Exploiting the C-H bond in metal catalyzed C-C bond forming reactions

Michael Schnürch,Viktor V Zhdankin

doi:10.3998/ark.5550190.p008.906

Abstract

This account summarizes our work in the field of direct C-H bond functionalization. We have explored methods in the area of directing group assisted C(sp 2 )-H and C(sp 3 )-H activation and investigated arylation as well as deuteration reactions. In these transformations either ruthenium or palladium catalysts were applied. In case of C(sp 2 )-H activation, we developed a protocol for the synthesis of ortho arylated anilines and disclosed the first method for a direct arylation in a continuous flow reactor. Additionally, we applied a direct arylation in the synthesis of compounds which can accelerate cell differentiation. In the field of C(sp 3 )-H activation we developed a protocol for the selective mono-arylation of piperidine and three different arylation protocols for acyclic amines employing either aryl chlorides, aryl bromides, aryl iodides, or arylboronic acid esters as the aryl donor.

Highlights

The field of organic synthesis can be considered as well established and matured with great achievements throughout its history.[1]
A certain method might have different mechanistic pathways through which it can proceed. This is reflected in our work in this area, in which we investigated C(sp2)-H and C(sp3)-H activation reactions via one-site C-H functionalization methods where we could show that the very same products can be formed via different reaction mechanisms
We identified a ruthenium (II) catalyzed method which could be modified in a way that it fulfilled our requirements.[42,43]

Summary

Introduction

The field of organic synthesis can be considered as well established and matured with great achievements throughout its history.[1]. Metal catalyzed cross-coupling reactions[2,3] have been very successful during the last decades, which were recognized by the Nobel Prize in chemistry 2010 for Akira Suzuki,[4,5] Ei-ichi Negishi,[6,7] and Richard Heck[8] for their achievements in this field As it is generally known, most of the cross-coupling reactions take advantage of an organometal reagent and a halide or pseudohalide (e.g. triflate) component for the C-C bond formation process (Figure 1).[2] Neither of these two functional groups remains in the final product and has to be considered as “waste” in these reactions. Elimination of one functional group from the starting materials (as compared to a cross-coupling reaction) can greatly contribute to increased reaction efficiency For this type of reactions, the term C-H activation has become generally accepted vocabulary among the community of synthetic organic chemists. Within this account we present our research efforts in this field

Findings

Discussion

Conclusions