Acetoacetates allyl esters

In situ IR (infrared) and NMR spectroscopy and product studies have shown that acetoacetate allyl esters with an electron-withdrawing group on the C=C bond of the allyl moiety undergo an intermolecular 5 N2 -decarboxylation-5 N2 reaction when treated with a base such as Et3N or triphenylphosphane (Scheme 4). Overall yields... 

A particularly important advance in the nature of the leaving group, X, used in ir-allylpalladium precursors, has been the development of substrates that allow functionalization of the incipient allyl complex under neutral conditions. With these precursors, the leaving group, X, is, or can react further to become, sufficiently basic so as to generate in situ Nu from Nu—H. In another variation, the X itself is transformed into the nucleophilic partner for the allyl ligand. Examples include vinyl epoxides,7 9-11 allyl esters of acetoacetate,7-9-11 allyl carbonates8-9-11 and carbamates (equation 11 ).8-9- 1... 

An alternative route to y,5-unsaturated ketones is via the Carroll-Claisen rearrangement, which uses allylic esters of 3-keto acids (which exist mainly in the enol form) as substrates. These are readily prepared by condensation of allylic alcohols with acetoacetic esters or diketene. Following rearrangement, the intermediate keto acid undergoes in situ decarboxylation on heating. 

Another synthetic method for the production of pseudoionone, which starts from myrcene [94a], [94b], has never been commercialized for the production of fragrance materials (see also p. 45, geranylacetone). The process consists of a rhodium-catalyzed addition of methyl acetoacetate to myrcene, transesterification of the resulting ester with allyl alcohol, and an oxidative decarboxylation of the allyl ester under palladium catalysis to obtain pseudoionone. 

In contrast to facile Pd(0)-catalyzed reactions of allyl esters with soft carbon nucleophiles via r-allylpalladium intermediate, propargyl esters such as acetate are less reactive toward soft carbon nucleophiles. However, /3-keto esters and malonates react under neutral conditions with propargyl carbonates using DPPE as a ligand [37], Acetoacetate reacts with meAyl propargyl carbonate (119) in THF at room temperature to afford 4-(methoxycarbonyl)-5-methyl-3-methylene-2,3-dihydrofuran (120) in 88 % yield. The furan 121 was obtained by isomerization of the methylenefuran 120 under slightly acidic conditions. 

Allylic esters of acetoacetic acid undergo Pd(OAc)2-PPh3-catalysed rearrangements to y,(S-unsaturated methyl ketones in high yield with elimination of carbon dioxide. As an illustration of this process the conversion of the /S-keto-ester (4) into a methyl ketone product is typical (Scheme 8). 

Shimizu I, Yamada T, Tsuji J. Palladium-catalyzed rearrangement of allylic esters of acetoacetic acid to give y, 8-unsaturated methyl ketones. Tetrahedron Lett. 1980 21 3199-3202. 

TT-Aliylpalladium chloride reacts with a soft carbon nucleophile such as mal-onate and acetoacetate in DMSO as a coordinating solvent, and facile carbon-carbon bond formation takes place[l2,265], This reaction constitutes the basis of both stoichiometric and catalytic 7r-allylpalladium chemistry. Depending on the way in which 7r-allylpalladium complexes are prepared, the reaction becomes stoichiometric or catalytic. Preparation of the 7r-allylpalladium complexes 298 by the oxidative addition of Pd(0) to various allylic compounds (esters, carbonates etc.), and their reactions with nucleophiles, are catalytic, because Pd(0) is regenerated after the reaction with the nucleophile, and reacts again with allylic compounds. These catalytic reactions are treated in Chapter 4, Section 2. On the other hand, the preparation of the 7r-allyl complexes 299 from alkenes requires Pd(II) salts. The subsequent reaction with the nucleophile forms Pd(0). The whole process consumes Pd(ll), and ends as a stoichiometric process, because the in situ reoxidation of Pd(0) is hardly attainable. These stoichiometric reactions are treated in this section. 

