Hydrogenation p-ketoesters

The resulting porous polymer was used in a transesteriflcation reaction giving ee values of 8% [39]. Reactants are confined in the pores and able to interact with pyridyl group attached to the chiral center. Subsequently, ee values of greater than 90% were reported for P-ketoester hydrogenation reactions over chiral porous zirconium phosphonates containing 2,2 -bis(diphenylphosphino)-l,T-binaphthyl... 

Among the various strategies [34] used for designing enantioselective heterogeneous catalysts, the modification of metal surfaces by chiral auxiliaries (modifiers) is an attractive concept. However, only two efficient and technically relevant enantioselective processes based on this principle have been reported so far the hydrogenation of functionalized p-ketoesters and 2-alkanons with nickel catalysts modified by tartaric acid [35], and the hydrogenation of a-ketoesters on platinum using cinchona alk oids [36] as chiral modifiers (scheme 1). 

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. 

The seven-membered ring containing chiral bisphosphine 121 (n = 1) was made as part of a series of bisphosphines (n = 1-6) to study the influence of ligand dihedral angles on the enantioselectivity of Ru-catalysed asymmetric hydrogenation of p-ketoesters . 

The previous volume of Organic Syntheses provides a detailed procedure for the asymmetric hydrogenation of p-ketoesters using a BINAP-ruthenium complex.15... 

Enantioselective hydrogenation of p-ketoesters with monodentate ligands. Angew, Chem., Int. Ed., 43, 5066-5096. 

Just as very few catalyst/modifier combinations give good optical yields, only certain types of substrate are suited (see Fig. 1). Reproducibly good ee values have been reported for a- and P-ketoesters (6, 1), a-ketolactone 7, p-diketone 2, p-ketosulfones (3) and methylketones (4, 5). C=N- and C=C-bonds are hydrogenated with poor to moderate optical yield. The hydrodehalo-genation of 22 is a unique case of substrate specificity [33]. 

Intramolecular Carbon-Hydrogen Insertion. The advantages of rhodium(II) catalysts for carbenoid transformations are nowhere more evident than with carbon-hydrogen insertion reactions. Exceptional regio- and diastereocontrol has been observed for Rh2(OAc)4 catalyzed transformations of a broad selection of diazoketones, a-diazo-p-ketoesters, a-diazo-P-keto-sulfones and -phosphonates which yield cyclopentanone derivatives in moderate to good yields (57-54). In contrast, poor yields and low regioselectivities characterize the corresponding copper catalyzed reactions. Applications of dirhodium(II) catalysts for C-H insertion reactions have even been extended to the synthesis of y-lactones (55), 3(2//)-furanones (56,57), P-laetones (58), and P-lactams (59,60). 

Functionalized P-hydroxy esters 64 e,f,g,h were obtained quantitatively with excellent enantiomeric excesses (> 98 %) by hydrogenation of p-ketoesters in the presence of chiral ruthenium catalysts. This convenient methodology gives both optical antipodes with equal ease using (/ ) or (5) atropoisomer ligand for the metal complex. 

The first transition metal catalysis using BINAP-ruthenium complex in homogeneous phase for enantioselective hydrogenation of P-ketoesters was developed by Noyori and co-workers [31]. Genet and co-workers described a general synthesis of chiral diphosphine ruthenium(II) catalysts from commercially available (COD)Ru(2-methylallyl)2 [32]. These complexes preformed or prepared in situ have been found to be very efficient homogeneous catalysts for asymmetric hydrogenation of various substrates such as P-ketoesters at atmospheric pressure and at room temperature [33]. 

By coupling the two sequential reactions catalytic hydrogenation and electrophilic animation, a general and practical method for the preparation of both enantiomers of anti-a-hydrazino-P-hydroxy esters (/ ,/ )-65 and (S,S)-65 from the corresponding P-ketoesters 66 has been proposed, and different synthetic applications have been developed [le] (Scheme 31). 

Cycloaddition reactions can also be pseudopericyclic. Bimey examined a number of these and a few examples involving the reactions of formylketene (91) are covered here. Formylketene reacts with alcohols to produce p-ketoesters from the enols 92. Bimey examined the model reaction of formylketene with water (Reaction 4.6). The reactants first come together to form a hydrogen-bonded complex (93) before passing though the transition state 94 to give the enol product 95. The activation barrier, defined as the energy for the reaction 93 94, is 6.4 kcal... 

When we commenced our studies in 1995, perhaps the most intriguing aspect of the literature on the enantioselective hydrogenation of P-ketoesters over supported Ni catalysts was the critical dependence between enantiomeric excesses obtained and system variables such as temperature, concentration of modifier, time of modification, pH, etc [6, 7]. The underlying cause of this behaviour became evident when we discovered that the adsorption behaviour of enantiopure (7 ,J )-tartaric acid... 

In this section, we focus on the Ni(llO) surface, the metal most commonly modified by tartaric acid, to yield the successful enantioselective catalytic system for the hydrogenation of P-ketoesters [6, 7], A detailed study [22, 23] of the adsorption of (/ ,/ )-tartaric acid on Ni(llO) as a function of temperature and coverage again shows a polymorphic system, (Fig. 5.8) with the local nature of the chiral adsorbate changing dynamically as conditions change, echoing the findings on Cu(llO). 

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