Synthesis of Planar Chiral Ferrocenes via Transition-Metal-Catalyzed Direct C-H Bond Functionalization.Acc Chem Res. 2017 02 21; 50(2):351-365.AC
Ferrocenes are of great interest in the fields of materials science, organic synthesis, and biomedical research. Of particular significance is the fact that ferrocenes bearing planar chirality have been demonstrated to be highly efficient ligands or catalysts in asymmetric catalysis, some of which have been employed in the industrial synthesis of pharmaceuticals and agrochemicals. So far, the main methods for the synthesis of planar chiral ferrocenes involve diastereoselective directed ortho-metalation (DoM), enantioselective DoM, and chiral resolution. Despite the fact that these approaches are well developed and widely applied, the use of chiral auxiliaries or external stoichiometric chiral bases is required in most cases. Additionally, the practicality of these processes is hampered by the requirement of sensitive organometallic reagents, the poor compatibility with functional groups, and the low atom economy in some cases. Therefore, the development of highly efficient strategies to introduce planar chirality on the backbone of ferrocene that do not possess these limitations is highly desirable. Meanwhile, transition-metal-catalyzed asymmetric C-H bond functionalization reactions have attracted much attention over the past few years owing to their emerging potential for providing a straightforward approach for the preparation of chiral molecules. In addition to the majority of the work focusing on the installation of central chirality, methods for the catalytic asymmetric synthesis of planar chiral compounds via C-H bond functionalization have also been explored. In this Account, we summarize our recent efforts aimed at the development of novel methods to synthesize planar chiral compounds via asymmetric C-H bond functionalization and also highlight related achievements by other groups. First, we briefly introduce the precedent examples of diastereoselective and enantioselective synthesis of planar chiral ferrocenes. Subsequently, asymmetric syntheses of structurally diverse planar chiral ferrocenes via Pd [Pd(II), Pd(0)]-, Ir-, Rh-, Au-, and Pt-catalyzed C-H bond functionalization are described. These methods have impressive advantages over traditional approaches for the synthesis of functionalized planar chiral ferrocenes in terms of both step- and atom-economies. Notably, the products of these processes are easily transformed into a variety of new catalysts or ligands, which have been demonstrated to promote efficient asymmetric reactions. Moreover, DFT calculations have been conducted to explore the origin of the excellent enantioselectivity of Pd-catalyzed enantioselective C-H bond functionalization reactions. Progress made in the area of asymmetric C-H bond functionalization provides an effective platform for the design and synthesis of planar chiral ferrocenes.