Handbook of Functionalized Organometallics Applications in S

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4 Polyfunctional Magnesium Organometallics for Organic Synthesis
The halogen±magnesium exchange is an equilibrium process favoring the formation
of the most stable organomagnesium compound. To shift this equilibrium
to the desired side, the resulting organomagnesium species has to be more stable
than the Grignard reagent used for the exchange reaction (sp>sp 2 (vinyl)>sp 2 (aryl)>sp
3 (prim.)>sp 3 (sec.)). Although the mechanism of the exchange reaction is not
fully clarified, a halogen-ate complex is believed to be an intermediate, as proposed
for the halogen±lithium exchange [32].
One of the first synthetically useful procedures, employing a halogen±magnesium
exchange reaction, was reported by McBee and coworkers who were successful
in preparing perfluoroalkylmagnesium halides of type 10 starting from the
perfluorinated iodide 11 and phenylmagnesium bromide (Scheme 4.6) [33].
C 3F 7 I
11
PhMgBr
Et 2O, 15 min
-40 to -50 ºC
C3F7 MgBr + Ph–I
O
C 3F 7
OH
10 90%
Scheme 4.6 Synthesis and reaction of heptafluoropropylmagnesium bromide (10).
This procedure had significant advantages compared to the oxidative addition,
such as higher yields or less side reactions and is still one of the best methods for
the synthesis of perfluorinated Grignard reagents [34].
The halogen±magnesium exchange reaction was later used by VilliØras, who developed
a general approach to magnesium carbenoids [35]. He showed, that the
reaction of iPrMgCl with CHBr 3 at ±78 C furnishes the corresponding magnesium
carbenoid 12 that could be trapped with chlorotrimethylsilane leading to
product 13 in 90% yield (Scheme 4.7). This pioneering workpaved the way to the
systematic study of magnesium carbenoids [36] demonstrating that the halogen±
magnesium exchange rate is enhanced by the presence of electronegative substituents.
CHBr 3
iPrMgCl
–78 ºC
CHBr 2MgCl iPrBr
Me 3SiCl
CHBr 2SiMe 3
12 13: 90%
Scheme 4.7 Preparation of magnesium carbenoid 12 via bromine±magnesium exchange.
This behavior was confirmed a few years later by the workof Tamborski who
showed that the electronic properties of both, the halogen atom and the organic
molecule play an important role in the formation rate of the new Grignard reagent
[37]. Only for very electron-poor systems, such as the tetra- or pentafluorobenzenes,
was the exchange of a chlorine possible, requiring elevated temperatures
and longer reaction times then for the corresponding bromines and iodines. The
reactivity order (I>Br>Cl>>F) is influenced by the bond-strength, the electronegativity
and the ease of polarizability of the halide. For these reasons, aryl iodides are
usually used as starting materials, although the use of bromides would be advan-