Hydrogenation BINAP-RuCl2-catalyzed

The BINAP/l,2-diamine-RuCl2 complexes require the addition of alkaline base to form reactive RuH2 species for the hydrogenation of simple ketones to neutralize releasing HC1. trans-RuH( /1-BH4)(xylbinap)(dpen) (31G) produces the active species without an additional base, while an even higher rate is obtainable in the presence of an alkaline base (Fig. 32.31) [102]. The base-free procedure can be applied to the hydrogenation of several base-sensitive ketones. For example, the reaction of ethyl-4-acetylbenzoate catalyzed by (S,SS)-31G quantitatively yields ethyl (R)-4-(l-hydroxyethyl)benzoate in 99% ee [102]. No transesterification is observed. 

Mikami et al. also reported the activation of a racemic catalyst in Ru-BINAP-catalyzed asymmetric hydrogenation (Scheme 9.22) [40]. The combination of racemic RuCl2[( )-39] and... 

Use of a BINAP/chiral diamine Ru complex trans- RuCl2[(R)-xylbinap][(R)-daipen] or the S,S complex efficiently catalyzes asymmetric hydrogenation of heteroaromatic ketones, with little influence of the ring properties on the enantioselectivity. Duloxetine, an inhibitor of serotonin and norepinephrine uptake carriers, has been synthesized in this way (Ohkuma, 2000b). 

The discovery by the recent Nobel-laureate, Ryoji Noyori, of asymmetric hydrogenation of simple ketones to alcohols catalyzed by raras-RuCl2[(S)-binap][(S,S)-dpen] (binap = [l,l -binaphthalene-2,2/-diyl-bis(diphenylphosphane)] dpen = diphenylethylenediamine) is remarkable in several respects (91). The reaction is quantitative within hours, gives enantiomeric excesses (ee) up to 99%, shows high chemoselecti-vity for carbonyl over olefin reduction, and the substrate-to-catalyst ratio is >100,000. Moreover, the non-classical metal-ligand bifunctional catalytic cycle is mechanistically novel and involves heterolytic... 

Except for unsaturated residues R, p-hydroxy esters (4) of excellent optical purity can also be obtained by enantioselective hydrogenation of the corresponding p-keto esters catalyzed by RuCl2(BINAP).i ... 

BINAP/DPEN/Ru(II)-catalyzed Asymmetric Hydrogenation of Simple Ketones. Ru(II) complexes having a formula of fra/w-RuCl2(diphosphine)(dpen) are most conveniently obtained by treatment of oligomeric RuCl2(diphosphine)(dmf) with 1.1 equiv of DPEN in DMF at room temperature [diphosphine = 2,2 -bis(diphenylphosphino)-1,1 -binaphthyl (BINAP), 2,2 -bis(di-4-tolylphosphino)-l,l -binaphthyl (TolBINAP), 2,2 -bis(di-3,5-... 

When the cyclic enone is hydrogenated with the racemic Tol-BINAP/Ru(II) complex and (5, 5)-DPEN under otherwise identical conditions, the 5 allylic alcohol is obtained in 95% ee and 100% yield. The ee value is close to the 96% attained with the enantiomerically pure (f )-TolBINAP/ 5, 5)-DPEN system. Hydrogenation of o-methylacetophenone catalyzed by RuCl2[( )-tolbinap](dmf) and (5,5)-DPEN results in the R alcohol in 90% ee and 100% yield (eq 6). The S/S,S catalyst gives the R product in 97.5% ee. 

The asymmetric ruthenium catalyst [RuCl2-(S)-tolyl-binap 2 NEtj ((S)-tolyl-binap = dichloro[(S)-(-)-2,2 -bis(di-p-tolylphosphino)-l,l -binaphthyl]) has been used in [BMIM][BF4]- PrOH to catalyze the hydrogenation of ( )-methyl-2-hydroxy-2-methylenebutanoate [see Eq. (5)] [64]. The effect ofhydrogen pressure was evaluated in this study and it was found that the highest ee of 98% was obtained at 4 MPa, although the yield of the product was quite low. 

The discovery by the recent Nobel laureate, Ryoji Noyori, of asymmetric hydrogenation of ketones to alcohols catalyzed by /ra 3-RuCl2[( y)-binap][(A,5)-dpen] (binap = [1,1 -binaphthalene-2,2 -diylbis(diphenylphosphane)] ... 

Y Sun, C LeBlond, J Wang, DG Blackmond, J Laquidara, JR Sowa Jr. Observation of a [RuCl2((S)-(—)-tol-binap)]2 N(C2H5)3-catalyzed isomerization hydrogenation network. J Am Chem Soc 117 12647-12648, 1995. 

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