Allyl ethers rearrangement reaction

Although the Claisen rearrangement was first observed in the enol allyl ethers, - the reaction is much more useful and important in the aromatic series. Some interesting observations have been made, however, with the open-chain systems. The original r iorts concerned the rearrangement of ethyl 0-allylacetoacetate, 0-allylacetylacetone (XI Va), and 0-allyloxymethylenecamphor (XV). 

The Claisen-Johnson rearrangement [7] is closely related to both Saucy vinyl allyl ether rearrangement and Eschenmoser rearrangement. The reaction proceeds via a ketene acetal, which results from the condensation between an ortho-ester and an aUylic alcohol giving rise to a mixed orthoester followed by the elimination of the low-boihng-point alcohol. This ketene intermediate forms after rearrangement of a y,d-unsaturated ester (Scheme 6.1). 

In certain cases the reaction may proceed by a concerted mechanism. With allyl ethers a concerted [2,3]-sigmatropic rearrangement via a five-membered six-electron transition state is possible " ... 

Unlike the acid-catalyzed ether cleavage reaction discussed in the previous section, which is general to all ethers, the Claisen rearrangement is specific to allyl aryl ethers, Ar—O—CH2CH = CH2. Treatment of a phenoxide ion with 3-bromopropene (allyl bromide) results in a Williamson ether synthesis and formation of an allyl aryl ether. Heating the allyl aryl ether to 200 to 250 °C then effects Claisen rearrangement, leading to an o-allylphenol. The net result is alkylation of the phenol in an ortho position. 

Evidence for this mechanism comes from the observation that the rearrangement takes place with an inversion of the allyl group. That is, allyl phenyl ether containing a 14C label on the allyl ether carbon atom yields o-allylphenol in which the label is on the terminal vinylic carbon (green in Figure 18.1). It would be very difficult to explain this result by any mechanism other than a pericyclic one. We ll look at the reaction in more detail in Section 30.8. 

Claisen rearrangement reaction (Sections 18.4, 30.8) The pericyclic conversion of an allyl phenyl ether to an o-allylphenol by heating. 

Rearrangements, especially those only involving heat or a small amount of catalyst to activate the reaction, display total atom economy. A classic example of this is the Claisen rearrangement, which involves the rearrangement of aromatic allyl ethers as shown in Scheme 1.2. Although... 

The basic pattern of the Claisen rearrangement is the conversion of a vinyl allyl ether to a y,8-enone. The reaction is also observed for allyl phenyl ethers, in which case the products are o-allylphenols. 

Some representative Claisen rearrangements are shown in Scheme 6.14. Entry 1 illustrates the application of the Claisen rearrangement in the introduction of a substituent at the junction of two six-membered rings. Introduction of a substituent at this type of position is frequently necessary in the synthesis of steroids and terpenes. In Entry 2, formation and rearrangement of a 2-propenyl ether leads to formation of a methyl ketone. Entry 3 illustrates the use of 3-methoxyisoprene to form the allylic ether. The rearrangement of this type of ether leads to introduction of isoprene structural units into the reaction product. Entry 4 involves an allylic ether prepared by O-alkylation of a (3-keto enolate. Entry 5 was used in the course of synthesis of a diterpene lactone. Entry 6 is a case in which PdCl2 catalyzes both the formation and rearrangement of the reactant. 

Entry 7 illustrates reaction conditions that were applicable to formation and rearrangement of an isopropenyl allylic ether. The tri-isopropylaluminum is thought to both catalyze the sigmatropic rearrangement and reduce the product ketone. 

The rearrangements of allylic sulfoxides, selenoxides, and amine oxides are an example of the first type. Allylic sulfonium ylides and ammonium ylides also undergo [2,3]-sigmatropic rearrangements. Rearrangements of carbanions of allylic ethers are the major example of the anionic type. These reactions are considered in the following sections. 

Further confirmation of the two-fold shift, and of the double inversion of the position of the 14C label, is provided by trapping (cf. p. 50) the first dienone intermediate (55a) with maleic anhydride in a Diels-Alder reaction. An exactly analogous rearrangement is found to occur in allyl ethers of aliphatic enols, e.g (58) ... 

In presence of the basic catalyst potassium t-butoxide, the solvent DMSO accelerates some rearrangement reactions. For example, allyl ethers are rearranged to cis-propenyl ethers. 

The dissociative mechanism of the Cope rearrangement casually mentioned above222 can be illustrated by two examples of Pd-catalyzed reactions. The migration of an allyl group from carbon to carbon in the pyridine system 466 occurs in the presence of a Pd° catalyst236. Refluxing dilute solutions of precursors 466 (R1, R2 = H, Me) in toluene for 7 h or in n -heptane for 24 h gave derivatives 468. The pyridine allyl ether 469 was also... 

An irreversible consecutive reaction as a driving force to shift an unfavorable Cope rearrangement equilibria in the needed direction can be illustrated by the Cope-Claisen tandem process used for the synthesis of chiral natural compounds243. It was found that thermolysis of fraws-isomeric allyl ethers 484 or 485 at 255 °C leads to an equilibrium mixture of the two isomers in a 55 45 ratio without conversion into any other products (equation 184). Under the same conditions the isomer 487 rearranges to give the Cope-Claisen aldehyde 491 (equation 185). Presumably, the interconversion 484 485 proceeds via intermediate 486 whose structure is not favorable for Claisen rearrangement. In contrast, one of the two cyclodiene intermediates of process 487 488 (viz. 490 rather than 489) has a conformation appropriate for irreversible Claisen rearrangement243. 

The [2,3] sigmatropic Wittig reaction, as exemplified by the rearrangement of fluorenyl allyl ethers under solidrliquid basic conditions is catalysed by tetra-n-butyl-ammonium bromide [14]. 

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