Fig. 1 Computed reaction profile of allenepalladium complex 1b–Pd.11
cycloadduct 6 (DDGR,298 = 16.6 kcal molꢀ1). Subsequent loss
of HCl (which produces intermediate 7) and H2O leads to
aromatic carbazole 8, a palladium(II) complex able to react
with the second allenic moiety.
Scheme 3 Mechanistic explanation for the palladium-catalyzed
preparation of 3-(buta-1,3-dienyl) carbazoles 5.
use of more diverse allenols 1 in this novel reaction. The
palladium-catalyzed carbocyclization–cross-coupling sequence
of hindered phenyl-substituted indole-tethered allenol 1c failed.
By contrast, non-substituted allenol 1d efficiently reacted to
afford the corresponding 3-(buta-1,3-dienyl) carbazole 5k
(Scheme 2). Importantly, all products were obtained as single
isomers, that is, with complete E selectivity with regard to the
newly established CQC double bond, as determined by quali-
tative homonuclear NOE difference spectra.
Palladacarbazole 8 is then transformed into the final carba-
zole 4a via protonolysis of the carbon–palladium bond
mediated by HCl. Our calculations (Fig. 2) suggest that this
step starts from complex 10, where HCl is weakly bonded to
the transition metal, which easily evolves into complex 12
through the saddle point TS2 (activation barrier of only
2.7 kcal molꢀ1
) in an exergonic process (DGR,298 =
ꢀ17.6 kcal molꢀ1). Subsequent decoordination of PdCl2 will
result in the observed carbazole 4a. Interestingly, complex 8 can
also coordinate a new allene ligand (model allene 9 in the
calculations) to produce the allenepalladium complex 11. This
species evolves into complex 13 via the transition state TS3, a
saddle point associated with the new carbon–carbon bond
formation. From the data in Fig. 2, this step is kinetically
disfavored with respect to the above-mentioned C–Pd protono-
lysis (DDGa298 = 9.7 kcal molꢀ1) but thermodynamically favored
(DDGR,298 = 5.4 kcal molꢀ1). This finding strongly supports our
hypothesis that carbazole 4a, derived from complex 12, is the
kinetically-controlled product whereas carbazoles 5, derived
from complex 13, are thermodynamically favored.
A possible pathway for the palladium-catalyzed generation
of functionalized carbazoles 5 is outlined in Scheme 3. Initial
Pd(II)-coordination to the 1,2-diene moiety leads to the allene–
palladium complex 1b,d–PdCl2. Species 1b,d–PdCl2 suffers an
intramolecular chemo- and regioselective 6-endo-trig carbo-
cyclization reaction to produce the palladadihydrocarbazole 6.
Loss of HCl with concurrent dehydration under the reaction
conditions produces aryl palladium intermediate 8. The coupling
of intermediate palladacarbazole 8 with 2 leading to species 13
takes place regioselectively at the central allene carbon atom of 2.
Finally, a trans-b-deacetoxypalladation generates, in a highly
stereoselective manner, 3-(buta-1,3-dienyl) carbazoles 5 as single
E-isomers with concomitant regeneration of the Pd(II) species.
Worthy of note, the carbopalladation of carbazolyl palladium
intermediate 8 to form the corresponding p-allylic palladium
intermediate is totally chemoselective towards the allenic
acetate 2 since homodimerization from the coupling with other
molecule of free allenol 1b did not occur.
The process leading to carbazoles 5 ends with the easy
rotation about the C–C bond in complex 13, which can
produce two different complexes, 14-trans and 14-cis. These
species possess the adequate geometry to undergo the final
deacetoxypalladation reaction via the corresponding saddle
points TS4-trans and TS4-cis, respectively. Strikingly, the
trans-deacetoxypalladation reaction (via TS4-trans) is kinetically
(DDGa298 = 2.2 kcal molꢀ1) and thermodynamically favored over
the analogous cis-process (via TS4-cis). This justifies the complete
stereoselectivity of the transformation which exclusively produces
3-(buta-1,3-dienyl) carbazoles 5 as single E-isomers. This step,
albeit exergonic, occurs with the highest activation barrier
(DGa298 = 19.7 kcal molꢀ1) computed for the entire reaction
profile, and therefore constitutes the bottleneck of the trans-
formation. Furthermore, this finding explains why a high
temperature is experimentally required to produce carbazoles 5
(easily formed by decoordination of ClPd(OAc) in complex 15).
Finally, the PdCl2 catalyst is regenerated by protonolysis of
To gain more insight into the reaction mechanisms of the
above palladium-catalyzed cyclization reactions, a computa-
tional (DFT) study was carried out.10 First, we computed the
experimentally observed preference of allenol 1b towards the
carbocyclization reaction in the presence of PdCl2 (Scheme 1). As
readily seen in Fig. 1, it can be concluded that the initially formed
allenepalladium complex 1b–Pd is completely transformed into
dihydrocarbazole 6 via the saddle point TS1. This extraordinary
regioselectivity takes place under both kinetic and thermo-
dynamic control, in view of the higher activation energy required
for the formation of dihydrofuran 60 (DDG2a98 = 5.2 kcal molꢀ1),
as well as the considerably lower reaction energy computed for
c
Chem. Commun.
This journal is The Royal Society of Chemistry 2012
Alcaide, Benito
