Handbook of Functionalized Organometallics Applications in S

4.4 Application of Functionalized Magnesium Reagents in Cross-coupling Reactions
4.4.3
Iron-catalyzed Cross-coupling Reactions
Despite the seminal contribution of Kochi and coworkers, [186] iron-catalyzed
cross-coupling reactions received less attention then the corresponding nickeland
palladium-mediated ones. The low cost and low toxicity of iron(iii) salts, initiated
a renaissance of this cross-coupling procedures in the search for new environmentally
benign carbon±carbon bond-forming processes. In addition, the ironcatalyzed
cross-coupling reactions most often can be carried out under ligand-free
conditions. Although the mechanisms of these reactions are far from clear, it is
speculated that highly reduced iron±magnesium clusters of the formal composition
[Fe(MgX) 2] n generated in situ may play a decisive role in the catalytic cycle
[187].
Cahiez and Knochel demonstrated the generality of iron-catalyzed alkenylation
and recognized the advantageous use of cosolvents, such as NMP [188,189]. For
example, the reaction of bromide 344 with BuMgCl furnishes in the presence of
only 1 mol% Fe(acac) 3 product 345 in 79% yield (Scheme 4.78) [188].
Cl
Hex
Br
344
346
Cl
+ BuMgCl
+ BuMgCl
Fe(acac) 3 (1 mol%)
THF/NMP,
-5 ºC to0ºC ,
15 min
Fe(acac) 3 (1 mol%)
THF/NMP,
-5 ºC to0ºC ,
15 min
Scheme 4.78 Fe(iii)-catalyzed cross-coupling reactions of
alkylmagnesium halides with bromo- and chloroolefins.
Cl
Hex
Bu
345: 79%
Bu
347: 75% (E >99.5%)
Similarly, (E)-1-chlorooctene (346) reacts with BuMgCl and leads exclusively to
the E-olefin 347 without isomerization of the double bond (Scheme 4.78).
This methodology can be extended to aromatic Grignard reagents as well, leading
to sp 2 -sp 2 cross-coupling reactions [189]. Thus, functionalized arylmagnesium
reagent 19 undergoes efficient cross-coupling reactions with polyfunctionalized
alkenyl iodides such as 348 in the presence of Fe(acac) 3 (5 mol%) leading to the
styrene derivative 349 in 69% yield.
Remarkably, the cross-coupling reaction is complete at ±20 C within 15±30 min
(Scheme 4.79). The arylmagnesium compound can bear various electrophilic
functions like a nonaflate [190] (see Grignard reagent 350). The iron(iii)-crosscoupling
reaction still proceeds with a good yield leading to the highly functionalized
nonaflate 351 in 73% yield (Scheme 4.79) [189].
Fürstner showed that the iron-catalyzed cross-coupling is a very powerful tool
for the performance of sp 2 -sp 3 cross-couplings. The reaction proceeds best when
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