Asymmetric catalysis isomerization

The commercialization in 1983 of the process illustrated in Eq. (1) is undoubtedly one of the most significant triumphs of asymmetric catalysis to date [2]. Takasago Chemical Company produced more than 22 000 tons of menthol by this route during the period 1983-1996, consuming only 125 kg of the chiral Hgand in the process. Rh(I)/Tol-BINAP-catalyzed isomerizations of allylic amines are beheved to proceed through the pathway outlined in Eq. (2) [3]. 

One of the landmark achievements in the area of enantioselective catalysis has been the development of a large-scale commercial application of the Rh(I)/BINAP-catalyzed asymmetric isomerization of allylic amines to enamines. Unfortunately, methods for the isomerization of other families of olefins have not yet reached a comparable level of sophistication. However, since the early 1990s promising catalyst systems have been described for enantioselective isomerizations of allylic alcohols and aUylic ethers. In view of the utility of catalytic asymmetric olefin isomerization reactions, I have no doubt that the coming years will witness additional exciting progress in the development of highly effective catalysts for these and related substrates. 

Organometallic compounds asymmetric catalysis, 11, 255 chiral auxiliaries, 266 enantioselectivity, 255 see also specific compounds Organozinc chemistry, 260 amino alcohols, 261, 355 chirality amplification, 273 efficiency origins, 273 ligand acceleration, 260 molecular structures, 276 reaction mechanism, 269 transition state models, 264 turnover-limiting step, 271 Orthohydroxylation, naphthol, 230 Osmium, olefin dihydroxylation, 150 Oxametallacycle intermediates, 150, 152 Oxazaborolidines, 134 Oxazoline, 356 Oxidation amines, 155 olefins, 137, 150 reduction, 5 sulfides, 155 Oxidative addition, 5 amine isomerization, 111 hydrogen molecule, 16 Oxidative dimerization, chiral phenols, 287 Oximes, borane reduction, 135 Oxindole alkylation, 338 Oxiranes, enantioselective synthesis, 137, 289, 326, 333, 349, 361 Oxonium polymerization, 332 Oxo process, 162 Oxovanadium complexes, 220 Oxygenation, C—H bonds, 149... 

During the past decade, metal-catalyzed asymmetric reactions have become one of the indispensable synthetic methodologies in academic and industrial fields. The asymmetric isomerization of allylamine to an optically active enamine is a typical example of the successful application of basic research to an industrial process. We believe that Takasago s successful development of large-scale asymmetric catalysis will have a great impact on both synthetic chemistry and the fine chemical industries. The Rh-BINAP catalysts, though very expensive, have become one of the cheapest catalysts in the chemical industry through extensive process development. 

Noyori s BINAP catalysts deserve special attention because their chirality is based on the bulkiness of the naphthalene groups, rather than on carbon or phosphorus asymmetric centers (Figure 3.28, inset) [77]. One of the many examples of asymmetric catalysis using BINAP is the synthesis of (—)-menthol, an important additive for flavors, fragrances, and pharmaceuticals. Starting from myrcene, the process is carried out by Takasago International on a multi-ton scale. The key step is the isomerization of geranyldiethylamine to (R)-citronellal enamine [78], which is then hydrolyzed to (R)-citronellal with nearly 99% ee. 

S. Otsuka, K. Tani, Asymmetric Catalytic Isomerization of Functionalized Olefins, In Asymmetric Synthesis, Vol. 5, Chiral Catalysis, J. D. Morrison, Ed. Academic Press Orlando, 1985,... 

S. Akutagawa, Isomerization of Carbon-Carbon Double Bonds, In Comprehensive Asymmetric Catalysis,... 

Asymmetric catalysis undertook a quantum leap with the discovery of ruthenium and rhodium catalysts based on the atropisomeric bisphosphine, BINAP (3a). These catalysts have displayed remarkable versatility and enantioselectivity in the asymmetric reduction and isomerization of a,P- and y-keto esters functionalized ketones allylic alcohols and amines oc,P-unsaturated carboxylic acids and enamides. Asymmetric transformation with these catalysts has been extensively studied and reviewed.81315 3536 The key feature of BINAP is the rigidity of the ligand during coordination on a transition metal center, which is critical during enantiofacial selection of the substrate by the catalyst. Several industrial processes currently use these technologies, whereas a number of other opportunities show potential for scale up. 

