Allyll acetoacetate

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... 

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. 

The unsaturated allyl /l-keto carboxylates 425 and 426, obtained by the Rh-catalysed reaction of myrcene (423) with allyl acetoacetate (424) (see 5.2), were... 

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. 

A modification of the Carroll reaction that enables the preparation of y,8-unsatu-rated ketones under milder conditions uses the dianion of allylic acetoacetates in a sequence of reactions depicted below. 

Homoallylic alcohols. Allylsamarium reagents prepared in tetrahydropyran are quite stable (in THF Wurtz coupling occurs, therefore the Barbier technique must be employed). The sequential procedure made possible by change of solvent gives cleaner products as side reactions such as pinacol formation from ketones and decarbonylation of acid chlorides are avoided. Because of the low basicity allylsamarium reagents can be used to allylate allyl acetoacetate. 

Not all substituted acac type complexes have simple structures. A nonanuclear clusters involving yttrium and the bidentate ligand allyl acetoacetate [MeC(0)CHC(0)0CH2=CH2] has been... 

Carroll reaction. Preparation of y,A-unsaturated ketones by base-catalyzed reaction of allylic alcohols with (1-ketoesters or thermal rearrangement of allyl acetoacetates. 

CARROLL Rearrangement of Allyl Acetoacetic Esters Thermal condensation of allyl alcohols with ethyl acetoacetate in the presence of a catalyst, with loss of C02 a one pot ester exchange-Claisen-lreland rearrangement with loss of C02 (see 1st edition). 

The rate of the Carroll rearrangement has been increased by formation of a dianion on treatment of allylic acetoacetates with two equivalents of lithium diisopropylamide in tetrahy-drofuran at — 78 CC followed by heating to reflux l0°. With one equivalent of base no reaction occurs. 

A further improvement is the ester enolate Carroll rearrangement of the dianion of allylic acetoacetates. generated by treatment with two equivalents of lithium diisopropylamide at — 78 C in tetrahydrofuran100. The dianions rearrange at 20 C to 65 C in 40-80% yield. For an example, see p 3320. 

More complex products are obtained from cyclizations in which the oxidizable functionality and the alkene are present in the same molecule. y9-Keto esters have been used extensively for Mn(III)-based oxidative cyclizations and react with Mn(OAc)3 at room temperature or slightly above [4, 10, 11, 15], They may be cyclic or acyclic and may be a-unsubstituted or may contain an a-alkyl or chloro substituent. Cycloalkanones are formed if the unsaturated chain is attached to the ketone. y-Lactones are formed from allylic acetoacetates [10, 11]. Less acidic /3-keto amides have recently been used for the formation of lactams or cycloalkanones [37]. Malonic esters have also been widely used and form radicals at 60-80 °C. Cycloalkanes are formed if an unsaturated chain is attached to the a-position. y-Lactones are formed from allylic malonates [10, 11]. yff-Diketones have been used with some success for cyclizations to both alkenes and aromatic rings [10, 11]. Other acidic carbonyl compounds such as fi-keto acids, /3-keto sulfoxides, j8-keto sulfones, and P-nitro ketones have seen limited use [10, 11]. We have recently found that oxidative cyclizations of unsaturated ketones can be carried out in high yield in acetic acid at 80 °C if the ketone selectively enolizes to one side and the product cannot enolize... 

Intramolecular Michael addition occurs under mild conditions [216]. In the Pd-catalyzed reaction of allyl acetoacetate with benzylidenemalononitrile (151), the Michael addition of acetone enolate to benzylidenemalononitrile (151), followed by electrophilic allylation took place to afford 603 [217]. 

This type of reaction occurs at lower temperatures with the dianions formed from allylic acetoacetates, which can be prepared from the reaction of acetoacetates with two equivalents of lithium diisopropylamide (LDA, equations 11.13 and 11.14). 

Startg. allyl acetoacetate treated with 5 mol% Pd(OAc)2 and 10mol% acetonitrile at room temp, for 4 h - product. Y 82% erythro.threo 1 5). Almost no competitive reactions, such as allylation, dehydrogenation or hydrogenolysis, were observed. F.e. incl. spiro compds., and in aq.-organic media s. J. Nokami et al, J. Am. Chem. Soc. Ill, 4126-7 (1989). 

This observation led to the proposal of an alternative mechanism similar to the Claisen mechanism involving aUyl enol ethers. They proposed that, in the case of Carroll s observations, the first step was a trans-esterification of the allylic alcohol, catalyzed by NaOAc, to the allyl acetoacetate, followed by a Claisen-type rearrangement to the ) -keto acid, which subsequently decarboxylated under the elevated reaction temperature (Scheme 8.4). 

In 1912, Claisen first observed the thermal rearrangement of O-allyl acetoacetate 20 to yield the j, 5-unsaturated ketone 21. The reaction later proved to be general for a broad series of compounds which presented the allyl vinyl ether motif. Carpenter demonstrated that substituents have an important role in the reaction and the presence of anionic 7t-donor as illustrated in (22) greatly accelerate the reaction as documented by Denmark. ... 

The accessibility of nonracemic allyl acetoacetates makes the Carroll rearrangement an attractive strategy to assemble molecular complexity with adjacent tertiary and quaternary stereocenters. In the late 1950s, researchers at Hoffmann-La Roche utilised propargylic acetoacetate 194 to synthesise pseudoinone 195. Pyrolysis in the presence of Bronsted acid initiated the Carroll rearrangement to yield allenyl ketone 198 which tautomerised to pseudoinone 195. The minor product 196 resulted from Bronsted acid-mediated r-cation cyclisation of 199. 

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