Asymmetric epoxidation homogeneous catalysis

The first successful achievements using asymmetric homogeneous transition metal catalysis were obtained in the asymmetric hydrogenation of alkenes24 25, This method has been successfully used in many synthetic applications (Section D.2.5.1.)26-29. In addition, chirally modified versions of the transition metal catalyzed hydrosilylation of olefins and carbonyl compounds (Sections D.2.3.1. and 2.5.1.) and olefin isomerization (Section D.2.6.2.) have been developed. Transition metal catalyzed asymmetric epoxidation constitutes one of the most powerful examples of this type (Section D.4.5.2.). 

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. 

Direct air epoxidation of propylene to propylene oxide suffers from selectivity problems. Epoxidation by alkyl hydroperoxide, as practiced by Arco, is based on the use of Mo(CO)g as a homogeneous catalyst. The most impressive use of homogeneous catalysis in epoxidation, however, is in the Sharpless asymmetric oxidation of allylic alcohols. In view of its importance, this enantioselective reaction is included in Chapter 9 which is devoted mainly to asymmetric catalysis. 

The application of fluorinated media seems to be a flourishing new area in homogeneous catalysis (103). However, until now enantioselective catalytic reactions in this alternative solvent are very rare. Chiral perfluoroalkylated SALEN-manganese complexes have been used for asymmetric epoxidation (104). 

The current research areas with ruthenium chemistry include the effective asymmetric hydrogenation of other substrates such as imines and epoxides, the synthesis of more chemoselective and enantioselective catalysts, COz hydrogenation and utilization, new methods for recovering and recycling homogeneous catalysts, new solvent systems, catalysis in two or three phases, and the replace-... 

The publication (70) in 1976 of the preparation of optically active epoxyketones via asymmetric catalysis marked the start of an increasingly popular field of study. When chalcones were treated with 30% hydrogen peroxide under (basic) phase-transfer conditions and the benzylammonium salt of quinine was used as the phase-transfer catalyst, the epoxyketones were produced with e.e. s up to 55%. Up to that time no optically active chalcone epoxides were known, while the importance of epoxides (arene oxides) in metabolic processes had just been discovered (71). The nonasymmetric reaction itself, known as the Weitz-Scheffer reaction under homogeneous conditions, has been reviewed by Berti (70). 

In the context of asymmetric catalysis, titanium silsesquioxanes containing the chiral ligand (lR,2S,5R)-(-)-menthoxo ligand (MentO) (figure 14.3) have been synthesized from the monosilanol la (R = cyclopentyl) and Ti(OPr )4 [70]. The molecular complexes were tested as asymmetric homogeneous catalysts for the epoxidation of cinammic alcohol with tert-butyl hydroperoxide and compared... 

In the presence of the immobilized (2S,4S)-4-hydroxyproline Mo catalyst (13b), nerol and geraniol react selectively with r-BuOOH to form the 2,3-epoxide with ee values of 64 and 47%, respectively. Surprisingly, when Mo is complexed by the diastereomeric (2S,4R) form (13a), racemic epoxidation is observed. The enantioselective catalysis appears to be promoted by immobilization in the zeolite USY pores. Indeed, in the epoxidation of nerol, an ee of 10% was found for the homogeneous asymmetric Mo complex, whereas the supported catalyst favors the selective production of the (2S,3R)-epoxide (64% ee). 

From a historical perspective, the Monsanto process for the preparation of (l.)-DOPA in 1974 laid the foundation stone for industrial enantioselective catalysis. Since then it has been joined by a number of other asymmetric methods, such as enantioselective Sharpless epoxidation (glycidol (ARCO) and disparlure (Baker)), and cyclopropanation (cilastatin (Merck, Sumitomo) and pyre-throids (Sumitomo)). Nevertheless, besides the enantioselective hydrogenation of an imine for the production of (S)-metolachlor(a herbicide from Syngenta), the Takasago process for the production of (-)-menthol remains since 1984 as the largest worldwide industrial application of homogeneous asymmetric catalysis. [124]... 

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