R-Butyl acetoacetate

By condensation of the dianion of r-butyl acetoacetate and (—)-menthyl (S)-p-toluenesulfinate, the corresponding p-keto sulfoxide was obtained in high yield (eq 15) and shown to be an efficient... 

Recently, a new method for synthesizing coumarin derivatives has exploited the properties of aryl-cerium reagents, as illustrated in Scheme 19/ Interestingly, the bulky arylcerium reagent (13) adds to the easily enolizable r-butyl acetoacetate in satisfactory yield. 

One of the most complex molecules yet prepared by these biomimetic approaches is the x-etetramid (158 Scheme 7). The 3-pyrrolidinoglutaric acid diamide (153) is condensed with two equivalents of the dianion of r-butyl acetoacetate. The putative intermediate (154) undergoes spontaneous cyclization to provide the naphth ene derivative (155). This substance is transformed by a sequence of steps into naph-thalenopyrone (156), which is extended by reaction with an isoxazole dianion. Spontaneous aldolization again occurs, yielding the anthracene derivative (157). Closure of the final ring ensues when (157) is treated with HI. 

Starting with a preformed A-ring, in the form of phthalide (162), Harris and cowotkers assembled the anthracene derivative (164) as shown in Scheme 8. The intermediate tetraketo diester (163) closes spontaneously under the conditions of its synthesis from (162) and the dianion of r-butyl acetoacetate. 

Acetoxy-2-cyclopenten-l-one in r r/-butyl acetoacetate added drop wise to a stirred soln. of K-rerr-butoxide in f rr-butyl acetoacetate, and allowed to stand overnight di-r rf-butyl 3-hydroxy-3-methyl-5,9-dioxobicyclo[5.3.0]decan-2,6-di-carboxylate. Y 88%. V. Osterthun and E. Winterfeldt, B. 110, 146 (1977). 

Significant asymmetric induction (18-60% e.e.) is observed in the alkylation of the chiral alkyl complexes [Fe(T7-C5H5)(CO)(L)(CH2Cl)] [(5) L = PPh3 or tri(o-biphenyl)phosphite] by the prochiral nucleophiles sodium r-butyl acetoacetate and pyrrolidine cyclohexanone enamine. The product diastereomer ratio in the former case was shown to be thermodynamically controlled, while kinetic control was assumed in the latter reaction. 

The carboxylation reaction (Scheme 13) nicely illustrates the advantage of using the hindered azobenzenes azobenzene is itself carboxylated under the reaction conditions used whereas the di-r-butyl compound is too hindered and acts only as a probase. Entry 8 is an example of both condensation (of ethyl acetate to ethyl acetoacetate) and subsequent alkylation. Yields are often high and the reaction conditions are usually convenient. The electrogenerated bases are effectively produced in either dimethylformamide or acetonitrile in the latter case the cyanomethyl anion must also be present but this does not seem to interfere with alkylation reactions. 

O-Alkylation is most pronounced when the enolate is least solvated. When the potassium salt of ethyl acetoacetate is treated with ethyl sulfate in the polar aprotic solvent HMPA, the major product (83%) results from O-alkylation. In THF, where ion clustering occurs, all of the product is C-alkylated. In r-butyl alcohol, where the acetoacetate anion is hydrogen bonded by solvent, again only C-alkylation is observed. 

A -ButenoUdes, 53, 339, 411 / Butoxybi (dimetliylainino)methane, 41 t-Butyl acetoacetate, 50, 51 1-r-ButylalIene oxide, 279 r-Butyl azidoformate, 41-42 r-Butylbenzene, 362... 

