Pd(0)-Catalyzed Carboiodination: Early Developments and Recent Advances - New Trends in Cross-Coupling: Theory and Applications - page 295

sterically encumbering substituents. The reaction is also compatible with
starting materials containing an additional halogen (Br or I) on the aromatic
ring, which exemplifies the ability of P t Bu 3 in enabling reversible oxidative
addition. This study highlights the first selective Buchwald-Hartwig cross-
coupling of a vinyl bromide in the presence of an aryl iodide, which is
typically dicult owing to inherent chemoselectivity issues.
To demonstrate (a) that the product 7.29 is more susceptible to oxidative
addition than the starting material 7.27 and (b) that the unproductive oxi-
dative addition complex 7.30a can re-form the active catalyst through C-X
reductive elimination (i.e., oxidative addition to the product carbon-
bromine bond is a reversible process), mechanistic studies were carried out.
In the first study, 2-bromoindole was mixed with 1 equivalent of Pd(P t Bu 3 ) 2
in C 6 D 6 , stirred at room temperature and monitored by 31 P NMR spec-
troscopy over 3 days (Scheme 7.18). The disappearance of the peak corres-
ponding to the Pd precatalyst at 84.9 ppm was accompanied by the
appearance of two new peaks: one corresponding to free P t Bu 3 ligand at 62.2
ppm and the second to a new phosphorus-containing compound at 65.1
ppm in a 1 : 1 ratio. This finding is consistent with the formation of 7.30a
presumably arising from oxidative addition to 7.29.
A competition experiment was carried out to test if indole 7.29 is more
prone to oxidative addition than the starting gem-dibromoolefin 7.27.
Pd(P t Bu 3 ) 2 , 7.27 and 7.29 were combined in a 1 : 1 : 1 ratio in C 6 D 6 and stirred
at room temperature for 3 days (Scheme 7.19). The authors observed the
appearance of complex 7.30a at 65.1 ppm in the 31 P NMR spectrum once
again, while 7.27 was completely recovered. Under these conditions, the
oxidative addition product of 7.27 was never observed by 31 P NMR spec-
troscopy, suggesting that oxidative addition into 7.29 is thermodynamically
(and likely kinetically) favored.

P t Bu 3

Pd(P t Bu 3 ) 2

Br + Pd +

P t Bu 3

C 6 D 6 , rt, 3 d

N
H

H

(1 equiv)
31 P: 84.9 ppm

Br

31 P: 62.2 ppm

7.29 7.30a

31 P: 65.1 ppm

Scheme 7.18 Stoichiometric studies on oxidative addition of 7.29.

Adapted from Ref. 83. Copyright 2010 American Chemical Society.

P t Bu 3

Br

Br

Pd(P t Bu 3 ) 2
C 6 D 6 , rt, 3 d

+ Br

Pd +

Br

H

Br

H

NH 2

Br NH 2

7.27 7.29 7.30a 7.27

31 P: 65.1 ppm

recovered

Scheme 7.19 Competition experiments between 7.27 and 7.29.
Adapted from Ref. 83. Copyright 2010 American Chemical Society.