Ethers, aryl allyl, Claisen phenols

When, furthermore, phenols (368) are coupled with 1 in the presence of a Pd° catalyst, the phenoxy-methyl-1,3-dienes 369 are produced [158]. As aryl allyl ethers, these can be made to undergo a Claisen rearrangement (205 °C, DMF) and the ensuing 2-(l,3-dienylmethyl)phenols 370 finally cydize in the presence of a trace of acid to a mixture of exo-methylene chromans 371 (major product) and dihydrobenzofur-ans 372 - a remarkable generation of functional and structural complexity from simple starting materials with 100% atom economy and underlining impressively the synthetic versatility of modern allene chemistry ... 

Substituted allyl aryl ethers undergo a Claisen rearrangement similar to the reaction described in text Section 24.13 for allyl phenyl ether. 2-Butenyl phenyl ether rearranges on heating to give o-( 1-methyl-2-propenyl)phenol. 

Recall that the Claisen rearrangement converts an aryl allyl ether to an ortho-substituted allyl phenol. The presence of an allyl substituent in the product ortho to an aryl ether thus suggests the following retrosynthesis ... 

The thermal [3,3]-sigmatropic rearrangement of allyl vinyl ethers, first reported by Claisen in 1912, allows the preparation of y,6-unsaturated carbonyl compounds. This reaction is called [3,3]-sigmatropic rearrangement because the new a-bond has a 3,3 relationship to the former a-bond. The aromatic variant of the Claisen rearrangement, in which an aryl allyl ether (5) is converted thermally to the corresponding y,6-unsaturated carbonyl compound (6), is followed by a re-aromatization providing an ortho-di y phenol (7). 

Of greater preparative value is the rearrangement of allyl aryl ethers to allyl-phenols, also discovered by Claisen ... 

Vinyl allyl ethers and allyl aryl ethers are converted by heating to y,6-unsaturated carbonyl compounds and allyl phenols, respectively. The two groups of reactions are mechanistically related, and are referred to as Claisen rearrangements. Claisen rearrangements of allyl aryl ethers have been reviewed and their kinetics are discussed in Chapter 3 Volume 13 of this series. The present discussion is limited to thermal isomerizations of vinyl allyl ethers. 

The original sigmatropic rearrangement occurred when an aryl allyl ether was heated without solvent and an ortho-allyl phenol resulted. This is the Claisen rearrangement. The first step in this reaction is a pericyclic reaction of a type that you will learn to call a [3,3]-sigmatropic rearrangement. 

Thermal [3,3]-sigmatropic rearrangements of allyl aryl ethers and allyl vinyl ethers are known as the Claisen rearrangements [68], These reactions are sensitive to solvent polarity and the rates of the reactions are increased by increasing the solvent polarity [69]. The simplest examples are the thermal conversion of allyl phenyl ether to ort/io-allyl phenol and of allyl vinyl ether to 4-pentenal [70]. 

A similar process leading to dihydrobenzofurans 6 through a PhgPAuOTf-catalyzed Claisen rearrangement of aryl allyl ethers 5 followed by a tandem phenol addition was reported by He et al. Controlled experiments revealed that... 

The same catalytic system was used to prepare dihydrobenzofurans 52 from aryl allyl ethers 51 through an intramolecular process (Scheme 26) [169]. This reaction proceeds by a Claisen rearrangement, followed by gold(I)-catalyzed addition of the resulting phenol to the allyl group. 

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. 

The classical Claisen rearrangement is the first and slow step of the isomerization of allyl aryl ethers to orlho-a ly lated phenols (Figure 14.46). A cyclohexadienone A is formed in the actual rearrangement step, which is a [3,3]-sigmatropic rearrangement. Three valence electron pairs are shifted simultaneously in this step. Cyclohexadienone A, a nonaromatic compound, cannot be isolated and tautomerizes immediately to the aromatic and consequently more stable phenol B. 

Claisen rearrangement of an allyl aryl ether to yield an o-allyl phenol (Secs. 18.4,30.8)... 

For this reaction, the rate was found to vary by a factor of 34 in going from the least polar ( -tetradecane) to the most polar solvent (phenol), and by a factor of 102 in going from the gas phase to the most polar solvent [153]. The small solvent and substituent effects observed suggest that a slightly dipolar activated complex must be formed during the Claisen rearrangement of this allyl aryl ether [153]. 

In the Claisen rearrangement, an allyl aryl ether gives an o-allylphenol on heating. The mechanism here is not a Whitmore 1,2-shift, but is a concerted peri cyclic [3,3] sigmatropic rearrangement, that results in a cyclohexadienone, which, after tautomerisation, gives the phenol. 

The overwhelming majority of literature devoted to isomerizations of allyl aryl ethers is connected with the aromatic Claisen rearrangement and is summarized in detail in many reviews . Although the [3,3]-sigmatropic isomerization of phenol ethers to the corresponding C-alkylated derivatives has enjoyed widespread application in organic synthesis for over seventy years, it continues to be a very important reaction for the construction of a carbon-carbon bond. This section presents only recent reports. 

Danishefsky et al. developed a stereospedfic route for the synthesis of deoxy analog of mitomycin via an aromatic Claisen rearrangement [84]. The aUyl aryl ether 112 was prepared from allylic alcohols and phenol derivative via the Mitsu-nobu reaction. The aromatic Claisen rearrangement of 1,3-disubstituted aUyhc ether 112 proceeded under thermal conditions (N,N-dimethylaniline reflux) to afford the ortho rearrangement product 113 in 80% yield. 

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