A mixture of piperidine and abs. ethanol added with stirring at —5° to n-butyraldehyde and ferf-butyl acetoacetate, stirring continued 5 hrs., then kept 44 hrs. at ca. —15°, and the crude intermediate heated at 130-140° in the presence of p-toluenesulfonic acid until a constant pressure indicates completion of the decomposition 3-hepten-2-one. Y 93%. F. e. s. S.-O. Lawesson et al., Acta Ghem. Scand. 17, 2216 (1963) C-decarbo-ferf-butoxylation with simultaneous dehydration, 2-cyclohexenones, s. R. 83, 464 (1964) reactions with ferf-butyl cyanoacetate s. Arkiv Kemi 23, 453 (1965). 

Diketene added with stirring during 1.5 hrs. to refluxing ferf-butanol containing triethylamine at such a rate that the internal temp, remains below 100 , and the product isolated after an additional 30 min. ferf-butyl acetoacetate. Y 93%. J. W. Gornforth, R. H. Gornforth, and K. K. Mathew, Soc. 1959, 2539. 

Thus if R = ra-propyl (ethyl n-propylacetoacetate), methyl n-butyl ketone is produced. The preparation of this ketone is described in Section 111,152 under Ethyl Acetoacetate. 

A new carbon-carbon bond is formed during the reaction of lactim ethers with compounds containing active methylene groups, such as malonic ester and its derivatives, acetylacetone, barbituric acid, rhodanine, nitromethane, and oxindole.8 9 33 100-102 Examples are the condensation of the lactim ether of tetrahydro-/S-carbolinone with acetoacetic ester103 [Eq. (5)] and the condensation of the bislactim ether of 2,2 -dipyrrolidine-5,5 -dione (48) with butyl cyanoacetate20 [Eq. (6)]. Another instance is the reaction of 2 (R = Me) with 2-phenyloxazolin-5-one, to give 3,4-pentamethyleneimidazoles (49) via the intermediate 4-(homopiperid-2-ylene)oxazolin-5-one (50)104 (Scheme 16). 

Z)-2-butenylene dicarbonate with dimethyl malonate gives a low yield (20—40%) of 2-vinylcyclopropane-l,l-dicarboxylate with up to 70% ee (Scheme 2-38) [54], Reaction with methyl acetoacetate or acetylacetone takes place in a different manner to give a dihydrofuran derivative (59% ee), which results from nucleophilic attack of enolate oxygen at the cyclization step, (c) Asymmetric elimination of an acetyl-acetate ester gives (R)-4-rerr-butyl-l-vinylcyclohexene of up to 44% ee (Scheme 2-39) [55]. (d) Palladium-catalyzed allylic silylation is also applied to asymmetric synthesis... 

Acylation of t-alcohok and of ethyl acetoacetate. 7-Butyl acetate can be prepared in moderate yield by reaction of r-butanol with acetyl chloride and magnesium in... 

The acetylenic side chain of (58) has been hydrogenated in the presence of Lindler catalyst to give the Z-allylic alcohol (70). This olefin was stereoselectively epoxidized at -78° with t-butyl hydroperoxide and a catalytic amount of vanadyl acetoacetate to give an 85 15 mixture of products (71) and (72). The major isomer (71) was separated and converted to 24(R),25-dihydroxycholesterol (73) by the subsequent steps of lithium aluminum hydride reduction and A-ring depfotection (143). These steps provide the means for selectively preparing 24,25-dihydroxy-vitamin D compounds with the natural configuration at the 24-position. 

Ethyl (R)-3-hydroxybutyrate was prepared from the bioreducrion of ethyl acetoacetate using Acetobacter sp. (CCTCC M209061) cells in l-butyl-3-methyl-imidazolium hexafluorophosphate (C4mim PF6), an ionic liquid with good biocompatibility. The reaction was performed with a 1 1 ratio of buffer to C4mim PF6 and a substrate concentration of 55 mmol/L in buffer at pH 5.5. The reaction provided 90.8% conversion and more than 99% ee and was scaled to a 450 mL reaction volume. Also demonstrated in the paper was the successful recycle of the catalyst up to 10 times as an immobilized alginate [60]. 

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