Aryl magnesium bromide

The general method of preparation of these bodies is as follows Fifty grams of lead triphenyi bromide is added in small quantities, with continual shaking, to an ice-cooled solution of one and a half times the calculated quantity of magnesium aryl bromide, in 400 c.c. of ether. When the reaction ceases the product is boiled for one to two hours under refiux, then cooled and decomposed with aqueous ammonium chloride solution. The ether layer is separated off, dried, and after evaporation the residue is recrystallised from alcohol or alcohol-ether. ... 

Remarkably, balogeti-magnesium exdiatige can also be extended to aryl and beteroaryl bromides [24, 25]. Tlius, tlie functionalized aryl bromides 28 and 29 iSdieme 2.7) were converted, at 0 C and at -30 C, respectively, into tlie corte-sponding Grignatd reagents. After treatment witli CuCN, tlie copper derivative 30 and 31 were obtained. Subsequent treatment witli typical electropb des sudi as benzoyl bromide or aliyl bromide fiirnisbed tlie products 32 and 33, in 70 and 8096 yields. 

The cobalt-catalysed reaction between aryl bromides and Grignard reagents assisted by IMes HCl is also known, however the substrate scope is quit narrow and good yields are only obtained when non-branched long chain alkyl magnesium chlorides are used as coupling reagents [80] (Scheme 6 19)... 

The order of reactivity of halides with magnesium is RI > RBr > RC1 (very few organomagnesium fluorides have been prepared), i) Aryl Grignard reagents are more easily prepared from aryl bromides and aryl iodides than from aryl chlorides, which react very sluggishly. 

Pei and coworkers reported that the homocoupling product can be obtained by adding an aryl bromide to a mixture of magnesium and 2% iron salts in THF (Scheme 47). All reactions were performed on a 1 mmol scale. 

TABLE 7. Bromine-magnesium exchange of aryl bromides with BusMgLi... 

Reaction IX. (a) Action of Magnesium Alkyl or Aryl Halide on certain Alkyl or Aryl Halides in the presence of Absolute Ether (Grignard). (C. 1906, II., 748.)—The Grignard reaction has perhaps a wider application than even the Friedel-Crafts or the diazo reaction. When an alkyl or aryl bromide or iodide is treated with magnesium powder, usually in presence of absolute ether, a magnesium alkyl or aryl halide is formed. 

In a separate project, methods for microwave-assisted generation of Grig-nard reagents from aryl chlorides and aryl bromides were developed [81]. One of the aryl magnesium bromides generated was used with the unsymmetric 42, 2% Pd2(dba)3 and 4% [ t-Bu3PI I ]BF4 in a microwave-promoted Kumada coupling to provide 46 in 67% isolated yield, a compound unfortunately found to be a relatively poor HIV-1 protease inhibitor (Scheme 21). 

Polyfunctional aryl bromides, bearing a chelating function ortho to bromine readily undergo a bromine-magnesium exchange.39,40 40a Even the less effective methoxy group directs the substitution in the case of 2,4-dibromoanisole (Scheme 14).41... 

A number of methods were developed for the electrophilic amination of Grignard reagents306,30 3 to prepare primary amines. One of the recent examples uses l,3-dioxolan-2-one O-sulfonyloxime.307 The reaction gives imine, which affords primary amine after hydrolysis (Scheme 106). By using acetone 0-(mesitylsulfonyl)-oxime the amination can be performed under Barbier conditions from aryl bromide and magnesium.308... 

The first preparation, of cyclomagnesium chloride, exemplifies the traditional procedure [29], using magnesium turnings, with diethyl ether as the solvent, and no provision of an inert atmosphere other than the solvent vapour. This type of procedure is satisfactory for most primary and many secondary and tertiary alkyl chlorides and bromides and for many aryl bromides. Iodides may also be used, but the additional expense is rarely justified, particularly as they tend to suffer more side-reactions such as Wurtz-type coupling. Early work on the factors affecting such reactions has been thoroughly reviewed [A],... 

Grignard Synthesis.— The most important method for synthesizing aromatic alcohols is by the Grignard reaction, with magnesium alkyl or aryl halides (p. 77). The one given as an example of a tertiary aromatic alcohol may be prepared by the action of magnesium phenyl bromide, CeHs—Mg—Br, upon acetone. 

The analogous ether cleavage reaction of the crown-5 analog of 40 rendered its synthesis from the aryl bromide and magnesium next to impossible isolation of crystalline 2-bromomagnesio-I,3-xylyl-18-crown-5 (41), formed in 16% yield, from the crude reaction mixture was not feasible. Therefore, pure 41 had to be obtained by treatment of the aryl bromide with /j-butyllithium, followed by the addition of 1 equiv magnesium bromide. The crystal structure of 41 contained two independent residues (41a and 41b) and proved to be very irregular the conformation of its crown... 

The monoaryl boric acids, RB(OH)2, arc usually isolated, as stated al >o x, l)y the action of water on the type RBXg, aitliough in certain cases this leads to the formation of the oxide RBO. The phenyl eom >ound has l)ecn obtained b " boiling with water the product of reaction from magnesium phenyl bromide and boron trifluoride. The most remarkable feature of the type RE(OH)2 is that the action of iiiercuric chloride upon them leads to the production of mercury aryl halides (RHgX). The anisyl and phenetyl compounds do not yield oxides when heated, or form salts, and tlie jS-naphthyl acid exists in two modifications. Dehydration of the acids in maw gives the oxides, RBO. 

The Pd-catalyzed reactions of alkynylzinc chlorides 22, which are readily obtainable in situ from anhydrous zinc chloride and alkynyllithium or -magnesium, with alkenyl iodides or bromides 21 provide the corresponding terminal or internal enynes 23 in high yield and with high (>97%) stereospecificity [Eq. (9)] [16]. Aryl bromides or iodides can also be used to produce arylalkynes [17]. 

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