Methylsuccinic acid has been prepared by the pyrolysis of tartaric acid from 1,2-dibromopropane or allyl halides by the action of potassium cyanide followed by hydrolysis by reduction of itaconic, citraconic, and mesaconic acids by hydrolysis of ketovalerolactonecarboxylic acid by decarboxylation of 1,1,2-propane tricarboxylic acid by oxidation of /3-methylcyclo-hexanone by fusion of gamboge with alkali by hydrog. nation and condensation of sodium lactate over nickel oxide from acetoacetic ester by successive alkylation with a methyl halide and a monohaloacetic ester by hydrolysis of oi-methyl-o -oxalosuccinic ester or a-methyl-a -acetosuccinic ester by action of hot, concentrated potassium hydroxide upon methyl-succinaldehyde dioxime from the ammonium salt of a-methyl-butyric acid by oxidation with. hydrogen peroxide from /9-methyllevulinic acid by oxidation with dilute nitric acid or hypobromite from /J-methyladipic acid and from the decomposition products of glyceric acid and pyruvic acid. The method described above is a modification of that of Higginbotham and Lapworth. ... 

The disconnection is the same (40a), we must again remember to invert the allyl group, and the only difference is the use of the acetoacetic ester (41) in the synthesis. 

However, if only two carbon atoms are present (15) they may be disconnected to give an allylic alcohol 16 and the acetoacetic ester, through a retro-Carroll rearrangement [6] (Scheme 7.6). 

The method of preparation of 5-dodecen-2-one presented here is a version of the literature procedure published earlier. It offers several advantages over existing methodology (1) The ester enolate modification of the Carroll rearrangement provides the allylic acetoacetates via a mild, fast, and high yield synthesis. This procedure represents a significant Improvement over... 

Keto esters such as acetoacetate without a substituent at the a-carbon. namely with two acidic protons, first attack the central carbon of the allenylpal-ladium to form the zr-allyl complex 89. Then intramolecular attack of the enolate oxygen of the 0-keto ester at the rr-ully l system takes place to form the nieihv-lenedihydrofuran 90 as a primary product, which is easily isomerized to the turn 91. The /3-diketone 92 reacts similarly to give the furan 93[40], The reaction can be applied to the synthesis of the phenyIthiomethyl-substituted furan 94. which is useful for the synthesis of natural products such as neoliacine. [41]... 

The Carroll rearrangement, a variation on the ester Claisen rearrangement, is a useful method for the preparation of y, 8-unsaturated ketones from allyl acetoacetates, and has been adapted to provide a method for the synthesis of a number of specific arylacetones. Thus, treatment of the p-quinol 1 with diketene and a catalytic amount of DMAP at room temperature gave a 72% yield of the arylacetone 2 together with 5% of the benzofuran 3. 

With an w-propyl halide and an allyl halide as the alkylating agents, the acetoacetic ester syn- allyl group... 

An improved version of the Carroll reaction, the ester enolate Carroll rearrangement, was reported in 1984 by Wilson and Ptice. Dianions of allylic acetoacetates, generated by treatment with 2 equiv. of LDA at -78 °C in THF, were rearranged at room temperature or 65 C to yield >keto acids in 40-80% yield (equation 12). In the course of a synthesis of the sesquiterpene isocomene, Snider and Beal used this method for the rearrangement of acetoacetate (73), prepared in 83% yield from reaction of cyclopen-tene (72) with diketene and a catalytic amount of DMAP (Scheme 11). The ( )-isomer of ketone (74) is obtained stereospecifically, since there is a severe steric interaction between the methyl groups in the Carroll rearrangement transition state leading to the (Z)-isomer. 

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... 

Tseou, H.-F., Wang, Y.-T. Abnormal acetoacetic ester synthesis. I. The reaction of sodium with allyl, benzohydryl and cinnamyl acetates. J. Chinese Chem. Soc. 1937, 5, 224-229. 

The group of Tietze has described syntheses of variously substituted pyrazolones 20 starting from solid-phase-bound p-keto esters. Single or iterative alkylation of the dianion of immobilized acetoacetate with allyl-, benzyl- or alkyl halides produced a set of y-substituted ketoesters 18 that could be transformed to the phenyl-hydrazones 19. Treatment of these intermediates in toluene at 100 °C produced 1-phenylpyrazolone derivatives 20 in 40-75% yield (Scheme 6) [14]. 

Among the most favorable features of the Carroll variant of the Claisen rearrangemoit are the relative ease of preparation of the parent system by condensation of allylic alcohols with acetoacetic ester or di-ketene and the defined configuration of the intermediately generated double bond. The Carroll rearrange-... 

---