Pd(0)-Catalyzed Carboiodination: Early Developments and Recent Advances - New Trends in Cross-Coupling: Theory and Applications - page 308

7.8 Expanding the Scope of Pd-Catalyzed
Carbohalogenation

7.8.1 Bromide to Iodide Exchange and Domino
Carbohalogenation
In 2011, Lautens and co-workers reported a Pd-catalyzed carbohalogenation re-
action with aryl bromides, which, in the presence of an iodide source, gave rise to
formal carboiodination products (Scheme 7.30). 101 The success of this trans-
formation is based on a halide exchange (bromide to iodide) at Pd, which allows
carbon-iodine reductive elimination to occur from the key alkylpalladium(II)
halide intermediate. This protocol is reminiscent of the work of Buchwald and
co-workers on Pd-catalyzed aromatic halogen exchange reactions, 86 and permits
the use of cheaper and more readily available starting materials.
In the same report, 101 the authors demonstrated that polyunsaturated aryl
iodides are also suitable substrates for carbohalogenation. Upon oxidative
addition of the aryl iodide, multiple olefin insertions can be terminated by
C-I reductive elimination, giving rising to complex polycyclic alkyl iodide
products. Using aryl iodide 7.59, a diastereoselectivity of 420 : 1 could be
achieved (Scheme 7.31a). Additionally, aryl bromides such as 7.61 could be
used in the domino carbohalogenation by utilizing the halide exchange
conditions (Scheme 7.31b).

7.8.2 Diastereoselective Pd(0)-Catalyzed Carboiodination
In 2012, Lautens and co-workers reported the application of the carboiodina-
tion methodology

to the diastereoselective synthesis of functionalized

Br Pd(QPhos) 2 (5-7.5 mol%)

KI (2 equiv)
PhMe, 100 ° C, 16 h

I

R

R

X

n

n

X

Selected examples:

I

I I

MeO

O

O O

89% 92% 87%

I

I

I

Cl

O

Boc

Boc

F 3 C

93% 71%

91%

Scheme 7.30 Scope of Pd-catalyzed carboiodination via Br to I exchange.