Allyl asymmetric hydrogenation

Enzymatic hydrolysis of A/-acylamino acids by amino acylase and amino acid esters by Hpase or carboxy esterase (70) is one kind of kinetic resolution. Kinetic resolution is found in chemical synthesis such as by epoxidation of racemic allyl alcohol and asymmetric hydrogenation (71). New routes for amino acid manufacturing are anticipated. 

Asymmetric hydrogenation of geraniol and nerol in methanol at room temperature and an initial hydrogen pressure of 90-100 atm gives citronellol in 96-99% ee and in quantitative yields. The allylic and non allylic double bonds in the substrate can be clearly differentiated to obtain the product contaminated with less than 0.5% dihydrocitronellol (Mookherjee, 1997). 

Thus, [HRh(C0)(TPPTS)3]/H20/silica (TPPTS = sodium salt of tri(m-sulfophenyl)phopshine) catalyzes the hydroformylation of heavy and functionalized olefins,118-122 the selective hydrogenation of a,/3-unsaturated aldehydes,84 and the asymmetric hydrogenation of 2-(6 -methoxy-2 -naphthyl)acrylic add (a precursor of naproxen).123,124 More recently, this methodology was tested for the palladium-catalyzed Trost Tsuji (allylic substitution) and Heck (olefin arylation) reactions.125-127... 

Enantiomencally pure (+)- and (-)-diphenylethylenediamines have recently been used for highly stereoselective Dlels-Alder, aldol,8 allylation,9 osmylation,10 and epoxidafion11 reactions. Other synthetic applications involve enantioselective Michael addition12 and asymmetric hydrogenation.13... 

Complexes containing one binap ligand per ruthenium (Fig. 3.5) turned out to be remarkably effective for a wide range of chemical processes of industrial importance. During the 1980s, such complexes were shown to be very effective, not only for the asymmetric hydrogenation of dehydroamino adds [42] - which previously was rhodium s domain - but also of allylic alcohols [77], unsaturated acids [78], cyclic enamides [79], and functionalized ketones [80, 81] - domains where rhodium complexes were not as effective. Table 3.2 (entries 3-5) lists impressive TOF values and excellent ee-values for the products of such reactions. The catalysts were rapidly put to use in industry to prepare, for example, the perfume additive citronellol from geraniol (Table 3.2, entry 5) and alkaloids from cyclic enamides. These developments have been reviewed by Noyori and Takaya [82, 83]. 

Allylic alcohol derivatives are quite useful in organic synthesis, so the asymmetric synthesis of such compounds via asymmetric hydrogenation of dienyl (especially enynyl) esters is desirable. The olefin functionality preserves diverse synthetic potential by either direct or remote functionalization. Boaz33 reported that enynyl ester and dienyl ester were preferred substrates for asymmetric hydrogenation using Rh-(Me-DuPhos) catalyst [Rh(I)-(R,R)-14], and products with extremely high enantioselectivity (>97%) were obtained (Schemes 6-11 and 6-12). 

Related catalytic enantioselective processes It is worthy of note that the powerful Ti-catalyzed asymmetric epoxidation procedure of Sharpless [27] is often used in the preparation of optically pure acyclic allylic alcohols through the catalytic kinetic resolution of easily accessible racemic mixtures [28]. When the catalytic epoxidation is applied to cyclic allylic substrates, reaction rates are retarded and lower levels of enantioselectivity are observed. Ru-catalyzed asymmetric hydrogenation has been employed by Noyori to effect the resolution of five- and six-membered allylic carbinols [29] in this instance, as with the Ti-catalyzed procedure, the presence of an unprotected hydroxyl function is required. Perhaps the most efficient general procedure for the enantioselective synthesis of this class of cyclic allylic ethers is that recently developed by Trost and co-workers, involving Pd-catalyzed asymmetric additions of alkoxides to allylic esters [30]. 

ASYMMETRIC HYDROGENATION OF ALLYLIC ALCOHOLS USING BINAP-RUTHENIUM COMPLEXES (S)-(-)-CITRONELLOL (6-Octen-1-ol, 3,7-dimethyl, (S)-)... 

The next four procedures are based on some recent advances in catalysis. The first of these, an asymmetric hydrogenation of an allylic alcohol, illustrates yet another... 

The enantioselectivity is not very sensitive to the nature of the allylic alcohol. By contrast, titanium and tartrates are essential to the success. This catalyst components combination is unique note the difference with the L-Dopa asymmetric hydrogenation, which can be carried out with hundreds of C2-chiral diphosphines, even monophosphines, but with a limited number of substrates only. 

The use of surface bound triflate ions has been exploited by Raja et al. to immobilize the complexes [Rh(COD) fSj-(-i-)-PMP ], [Pd(allyl) fSj-(-i-)-PMP ], [Rh(COD) fSj-(-)-AEP rand[Rh(COD) flR,2Rj-(-t)-DED ]"in the pores of silicas possessing various pore sizes with narrow distributions [128]. These constrained chiral catalysts were then tested for the asymmetric hydrogenation of methyl ben-zoylformate to its corresponding methyl mandelate (40°C, methanol, 2 MPa H2). In the homogenous form, only the catalysts [Rh(COD) fSj-(-i-)-PMP ], [Pd(allyl) (Sj-(-i-)-PMP ] exhibit any signiflcant e.e.s under the reaction conditions (53%... 

Substituted acrylates (which reseitible the enamide substrates employed 1n asymmetric hydrogenation) may be deracemized by reduction with an optically active catalyst, especially DIPAMPRh . Selectivity ratios of 12 1 to 22 1 have been obtained for a variety of reactants with compounds of reasonable volatility, separation of starting material and product may be effected by preparative GLC. Recovered starting material can then be reduced with an achiral catalyst to give the optically pure anti product. Examples of kinetic resolutions by this method are given in Table II. More recently very successful kinetic resolutions of allylic alcohols have been carried out with Ru(BINAP) catalysts. 

Kissel, Ramsden, and other researchers at Pfizer and Chirotech jointly published a novel chiral synthesis of pregabalin (2) in 2003 based on asymmetric hydrogenation (Burk et al., 2001, 2003). Their synthesis started with the condensation of isobutyralde-hyde with acrylonitrile under Baylis-Hillman conditions to give allylic alcohol 65. This alcohol was activated as the carbonate 66 and subjected to palladium-catalyzed car-bonylation conditions to give cyanoester 67. The ester 67 was hydrolyzed and converted to... 

SCH EME 29. Asymmetric hydrogenation of allylic alcohols catalyzed by Ru(OCOCH3)2-[(S)-binap] in methanol at 4 and 100 atm. 

A cationic Ir complex possessing phosphanodihydrooxazole 26 is usable for asymmetric hydrogenation of allylic alcohols. (E)-2-Methyl-3-phenyl-2-propen-l-ol can be converted in CH2C12 containing 1 mol % of the Ir complex to the saturated product in 95% yield and 96% ee (Scheme 1.26) [141]. The process is used in the enantioselective synthesis of the artificial fragrance filial. 

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