Carroll decarboxylation

Many monoterpenes are desired fragrances in perfumery and flavors in food. They are produced on a larger scale from acetone (C3) and ethyne (acetylene C2) involving repetitive synthetic steps (Fig. 5). Initially, acetone is ethynylated by acetylene in the presence of a base (sodium hydroxide, amines with sodium carbonate) yielding 3-butyn-2-ol (C5) which is partially hydrogenated in the presence of deactivated catalysts (Lindlar catalysts) to 2-methyl-3-buten-2-ol. This can be converted to the key intermediate 6-methyl-5-hepten-2-one (Cg) via two pathways, either by transetherification with methylpropenylether and subsequent oxa-CoPE rearrangement, or by transesterification with methyl acetoacetate and subsequent Carroll decarboxylation. 

Transesterifieation of linalool with methyl aeetoaeetate followed by CARROLL decarboxylation provides aceess to 6,10-dimethylundeea-5,9-dien-2-one (C13). This is ethynylated to the sesquiterpene dehydronerolidol (C15), which is partially hydrogenated to nerolidol. Finally, nerolidol is subjected to an allyl rearrangement for the production of famesol (Fig. 5). 

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. 

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 Carroll rearrangement, an old and well-established thermal rearrangement, involves the rearrangement of allyllc esters to B keto acids followed by decarboxylation to provide y,6-unsaturated methyl ketones. Even though the Carroll rearrangement fs a versatile complement to the Claisen rearrangement, It is not of widespread use. This may be due to (a) the... 

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). 

In 1940 Carroll reported the rearrangement of P-keto allyl esters (49) followed by decarboxylation to yield y,5-unsaturated ketones (53) via a [3,3]-sigmatropic (Claisen) rearrangement (Scheme 4.13) [31]. The reaction has found limited scope in organic synthesis due to the harsh conditions required (130-220 °C) to induce the rearrangement. 

From an historical point of view, in 1940, Carroll [3] reported the base-catalyzed rearrangement of acetoacetic esters of aUyUc alcohols alForded after decarboxylation of y-unsaturated ketones (Scheme 6.1). 

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). 

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. 

Rodriguez and co-workers envisioned the Carroll rearrangement as the key step in the preparation of the Prelog-Djerassi lactone 204. The dienolate of 200 conveniently rearranged via a chair-like transition state 201 to the y0-keto acid which underwent decarboxylation to give a 4 1 mixture of cyclopentanone epimers. Epimerization under thermodynamic conditions... 

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... 

This acetaoacetate derivative undergoes Carroll rearrangement, accompanied by decarboxylation, to give the desired product... 

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