Cyclic /i-ketoesters

In addition, chiral nitrogen-substituted quaternary stereocenters can be accomplished by using 1,3-dicarbonyliccompounds as substrates in the direct a-amination process. Thus, several cyclic (i-ketoesters 46 (Scheme 27.9) were submitted to electrophilic amination under phase-transfer conditions catalyzed by the chiral binaphthyl phosphonium salt 47 [50a], Different substituents on the aromatic ring were tolerated, but lower yields were obtained using a six-membered ring cyclic... 

A highly efficient synthesis of spirolactone 110 was described by Marini et al. in 2011 [82] using the addihon of cyclic (i-ketoester 111 to vinyl selenone 99 and subsequent cyclizahon of intermediate 112 in the presence of silica (Scheme 34.39) under mild condihons. This reachon exhibited a wide scope (selected examples are given in Scheme 34.39) but was limited to (i-ketoesters with a cyclopentanone core. Moreover this process could be extended to stereodivergent parallel kinetic resolution of a racemic mixture of chiral [i-ketoesters with a high degree of enantioselectivity. 

By its characteristic carbonyl IR absorption band the product of intramolecular termination, i. e. the cyclic B-ketoester was detected by Goode et al. (58), Glusker et al. (59), and Owens et al. (6o) as one of the products of the oligomerization of MMA with phenylmagnesium bromide or fluorenyllithium in toluene. The same compound was found by Lochman et al. (61) when using metalated methylisobutyrate as the initiator in a THF/pentane mixture at high initiator/monomer ratios. 

In the presence of Mn(OAc)3- 2ll,() in AcOH, allyltrimethylsilane reacts with 1,3-diketones and /I-ketoesters to give trisubstituted dihydrofurans in good to high yield (Scheme 10.187) [502], Mn(OAc) j serves as an oxidizing agent to generate an electrophilic carbon radical intermediate from the substrate. It is probable that annulation of the carbon radical with the allylsilane followed by oxidation with another equivalent of Mn(III) forms the silicon-containing cyclic products. 

Coman, S., Bendic, C., Hillebrand, M., Angulescu, E., Parvulescu, V.I., Petride, A (1998) Diastereoselective hydrogenation of cyclic beta-ketoesters over modified Ru-Zeolite catalysts. Chemical Industries Series (Catalysis of Organic Reactions, Herkes F.E., ed.) 75,169-181. 

Lattanzi and coworkers disclosed that L-diaiyl prolinols served as suitable catalysts in one of the most popular Michael addition reaction, i.e. the reaction of malonate esters and cyclic p-ketoesters to nitroalkenes to generate functionalised products amenable to further manipulation (Scheme 7.7). 

J. Kassanyi, J. Perales, A. Laachach, I. Kawenoki and J.P. Morizur. Preparation of w-Formylalkenoates from cyclic B-Ketoesters, Synthesis 1979, 279-281. 

Five-membered cyclic p-ketoesters (p-ketolactones 1) and cyclic p-ketothioesters (p-ketothiolactones 2) differ from their acyclic counterparts in at least two regards (1) by being mostly enolized and (2) by being so acidic that they are called tetronic acids (1) and thiotetronic acids (2), respectively (Fig. 1). Even 5-membered cyclic p-ketoamides, i.e., p-ketolactams 3, are sufficiently acidic to be known as tetramic acids. The parent compound 3 (Fig. 1 R t = H), for instance, exhibits a pKa of 6.4." Standard tetramic acids prefer the keto (keto-3) over the enol tautomer enol-3). 

Rhenium(I) carbonyl complexes are efficient catalysts to promote an intriguing two-carbon ring expansion leading to cyclooctene formation. Thus, the coupling of cyclic p-ketoesters and terminal alkynes in the presence of rhenium(I) catalyst under mild conditions gave cyclooctenones in excellent yields (Scheme 8.22) [39], The... 

When an a-chloroaldehyde or an a-chloroketone is condensed with a /3-ketoester, in the presence of aqueous base, a furan is produced bearing an ester substituent at the /3-position. It is thought that the reaction is of the aldol type intermediate dihydrofurans (256) have been isolated in certain cases (Scheme 70) (74BSF519). The condensation of ethyl bromopyru-vate and sodium oxaloacetate follows a similar mechanism (54JOC1671). The one-pot synthesis of 2,4,5-trisubstituted furans (257) from ketones and ethyl 3,4-dibromo-2-butenoate is a useful addition to a well known route (80S52). The analogous reaction of cyclic /3-diketones, i.e. cyclohexane-1,3-dione and 5,5-dimethylcyclohexane-l,3-dione, results in the formation of the condensed furans (258) and (259). These reactions are preformed either in ethanol with sodium ethoxide or in DMF with potassium carbonate. 

