Chemistry Reference
In-Depth Information
M
e
HN
Ph
ArBr
LPd(0)
Ar
M
e
L
Ar
M
e
Racemizatio
n
Pd
Me
Ar
L
Ar
L
L
N
H
Ph
Pd
Pd
N
H
Ph
Ph
1/2 [LPd(Ar)Br]
2
-Hydride Elimination
Prevented by Chelate
β
HN
NaBr
t
BuOH
NH
2
Ar
L
Br
NH
2
Pd
Ph
Me
NaO
t
Bu
Ph
Me
Figure 2.28 Mechanistic rationale for the racemization of a-chiral amines in Pd-
catalyzed amination reactions.
Adapted from Ref. 107.
The mechanism of aryl amination catalyzed by Pd/BINAP has been a
subject of intense discussion. On the basis of kinetic studies, in 2000
Hartwig and co-workers proposed a mechanism in which Pd(BINAP)
2
in the
catalytic cycle underwent a ligand dissociation to generate Pd(BINAP) as the
turnover-limiting step and ligand reassociation was required to release
the product (Figure 2.29, left),
113
This was largely based on the fact that the
amination reaction appeared to be zeroth order in [ArBr]. Subsequently, in
2002 Buchwald and co-workers proposed a different mechanism based on
kinetic studies of the catalytic amination of bromobenzene with both
primary and secondary amines using reaction calorimetry.
114
A positive
order in both [ArBr] and [amine] was observed, but only after an induction
period. This was attributed to slow catalyst activation. These data were used
to rationalize the apparent zeroth-order rate dependence on [ArBr] observed
by Hartwig and co-workers.
113
It was further proposed that oxidative add-
ition of the aryl bromide occurs more rapidly to the amine-bound Pd-BINAP
complex than to Pd(BINAP) based on kinetic modeling (Figure 2.29, right).
However, in 2006 Hartwig's group studied the rate of the stoichiometric
oxidative addition of bromobenzene to Pd(BINAP)
2
in the presence and ab-
sence of various concentrations of primary and secondary amines.
115
It was
determined that oxidative addition with (amine)Pd(BINAP) is not faster
than that with Pd(BINAP), and even in the presence of an amine oxidative
addition still occurs with Pd(BINAP). The mechanism was subsequently
reexamined and revised in 2006 by Hartwig, Buchwald, Blackmond and
co-workers.
116
New kinetic data were obtained which revealed that the
catalytic rate of the reactions is zeroth order in [amine], first order in [aryl
bromide] and inverse first order in [ligand]. A new mechanistic proposal was
set forth based on these data: oxidative addition occurs to Pd(BINAP), amine
and base react with the oxidative addition complex to generate the corres-
ponding amido complex and reductive elimination releases the arylamine.
Search WWH ::
Custom Search