Asymmetric Hydrogenation of 3-Keto Esters

Table 9.1 Asymmetric hydrogenation of (3-keto esters using [Ru(BiNAP)] complexes (results according to the relevant publications).

BTNAP is available as either the (+)- or (- )-enaiitionier and displays broad utility in rhodium- and ruthenium-catalyzed asymmetric hydrogenations of (3-keto esters and alkenes. ... 

King, S. A. Thompson, A. S. King, A. O. Verhoeven, T. R., An Improved Procedure for the Synthesis and Use of [RuC12(BINAP)]2 NEty Dependence of the Ru(II)-BINAP Catalyzed Asymmetric Hydrogenation of 3-Keto esters on Trace Amounts of Acid. J. Org. Chem. 1992, 57, 6689. 

Asymmetric hydrogenation of (3-keto esters is most successfully achieved by using BINAP-Ru(II) catalysts [8, 9, 18, 19, 20]. Halogen-containing complexes... 

Diphosphine 37 forms a Pd complex to catalyze allylic substitution, and it also derives a Ru catalyst for asymmetric hydrogenation of (3-keto esters. ... 

Asymmetric hydrogenation of (3-keto esters has been very successful using chiral Ru catalysts and a detailed review on this subject is available.1 The BINAP-Ru catalyst gives high enantioselectivity on a variety of (3-keto esters.228 Furthermore, a Josiphos-Rh complex is found to be effective for hydrogenation of ethyl 3-oxobutanoate 76 to afford p-hydroxy ketone 77 with good enantioselectivity.34... 

The synthesis of the C6-C13 subunit was started with asymmetric hydrogenation of (3-keto ester 44 promoted by Ru(II)-(5)-SYNPHOS catalyst. Reaction was accomplished in EtOH at 80°C and 11 bar H2-pressure affording (S)-45 in 82% yield and 97% ee. After protection and chain elongation, (5)-46 was hydrogenated in methanol at room temperature under 80 bar hydrogen pressure in the presence of Ikariya-Mashima s catalyst 47 that bear (5)-SYNPHOS as a chiral ligand. Under these conditions, (35,55)-48 was obtained in 93% yield with 98% de. 

SCHEME 30.16. Asymmetric hydrogenation of 3-keto esters a highly efficient method for the introduction of stereogenic centers in (—)-pateamine A, (+)-brefeldin A, and (—)-mdolizidine 223AB. 

Asymmetric hydrogenation of a-keto esters and amides has been extensively studied with a variety of chiral Rh and Ru catalysts [3,4,46]. A limited number of catalysts have achieved high enantioselectivity. 

Chiral PCPs can be used for heterogeneous asymmetric catalysis.43,52 162 164 167 The chiral porous ZrIV phosphonate with Run-binap fragments (binap = 2,2 -bis(diphenylphosphanyl)-1,1 -binaphthyl) has a permanent porosity, and shows asymmetric catalytic activity in the hydrogenation of (3-keto esters with enantiomeric excess values of up to 95%.162... 

Ruthenium catalysts that contain Cl-MeO-BIPHEMP have been used in the asymmetric hydrogenation of P-keto esters (99% ee)126 and the dynamic kinetic resolution of substituted P-keto esters (Scheme 12.33).121 The asymmetric hydrogenation of methyl 3,3-dimethyl-2-oxobutyrate to the corresponding a-hydroxy ester has been reported with ruthenium catalyst, RuBr2[(-)-Cl-MeO-BIPHEMP] 2 (Scheme 12.34).121... 

Rhodium and ruthenium complexes of CHIRAPHOS are also useful for the asymmetric hydrogenation of p-keto esters. Dynamic kinetic resolution of racemic 2-acylamino-3-oxobutyrates was performed by hydrogenation using ((5,5)-CHIRAPHOS)RuBr2 (eq 3). The product yields and enantiomeric excesses were dependent upon solvent, ligand, and the ratio of substrate to catalyst. Under optimum conditions a 97 3 mixture of syn and anti p-hydroxy esters was formed, which was converted to o-threonine (85% ee) and D-allothreonine (99% ee) by hydrolysis and reaction with propylene oxide. 

