Barbier Reactions with Allylic Halides

Neither Shriner [17] in 1942, nor Rathke [18] in 1974, in their review articles on the Reformatsky reaction have come to the conclusion that zinc could in general be replaced by magnesium in this synthetic procedure. 

However, as has been demonstrated above, in special instances magnesium is to be preferred. 

3 Barbier Reactions with Allylic Halides 2.3.1 Introduction 

As mentioned in Sect. 1.2.4, Alexander SaytzeflF and his coworkers, at the end of the nineteenth century, started using allylic halides in the one-batch , one-pot or one-step synthesis of alcohols, a procedure often referred to as the Saytzeff reaction, e.g. by Barbier [3]. 

In his doctoral thesis Grignard had come to the conclusion that his reaction could not be applied to allylic halides [19]. Attempts to prepare allylmagnesium halides led to unidentifiable products and the results of their reactions with e.g. aldehydes were 

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Hartog 1978. After Dreyfuss studies on the Barbier reaction with allylic halides (particularly after his final remarks in which he referred to Davies and Kipping s recommendation of the one-step procedure) one would have expected a general acceptance of this simple procedure involving intermediate organometallics. 

In his German patent [42] on Barbier reactions with allylic halides, Knorr, in 1932, included reactions with crotyl bromide (l-bromo>2-butene)... 

Lespiau s [23] synthesis (in the same period) of 3-buten-l-ol (in 30% yield) by a Barbier reaction with allyl bromide, magnesium and trioxane - one of the earliest reports of Barbier reactions with allylic halides - has been mentioned in Sect. 2.3 (p. 20)... 

Alcohols as the Solvent. Rather surprising was the introduction of alkanols such as ethanol or tert-hntyl alcohol as the solvent in Zn-Barbier reactions with allylic halides [87] ... 

It should also be underlined that in the Zn-Barbier reaction with allylic halides the use of sonication did not necessarily lead to better results. 

More than hundred years after Pebal s and Reith and Beilstein s reports on starting problems of an organometallic reagent formation reaction, Dreyfuss [3] noted that the start of Barbier reactions with allylic halides... 

With Trimethylchlorosilane. Rather recently [60] it was found that activation of zinc with TMClSi augmented the yield of Zn-Barbier reactions with allylic halides considerably. This unexpected activation by the silane was found earlier for Reformatsky reactions with ethyl 2-bromopropanoate [61] also trimethylchlorosilane-activated lead was applied in Pb-Barbier reactions with crotyl bromide [62] and allyl bromide [63]. 

More Barbier-Type Reactions with Allylic Halides... 

Table 2.7. Results of Barbier reactions of allylic halides with benzophenone in different solvents [53]...

A recent publication on the Zn-Barbier reaction of allylic halides and nitriles with Zn/Gr showed that often the best yields were obtained with a 3 1 ratio of the allylic halide to the nitrile [118] ... 

Scheme 168 Samarium-mediated Barbier-type reaction of carbonyl compounds with allyl halides.

Another important metal for Barbier-type reaction is samarium. Allyl bromide reacts with a ketone and Sm to give the homoallylic alcohol. Samarium compounds, such as Sml2, can also be used with allylic halides. 

Tetraorganotins can be conveniently prepared from the coupling reaction of allyl halides with organotin halides under ultrasonic-assisted Barbier conditions [Eq. (37)]. 

The Barbier-type reaction of aldehydes and ketones with allyl halides (485) in the presence of Smh, leading to homoallyl alcohols (486), has received recent interest as a one-step alternative to the Grignard reaction. However, the reactions require the use of stoichiometric amounts of the reducing Sm(III) species. Recently, the electroreductive Barbier-type allylation of carbonyl compounds in an Sml2-mediated reaction has been developed [569]. The electrolysis of (485) is carried out in a DMF-SmCl3-(Mg/Ni) system in an undivided cell to give the adduct (486) in 50 85% yields (Scheme 168) [569]. Electrosynthesis of y-butyrolactones has been achieved by the reductive coupling of ethyl 3-chloropropionate with carbonyl compounds in the presence of a catalytic amoxmt of SmCfi [570]. 

More recent results from systematic investigations of the Barbier reaction clearly speak in favour of the one-step reaction of allylic halides as will be demonstrated in Sect. 2.3.4. Furthermore chap 3 will show that such one-step reactions can also give excellent yields with metals other than magnesium. 

The results of Barbier reactions with benzophenone and allylic halides, as presented in Table 2.7, show that the yields are almost quantitative. 

Hartog 1978. In Sect. 2.3.4 (Tables 2.7 to 2.13) several results with allylic halides have been mentioned of an in-depth research on the Barbier reaction that took place at the end of the 1970 s [53]. 

Zn-Barbier Reactions with Nitriles. The reaction of allylic halides with zinc in the presence of nitriles, was first studied by Blaise [102] in 1901. Later investigations showed that much better yields of the jS-unsaturated ketones could be obtained if benzene was employed as the solvent and when a zinc-silver couple was used [103, 104] (prepared from zinc and 0.1% silver acetate in methanoic acid). 

Despite the lower reactivity of solvated perfluoroalkylzinc reagents, perfluoroalkyl iodides undergo synthetically useful zinc-mediated reactions under Barbier conditions which often employ ultrasound and co-catalysts. Under these conditions, the zinc reagents are not well characterized and radical intermediates and SET mechanisms are proposed in some cases. Representative examples are presented below and include the ultrasound-promoted, zinc-mediated perfluoroalkylation of various substrates as reported by Ishikawa and coworkers (Scheme 10)123 126. Yields of carbinols could be improved by use of Ti(II) co-catalyst. Ultrasound promoted the coupling of perfluoroalkyl iodides with vinyl and allyl halides in the presence of Pd co-catalysts. 

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