Reduction of a ketoester

SYNTHESIS AND RU(II)-BINAP REDUCTION OF A KETOESTER DERIVED FROM HYDROXYPROLINE 2(S)-(p tert-BUTOXYCARBONYL-a-(S) and a-(R)-HYDROXYETHYL)-4(R)-HYDROXYPYRROLIDINE-1 -CARBOXYLIC ACID, tert-BUTYL... 

The enantioselective reduction of a-ketoester was carried out using the cell suspension of Aureobasidium pullulans SC 13 849 to produce the corresponding (R)-alcohol in 94% isolated... 

Figure 7.18 Reduction of a-ketoesters by a carbonyl reductase from Sporobolomyces salmonicolor (SSCR)...

The enantioselective hydrogenation of prochiral substances bearing an activated group, such as an ester, an acid or an amide, is often an important step in the industrial synthesis of fine and pharmaceutical products. In addition to the hydrogenation of /5-ketoesters into optically pure products with Raney nickel modified by tartaric acid [117], the asymmetric reduction of a-ketoesters on heterogeneous platinum catalysts modified by cinchona alkaloids (cinchonidine and cinchonine) was reported for the first time by Orito and coworkers [118-121]. Asymmetric catalysis on solid surfaces remains a very important research area for a better mechanistic understanding of the interaction between the substrate, the modifier and the catalyst [122-125], although excellent results in terms of enantiomeric excesses (up to 97%) have been obtained in the reduction of ethyl pyruvate under optimum reaction conditions with these Pt/cinchona systems [126-128],... 

The lactone (46) was obtained in 65% yield via reduction of a ketoester with sodium borohydride in MeOH and subsequent acidic workup (Equation (21)) <90H(30)223>. 

Synthesis and Ru(ll)-BINAP Reduction of a Ketoester Derived from Hydroxyproline. 

The reaction is extended [3] to the reduction of a-ketoesters, another class of ketones, possessing powerful electron-withdrawing ester group. The reduction of a-ketoesters with 40% excess of neat Alpine-Borane proceeds rapidly at 25 °C (Eq. 26.4 Table 26.9) [3,4b]. 

In the asymmetric reduction of a-ketoesters, the asymmetric induction depends on the steric inequality of two moieties attached to the carbonyl group [9]. The reduction of hindered a-ketoesters yields the corresponding a-hy-droxyesters with optical purities approaching 100% ee (Eq. 26.28). This contrasts strongly with the 11% ee realized in the reduction of 7 (R= i-Pr) with neat Alpine-Borane [9b]. Alpine-Borane (from (-t)-pinene) yields (S)-alcohols in the reduction of both alkylaromatic ketones and a-ketoesters. On the other hand K-glucoride yields (R)-alcohols with aralkylketones and (S)-alcohols with a-keto esters (Table 26.27) [7]. 

R. Kinishi, Y. Nakajima, J. Oda, and Y. Inouye. Asymmetric reduction of a-ketoesters with sodium borohydride by chiral phase transfer catalysts. Agric. Biol. Ghem., 1978,42,869. 

Hydroxy-esters.—Some success has been achieved with asymmetric reduction of a-ketoesters to the corresponding i -hydroxy esters using chiral Hantzsch esters in the presence of mono-zinc species formed in a standard Reformatsky reaction. Although yields, both chemical and optical, are variable the method offers some synthetic utility, and is also interesting as a model of biological NAD(P)H reductions. 

The carbonyl reductase from Candida magnoliae catalyzed the enantioselective reduction of a diversity of ketones, including aliphatic and aromatic ketones and a- and /3-ketoesters (Figure 7.17), to anti-Prelog configurated alcohols in excellent optical purity (99% ee or higher) [56]. 

Zhu, D., Mukherjee, C., Rozzell, J.D. et al. (2006) A recombinant ketoreductase tool-box. Assessing the substrate selectivity and stereoselectivity toward the reduction of beta-ketoesters. Tetrahedron, 62 (5), 901-905. 

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

Novel C2-symmetric thiophene-containing ligands have recently been prepared and utilized in asymmetric synthesis. Dithiophene 158 was utilized as a ligand in the asymmetric reduction of p-ketoesters (prostereogenic carbonyl) and acrylic acids (carbon-carbon double bond) <00JOC2043>. Dibenzo[b]thiophene 159 was utilized as a ligand in enantioselective Heck reactions of 2-pyrrolines <00SL1470>. 

Reduction of p-ketoesters in aqueous ethanolic sulphuric acid leads to removal of both functional groups and the formation of a hydrocarbon. This reaction which was discovered in 1907 [117] and recognised in 1912 [118] as involving a skeletal rearrangement is now termed the Tafel rearrangement. Conversions of the type 26 into 27 occur in 30 - 60 % yields [118,119] and the hydrocarbon is easily separated... 

Quallich and Woodall described the first asymmetric synthesis utilizing a catalytic enantioselective reduction of the ketoester 35 with (S)-terahydro-l-methyl-3,3-diphenyl-lH,3W-pyrrolo[l,2-c][l,3.2]oxazaborole (CBS) to give the desired hydroxyester 36 (90% ee). After mesylation, Sn2 displacement with a higher-order cuprate derived from copper cyanide gave the diaryl r-butyl ester 37 with good chirality transfer. Intramolecular Friedel-Crafts cyclization gave the tetralone 31 in 90% ee (Scheme 7). ... 

Baker s yeast reduction of organic compounds, especially carbonyl compounds, is an extremely useful method of obtaining chiral products255-257. Recently, much effort has been expended to improve the ee obtained in this process. In one very useful example, l-acetoxy-2-alkanones have been reduced enantioselectively into (5 )-l-acetoxy-2-alkanols in 60-90% yields and with 95-99% ee258. The reaction readily occurs in a variety of solvents, both aqueous and nonaqueous. The reduction is fairly selective and so may be brought about in the presence of a-amide, ether, ester and other acid functional groups, in reasonable yields and with excellent ee (equation 65)259 -261. Thus, in the synthesis of the C-13 side chain of taxol, the key step was the reduction of a w-ketoester to the corresponding alcohol in 72% overall yield (equation 66)262. 

Sometimes both diastereomers of a compound are needed and then poorly diastereoselective reactions are a boon. Both syn and anti tosylates 55 were needed to study the stereochemistry of reactions.11 Reduction of the ketoester (see preparation in chapters 19 and 21) in two stages gave a mixture of syn and anti diols 54, separable by column chromatography. 

RN Patel, CG McNamee, A Banerjee, JM Howell, RS Robison, LJ Szarka. Stereoselective reduction of P-ketoesters by Geotrichum candidum. Enzyme Microb Technol 14 731-738, 1992. 

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