Fries enolization

Critical region behavior of the diffusion coefficient can have effects on product ratios. This is probably the explanation of the increase in yield of the photo-Fries enolization products near the critical density in the photochemical... 

The photo-Fries enolization products are formed within the solvent cage, and diffusion out of the cage is necessary to give the other product, 1-naphthol. Outside the critical region the ratio of photo-Fries enolization products to naphthol is around four, but this increases to more than 12 near the critical density. 

A second process that occurs concurrently with the dissociation— redistribution process is an intermolecular rearrangement by which cyclohexadienone groups move along a polymer chain. The reaction maybe represented as two electrocycHc reactions analogous to a double Fries rearrangement. When the cyclohexadienone reaches a terminal position, the intermediate is the same as in equation 8, and enolization converts it to the phenol (eq. 9). 

The photo-Fries rearrangement of aryl hydrogen (or methyl) succinates 267 leads to 4-(2-hydroxyaryl)-4-oxobutanoic acids (or methyl esters 268), which are readily cyclized to 5-(2-acetoxyaryl)-2(3//)-furanones (269) (Scheme 68). [189-191] Photolysis of 269 [191] or the analogous open-chain enol acetates [192,193] leads to chromones. 

P-Keto acids 34 can be converted into 5,6-dialkyl-4-hydroxypyran-2-ones by thermolysis of the Meldrumls acid derivatives 35. A Fries rearrangement of the derived enol acylates and reduction of the resulting 3-acylpyranone with EtjSiH provides a route to the 3,6-dialky Ipyranones 36 (Scheme 17) <99T4783>. 

A novel base-catalyzed Fries-like rearrangement of a 3-acetoxythiophene has been reported (Scheme 149) (79JOC3292). This has been explained as the result of iodide-induced deacylation and subsequent C-acylation of the intermediate enolate anion. Some transformations of 4-hydroxy-2-methylthiophene-3-carboxylic ester are shown in Scheme 150 (69KGS567,75KGS914,71KGS759). 

Hydroxythiocoumarins are, of course, enolic and react as acetoacetate analogues. Electrophiles such as Mannich reagents, aromatic aldehydes and enones react readily (Scheme 22), while acylation can be direct, or via a Fries-type rearrangement of 4-acyloxy precursors. 

The Fries rearrangement of phenol esters gives a mixture of 2- and 4-acylphenols. Similarly, enol esters undergo rearrangement to give the corresponding 1,2-di ketones. 

The enol ester (307) undergoes a photo-Fries rearrangement, giving a (3-diketone, isolated in its enolic form (308).245... 

Tabuchi, H., Hamamoto, T., Ichihara, A. Modification of the Fries type rearrangement of the O-enol acyl group using W,W-dicyclohexylcarbodiimide and 4-dimethylaminopyridine. Synlett 1993, 651-652. 

Patterson and Fried found that the clean lithium enolate (14), generated by conjugate addition of the lithium divinylcuprate (15) to cyclopentenone with subsequent trapping of the initial enolate with TMS-Cl and cleavage of the TMS enol ether with lithium amide in liquid ammonia-THF, could be alkylated in a reasonable yield with the (Z)-allylic iodide (16) to give the 11-deoxyprostaglandin derivative (17 ... 

In the presence of a stoichiometric amount of SbCls, Friedel-Crafts acylation proceeds with acyl hahdes and acid anhydrides [47], SbCls also promotes the Fries rearrangement of phenyl acetates [48], The electrophilic acylation of fluoro-olefins with acetyl fluoride or benzoyl fluoride is promoted by SbFs in liquid SOy [49], The Friedel-Crafts acylation of benzene and electron-rich arenes is successfully catalyzed by SbCl5-AgClO4 [50], SbCl, Ar.BCl [51], SbCl5-LiClO4 [52], or CaCI, AgSbFg [53] (Scheme 14,19), Acyl chlorides, acid anhydrides, and acyl enolates are used as sources of acyl groups. 

Patterson and Fried [139] inserted the a-side chain by alkylation of a cyclo-pentatone enol ether. Intermediate (127) was first obtained by reaction of cyclopent-2-enone with an organocopper reagent followed by formation of the silyl enol ether and the a-chain then added by alkylation of 127 with c/s-7-bromooct-5-enoate, thus leading to ( )-l l-deoxy-PGE2 methyl ester. 

Titanium tetrachloride is a moisture-sensitive, highly flammable liquid reacting violently with water (34). It is a strong Lewis acid capable of promoting Diels-Alder reactions (35) and induces the addition of silyl enol ethers and allyl silanes to carbonyl compounds and derivatives (34r-36). It is a less commonly used catalyst in Friedel-Crafts reactions but very useful for the acylation of activated alkenes and in the Fries rearrangement. 

The regioselectivity of photoaddition of the enol acetate of 40 depends on reaction temperature, and the ratios of 41 to 42 are 11 89, 2 3, and 51 49 at -70 °C, 25 °C, and 65 °C, respectivelyOf note is that the acetylation of 1,3-diketone 40 is not regiospecific, but the two enol acetates interconvert via a photo-Fries process. However, only the enol acetate leading to 41 and 42 participates in the cycloaddition. Fragmentation of adducts 41 and 42 gives diketone 44 and the aldol product 45 via diketone 43. 

The photochemical reactivity of P-ketoesters is different form that of P-diketones. Irradiation of a P-ketoester in the presence of an alkene produces oxetane via the ketone carbonyl instead of the desired cyclobutane ring system. Therefore, it is necessary to covalently lock the ketoesters as the enol tautomers. To this end, silyl enol ethers, 129 and 132a, and enol acetates, 130 and 132b, were prepared, but these substrates still fail to undergo the desired intramolecular [2 + 2] photocycloaddition with olefins. The only new products observed in these reactions result from the photo-Fries rearrangement of the cyclic enol acetate (130 to 131) and cis-trans isomerization of both acyclic substrates 132a/b. However, tetronates are appropriate substrates for both intermolecular and intramolecular photocycloadditions with olefins. In addition, enol acetates and silyl enol ethers of p-keto esters are known to undergo [2 + 2] photoaddition with cyclic enones (vide infra). 

The Lewis acid-catalyzed Fries rearrangement is performed under strong acidic conditions and therefore reqnires protection of sensitive functional groups. Conversely, the PFR can be achieved nnder milder conditions (organic solvents, nentral media, room temperature, etc.) and is therefore free from this type of problems. Moreover, polyacylation of aromatics is usually difficult to achieve. In the PFR, this problem can be solved by using acetals [144—146] or enol esters [147] as carbonyl protecting groups. Addition of anhydrous K CO is convenient to avoid deprotection [148]. 

Rearrangement of the -acetylated dienolate 4 presents a wide scope and, like the Fries rearrangement, is polar. The plausible intermediates are titanium enolate and acetyl chloride. 

---