Introduction to New Trends in Cross-Coupling - New Trends in Cross-Coupling: Theory and Applications - page 6

branched

R 1

R

OR

linear

Reductive
Elimination

R 1

R

R − R 1

R

R 1

R 1

R

Base

OR

-HX

H Pd(II)L n
X

HPd( I)L n
X

L n Pd(0)

R

b -Hydride
Elimination

L n Pd(II) Oxidative

Addition

R − X

R

R 1

PdXL n

H

PdXL n R 1

L n Pd(II )

OR

H

R 1 R

H R

X

M − X

Migratory
Insertion

R 1

R 1 − M

Transmetallation

Heck-Mizoroki

Negishi (M = Zn)
Suzuki-Miyaura (M = B)
Kumada-Corriu (M = Mg)
Stille (M = Sn)
Hiyama ("M" = Si)
Sonogashira (M = Cu)

Scheme 1.1 General mechanism of cross-coupling reactions and the Heck-
Mizoroki reaction.

pseudohalide, R-X, to L n Pd(0) to generate an R-Pd(Ar)(X)(II) intermediate. In
the second step, the other partner (R 1 ) in the form of R 1 -M also forms a
connection with the matchmaker so that R and R 1 can communicate with
each other through the Pd. This is the second step, called transmetallation,
where M (a friend or family member of R 1 ) forms a ''bond'' with X. In the
third step, R and R 1 are united and detach from the matchmaker (Pd cata-
lyst) in an event called reductive elimination. The success of a matchmaker
depends on how many challenging coupling partners are successfully
coupled (get married) without any deleterious incidents, within a short time
frame. This is related to the TON and TOF of the catalyst. Although Heck
shared the 2010 Nobel Prize for Pd-catalyzed cross-coupling reactions with
Suzuki and Negishi, some argue that the Heck-Mizoroki reaction (often
shortened to the Heck reaction) is not a true cross-coupling reaction as it
does not involve a transmetallation step. In the Heck reaction, the Pd(II)-R
species undergoes a migratory insertion with the alkene substrate, followed
by a syn-periplanar b-hydride elimination event to give the product. This
step was well established by the work of Fu and Hartwig. 7 Base is necessary
to turn over palladium catalyst by inducing the reductive elimination of HX
in the last step. Depending on the nature of substituents on the olefin,
linear or branched coupled products are obtained, as these olefin substitu-
ents can influence the regioselectivity of the product. The general rule
of thumb is that electron-withdrawing groups on the olefin favor
linear products with neutral Pd complexes. Bidentate ligands such as dppf