Tetronates Tetronic acids

Chemoselective C-alkylation of the highly acidic and enolic triacetic acid lactone 104 (pAl, = 4.94) and tetronic acid (pA, = 3.76) is possible by use of DBU[68]. No 0-alkylation takes place. The same compound 105 is obtained by the regioslective allylation of copper-protected methyl 3,5-dioxohexano-ate[69]. It is known that base-catalyzed alkylation of nitro compounds affords 0-alkylation products, and the smooth Pd-catalyzed C-allylation of nitroalkanes[38.39], nitroacetate[70], and phenylstilfonylnitromethane[71] is possible. Chemoselective C-allylation of nitroethane (106) or the nitroacetate 107 has been applied to the synthesis of the skeleton of the ergoline alkaloid 108[70]. 

Table 1 Hsts the polyether antibiotics arranged by the number of carbons in the skeleton. Many of these compounds were isolated independendy in separate laboratories and thus have more than one designation. The groups are subdivided depending on the number of spiroketals. Two classes fall outside this scheme the pyrrole ether type containing a heterocycHc ring, and the acyltetronic acid type, that has an acyHdene tetronic acid instead of a carboxyHc acid. These compounds are ionophores and because of their common features are included as polyethers.

Butenolide, 2-hydroxy — see Isotetronic acids Butenolide, 3-hydroxy — see Tetronic acids But-2-enolide, 4-alkylidene-synthesis, 4, 697 Butenolides H NMR, 4, 578 mass spectrometry, 4, 585 structure, 4, 551 synthesis, 1, 416 trimethylsilylation... 

The Reforrnatsku reaction of a-halogenated carboxylic esters with silylated cyanohydrins combined with an intramolecular acylation reaction gives fluorinated derivatives of tetronic acid [28] (equation 17) It is noteworthy to mention that this particular reaction sequence only proceeds with ultrasonic irradiation A very... 

Methoxyethoxymethyl, 365 Enamino Derivatives, 365 4-Methyl-1,3-dioxolanyl Enol Acetate, 365 Pyrrolidinyl Enamine, 365 Benzyl Enol Ether, 366 Butylthio Enol Ether, 366 Protection of Tetronic Acids, 366 Trimethylsilyl Enol Ether, 367... 

The synthesis of a selenonium ylide with a tetronic acid anion moiety was reported (83TL75 84CPB2666). 3-Enamino-tetronie aeids have also been investigated (82SC431). 

For 3-acetylthiotetronic acid the same type of tautomerization process (90 91, 92 93 as a result of prototropy between internal tautomers 90, 91 92, 93, rotation of the side-chain group, between external tautomers) was observed as for the corresponding 3-acetyl-tetronic acids ( H NMR, NMR) [76JHC533 78BCJ651 79JCS (P2)1605],... 

Tetronic acids exist predominantly in the dioxo form (32) in solvents of low polarity, while the existence of the monoenol form (33) has been established in other solvents by infrared " and ultraviolet spectral comparisons- and from dipole moment data. " Haynes and Pliramer " have recently reviewed the structure of these compounds [see also reference 28(a)], and the tautomerism of vitamin A (34), which has a related structure, has also been surveyed.- Analogous compounds carrying an amino group in the 3-position are also know n. ... 

The allylation reaction of the optically active tetronic acid derivatives 146 was shown to give a variety of isomers depending on the reaction conditions (temperature and reaction time) (Scheme 44 and Table I) (99H1321). The reaction is carried out by treating 146 with allyl bromide in DMF and in the presence of K2CO3. 

Recently, the Michael addition of the optically active Q ,y-disubstituted tetronic acids 146c,e with a variety of Q ,/3-unsaturated aldehydes, ketones, esters, and nitriles was studied (Scheme 53) (99H1321). 

