BINAP-Ru-catalyst

This facilitates intramolecular hydride transfer resulting in a Ru-hydroxy ester complex (66) which readily releases the chiral product. When an (R)-BINAP-Ru catalyst is used, the R enantiomer is obtained in >99% ee. The chirality of the BINAP ligand accounts for the difference in energy between the possible transition states TS and TS. ... 

Many synthetic applications of Rh-catalyzed hydrogenation of a-dehydroamino acid derivatives have recently been explored (Scheme 26.2). Takahashi has reported a one-pot sequential enantioseiective hydrogenation utilizing a BINAP-Rh and a BINAP-Ru catalyst to synthesize 4-amino-3-hydroxy-5-phenylpentanoic acids in over 95% ee. The process involves a first step in which the dehydroami-no acid unit is hydrogenated with the BINAP-Rh catalyst, followed by hydrogenation of the / -keto ester unit with the BINAP-Ru catalyst [87]. A hindered pyridine substituted a-dehydroamino acid derivative has been hydrogenated by a... 

Enantioselective hydrogenation of unsaturated alcohols such as allylic and homoallylic alcohols was not very efficient until the discovery of the BINAP-Ru catalyst. With Ru(BINAP)(OAc)2 as the catalyst, geraniol and nerol are successfully hydrogenated to give (S)- or (R)-citronellol in near-quantitative yield and with 96-99% ee [3 c]. A substratexatalyst ratio (SCR) of up to 48 500 can be applied, and the other double bond at the C6 and C7 positions of the substrate is not reduced. A high hydrogen pressure is required to obtain high enantioselec-... 

BINAP-Ru catalysts also show high enantioselectivity in the hydrogenation of/ -keto sulfonates. Reaction of sodium yS-keto sulfonates with (R)-BINAP-Ru catalyst quantitatively gives the (R)-/1-hydroxy sulfonates in up to 97% ee (Fig. 32.21) [15]. In the same manner, hydrogenation of / -keto sulfones in the presence of an (R)-MeO-BIPHEP-Ru catalyst affords the (R)-hydroxy sulfones in >95% ee [71]. 

In contrast to their success in the asymmetric hydrogenation of functionalized ketones, BINAP-Ru catalysts fail to give good results with simple ketone because such substrates lack heteroatoms that enable the substrate to anchor strongly to the Ru metal. 

BINAP Ru catalyst and (lR,25 )-ephedrine (Scheme 8-53). This result is similar to that obtained when catalyzed by pure (R)-BINAP. In pure (R)-BINAP complex-catalyzed hydrogenation, (S )-2-cyclohexenol can also be obtained with over 95% ee. This means that in the presence of (R)-BINAP-Ru catalyst, (R)-cyclohexenol is hydrogenated much faster than its (S )-enantiomer. When ephedrine is present, (R)-BINAP-Ru will be selectively deactivated, and the action of (S -BINAP-Ru leads to the selective hydrogenation of (S)-2-cyclohexenol, leaving the intact (R)-2-cyclohexenol in high ee. 

When racemic methyl a-(l-hydroxyethyl)aciylate is hydrogenated by using the (S)-BINAP-Ru catalyst, the R substrate is depleted more easily than the S. At 76% conversion, the unreacted S enantiomer is obtained in greater than 99% ee, as well as a 49 1 mixture of the threo (2R,3R) and the erythro saturated products. Hydrogenation of the S substrate with either antipodal Ru catalyst results in 2S,3S hydroxy ester with equally high threo selection (>23 1). These data indicate operation of overwhelming substrate control in this particular reaction. 

When racemic 3-methyl-2-cyclohexenol is hydrogenated by the BINAP-Ru catalyst at 4 atm H2, trcms- and cis-3-methylcyclohexanol are produced in a 300 1 ratio (Scheme 33). The reaction with the (/ )-BINAP complex affords the saturated R,3R trans alcohol in 95% ee in 46% yield and unreacted S allylic alcohol in 80% ee with 54% recovery. 

Kinetic Resolution of a Racemic Ketone. Kinetic resolution is a process by which one of the enantiomeric constituents of a racemate is more readily transformed into a product than the other (63b). For example, in the presence of an (/ )-BINAP-Ru catalyst, the S enantiomer of the a-hydroxy ketone is hydrogenated 64 times faster than R enantiomer, and, after 50.5% conversion, both the syn 1,2-diol and unreacted R hydroxy ketone are obtained in high ee (Scheme 61). 

Use of BINAP/Ru catalysts has achieved excellent optical yields, as high as >99%, in the hydrogenation of a variety of p-keto esters [1, 2, 14]. Following this success, methyl and ethyl 3-oxobutanoates have been used as representative substrates to check the enantioselective efficiency of new chiral ligands [3, 4,46]. 

It is difficult to hydrogenate benzoylacetic acid derivatives with a high optical yield. Recently, an (R)-SEGPHOS/Ru complex-catalyzed hydrogenation of the ethyl ester with an S/C of 10,000 under 30 atm of H2 afforded the S alcohol in 97.6% ee (Table of Scheme 20) [36]. MeO-BIPHEP and Tol-P-Phos also performed with a high level of enantioselection [49, 60], Hydrogenation of N-methylbenzoylacetamide with the (R)-BINAP/Ru catalyst gave the S alcohol in >99.9% ee and 50% yield [61]. 

Catalytic asymmetric hydrogenation processes have been at the forefront of practical applications. Following the classical Monsanto s L-DOPA production using DiPAMP-Rh catalyst, BINAP-Ru catalysts have been used in the industrial synthesis of a P-lactam key intermediate to caibapenem antibiotics (Takasago Int. Corp.), 1,2-propanediol (50 tons/year),... 

The minor R enantiomer is also produced via the same, but diastereomorphic, reaction path vay as proved by a detailed analysis of isotope incorporation patterns of both enantiomeric products. The enantioselectivity is determined at the first irreversible hydrogenolysis step, but practically at the formation of the cat/sub complexes 18s and 18j e. 18s is unfavored because of the existence of steric repulsion between alkoxycarbonyl group in the substrate and one of benzene rings on P atom of BINAP-Ru catalyst. In contrast to the Rh-catalyzed hydrogenation where the minor... 

A BINAP-Ru catalyst effectively discriminates between a hydroxy group and an alkoxy or aryloxy group, and even between u-octadecyl and triphenylmethoxy groups [174]. The S enantiomer of racemic l-hydroxy-l-phenyl-2-propanone is selected by (R)-BINAP-Ru complex to be hydrogenated to the corresponding 1S,2R diol in 92% e.e. (50.5%, syn-.anti = 98 2) [5c]. The rmreacted R hydroxy ketone in 92% e.e. (49.5%) is recovered, and the relative hydrogenation rate of the enantiomers, ks/kn, is calculated to be 64 1. 

Scheme 22 illustrates an industrial synthesis of l-DOPA (76) by Monsanto, USA. Other intermediates are manufactured similarly [79]. Relevantly, an (S)-BINAP-Ru" catalyst effects enantioselective hydrogenation of the suitable enamide (substrateicatalyst = 4000 1) to give, after recrystallization, optically pure Clozylacon (77), an excellent fungicide (Scheme 23) [34]. 

---