Handbook of Functionalized Organometallics Applications in S

I
O
O
OBn
Pd(t-Bu 3P) 2 (10 mol%)
4.4 Application of Functionalized Magnesium Reagents in Cross-coupling Reactions
TMS
1) iPrMgCl,
THF, -30 ºC
2) ZnBr2 332 331
rt
Cbz
N
BnO
CHO
O
OBn
ZnBr
O
333: 87%
O
O
TMS
TMS
Scheme 4.74 Pd-catalyzed cross-coupling of highly functionalized arylzinc reagents.
4.4.2
Nickel-catalyzed Cross-coupling Reactions
I CHO
N
Cbz
As already mentioned, Kumada and Corriu simultaneously developed the first
cross-coupling reactions, between aromatic halides and Grignard reagents catalyzed
by nickel salts [4,5,172b]. A variety of nickel salts and ligands have been
studied [182] since these early reports and even enantioselective versions have
been reported. Herrmann reported a cross-coupling between inactivated aryl chlorides
and aryl Grignard reagents in the presence of Ni(acac) 2 and tris-(tert-butyl)phosphane
as ligand [183]. Thus, chlorobenzene (334) reacts with the magnesium
derivative 335 at room temperature within 18 h and leads to the desired biphenyl
336 in 99% yield (Scheme 4.75).
334
Ni(acac) 2 (3 mol%)
P(tBu) 3 (3 mol%)
Cl + BrMg OMe
THF, 25 ºC, 18 h
OMe
335 336: 99%
Scheme 4.75 Ni-catalyzed cross-coupling using aryl chlorides and aryl Grignard reagents
The functional-group tolerance is again moderate and therefore a transmetallation
to the corresponding zinc reagent is advantageous. Functionalized arylzinc
compounds allow the performance of sp 2 -sp 3 cross-coupling reactions using
Ni(acac) 2 (10 mol%) as catalyst in the presence of 4-trifluoromethylstyrene or
4-fluorostyrene as promoter of the reductive elimination step. Under these conditions,
the Grignard reagent 337 reacts with the iodothioketal 338 providing the
desired cross-coupling product 339 in 72% yield (Scheme 4.76) [184].
157