Transition-Metal-Catalyzed Enantioselective Heteroatom–Hydrogen Bond Insertion Reactions

Abstract

Carbon-heteroatom bonds (C-X) are ubiquitous and are among the most reactive components of organic compounds. Therefore investigations of the construction of C-X bonds are fundamental and vibrant fields in organic chemistry. Transition-metal-catalyzed heteroatom-hydrogen bond (X-H) insertions via a metal carbene or carbenoid intermediate represent one of the most efficient approaches to form C-X bonds. Because of the availability of substrates, neutral and mild reaction conditions, and high reactivity of these transformations, researchers have widely applied transition-metal-catalyzed X-H insertions in organic synthesis. Researchers have developed a variety of rhodium-catalyzed asymmetric C-H insertion reactions with high to excellent enantioselectivities for a wide range of substrates. However, at the time that we launched our research, very few highly enantioselective X-H insertions had been documented primarily because of a lack of efficient chiral catalysts and indistinct insertion mechanisms. In this Account, we describe our recent studies of copper- and iron-catalyzed asymmetric X-H insertion reactions by using chiral spiro-bisoxazoline and diimine ligands. The copper complexes of chiral spiro-bisoxazoline ligands proved to be highly enantioselective catalysts for N-H insertions of α-diazoesters into anilines, O-H insertions of α-diazoesters into phenols and water, O-H insertions of α-diazophosphonates into alcohols, and S-H insertions of α-diazoesters into mercaptans. The iron complexes of chiral spiro-bisoxazoline ligands afforded the O-H insertion of α-diazoesters into alcohols and water with unprecedented enantioselectivities. The copper complexes of chiral spiro-diimine ligands exhibited excellent reactivity and enantioselectivity in the Si-H insertion of α-diazoacetates into a wide range of silanes. These transition-metal-catalyzed X-H insertions have many potential applications in organic synthesis because the insertion products, including chiral α-aminoesters, α-hydroxyesters, α-hydroxyphosphonates, α-mercaptoesters, and α-silyl esters, are important building blocks for the synthesis of biologically active compounds. The electronic properties of α-diazoesters and anilines markedly affected the enantioselectivity of N-H insertion reaction, which supports a stepwise ylide insertion mechanism. A novel binuclear spiro copper complex was isolated and fully characterized using X-ray diffraction analysis and ESI-MS analysis. The positive nonlinear effect indicated that binuclear copper complexes were the catalytically active species. The 14-electron copper centers, trans coordination model, perfect C(2)-symmetric chiral pocket, and Cu-Cu interaction facilitate the performance of the chiral spiro catalysts in X-H insertion reactions.