Handbook of Functionalized Organometallics Applications in S

4.2Methods of Preparation of Grignard Reagents and their Uncatalyzed Reactions
out that a catalytic amount of iPr 2NH is sufficient to accelerate the deprotonation
reaction. In addition, magnesium bisamides are used for the regio- and stereoselective
formation of enolates [25] and the use of optically pure magnesium amides
opens the field of asymmetric synthesis to this versatile substance class [26].
4.2.3
The Halogen±Magnesium Exchange Reaction
The halogen±lithium exchange reaction discovered by Wittig [27] and Gilman [28]
allows the preparation of a broad range of organolithium compounds and has
become one of the most important ways for the preparation of aromatic, heteroaromatic
and alkenyl lithium compounds, starting from the commercially available
alkyllithium reagents and the corresponding organic halides, mainly bromides
and iodides [29]. Although this reaction is very fast and normally proceeds
at low temperatures (typically ±78 C) the functional-group tolerance is only moderate.
In contrast, the halogen±magnesium exchange has been found to be the
method of choice for preparing new functionalized organomagnesium reagents
of considerable synthetic utility. The major reason for this great functional-group
tolerance of Grignard reagents is that the reactivity of carbon±magnesium bonds
is strongly dependent on the reaction temperature. Only reactive electrophiles like
aldehydes and most ketones react rapidly at temperatures below 0 C. Performing
the halogen±magnesium exchange at temperatures below 0 C has therefore the
potential for the preparation of magnesium organometallics bearing reactive and
sensitive functional groups.
4.2.3.1 Early Studies
The first example of a bromine±magnesium exchange reaction was briefly
reported in 1931 by PrØvost [30]. Thus, the reaction of cinnamyl bromide 7 with
EtMgBr furnished cinnamylmagnesium bromide 8 although only in modest yield
(Scheme 4.5). Similarly, Urion reported the preparation of cyclohexylmagnesium
bromide 9 via a Br/Mg-exchange [31].
Br
Br
EtMgBr
7 8: 14%
EtMgBr
9: 12%
Scheme 4.5 First examples of a bromine±magnesium exchange.
MgBr
MgBr
EtBr
EtBr
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