Hydrogenation enantioselective homogeneous

This thoroughly revised and updated new edition is a must for every synthetic organic chemist. New material has been added on homogene- ous diastereoselective hydrogenations, enantioselective oxidations, and novel chiral auxiliaries. 

In 1968, Knowles et al. [1] and Horner et al. [2] independently reported the use of a chiral, enantiomerically enriched, monodentate phosphine ligand in the rhodium-catalyzed homogeneous hydrogenation of a prochiral alkene (Scheme 28.1). Although enantioselectivities were low, this demonstrated the transformation of Wilkinson s catalyst, Rh(PPh3)3Cl [3] into an enantioselective homogeneous hydrogenation catalyst [4]. 

A wide range of a,fi-unsaturated carboxylic acids, including substituted acrylic acids, undergo enantioselective homogeneous hydrogenation when catalyzed by... 

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... 

As an aside, decades of work have gone into the study of enantioselective homogeneous hydrogenation processes in both organic and aqueous systems. There is increasing commercial interest in this field spurred by the spectacular, time-encrusted development of a complex catalyst for the enantioselective hydrogenation of an imine to a chiral amine needed for manufacture of the important herbicide, (,S )-Metolaclor. The technical success of this program (Scheme l)25 owed much to the perserverance... 

SCHEME 1. Enantioselective homogeneous hydrogenation in the manufacture of (S)-metolaclor.25... 

Fig. 17.77. Enantioselective homogeneous catalytic hydrogenations of two stereoiso-meric -(acylamino)acrylic acids to one and the same R-amino acid. - The mechanism of the hydrogenation of these acids is exemplified by their Z-isomer Figure 17.78.

Enantioselective homogeneous catalytic hydrogenations of an a-(acylamino)acrylic acid to an R-amino acid. 

Enantioselective homogeneous hydrogenation catalyzed by chiral transition metal complexes is one of the most well established transformations in asymmetric synthesis [1]. Excellent enantioselectivities have been achieved in the hydrogenation of a wide range of substrates, often with very low catalyst loadings. High reliability, mild reaction conditions, and perfect atom economy are further attractive attributes of this method. In particular complexes based on Ru or Rh have found broad application in industrial processes [1] and the impact of these catalysts has been recognized by the Nobel Prize awarded to Ryoji Noyori and William S. Knowles in 2001 [2]. 

Together with hydrogenation and isomerization, epoxidation completes the trio of commercially significant applications of enantioselective homogeneously catalyzed reactions. Stereospecific olefin epoxidation is distinctive in that it creates two chiral centers simultaneously. The enantioselective epoxidation method developed by Sharpless and co-workers is an important asymmetric transformation known today. This method involves the epoxidation of allylic alcohols with tert.-butyl hydroperoxide and titanimn isopropoxide in the presence of optically active pure tartrate esters (Eq. 3-14). 

It seems likely that the principal reactions discussed before, namely asymmetric hydrogenation, isomerization, and epoxidation, wUl ultimately find extensive use in the production of pharmaceuticals, given the regulatory trend towards the treatment of enantiomers of the same compound as distinct therapeutic agents. The complex chemistry in this area comprises a relatively young discipline, but there can be no doubt that commercial applications of enantioselective homogeneous catalysis are set to increase rapidly. 

Knowles and co-workers reported that DiPAMP, the most well-known P-stereogenic phosphine, gave 12 with an outstanding (at that time) 96% ee. With this phosphine many other enamides, enol esters and similar compounds could be hydrogenated in high ee. This work can be considered a milestone in the field of enantioselective homogeneous catalysis and have been profusely cited. William S. Knowles was awarded (along with Ryoji Noyori and Barry Sharpless) the Nobel Prize in Chemistry for the year 2001 for his contributions to enantioselective catalysis. ... 

This is the classical asymmetric hydrogenation mechanism, taught in every course on enantioselective homogeneous catalysis. By the end of 1990s, each step of this mechanism had been studied in detail, including the preparation and characterisation of all the intermediates, with the exception of dihydride complexes 14, whose detection remained elusive. ... 

Figure 2.29. The enantioselective hydrogenation by homogeneous Rh-BINAP catalyst.

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