Pd(0)-Catalyzed Carboiodination: Early Developments and Recent Advances - New Trends in Cross-Coupling: Theory and Applications - page 304

reaction developed by Lautens and co-workers requires the use of ex-
ceptionally bulky phosphine ligands such as QPhos and P t Bu 3 . One of the
main limitations of this chemistry is the greatly attenuated reactivity of aryl
chlorides and bromides under the standard conditions. The use of aryl
chlorides and bromides would be beneficial, as they are typically cheaper and
more readily available than the analogous aryl iodides. The carboiodination
reaction also requires the use of 1,1-disubstituted olefins to prevent Heck-type
processes from occurring. In substrates that possess a suitable b-hydrogen,
b-hydride elimination is faster than the desired C-I reductive elimination.
Towards the goal of gaining a fundamental understanding to aid in solving
these problems, computational studies were undertaken by Lautens and so-
workers, and the mechanism, ligand effects and the origins of reactivity and
selectivity in the Pd-catalyzed carboiodination reaction were explored. 100
In the system under study, P t Bu 3 exhibits similar reactivity and eciency
to QPhos. Therefore, for all calculations, P t Bu 3 was used as the ligand rather
than QPhos owing to the reduced computational cost. The proposed catalytic
cycle of carboiodination with aryl halide 7.46 is shown in Scheme 7.28.
Starting from the active PdL 2 complex, substrate binding and ligand dis-
sociation constitute the first step of the catalytic cycle, which generates the
Z 2 complex 7.47. Next, oxidative addition of the aryl halide occurs, giving rise
to Pd(II) complex 7.48. Isomerization allows coordination of the pendent
olefin to occur, forming 7.49, which is followed by syn-carbopalladation to
form a new C-C bond in the alkylpalladium(II) halide intermediate 7.50. The
C-X reductive elimination proceeds via a three-membered transition state,
generating the new C-X bond and the product-bound Pd(0) complex 7.51.
The I Pd coordination is weak and 7.51 readily liberates the product 7.52 to

bind another molecule of ligand to regenerate the initial PdL 2 catalyst.
Based on the DFT calculations, the rate-limiting step of the trans-
formation is carbon-halogen reductive elimination with a barrier of
24.9 kcal mol 1 for substrate 7.46a. The high activation energy is related to
the endothermicity of the transformation. Overall, the main driving force for
the reaction is the formation of a C-C s-bond from a C ¼ C p-bond.

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7.7.2 Origin of Reactivity Differences in Aryl Halides
The catalytic cycles implementing aryl bromide 7.46b and chloride 7.46c
were also computed to understand why these halides showed poor reactivity
under the reaction conditions. The carbon-halogen reductive elimination
was found to be the rate-limiting step in all cases, with barriers of 27.4 and
27.9 kcal mol 1 for the aryl bromide and chloride, respectively. Both of these
values are higher than the activation energy associated with C-I reductive
elimination (24.9 kcal mol 1 ). The reactivity of different halides can be at-
tributed to the barrier of carbon-halogen reductive elimination, which is in
turn correlated with the differences in Pd-X bond dissociation energies
(Figure 7.2). Hence the breaking of a weak Pd-I bond is favored over
breaking of a stronger Pd-Br or Pd-Cl bond.