CARROLL Rearrangement of Allyl

Asymmetric decarboxylative rearrangement (Carroll rearrangement) of allyl a-acetamido-/3-ketocarboxylates, catalysed by a palladium complex modified with a chiral phosphine ligand, has been reported to give optically active /,5-unsaturated a-amino ketones with up to 90% ee (Scheme 92).135 The mechanism for the Carroll rearrangement is shown in Scheme 93. 

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 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. 

Since its discovery in 1912, the Claisen rearrangement of allyl vinyl ethers (1 - 2 equation 1) has become one of the most powerful tools for stereoselective carbon-carbon bond formation. Much of its current popularity is due to the subsequent development of a series of new variants of this 3,3-sigma-tropic rearrangement. In 1940, Carroll reported the base-catalyzed rearrangement of -keto esters and allylic alcohols to alkenic ketones (3 4 5 equation 2). Twenty years later. Saucy and Marbet dem-... 

J. Rodriguez et al. have investigated the stereoselective ester dienolate Carroll rearrangement of ( )- and (Z)-allylic (3-keto esters and found a new, attractive approach to the synthesis of the Prelog-DJerassi lactone and related... 

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

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. 

Very recently, complexes of ruthenium derivatives with hexacoordinated phosphorus ligands have been recognized as efficient catalysts in the field of organic synthesis. This includes, among others, the decarboxylative Carroll rearrangement of secondary and tertiary allyl jS-ketoesters which is... 

The rearrangements of various allylic compounds catalyzed by both Pd(II) and Pd(0) are treated in this section[491]. Related reactions such as the Carroll rearrangement are treated in Section 2.10.1 and the Pd(II)-catalyzed Cope rearrangement is treated in Chapter 5, Section 3. 

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. 

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

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 Ciba-Geigy group used the Carroll reaction for the synthesis of hydroxyethylene dipeptide iso-steres. Alcohol (80) was converted with diethyl isopropylmalonate to the mixed malonic ester derivative (81) by Ti(OEt)4 catalysis. Subsequent sigmatropic rearrangement of (81) was also effectively catalyzed by Ti(OEt)4, thereby allowing a one-step conversion of the allylic alcohol (80) to ester (82) (Scheme 13). 

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. 

ZnS04, toluene, 60-80°C, 66-97% yield. This method works for allylic alcohols, which will often undergo the Carrol rearrangement followed by decarboxylation. The method can also be used to prepare esters of 3° alcohols. ... 

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 linear analysis of the sinensals starts at the right hand end with a rehydration and a Grignard disconnection to ketone (70). This is y,5-unsaturated and so can be made by a Carroll rearrangement (Chapter 35) (remembering to invert the allylic alcohol). This allylic alcohol can again be made by vinyl Grignard addition to a ketone (64) already made for the convergent approach, ... 

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]. 

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