Phenol acylation metal phenolates

Additional examples of type d (Scheme 5.1) bifunctional reactants are provided by the alkaline-earth metal ion complexes of lariat ethers 8-10, bearing a sulfhydryl side arm, instead ofthe phenolic hydroxyl of a calixcrown [23,24]. Here the acyl-receiving and acyl-releasing unit, like in papain and ficin, is a sulfhydryl group. 

In a bifunctional compound, if a reagent reacts with one functional group preferentially, even though the other is apparently susceptible to the reaction conditions, the reaction is said to be chemoselective. Two illustrative examples are the reduction of a carbonyl group in the presence of a cyano, nitro or alkoxycarbonyl group (Section 5.4.1, p. 519 see also Metal hydrides, Section 4.2.49, p. 445) and the acylation of an aromatic amino group in the presence of a phenolic group (Section 6.9.3, p. 984). 

To expand the diversity of their libraries Brill et al.16 also modified various heterocycles by alkylation, acylation, or metal-mediated coupling reaction prior to resin capture. A remaining chloro substituent was still available for nucleophilic displacement or a palladium-mediated coupling reaction with anilines, phenols, and boronic acids on solid phase [see Fig. 10 for the preparation of purine derivative (62)]. 

The mechanism of the Rosenmund reduction has attracted occasional attention. The discovery of Tsuji et al that palladium metal can catalyze the conversion of acyl chlorides (11) into alkenes (13), carbon monoxide and HCl, presumably via intermediates of the form (12 Scheme 5), suggests that (12) may also be an intermediate in the Rosenmund reaction. Consistent with this suggestion is the observation that the unsaturated acyl chloride (14) is converted to phenol by a palladium catalyst.22... 

V. Snieckus and co-workers developed a new carbamoyl Baker-Venkataraman rearrangement, which allowed a general synthesis of substituted 4-hydroxycoumarins in moderate to good overall yields. The intermediate arylketones were efficiently prepared from arylcarbamates via directed ortho metallation and Negishi cross coupling. The overall sequence provided a regiospecific anionic Friedel-Crafts complement for the construction of ortho-acyl phenols and coumarins. 

Recently, Eberlin and coworkers130 proposed an EI-MS/MS approach for the direct structural assignment of ortho- and metal para-substituted acyl and amidyl anilines in general (as well as phenols). The approach is based on the assertion that most compounds of this class should produce upon El the respective aminoacylium ion (Scheme 39), and that these diagnostic ions (and hence the position of the ring substituents) could be distinguished via selective ion/molecule reactions. 

The initial step of both the above reactions, the formation of an acyl radical, is catalysed by light and by metal ions that are capable of a one-electron reduction transition (e.g. Fe3+ -+ Fe2 + ). Thus, the autoxida-tion of aldehydes can be greatly slowed by keeping the compounds in the dark and by very careful purification. Flowever, the most efficient method is the addition of antioxidants, such as phenols and aromatic amines, which react preferentially with any radicals that may be present. 

From a synthetic point of view, the process can be efficiently applied to the preparation of a large variety of ortho-hydroxyaryl ketones, as summarized in Table 5.1. Results from Table 5.1 are a proof of the powerful metal-template effect in promoting ortho-regioselective electrophilic acylation of phenol substrates. 

A further application of the metal-template effect in the ortho-regioselective acylation of phenols is represented by the direct synthesis of salicyloyl chloride and derivatives by the reaction of bromomagnesium phenolates 4 with phosgene. The reaction affords the unstable salicyloyl chloride-magnesium complexes 5 by a pathway similar to the mechanism depicted in Scheme 5.2. These intermediates can be in situ converted into the corresponding acids 6 (Scheme 5.3), esters, amides, or ketones by reaction with suitable reagents. 

The metal-template effect is also exploited as a powerful instrument to achieve highly selective ortho-acylation of the phenol ring in the... 

The positive effect of zinc chloride-AAN reagenf in the acylation of phenol derivatives can be exploited in the production of various poly-hydroxyacefophenones (Table 5.2). When the reagent is applied to acylation of phenol, an equimolecular mixfure of 2- and 4-hydroxyacetophenone (36% and 40% yield, respectively) is produced. This result allows exclusion of any remarkable metal-femplafe effecf in fhe presenf system. 

Metal triflates are efficiently utilized as reusable catalysts in the direct acylation of phenols as well as in the Fries rearrangement. Scandium triflate is employed as catalyst (5% mol) in the direct acylation of phenols and naphfhols wifh acyl chlorides in toluene-nitromefhane mix-fures af 100°C for 6 h. Resulfs from Table 5.3 show fhaf fhe reacfion is very efficienf complefe regioselecfivify is observed wifh mefa-cresol and 1-naphfhol derivafives. 

Sartori, G., Casnati, G., Bigi, R, and Bonini, G. 1988. Metal template ortho acylation of phenols direct synthesis of salicylic acid chlorides and derivatives. Synthesis 763-766. 

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