Methylation of aryls

Although the reaction of alkylboronic acids is significantly slower than that of trialkylboranes, methylboroxine (MeBO)3 or methylboronic acid exceptionally alkylates bromo- and chloroarenes [125, 126]. Methylation of electron-poor bromoarenes was efficient, whereas prolonged reaction time was required for more electron-rich substrates. The reaction times can be shortened by use of the polar solvent DMF at 115 °C. B-Methyl-9-BBN and its oxy-derivative (48) [127] undergo methylation of aryl and vinyl halides under more mild conditions (Scheme 22). 

Cyanomethyltributyltin is a reagent for Pd-catalyzed cyanomethylation of aryl bromides with the Me, MeO or Cl substituent, but not with the MeCO, CN or NOj substituent (equation 111). ° Dicyano-methylation of aryl iodides can be achieved with a sodium salt of malononitrile in the presence of Pd complexes (equation 112). 2i... 

Methylation of aryl thiols. PTC methylation of l C-aryl thiols with methyl Iodide (2 ) Is very useful for microscale synthesis of C-labeled aryl methyl sulfides (2j ). The reaction, using tetrabutylammonlum hydrogensulfate as catalyst and sodium hydroxide as base In methylene chloride and water, proceeds at ambient temperature In 50-100Z yield. 

Recently, Li s group reported an unexpected efficient Pd-catalyzed methylation of aryl C—H bonds using a peroxide as a source of methyl groups (Equation 11.35) [74], This study provided a new avenue for the direct alkylation of aryl C—H bonds using alkyl radicals rather than organometallic reagents. Moreover, this work presents an excellent example of the control of radical decomposition. 

Organophosphorus compounds. Phosphorus-carbon bond fonnation takes place by the reaction of various phosphorus compounds containing a P—H bond with halides or tritlates. Alkylaryl- or alkenylalkylphosphinates are prepared from alkylphosphinate[638]. The optically active isopropyl alkenyl-methylphosphinate 778 is prepared from isopropyl methylphosphinate with retention[639]. The monoaryl and symmetrical and asymmetric diarylphosphi-nates 780, 781, and 782 are prepared by the reaction of the unstable methyl phosphinate 779 with different amounts of aryl iodides. Tnmethyl orthoformate is added to stabilize the methyl phosphinate[640]. 

The nucleophilic reactivity of the oxygen has been observed in acetylation by acetic anhydride of 2-aryl- and 2-heteroaryl-A-2-thiazoline-4-ones (181) (388, 397, 410, 414, 416, 419, 422, 426. 427) and methylation of 5-(4 -chlorophenyl)-A-2-thiazoline-4-one (416) (Scheme 94). 

Naphthol is mainly used in the manufacture of the insecticide carbaryl (59), l-naphthyl A/-methyicarbamate/ iJ-2j5 - (Sevin) (22), which is produced by the reaction of 1-naphthol with methyl isocyanate. Methyl isocyanate is usually prepared by treating methylamine with phosgene. Methyl isocyanate is a very toxic Hquid, boiling at 38°C, and should not be stored for long periods of time (Bhopal accident, India). India has developed a process for the preparation of aryl esters of A/-alkyl carbamic acids. Thus l-naphthyl methylcarbamate is prepared by refluxing 1-naphthol with ethyl methylcarbamate and POCl in toluene (60). In 1992, carbaryl production totaled > 11.4 x 10 t(35). Rhc ne-Poulenc, at its Institute, W. Va., facihty is the only carbaryl producer in United States. 

Photolysis of Cp2TiAr2 in benzene solution yields titanocene and a variety of aryl products derived both intra- and intermolecularly (293—297). Dimethyl titan ocene photolyzed in hydrocarbons yields methane, but the hydrogen is derived from the other methyl group and from the cyclopentadienyl rings, as demonstrated by deuteration. Photolysis in the presence of diphenylacetylene yields the dimeric titanocycle (28) and a titanomethylation product [65090-11-1]. 

Oxidation (low yield) of aryl or cycloalkyl methyl groups to aldehydes with chromyl chloride... 

