Keto-enolate Syntheses

Some General Observations on the Syntheses of Metal /3-keto-enolate Compounds 

The syntheses of very volatile fluorine-containing metal 0-keto-enolates led Sievers and co-workers to use the volatility in the development of chromatographic techniques for metalion microanalyses.7 

High-coordination-number complexes of 0-keto-enolates continue to be obtained with the metals such as zirconium(IV),8 hafnium(IV),8 cerium(IV),9 and the lanthanons(III),10 the last being tetrakis anionic species. At least one example of a volatile tetrakis 0-keto-enolate salt has been reported,11 Cs[Y(CF3-COCHCOCF3)4]. The ionic charge on the 0-keto-enolate complex has been shown to produce12 a high field nuclear magnetic resonance for anions and low field shifts for cations, relative to the positions observed for the neutral species. 

Collman18 described numerous ligand reaction methods for preparing methylene-substituted 0-diketone complexes. Often these materials cannot be prepared by other techniques because of the lack of stability either of the ligand or its alkali metal salt. A particularly useful procedure leading to the introduction of a functionally active substituent has been reported.14 

Moshier and R. E. Sievers, Gas Chromatography of Metal Chelates, Pergamon Press, New York, 1965 D. W. Meek and R. E. Sievers, Inorg. Chem., 6, 1105 (1967). 

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Keto-enol tautomerism, 264, 842-844 Kiliani, Heinrich, 994 Kiliani-Fischer synthesis, 994-995 Kimbail, George, 216 Kinetic control, 491 Kinetics, 362... 

Another approach for the synthesis of enantiopure amino acids or amino alcohols is the enantioselective enzyme-catalyzed hydrolysis of hydantoins. As discussed above, hydantoins are very easily racemized in weak alkaline solutions via keto enol tautomerism. Sugai et al. have reported the DKR of the hydantoin prepared from DL-phenylalanine. DKR took place smoothly by the use of D-hydantoinase at a pH of 9 employing a borate buffer (Figure 4.17) [42]. 

Some representative Claisen rearrangements are shown in Scheme 6.14. Entry 1 illustrates the application of the Claisen rearrangement in the introduction of a substituent at the junction of two six-membered rings. Introduction of a substituent at this type of position is frequently necessary in the synthesis of steroids and terpenes. In Entry 2, formation and rearrangement of a 2-propenyl ether leads to formation of a methyl ketone. Entry 3 illustrates the use of 3-methoxyisoprene to form the allylic ether. The rearrangement of this type of ether leads to introduction of isoprene structural units into the reaction product. Entry 4 involves an allylic ether prepared by O-alkylation of a (3-keto enolate. Entry 5 was used in the course of synthesis of a diterpene lactone. Entry 6 is a case in which PdCl2 catalyzes both the formation and rearrangement of the reactant. 

The formation of methyl-oxazole compounds was also described by Wang et al. [34] utilizing an analog of the keto-enol intermediate (22) described in Sect. 2.1.1, Scheme 2. Scheme 11 shows the synthesis of compound 57 which exhibits anti-tubulin activity of 7.7. iM [34], In addition, a range of oxazole COX-2 inhibitors has been reported by Hashimoto et al. [55] employing similar chemistry. 

Alternatively, the synthesis may begin by condensing aniline with the l-chloro-2-carboxy intermediate. Acridone vat dyes of this type have excellent light fastness but only moderate resistance to alkali due to the keto-enol equilibrium. It is interesting that this pentacyclic dye is approximately 30 nm more bathochromic than the closely related tetracyclic 1-amino-2-benzoylanthraquinone. 

The protective method has also been employed with 3-ketoesters. In this case, the goal is to avoid keto-enol photoisomerization that is an efficient energy-wasting channel. Scheme 74 shows that direct photorearrangement of aryl benzoyl acetates (298) to the ort/jo-hydroxydibenzoylmethanes (299) is poor, whereas irradiation of the related acetal derivatives gives higher yields [208]. The resulting ort/ o-hydroxydibenzoylmethanes are precursors for the synthesis of flavones. Related flavonoids can be obtained in similar yields by PFR of aryl dihydrocinna-mates [209]. 

A synthesis of 2-cyanocyclohexanone 4.45 from cyclohexanone is shown below. Formylation of cyclohexanone produces a mixture of keto/enol tautomers 4.42 and 4.43, the equilibrium lying to the side of the enol 4.42. Treatment with hydroxylamine affords isoxazole 4.44, and base-induced fragmentation of the isoxazole ring affords 4.45. Explain the regioselectivity of the isoxazole formation, and the mechanism of the fragmentation process. 

For weak acids, the proton is directly transferred from the acid to the substrate in a reagent-controlled manner and, in order to increase the selectivity, extremely shielded 2 -substituted m-terphenyls have been developed as concave protonating reagents inspired by the geometry of enzymes. Thus, the diastereoselective protonation by a series of substituted phenols of endocyclic keto enolates, obtained by the stereocontrolled 1,4-addition of lithiocuprates onto substituted cyclohexenones, was reported by Krause and coworkers354 355 and applied to the synthesis of racemic methyl dihydroepijasmonate356. 

Clerici A, Pastori N, Porta O (2001) Mild acetalisation of mono and dicarbonyl compounds catalysed by titanium tetrachloride. Eacile synthesis of (3-keto enol ethers. Tetrahedron 57 217-225... 

From a synthetic point of view, the CHT-NCD equilibrium has been exploited in a total synthesis of colchicine and, more recently, in syntheses of tropones (115) and tropolones (119) from 7-halobicy-clo[4,1.0]heptenones (112) or 7-halobicyclo[4.1.0]heptane-3,4 diones (116), respectively. Keto-enol tautomerism of (112) to (113) followed by ring opening to the cycloheptatrienols (114) and loss of HX would explain the formation of the tropone (115). The tropolone (119) probably results from a similar sequence. These examples represent one of few cases that exemplify 6e retro electrocyclizations presented dius far in this review. Additional examples will be presented later in Section 6.2.4.1. 

Problem 27.5 Acrolein, CH2 CHCHO, is prepared by heating glycerol with sodium hydrogen sulfate, NaHS04. (a) Outline the likely steps in this synthesis, which involves acid-catalyzed dehydration and keto-enol tautomerization. (Hinf Which OH is easier to eliminate, a primary or a secondary ) (b) How could acrolein be converted into acrylic acid ... 

Enynes of the structural type (57) have been used as key intermediates in the total synthesis of vitamin D. The enyne (57) can be obtained by a simple synthesis based on Pd-catalyzed coupling of the keto-enol triflate (56) and an alkynic compound containing the vitamin D A-ring fragment (Scheme 38). ... 

There are scanty reports about the Baker-Venkataraman rearrangement which is used in synthesis very seldom. Thus, in the approach mentioned in equation 106 the C-glycoside 239 undergo O-benzoylation to afford the ester 240, which rearranges into the 1,3-dicarbonyl compound 241 formed as a keto-enol mixture in 48% yield (equation 109) ° . 

K-13 1315, 1321 synthesis of 1318 Kalman filter 929, 987 Katsurenone, synthesis of 1240, 1245 Kerosene, phenohc compounds in 948 Ketenes—see Dienylketenes Ketides—see Polyketides Keto-enols, formation of 1028 Ketones,... 

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