Ester enolate Carroll

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. 

In the laboratory of A.M. Echavarren, the total synthesis of the antibiotic (+)-4-ep/-acetomycin was completed by using the stereoselective ester enolate Carroll rearrangement of ( )-butenyl-2-methylacetoacetate as the key step, followed by ozonolysis and acetylation. The stereochemistry of the major isomer resulted from the rearrangement of the ( )-enolate through a chair-like transition state. ... 

Echavarren, A. M., De Mendoza, J., Prados, P., Zapata, A. Stereoselective synthesis of ( )-4-epiacetomycin by the ester enolate Carroll rearrangement. Tetrahedron Lett. 1991, 32, 6421-6424. 

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. 

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... 

Besides the steric requirements of the X groups in the C-2 position of A, reaction conditions are important for the stereochemical outcome of the rearrangements. Thus, Ireland rearrangements, which can be performed under mild conditions, yield EjZ ratios >99% (see, for example, p 3324). Similarly, the Carroll rearrangement of an ester enolate proceeds smoothly (in refluxing tetrahydrofuran) to give E selectivities >90% l0°. 

The reductive coupling of the 7i-allylpalladium enolates 400 gives the allylated ketones 403. This reaction is also possible thermally and is called the Carroll reaction. Whereas the Carroll reaction proceeds by heating up to 200 °C, the Pd-catalysed Carroll-type reaction can be carried out under mild conditions (even at room temperature) by reductive elimination of the 7t-allylpalladium enolate 400 [177,178], The Pd-catalysed reaction is mechanistically different from the thermal reaction and more versatile, which is explained by the [3,3] sigmatropic rearrangement of the enolate form. For example, thermal Carroll rearrangement of the a,a-disubstituted keto ester 410 is not possible, because there is no possibility of the enolization. However, it rearranges to ketone 411 smoothly with the Pd catalyst, via the 7i-allylpalladium enolate. 

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. 

The Carroll reaction uses an acetoacetate ester (54), made by ester exchange or with diketene (Chapter 33), to give enol (55) which can do the [3,3] sigmatropic shift and give keto acid (56) which decarboxylates under the reaction conditions. The synthesis of (53) is standard acetylene chemistry (Chapter 16). 

Formation of allylketones 567 from allyl -ksto esters 563 and allyl enol carbonates 566 is the Pd-catalyzed Carroll rearrangement. As a related reaction, Pd-catalyzed regioselective intramolecular allyladon of the allyl enol ether of 6-keto ester 574 occurred as shown by 575 in DMSO, and afforded a mixture of the endo- and eJco-bicyclo[3.2.1]octane frameworks 576 and 577 using DPPE as a ligand. PPh3 is not suitable [207]. 

The Carroll rearrangement involves thermal- or base-mediated [3,3]-sigmatropic rearrangement of a y9-keto allyl ester (180) to a y -unsaturated ketone (184). The reaction passes through the isolable -keto carboxylic acid (182) that readily decarboxylates to give rise to the enol 183 which tautomerises to the more stable ketone. 

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