Tnfluorometltylation of aryl, alkenyl, and alkyl halides can be accomplished by heating methyl fluorosulfonyldifluoroacetate and the appropriate halide precursor with copper(I) iodide at 60-80 °C in DMF [27 7] (equation 145). Similar trifluoromethylations of aryl, benzyl, and vinyl halides can be carried out with fluorosulfonyldifluoromethyl iodide and copper metal in DMF at 60-80 °C [2 75] (equation 146). 

Sodium ethanethiolate has been examined for the selective cleavage of aryl methyl ethers. Methyl ethers para to an electron-withdrawing group are cleaved preferentially. ... 

In 1968, the aforementioned reaction was repeated and found to produce a rearranged product (11). This was the first report of aryl migration with the Pictet-Gams conditions. The expected product was l-methyl-3-phenyl isoquinoline, but only 1-methyl-4-isoquinoline (11) was observed. Interestingly, the authors did not suggest a mechanism for the formation of the isolated product. 

Fewer methods are available for the generation of alkyl than of aryl radicals and a number of these can only be used to produce methyl radicals. Methylation has been, therefore, the most commonly studied alkylation. 

Xn. Demethylation of Aryl Methyl Ethers by Boron Tribromide... 

Pyridinium chloride ([PyHjCl) has also been used in a number ofcyclization reactions of aryl ethers (Scheme 5.1-4) [4, 18]. Presumably the reaction initially proceeds by deallcylation of the methyl ether groups to produce the corresponding phenol. The mechanism of the cyclization is not well understood, but Pagni and Smith have suggested that it proceeds by nucleophilic attack of an Ar-OH or Ar-0 group on the second aromatic ring (in a protonated form) [4]. 

The thermolysis of aryl azides in alcoholic solution has been used to prepare 2-alkoxy-37f-azepines. Thermolysis of 3-azidophenyl methyl ketone in methanol in a sealed ampule furnishes a mixture of the 6-acetyl- (36a) and 4-acetyl-2-methoxy-3//-azepine (37a) in superior yields to those obtained in the corresponding photolytic reaction.78 Other 3-substituted azides behave similarly, with a preference for the 6-substituted isomers 36, as is observed for azide photolyses in amine solutions. 

In principle, sulfonyl compounds bearing highly-electron-accepting substituents are able to transfer the sulfonyl group as an electrophile. Thus, the exchange of aryl substituents in methyl aryl sulfones under catalysis of trifluoromethanesulfonic acid takes place258 (equation 46). This reaction represents a further example for the reversibility of Friedel-Crafts reactions. 

Two more recent studies of the nature of the sulfur-carbon bond cleavage in sulfoxide photolyses have been conducted, using ESR5 and CIDNP6 detection methods, respectively. In the latter case there is some evidence for a triplet process being involved in the photocleavage of aryl methyl sulfoxides. 

Most of the above reactions are used for the cleavage of aryl sulphones. Recently, a note has appeared109 in which the use of potassium metal dispersed ultrasonically in toluene to cleave saturated cyclic sulphones is described. Addition of iodomethane permits the isolation of acyclic alkyl methyl sulphones (as outlined in equation (44)). 

Kinetic studies of the oxidation of diaryl sulfoxides by Crvi led to the proposition of a single electron transfer67 as in the case of aryl methyl sulfoxides68. These reactions were performed in aqueous acetic acid/perchloric acid medium, HCr03+ being the active... 

HECK REACTIONS OF ARYL CHLORIDES CATALYZED BY PALLADIUM/TRI-tert-BUTYLPHOSPHINE (E)-2-METHYL-3-PHENYLACRYLIC ACID BUTYL ESTER AND (E)-4-(2-PHENYLETHENYL)BENZONITRILE... 

In the case of a diketone (e.g., 3-tosyloxypentane-2,4-dione), the formation of 5-acetyl-4-methyl-2-aryl-l,3-thiazole derivatives can be realized in very good yields (86-89%) (Scheme 7). All these experiments where performed in a Sears Kenmore unmodified household microwave oven (990 W) equipped with a turntable. The average bulk temperature was estimated by inserting a thermometer in the alumina bath housing the reaction vessel. 

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