Aromatic Grignard compounds

Aromatic Grignard compounds can be arylated (Figure 16.11) and alkenylated (in analogy to Figure 16.10). 

In 1942 two further methods for preparing a-tocopherol were published (Fig. 4). The essential step in the synthesis developed by John and Pini (1942) was the Grignard reaction of the aromatic ketone (I) with hexahy-drofarnesylmethylmagnesium bromide (II). After several further steps, totally racemic a-tocopherol was obtained. Smith and Miller (1942) used the C18-ketone (IV), prepared by ozonolysis of natural phytol and the aromatic Grignard compound (III) to get finally (2RS 4 R 8 R)-a-toco-pherol. 

The latter reagent also methylates certain heterocyclic compounds (e.g., quinoline) and certain fused aromatic compounds (e.g., anthracene, phenanthrene). The reactions with the sulfur carbanions are especially useful, since none of these substrates can be methylated by the Friedel-Crafts procedure (11-12). It has been reported that aromatic nitro compounds can also be alkylated, not only with methyl but with other alkyl and substituted alkyl groups as well, in ortho and para positions, by treatment with an alkyllithium compound (or, with lower yields, a Grignard reagent), followed by an oxidizing agent such as Bra or DDQ (P- 1511). 

Use of benzotriazole in the preparation of diphenylmethanes and triphenylmethanes has been reviewed." Benzotriazole is condensed with an aldehyde and then allowed to react with naphthols to form a diphenyl-methane benzotriazole derivative such as 69 (Scheme 9). The benzotriazole moiety in 69 is displaced by a Grignard reagent to give triphenylmethanes.79 100 This method allows for the preparation of triarylmethanes which contain three different aromatic rings. Compounds 70-72 are prepared by this method. 

Alkyl lithium and alkyl Grignard reagents react with aromatic nitro compounds in a similar way to give alkylated products (Eq. 9.23).37... 

Tertiary and aromatic nitroso compounds react with aryl Grignard or aryl-lithium reagents giving the corresponding hydroxylamines . This reaction is useful for preparation of alkyl- and aiylhydroxylamines (e.g. 109, equation 80 and 110, equation 81) and can be considered as complementary to arylation of hydroxy lamines with activated aryl halides. It has been used for functionalization of cyclophanes with the hydroxy amino group. The main limitation of the reaction is the relatively restricted choice of available aliphatic nitroso components, so most of reactions were done with 2-nitroso-2-methylpropane. There is no literature data about the possibility of removal of the tert-butyl group from these compounds. 

Addition of organometallic reagents to nitro compounds is possible but is sparingly used. Reaction of aromatic nitro compounds with large excess of phenyl magnesium bromide produces hydroxylamines in moderate yield . Similar addition of Grignard compounds to nitromethane proceeds in low yield ° while addition of excess methyllithium to tertiary nitro compound 113 results in formation of hydroxylamine 114 (equation 83) . ... 

Fig. 5.44. Electrophilic functionalization of an aromatic di-Grignard compound synthesis offi-BINAP. (Enantiomerically pure BINAP is one of the most important ligands in asymmetric catalysis, cf. Figures 17.76 and 17.77.)...

Fig. 10.28. The addition of a Grignard reagent to aromatic carbonyl compounds proceeds via SET in part, which is demonstrated by the partial racemizations observed here the sec-alkyl radical that occurs as an intermediate undergoes an extremely rapid racemiza-tion. The more stable the simultaneously formed magnesium-bound ketyl radical is, the larger is the share of the racemization.

Fig. 5.37. Electrophilic functionalization of an aromatic di-Grignard compound synthesis of /M1INAR...

The last electrophilic substitution reaction of a Grignard compound we want to consider is a transmetallation, namely one that leads to an arylboronic ester (Figure 5.38). Arylboronic esters or their hydrolysis products, the arylboronic acids, are valuable reagents in modem aromatic chemistry. They react with a series of electrophiles that would not react with Grignard or organohthium compounds (Sections 5.3.3 and 13.3.2). 

Reaction of aryl Grignard compounds, obtained in situ by iodine-magnesium exchange, with C0CI2, presumably generates aryl radicals. In the presence of a double bond or aromatic ring an intramolecular radical cyclization may take place. This reaction was used for the synthesis of spiro-indolines.244 Oshima has applied cobalt-mediated tandem radical cyclization-cross-coupling reaction for the synthesis of benzyl-substituted heterocycles (Scheme 80).245... 

Arenetellurolates are obtained when tellurium is reacted with aromatic lithium compounds in THF or diethyl ether (p. 154) or with aromatic Grignard reagents in THF. The arenetellurolates thus formed are hydrolyzed to tellurols. The tellurols are oxidized to the diaryl ditellurium products. 

Many straight-chain and branched secondary alcohols have been made by the action of organomagnesium compounds on higher aldehydes. The method is popular for the preparation of arylalkylcarbinols from either the aromatic aldehyde or the aromatic Grignard reagent. ... 

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