2,6-Disubstituted phenols, activation

In hydrogenation, early transition-metal catalysts are mainly based on metallocene complexes, and particularly the Group IV metallocenes. Nonetheless, Group III, lanthanide and even actinide complexes as well as later metals (Groups V-VII) have also been used. The active species can be stabilized by other bulky ligands such as those derived from 2,6-disubstituted phenols (aryl-oxy) or silica (siloxy) (vide infra). Moreover, the catalytic activity of these systems is not limited to the hydrogenation of alkenes, but can be used for the hydrogenation of aromatics, alkynes and imines. These systems have also been developed very successfully into their enantioselective versions. 

We were interested in the behaviour of polymeric catalysts in order to confirm that typical polymer effects may occur. Oxidative coupling of 2,6-disubstituted phenols, as developped by Hay (7), was chosen as a model reaction and the catalytic activities of coordination complexes of copper with several polymeric tertiary amines were compared with the activities of their low molecular weight analogs. The overall reaction scheme is presented in scheme 1. 

Scheme 6.20. This ruthenium catalyst (10 mol%) was active for the cydization of ds-1 -ethynyl-2-vinyloxiranes to afford various 2,6-disubstituted phenols in reasonable yields. Under similar conditions, 1,1,2,2,-tetrasubstituted oxiranes gave the 2,3,6-trisubstituted phenols with a skeleton reorganization [22]. The 1,2-deuterium shift of the alkynyl deuterium of d-Sle was indicative of mthenium vinylidene intermediates (Scheme 6.20).

This chapter presents various examples of enzyme catalysis by polymers including ester hydrolysis, decomposition of hydrogen peroxide, oxidation of disubstituted phenols and hydroquinone, interfacial catalysis and other types of reaction. Because metal ions (Fe, Zn, Cu. Mn, Co, etc.) are often involved as coferments during enzyme catalysis, some examples illustrating their catalytic action are also given. The catalytic activity of polymeric coordination compounds is shown to depend on the strength of the ligand-metal bond. 

The study of phenol alkylation has a long history. Claisen and co-workers (178) showed that metal phenoxides react with active alkyl halides (e.g., allyl and benzyl bromides) in nonpolar solvents to give o-alkylphenols. Cyclohexa-dienones may be prepared in this way starting from 2,6-disubstituted phenols... 

The catalytic activity of copper complexes in oxidative coupling of 2,6-DMP to PPO is significantly improved when polymer-bound 4-aminopyridine is used as ligand [92]. Basic copper-amine complexes also catalyze the oxidative coupling of 2,6-disubstituted phenols [82]. Depending on the size of substituents and the conditions, polymerization or diphenoquinone formation may predominate [83-86]. Small substituents like methyl favor the PPO product. 

A survey has appeared of the reactivity of 2,6-disubstituted phenols and 2-methyl-l-naphthol with A -methoxymethylmonoaza-12-crown-4 ether in the Mannich reaction. The acidity and the electrostatic charge of the aromatic compounds are indicators of their reactivity. Compound (20) was formed from the above naphthol in this reaction. In the presence of aluminium chloride, chlorothiophenes react with activated aromatic compounds to form arylthiophenes. The aluminium chloride-catalysed selfcondensation of chlorothiophenes produces mainly bi- and ter-thiophenes. 

The reaction with disubstituted formamides and phosphorus oxychloride, called the Vilsmeier or the Vilsmeier-Haack reaction,is the most common method for the formylation of aromatic rings. However, it is applicable only to active substrates, such as amines and phenols. An intramolecular version is also known.Aromatic hydrocarbons and heterocycles can also be formylated, but only if they are much more active than benzene (e.g., azulenes, ferrocenes). Though A-phenyl-A-methyl-formamide is a common reagent, other arylalkyl amides and dialkyl amides are also used. Phosgene (COCI2) has been used in place of POCI3. The reaction has also been carried out with other amides to give ketones (actually an example of 11-14),... 

In contrast, the structure of the diindoxyls (141) is controversial. Kalb and Bayer,3 followed by Jones,24 supported structure 146. On the other hand, Hassner and Haddadin94 and Bond,18 from a comparison of the UV spectra with those of 2,2-disubstituted indoxyls95 have argued for 141. Chemical evidence has also been presented in favor of 141.18 Indolones (138) do not form adducts with phenols, and their water and alcohol adducts are unstable. The adducts with active methylene compounds are more stable (Section V,A). The stability of the diindoxyls corresponds to a C—C rather than a C—O linkage at the 2-position of the indolone adducts. The present evidence overwhelmingly supports 141 as the correct structure for these compounds. 

There is evidence that 3-aryl-3-methylpiperidines closely related to the 4,4-disubstituted piperidines also mimic morphine in their associations with opiate receptors. Again all active derivatives of this type are phenols and some possess antagonist properties when carrying an allyl or CPM substituent at the basic center. N-Methyl derivatives are feeble analgesics but become more... 

F. Cularine.—New syntheses of ( )-cularine (ISO) and its derivatives using intramolecular Ullmann186 and phenolic oxidative coupling187,188 reactions as key steps have been reported. It is well known that 7,8-disubstituted isoquinolines cannot be prepared by the Bischler Napieralski reaction. This problem was circumvented (Scheme 14) by using an ethoxycarbonylamino-/ -phenethyl-amide (177) in order to activate the para-position and thus to effect the required cyclization reaction (177) — (178).186 Conventional steps then led to the phenol (179) which under Ullmann reaction conditions gave (+)-cularine (180). 

---