Applications in Enantioselective Hydrogenation of Alkenes

Ligand Sub- SCR strate Reaction conditions % ee of product (config.) Reference 

Several chiral ligands, such as PYRPHOS [78b], have been shown to be very efficient ligands for the hydrogenation of a-dehydroamino acid derivatives in terms of both high enantioselectivity and reactivity. 

In contrast to the high enantioselectivity achieved for the Z-isomeric substrates, hydrogenation of the S-isomeric substrates usually proceeds at a much lower rate and gives poor enantioselectivities [86]. With the Rh-BINAP system as the catalyst and tetrahydrofuran (THF) as solvent, hydrogenation of the Z-and S-isomeric substrates generates products with different configurations [2]. 

DIPAMP-Rh complex to give the corresponding chiral a-amino acid derivative in over 98% ee. The chiral product has been used for the synthesis of (S)-(-)-ac-romelobic acid [88]. Hydrogenation of a tetrahydropyrazine derivative catalyzed by a PHANEPHOS-Rh complex at -40 C gives an intermediate for the synthesis of Crixivan in 86% ee [82a]. Hydrogenation of another tetrahydropyrazine carboxamide derivative catalyzed by an (R)-BINAP-Rh catalyst leads to the chiral product in 99% ee [89]. 

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This chapter describes, from an historic perspective, the development of ligands and catalysts for enantioselective hydrogenations of alkenes. There is no in-depth discussion of the many ligands available as the following chapters describe many of these, as well as their specific applications. The purpose here is to provide an overall summary and perspective of the area. By necessity, a large number of catalyst systems have not been mentioned. The discussion is also limited to the reductions of carbon-carbon unsaturation. In almost all cases, rhodium is the transition metal to catalyze this type of reduction. In order to help the reader, the year of the first publication in a journal has been included in parentheses under each structure. 

As recently recognized by the Nobel Chemistry award committee, the conceptualization, development, and commercial application of enantioselective, homogeneous hydrogenation of alkenes represents a landmark achievement in modem chemistry. Further elaboration of asymmetric hydrogenation catalysts by Noyori, Burk, and others has created a robust and technologically important set of catalytic asymmetric synthetic techniques. As frequently occurs in science, these new technologies have spawned new areas of fundamental research. Soon after the development of... 

Abstract Chiral ferrocenyl phosphine ligands are certainly one of the most developed and successful classes of chiral ligands used in asymmetric catalysis. The literature describing their synthetic and coordination chemistry, as well as their metal-mediated applications in the field of catalysis, is extremely rich and varied. Moreover, they represent a rare example in which enantioselective chemical catalysts were used in industrial processes. The present chapter provides an account of the planar-chiral ferrocene ligands developed in the Authors laboratory, including their coordination chemistry with various metals as well as their use in different asymmetric catalytic reactions (allylic substitution, Suzuki coupling, methoxycarbonylation of alkenes, hydrogenation of ketones). 

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