Dehydrobromination of 12 to -tetronic acid (13) in high yield could be achieved only under narrowly circumscribed conditions 62). The molar ratio of barium hydroxide to 12 needed to solubilize 12 and to neutralize the liberated hydrobromicacid must be at least two to one. Deionized water was the preferred solvent because of ease of workup. The yields were found to be concentration dependent. Concentrations of 12 in water of about 16% gave good yields of 13, whereas at 33% concentration the yield was much lower. One gram of 10% Pd-on-C per 33 g of 12 was required less catalyst gave incomplete reductions. 

Schemes 16-19 present the details of the enantioselective synthesis of key intermediate 9. The retrosynthetic analysis outlined in Scheme 5 identified aldoxime 32 as a potential synthetic intermediate the construction of this compound would mark the achievement of the first synthetic objective, for it would permit an evaluation of the crucial 1,3-dipolar cycloaddition reaction. As it turns out, an enantioselective synthesis of aldoxime 32 can be achieved in a straightforward manner by a route employing commercially available tetronic acid (36) and the MEM ether of allyl alcohol (74) as starting materials (see Scheme 16).

Ketal 73 can be formed in a yield of about 60 % by refluxing a solution of tetronic acid (36), ethylene glycol, and a catalytic amount of para-toluenesulfonic acid in benzene for approximately 12 hours. With only one electrophilic site, 73 reacts smoothly with Dibal-H to give lactol 35 in 84% yield. Compound 35, a participant in a ring-chain tautomeric equilibrium process,18 should be regarded as a latent aldehyde. This substance can, in fact, serve as... 

Wittig reactions have also been employed in domino processes. For example, Schobert and coworkers developed an effective addition/Wittig reaction protocol which provides access to a, 3-disubstituted tetronic acids, tetronates, as well as to five-, six- and seven-membered O-, N-, and S-heterocycles [149]. 

It is assumed that in the formation of 2-509, a Knoevenagel condensation of the benzaldehydes 2-511 and tetronic acid 2-512 initially takes place, and this is followed by the generation of a hemiaminal with the aniline 2-510 and an electrophilic substitution. 

The reaction of a nitrile with a Reformatsky reagent is known as the Blaise reaction and when applied to (9-trimethylsilyl cyanohydrins leads to the formation of tetronic acids with high ee [79]. By working-up the Blaise reaction with ammonium chloride it is possible to isolate... 

Effenberger and coworkers have utilized the tolerance of methyl ketones by the recombinant enzyme to develop an alternative synthesis of tetronic acids and their amino derivatives, as shown in Figure 5.18. Treatment of O-acyl cyanohydrins with lithium disilazide resulted in base-induced ring closure to amino tetronic acid derivatives. Alternatively, the cyanohydrins could be converted to a-hydroxy esters prior to acylation, and the same base-induced cyclization then led to tetronic acid derivatives [89]. 

Duffield, J.J. and Regan, A.C. (1996) Asymmetric synthesis of tetronic acids by Blaise reaction of protected optically active cyanohydrins. Tetrahedron Asymmetry, 7, 663-666. 

This review of furan chemistry is meant to continue the earlier survey by Bosshard and Eugster1 and concentrates upon the period 1968 to the end of 1979. Like the earlier review, this one is limited to the chemistry of the monocyclic furan nucleus and does not deal, except incidentally, with fused rings such as benzofuran or its quinones. Nor does it deal in detail with dihydro- or tetrahydrofurans, nor with compounds like furylpyridine that contain some other heterocyclic nucleus as well. Some butenolides and tetronic acids are admitted to consideration since they are the carbonyl equivalents of hydroxyfurans regarded as enols, but side-chain reactions are wholly excluded unless the furan nucleus clearly affects them in some important way. 

Ally] esters (R2 = CH2C(R3)=CH2) could be transformed to the corresponding 3-allyltetronic acids by maintaining microwave irradiation at 120 °C for 60 min [59]. However, cleavage of the tetronic acids under the above mentioned conditions remained somewhat troublesome. To obtain satisfactory amounts of product, the polymer-bound intermediates had to be protected at the 04 position so that cleavage could be accomplished with a mixture of trifluoroacetic acid/dichloromethane (1 9) (Scheme 7.44). 

Scheme 7.44 Release of polymer-bound tetronic acids.

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