Adventure in Asymmetric Hydrogenation: Synthesis of Chiral Phosphorus Ligands and Asymmetric Hydrogenation of Heteroaromatics

Abstract

Catalytic asymmetric hydrogenations of prochiral unsaturated compounds, such as olefins, ketones, and imines, have been intensively studied and are considered as a versatile method of the synthesis of chiral compounds due to atom economy and operational simplicity. Since 2002, we mainly focused on synthesis of new phosphorus ligands, asymmetric hydrogenation of heteroaromatic compounds and palladium-catalyzed asymmetric hydrogenation. Significant contribution was made in the Dalian Institute of Chemical Physics. In this chapter, we hope to share our experience and adventure in the development of chiral monophosphite ligands and phosphine-phosphoramidite ligands, asymmetric hydrogenation of heteroaromatic compounds, and the development of new homogeneous palladium catalytic hydrogenation system, which have a wide range of applications in synthesis of chiral compounds.

Synthetic methods Part (ii) oxidation and reduction methods

“…71,72 Meanwhile, Hu et al presented an account on chiral phosphorous ligands in the asymmetric hydrogenation of various functional groups including alkenes. 73 Iridium-catalysed alkene reduction has dominated somewhat in 2011, with the vast majority of publications concerning iridium-catalysts using phosphorous-based ligands. Of these phosphorous based ligands, P,N-, P,O-and S,P-ligands have all been investigated.…”

Access to Enantiomerically Pure P-Chiral 1-Phosphanorbornane Silyl Ethers

“…Nowadays, AH is considered one of the most important enantioselective syntheses that gives access to many important optically active compounds. Among the widely used metals in such reactions, the iridium-catalyzed hydrogenations have been extensively studied [18][19][20][21][22]. The symmetric Crabtree catalyst [23], the chiral P,N bidentate PHOX ligand developed by Pfaltz et al [24][25][26] and BIPI ligands by Busacca et al [27] are key examples of Ir-based catalysts in hydrogenation reactions.…”

Asymmetric hydrogenation of 3-chloro-1-phenylpropan-1-one catalyzed by ruthenium complexes

“…Although many highly selective chiral catalysts have been successfully used for ketones hydrogenation, their industrial applications have been complicated by requirement to remove traces of the toxic metals from the product [9]. In order to overcome the problem, catalytic asymmetric reactions catalyzed by heterogeneous catalysts have been recently investigated, heterogeneous catalysts allowing for better reaction control and being easier separated off and recycled [10].…”

“…A recent report has also demonstrated the potential of ruthenium complexes [6]; on top of the promising catalytic promising, ruthenium compounds are better available and cheaper than rhodium or iridium ones. Several chiral triarylphosphine ligands have been successfully applied in asymmetric hydrogenation processes [7,8].Although many highly selective chiral catalysts have been successfully used for ketones hydrogenation, their industrial applications have been complicated by requirement to remove traces of the toxic metals from the product [9]. In order to overcome the problem, catalytic asymmetric reactions catalyzed by heterogeneous catalysts have been recently investigated, heterogeneous catalysts allowing for better reaction control and being easier separated off and recycled [10].…”