The butylated /J-ketoester C of Figure 13.26 is not the final synthetic target of the acetoacetic ester synthesis of methyl ketones. In that context, the /J-ketoester C is converted into the corresponding /J-ketocarhoxylic acid via acid-catalyzed hydrolysis (Figure 13.27 for the mechanism, see Figure 6.22). This /i-ketocarboxylic acid is then heated either in the same pot or after isolation to effect decarboxylation. The /f-ketocarboxylic acid decarboxylates via a cyclic six-membered transition state in which three valence electron pairs are shifted at the same time. The reaction product is an enol, which isomerizes immediately to a ketone (to phenyl methyl ketone in the specific example shown). 

Fig. 13.29. Synthesis of complicated ketones in analogy to the acetoacetic ester synthesis II generation of a cyclic ketone. In the first step, the /3-ketoester is alkylated at its activated position. In the second step, the /3-ketoester is treated with Li I . SN2 reaction of the iodide at the methyl group generates the /3-ketocar-boxylate ion as the leaving group. The /3-ketocarboxylate decarboxylates immediately under the reaction conditions (temperature above 100 °C) and yields the enolate of a ketone.

Palladium-catalyzed asymmetric hydrosilation of cyclic and linear 1,3-dienes proceeds as 1,4-addition with moderate to good enantioselectivitiesT a-Ketoesters such as pyruvates can be hydrosilated with Rh(I)-(-l-)-DIOP catalysts to yield lactates with much better optical purity than simpler ketones (equation 22). This effect is likely to be caused by a ligand function of the ester moiety in the transition state. 

The first group is represented by the alcohol dehydrogenases (ADHs) that can be used for the synthesis of chiral alcohols. There are several commercially available ADHs isolated from yeast or horse liver (NADH dependent), or T. brockii (NADPH-dependent) that can be used for different types of substrates. Lactobacillus kefir produces an (/ )-ADH that accepts a broad variety of ketone substrates (ring halogenated, aliphatic, open-chain ketones, 2- and 3-ketoesters, and cyclic ketones), producing, for example, enantiomerically pure I -l-(2-pyridyl ethanol), / -(l-trimerhylsylyl)-l-butyn-3-ol or 5-phenylbutan-2-ol (Hummel 1990). 

The nickel-iminophosphine-catalysed 4- -2-cycloaddition of enones with allenes formed highly substituted dihydropyrans. The enantioselective amine-catalysed 4-I-2-cycloaddition of allenoates with oxo-dienes produced polysubstituted dihydropyrans in high yields and with high enantioselectivities. Novel enam-ine/metal Lewis acid bifunctional catalysis has been used in the asymmetric inverse-electron-demand hetero-Diels—Alder reactions of cyclic ketones with Q ,j9-unsaturated a-ketoesters. The 4- -2-cycloaddition of acylketenes (80) with 2-unsubstituted and 2-monosubstituted 3-aryl-2//-azirines (81) produced 1 1 (82) or 2 1 (83) adducts, being derivatives of 5-oxa-l-azabicyclo[4.1.0]hept-3-ene or 5,7-dioxa-l-azabicyclo[4.4.1]undeca-3,8-diene. The formation of the monoadducts proceeds via a stepwise non-pericyclic mechanism (Scheme 25). A-heterocyclic carbene-catalysed 4- -2-cycloaddition of ketenes with 1-azadienes yielded optically active 3,4-dihydropyrimidin-2-ones (93% ee) ... 

Ketoesters could be exploited to generate iminium intermediate employed as hydride acceptor. Gong et al. reported a chiral Brpnsted acid 85-catalyzed asymmetric cascade [1,5]-hydride transfer/cyclization of 2-pyrrolidinyl phenyl ketoesters 82 with anilines 83, which produced the enantio-enriched cyclic aminals 84 (Scheme 29) [113]. The iminium subunit in intermediate I served as hydride acceptor, which was generated in situ through the condensation of o-aminoben-zoketone 82 with aniline 83 in the presence of 85. 

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