Application of Phosphine-Phosphite Ligands in the Iridium Catalyzed Enantioselective Hydrogenation of 2-Methylquinoline

Miguel Rubio,Antonio Pizzano

doi:10.3390/molecules15117732

Abstract

The hydrogenation of 2-methylquinoline with Ir catalysts based on chiral phosphine-phosphites has been investigated. It has been observed that the reaction is very sensitive to the nature of the ligand. Optimization of the catalyst, allowed by the highly modular structure of these phosphine-phosphites, has improved the enantioselectivity of the reaction up to 73% ee. The influence of additives in this reaction has also been investigated. Contrary to the beneficial influence observed in related catalytic systems, iodine has a deleterious effect in the present case. Otherwise, aryl phosphoric acids produce a positive impact on catalyst activity without a decrease on enantioselectivity.

Highlights

The use of two coordinating functions of different nature in a chiral ligand constitutes as a very powerful approach in the field of asymmetric hydrogenation [1]
Among chelating ligands with unequal coordinating groups, we have focused on phosphinephosphites (P-OP) and their application in asymmetric catalytic hydrogenation reactions
The highly modular structure of the P-OP derivatives developed in our laboratory (Figure 2), enables a detailed catalyst screening covering the influence of phosphine, phosphite and backbone fragments

Summary

Introduction

The use of two coordinating functions of different nature in a chiral ligand constitutes as a very powerful approach in the field of asymmetric hydrogenation [1]. A variety of catalytic systems, mostly based on Ir complexes and chiral chelating ligands with either equivalent (C2 symmetric) or non equivalent (C1 symmmetric) coordinating functions, have provided satisfactory results for this transformation In this regard, Zhou et al have described a catalytic system of [IrCl(cod)]2, MeO-Biphep and I2 that hydrogenates a variety of substituted quinolines with high enantioselectivities [13]. The highly modular structure of the P-OP derivatives developed in our laboratory (Figure 2), enables a detailed catalyst screening covering the influence of phosphine, phosphite and backbone fragments This approach has successfully been applied in the Rh catalyzed enantioselective hydrogenation of several types of olefins [24,25,26]. As an extension of the scope of chiral phosphine-phosphites in the hydrogenation of C=N bonds, we describe preliminary results about the application of these ligands in the Ir catalyzed asymmetric hydrogenation of 2-methylquinoline

Results and Discussion

General

General Hydrogenation Procedure

Conclusions