Angewandte
Communications
Chemie
1r and 1s were converted into the corresponding indoles in
mined to be the rate-limiting step, which is in acceptable
diminished yields. Pleasingly, for all Bn- as well as for the two
PMB-protected indolines 1t and 1u, the reaction proceeded
in excellent yields. Generally, the reaction time and the yield
of the dehydrogenative oxidation were only marginally
influenced by the reaction scale.
We then investigated the mechanism of the dehydrogen-
ative indoline oxidation by kinetic and quantum-mechanical
experiments. DFT calculations at the PW6B95-D3//PBEh-3c
+ COSMO-RS level of theory[17] provided detailed mecha-
nistic insight into the borane-catalyzed dehydrogenation of
indoline 1a (Figure 2). Owing to steric hindrance at the
agreement with the determined Eyring activation energy of
25.7 Æ 6 kcalmolÀ1. This proposed mechanism implies that the
activation barrier of H2 liberation may be reduced when the
Brønsted acidity of the ammonium ion or the hydridic
character of the hydridoborate is enhanced. The Lewis acidity
of boranes in active FLPs has an immense impact on the
reversibility of H2 activation[9a,12b,19] and on the reaction
rates.[12a,20] The Lewis acidity of partially fluorinated borane 5
is 15% lower than that of 2,[12a,21] which in turn may result in
a lower energy barrier for the H2 release from the corre-
sponding ammonium borate owing to the increased hydride
donor ability.[21a]
Disappointingly, borane 5 was entirely inactive in the
dehydrogenative oxidation of 1a as a consequence of the
diminished Lewis acidity (Scheme 2). However, borane 5 may
Scheme 2. Rate enhancement of the indoline dehydrogenation by the
weak Lewis acid 5 acting as a hydride shuttle.
Figure 2. DFT-computed reaction free energies (in kcalmolÀ1) for the
B(C6F6)3 (2) catalyzed dehydrogenation of indoline 1a..
act as hydride shuttle as boranes can undergo hydride
exchange[22] in equilibrium. Indeed, when a 1:1 ratio of
catalytically active 2 and catalytically inactive 5 (5 mol%
each) was used for the dehydrogenation of 1a, a substantial
rate enhancement of krel = 2.28 was observed (Scheme 2).
This boost in reactivity can be rationalized by the hydride
N center of indoline 1a, Lewis basic indoline 1a and B(C6F6)3
(2) can only form an unstable frustrated Lewis pair (3.6 kcal
molÀ1 higher in free energy than separated 1a and 2; see the
Supporting Information) rather than a tight acid–base com-
À
exchange equilibrium between [H 2] and 5. The hydride is
preferably located at the stronger Lewis acid 2 but small
À
À
plex through formation of a B N donor bond. In solution,
quantities of the stronger hydride donor [H 5] may still be
accessible (Scheme 3). This leads to the transient formation of
borane 2 can selectively abstract a hydride from the C2
position of 1a to form the separated ion pair 4 over a low
barrier of 11.1 kcalmolÀ1 (TS1). From this intermediate, two
reactions are conceivable. The direct formation of indole 3a
and molecular H2 from intermediate 4 was considered as
kinetically incompetent[18] (not shown, see the Information
Supporting) in comparison to a lower-barrier proton transfer
(15.5 kcalmolÀ1; TS2) to the N atom of a second indoline 1a,
which is in accord with the results of the isotope-labeling
experiments (see the Supporting Information). The formation
the ion pair [1a H][H 5],[23] which is now capable to liberate
H2 more readily than the comparatively weaker hydride
donor [H 2] (right cycle). Furthermore, free borane 2
liberated in the equilibrium (left cycle) is again reactive in
hydride abstraction from 1a. In summary, the substantial rate
increase by a factor of 2.28 is due to direct hydrogen release
from the initially formed hydridoborate salt [1a H][H 2] as
well as to 5 acting as a hydride shuttle.
À
À
À
À
À
À
À
of this contact ion pair, [1a H][H 2], and 3a is exergonic by
À3.3 kcalmolÀ1, which enabled the NMR spectroscopic
characterization of this species at room temperature, includ-
ing the detection of the ion pairing by dihydrogen bonding.
Upon heating to 908C, proton–hydride recombination may
occur to release indoline 1a, molecular H2, and borane
catalyst 2, which is almost energy-neutral and involves
a moderate barrier of 18.5 kcalmolÀ1 at room temperature.
This reaction should be favored at higher temperatures owing
to favorable entropy effects. The overall catalyzed dehydro-
genation is thus exergonic by À3.8 kcalmolÀ1 with a barrier of
18.5 kcalmolÀ1; proton–hydride recombination was deter-
Scheme 3. Proposed function of borane 5 in the rate enhancement of
the dehydrogenation through a hydride shuttle mechanism.
Angew. Chem. Int. Ed. 2016, 55, 1 – 6
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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