Arylmagnesium halides

Formation of aryl Grignard reagents (Section 14 4) Aryl halides react with magnesium to form the corresponding arylmagnesium halide Aryl iodides are the most reac tive aryl fluorides the least A similar reaction occurs with lithium to give aryllithium reagents (Section 14 3)... 

The behavior of unsaturated azlactones with organometallic reagents has been studied in detail. Arylmagnesium halides and phenyllithium attack 4-arylidene-5-oxazolones at the carbonyl carbon to give ring-opened amido tertiary alcohols (26) and oxazolines (27) (by ring closure), usually as mixtures [Eq. (17)]. The nature of the... 

By reaction with the appropropriate aryl halides can be prepared a variety of aryltin compounds that are not accessible from the reactions involving arylmagnesium halides and organotin halides (88,89) there is evidence that an aryne intermediate may be involved (90). However, for some purposes, such as the addition to carbonyl compounds, ox-iranes, and oxetanes, to give hydroxyalkyltin compounds, the Sn-Mg reagents may have advantages (see Section II,E) (91-93). 

Cross-coupling of arylmagnesium halides with fluorodiazines has been studied by Queguiner. Nickel catalysts were used for this Kumada-type process. The reactions work at room temperature in THE. Only one example on a 1,2-diazine core was studied, namely the coupling of 3-fluoro-6-phenylpyridazine with 4-methoxyphenylmagnesium bromide <2002JOC8991>. 

Treatment of 148 <2002EJ0113> with TMSBt resulted in the formation of the 10/ -bromide 149 (not isolated) and subsequent reaction with arylmagnesium halides gave the (7-aryl glycosides 150 in acceptable yield (Scheme 19 Table 14). It was not possible to suppress formation of the glycal 25 <2003EJ02098>. 

Low reactive aryl chlorides are converted to the respective organomagnesium species in excellent yields through transition metal catalysis using 2 mol% FeCU (4-6, equation 3). Alternatively, a safe and reproducible method for activation of aryl chlorides or bromides 7 uses microwave irradiation (equation 4). In a synthesis of a novel HIV-1 protease inhibitor, microwave irradiation was essential to generate the starting arylmagnesium halide as well as to promote the subsequent Kumada coupling reaction. ... 

A similar Co-catalyzed reaction with arylmagnesium halides and alkenes 181, bearing a halogen in a suitable position, occurs via a radical intermediate, leading to cyclic acetals 182 (equation 109). ... 

Aryl halides of many different types, including simple unsubstituted halides, may be conveniently converted into phenols by an indirect route involving the preparation of an arylboronic acid and its subsequent oxidation with hydrogen peroxide. The arylboronic acid (3) is normally prepared by reaction of the corresponding arylmagnesium halide with a borate ester (typically tributyl borate) at between —60 and — 80 °C, to yield the dialkyl boronate ester (2) which is then hydrolysed to the arylboronic acid (3). The latter may be isolated, purified and then oxidised with hydrogen peroxide as described in the preparation of m-cresol (Expt 6.101). Alternatively the crude reaction mixture from the preparation of (3) may be treated directly with hydrogen peroxide.36... 

With the development of the cross coupling methodology, many 6-C-substituted purines have been prepared in the past decade. Thus, 6 halopurine derivatives react with arylmagnesium halides,25 alkyl(aryl)zinc or tin reagents,26 trialkylaluminum,27 or alkylcuprates28 to give the 6-alkylpurine derivatives. Also a reverse approach based on the reaction of purine-6-zinc iodide with aryl or vinyl halides has recently been described.29 For the synthesis of 6-arylpurines, an alternative approach makes use of radical photochemical reactions of adenine derivatives with aromatic compounds,30 but this method is very unselective and for substituted benzenes, mixtures of ortho-, meta-, and para substituted derivatives were obtained. 

Grignard Reaction. By addition of an arylmagnesium halide to a cyclic ketone, a carbinol is formed which can be dehydrated and dehydrogenated to a biaryl compound.89 4 > 41> 42 43 480 For example, m-tolyl-magnesium bromide and cydohexanol yield 1-m-tolylcyclohexanol, which on dehydration and dehydrogenation gives 3-methylbiphenyl. 

By using this method, 4-methyl-2 -cyanobiphenyl, an important intermediate for the synthesis of the antihypertensive drug Losartan, can be easily prepared.132 2-(t>-Chlorophenyl)-oxazoline reacts with excess of arylmagnesium halide without catalysis, as it was shown by Meyers for 2-(o-methoxyphenyl)-oxazolines.133 Cobalt(ll) salts catalyze the coupling of Grignard reagents with a-chloroazines at —40°C in ether (Scheme 47).134 135... 

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