The world s biggest application of asymmetric catalysis is Takasago Perfumery s synthesis of (-)-menthol from myrcene (see Sections 2.9 and 3.3.1) with about 1500 t/a (menthol and other chiral terpenic substances). The key step is the isomerization of geranyldiethylamine with an Rh -S-BINAP catalyst to citronellal ( )-enamine (eqs. (17)) (BINAP = 2,2 -bis(diphenylphosphine)-l,l -binaphthyl).The geometry of the double bond is 100% E. 

S. Akutagawa, Asymmetric Isomerization of Olefins in E. N. Jacobsen, A. Pfaltz, H. Yamamoto, Comprehensive Asymmetric Catalysis, Vol III, Springer-Verlag, Berlin 1999, p. 1461-1477. 

In pyridine solutions, the statistically corrected relative catalytic coefficients of tertiary amines for 1-methylindene isomerization decreased in the order24 4. quinuclidine, 80 DABCO, 10 triethylamine, 1. The smaller catalytic effectiveness of DABCO than quinuclidine is attributable to its weaker basicity is —30eu for each of these bicyclic bases. On the other hand, triethylamine is about as basic as quinuclidine, but must lose considerable rotational freedom in the rate-limiting proton transfer. This is reflected in the more negative entropy of activation (—39eu) for the triethyl-amine-catalyzed reaction. In pyridine solution, there is a close correlation between pa s of the catalyzing base and A// for 1-methylindene isomerization. Asymmetric catalysis was demonstrated in the quinine-catalyzed isomerization of optically active 1-methylindene in pyridine at 25°C the dextrorotatory indene isomerized nearly twice as fast as its enantiometer247. 

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. 

Especially noteworthy is the field of asymmetric catalysis. Asymmetric catalytic reactions with transition metal complexes are used advantageously for hydrogenation, cyclization, codimerization, alkylation, epoxidation, hydroformylation, hydroesterification, hydrosilylation, hydrocyanation, and isomerization. In many cases, even higher regio- and stereoselectivities are required. Fundamental investigations of the mechanism of chirality transfer are also of interest. New chiral ligands that are suitable for catalytic processes are needed. 

Note at the outset that asymmetric catalysis in the synthesis of fine chemicals is rarely a single-step process that converts a reactant directly to the final product. It is usually one of the steps in a total synthesis but is often the key step. Hence the analysis of the overall yield will be based on the methods described in Chapter 5. There are many types of reactions where asymmetric catalysis can be applied. The most important of these are C-C bond-forming reactions such as alkylation or nucleophilic addition, oxidation, reduction, isomerization, Diels-Alder reaction, Michael addition, deracemization, and Sharpless expoxidation (of allyl alcohols). A few representative examples (homogeneous and heterogeneous) are given in Table 9.6. 

Besides the more common reactions such as hydrogenation, isomerization, alkylation, and the Diels-Alder reaction. Sharpless epoxidation and dihydroxylation by asymmetrical catalysis are rapidly emerging as reactions with immense industrial potential. Table 9.7 lists some important syntheses based on asymmetric catalysis. These include processes for the pharmaceutical drugs (S)-naproxen, (S)-ibuprofen, (,S)-propranolol, L-dopa, and cilastatin, a fragrance chemical, L-menthol, and an insecticide (/ )-disparlure. Deltamethrin, an insecticide, is another very good example of industrial asymmetric synthesis. The total synthetic scheme is also given for each product. In general, the asymmetric step is the key step in the total synthesis, but this is not always so, as in the production of ibuprofen. Many of the processes listed in the table are in industrial production. 

Selective monosubstitution in the starting dibromide by PPh2 was realized at lowtemperatures [71]. Conversion of the second bromo substituent into the phosphorus diamide and final reaction with the diol produced the hybrid ligand. In the hydroformylation of 2,5-dihydrofuran, up to 91% ee with no isomerization was achieved, which is the best value reported to date. Noteworthy, the partially hydrogenated binaphthyl unit and the phenyl substituents in the 3,3 -positions are essential for the success of the asymmetric catalysis. Related ligands with a binaphthyl backbone, with or without Me-substituents in 3,3 -positions, resulted in poor conversions and stereoselectivities. 

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