Carroll reaction

In an imioortant industrial process, the Carroll reaction , an ahphatic version of the Claisen rearrangement occurs. See if you can find the right mechanism ... 

The reductive coupling of the 7r-allylpalladium enolates 679 gives the allylated ketones. This reaction is also possible thermally, as the Carroll reaction, which... 

Addition of acetylene to acetone results in the formation of 2-methyl-3-butyn-2-ol, which is hydrogenated to 2-methyl-3-buten-2-ol in the presence of a palladium catalyst. This product is converted into its acetoacetate derivative with diketene [38] or with ethyl acetoacetate [39]. The acetoacetate undergoes rearrangement when heated (Carroll reaction) to give 6-methyl-5-hepten-2-one ... 

In the synthesis of vitamin A, the dependence on natural sources as well as steadily increasing production via /3-ionone as an intermediate have led to the development of a method for synthesizing citral from dehydrolinalool (see p. 37). More recent routes employ dehydrolinalool as the starting material for pseudoionone. Dehydrolinalool is converted into pseudoionone by using either diketene [92] or a suitably substituted acetoacetate (Carroll reaction) [93] ... 

Linalool can be converted to geranyl acetone (63) by the Carroll reaction (34). By transesterification with ethyl acetoacetate, the intermediate ester thermally rearranges with loss of carbon dioxide. Linalool can also be converted to geranyl acetone by reaction with methyl isopropen ether. The linalyl isopropenyl ether rearranges to give the geranyl acetone. 

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. 

This reaction based on the petrochemical crude material isobutylene makes the synthetic route to P-ionone (36) substantially shorter and cheaper, especially since the isomeric double bond proves to be advantageous in the subsequent reactions. In addition, i-methylheptenone (37 a) can be converted into methylheptenone (37) by noble metal-catalyzed isomerization. The reaction steps ethynylation (C2 addition), Carroll reaction (C3 addition), ethynylation and partial hydrogenation (C2 addition) lead from methylheptenone (37) via dehydrolinalool (42), pseudoionone (43) and p-ionone (36) to the C15 alcohol p-vinylionol (44). With triphenylphosphine (15), the desired C15 phosphonium salt (13), which is the second important synthetic building block for vitamin A and carotenoids16), is obtained directly from p-vinylionol, by allyl rearrangement. 

Vinyllithiums of type 663 (R2 = R3 = H) reacted with primary alkyl bromides, carbonyl compounds, carbon dioxide, DMF, silyl chlorides, stannyl chlorides, disulfides and phenylselenyl bromide142,970-979. Scheme 173 shows the synthesis of dihydrojasmone 669 from the corresponding 1,4-diketone. a-(Phenylsulfanyl)vinyllithium 665, prepared from phenyl vinyl thioether, reacted with hexanal and the corresponding adduct 666 was transformed into its acetoacetate. This ester 667 underwent a Carrol reaction to produce the ketone 668, which was transformed into the cyclopentenone 669 by deprotection either... 

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). 

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. 

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

Methylhept-2-en-6-one, usually referred to simply as methylhep-tenone, is a useful synthon for the total synthesis of terpenes. One early synthesis of this intermediate employed the Carroll reaction, the substrate for which is prepared by the addition of acetylene to acetone and subsequent partial hydrogenation to 2-methylbut-3-en-2-ol, as shown in Scheme 4.5. Addition of acetylene to methylheptenone gives dehydrolinalool, which can be hydrogenated to linalool using a Lindlar catalyst. 

The Carroll reaction occurs when a /i-ketoester is treated with an allylic alcohol in the presence of base, or when an allyl ester of a / -ketoacid is heated. Scheme 4.6 shows the mechanism of the latter. 

Use of the Claisen rearrangement achieves the same conversion of methylbutenol into methylheptenone as does the Carroll reaction, but without the loss of carbon dioxide.The methanol produced instead can be recovered and recycled. In this process, as shown in Scheme 4.7, methylbutenol is treated with the readily available 2-methoxypropene to give the allyl vinyl ether, which then undergoes a Claisen rearrangement to give methylheptenone. 

Decarbonylation of the ozonolysis product of ot-pinene gives a methyl trimethylcyclobutyl ketone. Addition of acetylene to this, followed by the Carroll reaction, gives (trimethylcyclobutyl)heptadienone. The cyclobutane ring is opened by acid to give a methylated /-ionone which, on cyclization, produces irones. Once again, the Greek prefixes have the same significance as in the ionone series. 

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