Takasago process

Perhaps the most successful industrial process for the synthesis of menthol is employed by the Takasago Corporation in Japan.4 The elegant Takasago Process uses a most effective catalytic asymmetric reaction - the (S)-BINAP-Rh(i)-catalyzed asymmetric isomerization of an allylic amine to an enamine - and furnishes approximately 30% of the annual world supply of menthol. The asymmetric isomerization of an allylic amine is one of a large and growing number of catalytic asymmetric processes. Collectively, these catalytic asymmetric reactions have dramatically increased the power and scope of organic synthesis. Indeed, the discovery that certain chiral transition metal catalysts can dictate the stereo-... 

We now turn to the Takasago Process for the commercial synthesis of (-)-menthol (1),4 one of the most successful industrial applications of catalytic asymmetric synthesis. This exquisite synthesis is based on the BINAP-Rh(i)-catalyzed enantioselecdve isomerization of allylic amines, and has been in operation for the commercial production of (-)-menthol since 1984. 

Scheme 12. The Takasago process for the asymmetric synthesis of (-)-menthol (1).

In the Takasago process ZnBr2 is used as the Lewis acid catalyst for the ring closure. Recently, zeolite Sn-Beta has been reported [20] as a heterogeneous and... 

An important application of an isomerisation is found in the Takasago process for the commercial production of (-)menthol from myreene. The catalyst used is a rhodium complex of BINAP, an asymmetric ligand based on the atropisomerism of substituted dinaphthyl (Figure 5.5). It was introduced by Noyori [1],... 

Enantiomerically pure citronellal in both of its antipodal forms has outstanding importance as a key intermediate for the production of fine chemicals, especially for the production of fragrances and flavors. In this respect the isomerization of diethylgeranylamine to R) -citronellal enamine in the presence of Rh /(S) -BINAP is an exceptional industrial process, for instance as one of the key steps of the Takasago process for the production of (-) -menthol [22]. In the search for alternatives for this process, both Josiphos and Daniphos derivatives were evaluated (Scheme 1.4.5) [23]. 

Large-scale manufacturing processes involving isomerization reactions by homogeneous catalysts are few. Two important ones are the isomerization step in the SHOP process and the enantioselective isomerization of diethylgeranyl or diethylnerylamine as practiced by the Takasago Perfumery. The isomerization step in the SHOP process is discussed later on in this chapter. The Takasago process is discussed in Chapter 9. Isomerization of alkenes with nitrile functionalities is very important in DuPont s hydrocyanation process. The mechanism for this reaction is discussed in Section 7.7. 

An elegant example of a highly efficient catalytic asymmetric synthesis is the Takasago process [128] for the manufacture of 1-menthol, an important flavour and fragrance product. The key step is an enantioselective catalytic isomerisation of a prochiral enamine to a chiral imine (Fig. 1.44). The catalyst is a Rh-Binap complex (see Fig. 1.44) and the product is obtained in 99% ee using a sub-strate/catalyst ratio of 8000 recycling of the catalyst affords total turnover numbers of up to 300000. The Takasago process is used to produce several thousand tons of 1-menthol on an annual basis. 

Thermal rearrangement of / -pinene affords myrcene (Fig. 8.43) which is the raw material for a variety of flavor and fragrance compounds, e.g. the Takasago process for the production of optically pure L-menthol (see Chapter 1). Dehydro-... 

A later paper by workers associated with the Takasago process reported on ab initio MO calculations for the catalytic cycle. Their work suggested that steps b and c (Scheme 9.22) involved an intramolecular OA of C-H, followed by a RE in which the hydride ligand attached itself to the terminal carbon of the allyl group. See M. Yamakawa and R. Noyori, Organometallics, 1992, 11, 3167. It is not clear which pathway is correct because the theoretical study used only PH3 and not BINAP to model the Rh-catalyzed isomerization. See also C. Chapuis, M. Barthe, and J.-Y. de Saint Laumer, Helv. Chim. Acta, 2001, 84, 230. 

Since several decades, for the manufacturing of synthetic menthol, two industrial processes are employed the Haarmann-Reimer Process and the Takasago Process. BASF has developed a third one, which has recently gone into use. 

The starting material for the Takasago process is N,N-diethylgeranylamine, which is obtained either from isoprene or from myrcene. 

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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