Barbier-Grignard procedure

Prevention of coupling—One-step Barbier-Grignard procedure—4-Ethylene-alcohols from oxido compounds s. 19, 745... 

Following Henze, Allen and Leslie s nomenclature (vide supra), Dreyfuss referred to the Barbier reaction as the Barbier-Grignard procedure and there is little doubt that the conclusion, to be drawn from his interesting publication, is that the one-step procedure for the synthesis of homoallylic alcohols is to be preferred over the two-step Gilman-McGlumphy route. 

Grignard syntheses with allyl halides Prevention of coupling One-step Barbier-Grignard procedure... 

Name of the One-step Procedure. Early publications in this new field of organic chemistry reveal a bitter rivalry over priority and eponimy between the stu-dent/assistant Grignard (Nobel-prize winner 1912) and the teacher/head-of-the-department Barbier. Several modern historians have come to the conclusion [29] that the most reasonable name for this step-wise procedure would have been Barbier-Grignard reaction. 

The most systematic name would be the one in which the procedure is made clear to the reader such as one-pot reaction (e.g. in [30] and [31]) or one-flask reaction, in situ reaction [32], one-step reaction [33], etc. and such names are often encountered. However more often names such as modified) Wagner-Saytzejf reaction, Saytzeff reaction, Barbier-Grignard reaction [29], [34], [35] and [36], batch-method [36], Dreyfuss-Barbier reaction [37], Jaworsky reaction [38], Grignard-type reaction [39], [40], etc. are used. 

Developments of new working techniques such as better glassware, purified inert gasses, low temperature techniques, new solvents and many others have introduced new synthetic procedures which were simply inconceivable in the Saytzeff and Barbier-Grignard period. 

The Reformatsky reactions are run following two basic procedures (i) a two-step Grignard-type protocol which first involves the formation of an organometallic zinc eno-late derivative followed by addition of the electrophile, and (ii) a Barbier-type protocol where the bromoester and the electrophile are simultaneously exposed to the action of zinc metal. 

Even for reactions where the Barbier procedure has clearly and unambiguously proved to be superior over the Grignard-type of reaction, this two-step procedure was, till recently, much more generally used. 

Houben was among the first to adapt Barbier s synthetic procedure. Just as Grignard [19] and Arbusov [20] (see [21]) had experienced before him, he was unsuccessful in his attempts to prepare allylmagnesium halides which he required for the synthesis of 3-butenoic acid [22]. 

An interesting event in the history of the Barbier reaction was the publication in 1928, by Gilman and McGlumphy, of a new procedure to prepare Grignard reagents from allyhc halides [41]. 

The results of Li-Barbier reactions of bromobenzene and n-bromobutane with nitriles have also been compared with those from two-step procedures involving Grignard and organolithium reagents [23]. 

However, the results, listed in Table 3.6, show that the Li-Barbier reaction of (substituted) bromobenzenes and 2-methyl-2-nitrosopropanes, which leads to the formation of (substituted) aryl-tert-butylhydroxylamines (isolated as nitroxi-des because of spontaneous oxidation on exposure to air), is preferred over the two-step procedure with Grignard reagents. 

Since the number of systematic publications in the field of Barbier chemistry is rather limited also the number of reports on the use of activated magnesium in Barbier reactions is very small indeed. Nevertheless, since, in general, also with this type of reaction the start of the procedure may be the critical step, there is good reason to make mention of such techniques that have been helpful in two-step Grignard-type reactions in order to obtain the best possible results with one-step processes. 

When the two steps of a Grignard synthesis are combined, this is called a Barbier reaction. Such a procedure, which is normally not possible in a conventional batch procedure is frequently made possible by mechanical activation. This constitutes an added advantage. 

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