BINAP Ru complex

Caution BINAP-Ru complexes are rapidly oxidized in solution in the presence of air and all procedures should be carried out under anaerobic conditions using degassed solvents. 

Several chiral Ru complexes have been applied successfully for the asymmetric hydrogenation of a-, (3-, and y-diketones. Hydrogenation of an a-diketone, 2,3-butandione, catalyzed by an (i )-BINAP-Ru complex gives optically pure (R,R)-2,3-butanediol and the meso-diol in a ratio of 26 74 (Equation (73)).12a... 

BINAP-Ru is effective for the diastereoselective hydrogenation of some chiral yS-keto esters (Fig. 32.13). Reaction of N-Boc-protected (S)-y-amino / -keto esters 13A catalyzed by the (R)-BINAP-Ru complex results in the syn alcohols 13B exclusively [52]. The stereocenter at the / -position is controlled by the chirality of the catalyst therefore, use of the S catalyst affords the anti isomer, as predicted. Derivatives of statine, a key component of the aspartic proteinase inhibitor pep-... 

Fig. 32.17 Mono-hydrogenation of 1 -phenyl-1,3-butanedione catalyzed by a BINAP-Ru complex.

Enantioselective hydrogenation of / -keto phosphonates in the presence of an ( R)-BINAP-Ru complex under 1-4 atm H2 and at room temperature provides the (R)-yS-hydroxy phosphonates in up to 99% ee (Fig. 32.20) [69]. The sense of enantioface selection is the same as that observed in the reaction of / -keto carboxylic esters (see Fig. 32.14). A BDPP-Ru catalyst is also usable [70]. Similarly, / -keto thiophosphonates are hydrogenated with a MeO-BIPHEP-Ru catalyst with up to 94% optical yield [69 b]. 

Fig. 32.49 Hydrogenation of ketones catalyzed by racemic BINAP-Ru complexes and (S,S)-DPEN asymmetric activation.

Asymmetric hydrogenation of prochiral ketones,s Ketones substituted in the a- or (3-position by diverse polar groups, particularly OH,OR,NR2,COOR, can undergo highly enantioselective hydrogenation catalyzed by BINAP-Ru complexes. A key factor of asymmetric induction is undoubtedly chelation of the carbonyl group and the hetero atom to the Ru atom. 

Crude BINAP-Ru complex with consistent spectral characteristics can be used for hydrogenation of geraniol (98.7% pure commercial geraniol containing 1.3% of nerol, distilled from 4 A molecular sieves, 4.7 M substrate in 95% aqueous methanol, 2.8 mM Ru(OCOCH3)2[(R)-BINAP], 100 atm of H2, 20°C, 8 hr), to give (S)-citronellol in 96% ee, 97% isolated yield. 

Figure 1.13. Asymmetric hydrogenation of functionalized ketones catalyzed by BINAP-Ru complexes.

Double Hydrogenation of 1,3- and 1,2-Diketones. Scheme 57 illustrates another example of highly enantioselective formation of alcoholic products. The BINAP-Ru(II)-catalyzed hydrogenation of prochiral 1,3-diketones produces diastereomeric 1,3-diols, for which the dl or anti isomers are always dominant and ee values are uniformly high (92,105). For example, the reaction of 2,4-pentanedione catalyzed by an (R)-BINAP-Ru complex produces a 99 1 mixture of almost enantiomer-... 

BINAP-Ru complexes can catalyze the enantioselective hydrogenation of alkenyl ethers as shown in Scheme 1.15 [93], 2-Methyltetrahydrofuran with 91% ee and 87% ee can be synthesized by BINAP-Ru-catalyzed hydrogenation of 2-methylenetetrahydrofuran and the endo-type substrate, 2-methyl-3,4-dihydrofuran, in CH2C12 under 100 atm of hydrogen, respectively. With the same Ru complex, phenyl 1-phenylethyl ether, an acyclic alkenyl ether, is reduced in a moderate optical yield. 

P,y-Unsaturated carboxylic acids, shown in Scheme 18, are also enantioselectively hydrogenated with the aid of BINAP- or Hg-BINAP-Ru complexes to give the saturated acids with 80-90% ee [99,111]. 

The asymmetric hydrogenation of a-, fS-, or y-keto esters with BINAP-Ru complexes has been used for synthesis of a wide variety of natural chiral compounds as shown in Figure 1.11 [192], The asymmetric reduction determines the stereocenter labeled by R or S. 

The BINAP-Ru complex effectively differentiates enantiomers of 1-hydroxy-l-phenyl-2-propanone. Hydrogenation of the racemic compounds catalyzed by an (R)-BINAP-Ru complex gives the corresponding IS,2R diol with a 92% optical purity and unreacted R substrate with 92% ee at 50.5% conversion (Scheme 1.45) [lc]. The relative hydrogenation rate of the enantiomers, k /kR, is calculated to be 64 1. 

---