Boron Reagent Activation in Suzuki–Miyaura Coupling - New Trends in Cross-Coupling: Theory and Applications - page 326

also aid association to the electron-rich metal centre. Oxidative addition is
frequently found to be turnover limiting; therefore, the use of very electron-
rich ligands, such as trialkylphosphines, 10 can be used to promote this step
through their strong s-donating ability, formally destabilizing Pd(0) and
stabilizing Pd(II). In this way, organochlorides, 10 which are the cheapest but
often least reactive organohalide (with the exception of organofluorides), can
readily participate in cross-coupling reactions. Indeed, with the highly ac-
tivating electron-rich ligands that are now widely available, the rate-limiting
step can be switched from oxidative addition to the transmetallation or re-
ductive elimination event. Moreover, the interaction between the (pseudo)-
halide leaving group and the metal counter-ion to the nucleophilic boron
reagent can make the transmetallation step considerably more ecient with
chloride, as compared with say the bromide or iodide, thus reversing the
overall order of ''reactivity'' for the aryl halides noted above.
Base is essential for ecient turnover, but mechanistically its precise role
in transmetallation is not always clear; indeed, this aspect has been the
subject of considerable debate. 20,22 Boronic acids containing electron-rich
moieties tend to undergo the subsequent transmetallation with the oxidized
palladium(II) more readily than those bearing electron-poor moieties.
However, as discussed in more detail below, the multiple steps that are in-
volved in transmetallation make a detailed analysis of such an effect non-
trivial. Thus, although electron-donating substituents will make the boron
centre less Lewis acidic, decreasing its propensity for association with hy-
droxyl, it will also accelerate the transfer of the aryl group from the resulting
''ate'' complex.
After transmetallation by the boron reagent, the resulting diorganopalla-
dium complex must often undergo a series of ligand dissociation and as-
sociation events to isomerize the trans to the cis isomer, which can then
undergo reductive elimination. The resulting coordinatively unsaturated
palladium(0) complex is then released to undergo further catalytic cycles.
Typically, reductive elimination is rapid, especially with bulky ligands that
sterically enhance this step. Jutand and co-workers 22 elucidated an import-
ant additional role of hydroxide as the base in SM coupling: it was found to
accelerate the reductive elimination step via formation of a pentacoordi-
nated intermediate (Scheme 8.3), with Berry pseudorotation then by-passing
the requirement for a formal isomerization of ligands.

OH -

Ar-Ar'

L L

Pd II
L

Pd 0
L

Ar Ar'

Ar'

L
L

via

Pd II
OH

Ar

Scheme 8.3 Hydroxide-catalysed reductive elimination.