrical (bearing two different phosphorous centers), ferrocene-based phosphine ligand utilizing formic acid as a hydrogen donor. Interestingly, a ligand-to-metal ratio may be used to control the stereoselectivity of the semihydrogenation process: a ratio of 1:1 iridium to ligand led to the formation of ( Z )-alkene as a major product, whereas a ratio of 1:2 gave exclusively ( E )-alkene. The latter 1:2 catalytic system is distinguished by its unprecedented chemoselectivity and exceptional stereoselectivity, which is substantiated by the broad scope of tested substrates, including natural product derivatives. The intriguing difference in catalytic activity between unsymmetrical and symmetrical ferrocene-based ligands was attributed to divergent coordination and steric hindrance. The presented methodology constitutes a solution to the common limitations of the known catalytic systems for semihydrogenation. • Excellent stereoselectivity and functional-group tolerance • Stereoselectivity controlled by metal-to-ligand ratio • Catalytic activity affected by ligand symmetry Olefins are ubiquitous organic compounds which contain unsaturated double C–C bonds, and they may be found in many natural products and pharmaceuticals. Alkenes isomerism plays a vital role in the biological activity of drugs, to give one example. Thus, selective methods of their synthesis are highly coveted. Herein, we provide an unprecedented alternative to the other known catalytic systems for alkynes semihydrogenation, of which stereoselectivity may be controlled by the metal-to-ligand ratio. The ( E )-selective variant is distinguished by excellent stereo- and chemoselectivity. Reducible and problematic functionalities are tolerated under reductive conditions, and this makes our methodology a perfect tool for the late-stage functionalization of organic compounds. The environmentally friendly character of this catalytic system is proven by its efficiency and chemoselectivity, which allow one to avoid the use of protecting groups and allow the application of formic acid as a green and safe hydrogen donor. An iridium-based catalytic system for ( E )-selective transfer semihydrogenation of alkynes was developed. A unique feature of this method is the possibility of stereoselectivity control by the metal-to-ligand ratio. The catalytic system is distinguished by high functional-group tolerance, making it a valuable tool for organic synthesis. The observed intriguing dependence of ligand symmetry on catalytic activity may pave the way for efficient development of catalysts.