Fries rearrangement Regioselectivity

Since the Fries rearrangement is a equilibrium reaction, the reverse reaction may be used preparatively under appropriate experimental conditions. An instructive example, which shows how the regioselectivity depends on the reaction temperature, is the rearrangement of m-cresyl acetate 8. At high temperatures the ortho-product 9 is formed, while below 100°C the para-derivative 10 is formed ... 

BF3 Et20 is used for the regioselective rearrangement of polyprenyl aryl ethers to yield polyprenyl substituted phenols, e.g. coenzyme Q [92]. This reagent is used in the Fries rearrangement for example, 5-acetyl-6-hydroxycoumaran is obtained in 96 % yield from 6-acetoxycoumaran by use of this reagent (Eq. 48) [93]. 

The amide is a good ort/zo-director but so is the acetal function. The regioselectivity (actually there is the issue of chemoselectivity here too) of the lithiation reaction will depend upon which of the two is the more potent. Amides were one of our three kings of the ortho-directors and are more powerful than acetals. Now it is time for an anionic Fries rearrangement (in the retrosynthetic direction) to give the starting material 127. 

Acyl group migration can be effected photochemically in nitrogen-containing systems. Regioselective photo-Fries rearrangements in 5- and 6-acetoxyindoles have been observed in... 

The Fries rearrangement of phenyl- and 1-naphthyl esters can be efficiently performed in the presence of hafnium triflate. The method is based on the one previously described for the Friedel-Crafts acylation of arenes with acyl chlorides. The reaction occurs in toluene-nitromethane mixtures at 100°C for 6 h. Several examples of this Fries isomerization with synthetic application are reported in Table 5.5. In all cases, complete regioselectivity is obtained, and 2-acylated phenol or naphthol derivatives are isolated in good yields. 

The archetypal photochemical lateral-nuclear rearrangement in aromatic compounds is the photo-Fries rearrangement, and a relatively simple example is reported in which /Mjhlorophenyl salicylate (189) gives 5-chloro-2,2 -dihydroxybenzophenone. Use is made of the photo-Fries rearrangertient of 1-naphthyl esters (190) in the regioselective synthesis of tricyclic analogues of... 

Fries Rearrangement. Hf(OTf)4 was found to be an efficient catalyst in the Fries rearrangement of acyloxybenzene or the related naphthalene derivatives. The reactions proceeded smoothly in the presence of 5-20 mol % Hf(OTf)4. Regioselective direct acylation of phenol and naphthol derivatives with acid chlorides was also achieved by using Hf(OTf)4 as the catalyst (eq 32). ... 

Chan, A. C. and ChiUiard, P. R., Regioselectivity of the photo-Fries rearrangement in acetoxyin-doles. Tetrahedron Lett., 30, 6483, 1989. 

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