Takasago

International Flavors and Fragrances, Quest International, Givaudan, Takasago, Haarmann Reimer... 

Jptt Kokai Tokkyo Koho, 116,348 (1978) (to Takasago Perfumery Co.). 

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-... 

The disclosure, in 1982, that cationic, enantiopure BINAP-Rh(i) complexes can induce highly enantioselective isomerizations of allylic amines in THF or acetone, at or below room temperature, to afford optically active enamines in >95 % yield and >95 % ee, thus constituted a major breakthrough.67-68 This important discovery emerged from an impressive collaborative effort between chemists representing Osaka University, the Takasago Corporation, the Institute for Molecular Science at Okazaki, Japan, and Nagoya University. BINAP, 2,2 -bis(diphenylphosphino)-l,l -binaphthyl (Scheme 7), is a fully arylated, chiral diphosphine which was introduced in... 

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).

Takasago International Co. commercialized this hydrogenation method for the production of a chiral intermediate for the synthesis of carbapenem antibiotics (Equation (8)).29... 

R)-Citronellal purchased from Aldrich Chemical Company, Inc., Dragoco, Holzmlnden, or Takasago, Perfumery Co., Ltd., Tokyo was used as received. (R)-Citronellal can also be synthesized from pulegone with ee > 99%.3 The optical purity... 

Takasago A catalytic process for the enantioselective isomerization of allylic amines. The catalyst is a chiral rhodium complex. Used in the manufacture of (-)menthol. Named after Takasago International Corporation, the Japanese company which commercialized the process in 1983. 

Merck has developed a pilot process for the hydrogenation of an intermediate 20 for MK-0431 (Fig. 34.13) and carried out the reduction on a >50-kg scale with ee-values up to 98%, albeit with low to medium TONs and TOFs [84]. Takasago has developed a reductive animation version where the corresponding />-keto ester is hydrogenated in the presence of amines, giving directly the corresponding /5-ami-no ester, though as yet no details are available of this process [83]. 

One of the first applications of the then newly developed Ru-binap catalysts for a,/ -unsaturated acids was an alternative process to produce (S)-naproxen. (S)-Naproxen is a large-scale anti-inflammatory drug and is actually produced via the resolution of a racemate. For some time it was considered to be one of the most attractive goals for asymmetric catalysis. Indeed, several catalytic syntheses have been developed for the synthesis of (S)-naproxen intermediates in recent years (for a summary see [14]). The best results for the hydrogenation route were obtained by Takasago [69] (Fig. 37.15), who recently reported that a Ru-H8-binap catalyst achieved even higher activities (TON 5000, TOF 600 h 1 at 15 °C, 50 bar) [16]. 

R)-l,2-Propanediol is an intermediate for (S)-oxafloxazin, a bactericide which until recently was sold as a racemate. The (R)-diol is now produced by Takasago via hydrogenation of hydroxyacetone (see Fig. 37.23) using a Ru-Tol-binap catalyst on a 50 t y 1 scale [92 b[. Recently, it was reported that segphos - a newly developed biaryl diphosphine - shows even better results, achieving >98% ee and TON and TOF of 10000 and 1400 h, respectively [16, 93]. 

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