Vinyl acetoacetate synthesis

The rDA route to isopropenyl acetoacetate and to vinyl acetoacetate was apparently the first synthesis of acetoacetate esters of enols. The reaction between diketene (26) and norbomenols (25a) and (25b) generated the protected ethylene cycloadducts (27), which upon FVP gave the desired isopropenyl acetoacetate (28a) in 48% yield and vinyl acetoacetate (28b) in 61% yield (equation 20). ... 

Vinyllithiums of type 663 (R2 = R3 = H) reacted with primary alkyl bromides, carbonyl compounds, carbon dioxide, DMF, silyl chlorides, stannyl chlorides, disulfides and phenylselenyl bromide142,970-979. Scheme 173 shows the synthesis of dihydrojasmone 669 from the corresponding 1,4-diketone. a-(Phenylsulfanyl)vinyllithium 665, prepared from phenyl vinyl thioether, reacted with hexanal and the corresponding adduct 666 was transformed into its acetoacetate. This ester 667 underwent a Carrol reaction to produce the ketone 668, which was transformed into the cyclopentenone 669 by deprotection either... 

Among common carbon-carbon bond formation reactions involving carbanionic species, the nucleophilic substitution of alkyl halides with active methylene compounds in the presence of a base, e. g., malonic and acetoacetic ester syntheses, is one of the most well documented important methods in organic synthesis. Ketone enolates and protected ones such as vinyl silyl ethers are also versatile nucleophiles for the reaction with various electrophiles including alkyl halides. On the other hand, for the reaction of aryl halides with such nucleophiles to proceed, photostimulation or addition of transition metal catalysts or promoters is usually required, unless the halides are activated by strong electron-withdrawing substituents [7]. Of the metal species, palladium has proved to be especially useful, while copper may also be used in some reactions [81. Thus, aryl halides can react with a variety of substrates having acidic C-H bonds under palladium catalysis. 

Even with these developments, the synthetic potential of acetoacetic ester was still not completely exhausted. Notice in the transformations that not all four of the carbon atoms of this reagent are used. In the concluding step of the synthesis, the COOEt or CH3CO group is usually removed as if it were simply an extraneous pendant. The strive to find a 100% utilization of the acetoacetic ester carbon skeleton was realized with the development of a method for substitution at vinylic positions with the use of cuprate reagents (Section 2.12). It turns out that a similar reaction can be carried out with the enol esters of 1,3-dicarbonyl compounds. 

Asymmetric synthesis by a Michael reaction. Japanese chemists report that Michael addition to a,/(-unsaturated sulfoxides proceeds readily. Thus p-tolyl vinyl sulfoxide (2) reacts with diethyl malonate and ethyl acetoacetate in the presence of an equimolar amount of sodium ethoxide in ethanol to give the Michael adducts (3) and (4). 

Wislicenus introduced the use of molecular silver in the synthesis of adipic acid from iodopropionic acid, synthesised hydantoin from cyanic acid and glycocoll, glutaric acid (with L. Limpach), and methyl j8-butyl ketone from methylethylacetoacetic ester. He prepared cyclic ketones of dibasic acids by heating the calcium salts, and discovered vinyl ether and vinylacetic acid. The earlier history of acetoacetic ester has been dealt with (see p. 528) two theories of its structure were proposed that of Frankland and Duppa (1865), who represented it as CH3 CO CH2-COOC2H5, and that of Geuther, who discovered the compound (1863), and represented it at first by a type formula (C = 12, O=8) ... 

Synthesis of piperitone can be worked out from methyl vinyl ketone, ethyl acetoacetate and 2-bromopropane, where in aU steps alkylation, Michael addition and an aldol condensation medium strong base are needed, e.g., NaOEt/EtOH. For decarboxylation of intermediary TM 4.11b, mildly acidic conditions are convenient. 

Scheme 5.29 Synthesis of N-H pyrroles from vinyl azides and ethyl acetoacetate ...

Chiba and coworkers developed a Cu(NTf2)2-catalyzed synthesis of pyrroles from a-ethoxycarbonyl vinyl azides and ethyl acetoacetate through the 1,4-addition reaction of the acetoacetate to the vinyl azides [19]. Jiao and coworkers reported a copper- or nickel-catalyzed highly selective denitrogenative annula-tion of vinyl azides with acetaldehydes to 2,4- and 3,4-diaryl-substituted pyrroles. Cu(OAc)2 could catalyze the formation of 2,4-diaryl-substituted pyrroles. This selective polysubstituted pyrrole synthesis could proceed under mild conditions without any acidic or basic conditions [20] (Scheme 8.8). 

The reaction was extended to the synthesis of cyclopentane derivatives by moving the leaving group to position 4 of the acetoacetate ester (Scheme 25.3a) [5c,d]. Bromine was selected as leaving group since the 4-chloro derivative afforded only the Michael addition. More recently the reaction was extended to non-stabilized alkyl halides (Scheme 25.3b) [5e]. Somewhat surprisingly no O- or N-alkylation by-products were observed despite the fact that 12 cannot be stabilized by the formation of vinyl haUdes by enolization, such as in 2-haloethyl-malonates (9) (Scheme 25.3a). 

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