Noyori, R., Ohkuma, T., Kitamura, M., Takaya, H., Sayo, N., Kumobayashi, H., Akutagawa, S. Asymmetric hydrogenation of 3-keto carboxyiic esters. A practicai, pureiy chemicai access to P-hydroxy esters in high enantiomeric purity. J. Am. Chem. Soc. 1987, 109, 5856-5858. 

Scheme 15 illustrates the asymmetric hydrogenation of 3-keto phosphonates catalyzed by a BINAP-Ru complex, giving P-hydroxy phosphonates in up to 99% ee [61]. The sense of enantioface differentiation is the same as that of hydrogenation of P-keto carboxylic esters (see table of Scheme 3). The reactivity of the phosphonates is much higher than that of the carboxylic esters so that the hydrogenation proceeds even at 1 to 4 atm of hydrogen and at room temperature. A Ru complex of BDPP also shows high enantioselectivity [46b]. Chiral P-hydroxy phosphonates thus obtained are useful intermediates for the syntheses of phosphonic acid-based antibiotics as well as haptens of catalytic antibodies. Similarly, P-keto thiophosphates are hydrogenated enantioselectively with a MeO-BIPHEP-Ru catalyst [61b].

The same catalyst was used in the asymmetric hydrogenation of fi-keto esters in [BMIM][PF6], [BMIM][BF4] and [MMPIM][(CF3S02)2N] with complete conversions and ee values of up to 99.3% [117]. 

Relatively few examples of the asymmetric hydrogenation of P-keto esters using chiral rhodium complexes have been reported compared with their ruthenium analogs. The Josiphos-Rh system was found to be effective in the asymmetric hydrogenation of ethyl 3-oxobutanoate 178 to give 179 with 97% ee. ... 

Catalytic asymmetric hydrogenation is a relatively developed process compared to other asymmetric processes practised today. Efforts in this direction have already been made. The first report in this respect is the use of Pd on natural silk for hydrogenating oximes and oxazolones with optical yields of about 36%. Izumi and Sachtler have shown that a Ni catalyst modified with (i ,.R)-tartaric acid can be used for the hydrogenation of methylacetoacetate to methyl-3-hydroxybutyrate. The group of Orito in Japan (1979) and Blaser and co-workers at Ciba-Geigy (1988) have reported the use of a cinchona alkaloid modified Pt/AlaO.i catalyst for the enantioselective hydrogenation of a-keto-esters such as methylpyruvate and ethylpyruvate to optically active (/f)-methylacetate and (7 )-ethylacetate. 

Other prochiral units that can be trapped in rings are enolates. One famous application is the alkylation of [3-hydroxy acid derivatives available from the chiral pool (chapter 23), by asymmetric aldol reactions (chapter 27) and by asymmetric reduction of P-keto-esters either by catalytic hydrogenation (chapter 26) or by enzymes (chapter 29). Frater found that the alcohol 55, from the baker s yeast reduction of the ketoester 54, formed the enolate 56 held in shape by chelation. Alkylation occurred on the top face.8 This is not so much because the OH is down in 55 as that the methyl group is down in 56. 

Recently, homogeneous asymmetric hydrogenation of (3- or y-keto esters was successfully applied to synthesis of a wide variety of natural and unnatural useful compounds. Representative examples are illustrated in Fig. 7 [38]. 

The asymmetric reduction of various keto-esters has been reported. The hydrogenation of a-keto-esters to chiral lactates is catalysed by rhodium(l) complexes of the ligand (2) [equation (3)] the lactates are obtained quantitatively with optical yields of up to 76%. 

A similar asymmetric hydrogenation procedure employing dihydrogen and chiral R(ll)-catalysts with axial chiral diphosphines has been used for the reduction of an enormous number of (3-keto ester substrates as weU as for many of the stereoselective approaches to biologically active and potentially pharmacologically important drugs, drug... 

---