Communications
details).[12] Further, the supramolecular interaction of octanal
with both the neutral and the protonated acyl guanidine
(Kass = 30mÀ1, CDCl3, 408C) was confirmed by 1H NMR
spectroscopy (see the Supporting Information for experimen-
tal details).
On the basis of the above results, we propose a mecha-
nistic hypothesis for this hydrogenation reaction (Scheme 4).
The mechanism involves coordination of the aldehyde to the
Scheme 3. Chemoselective reduction of oct-2-enal: a) [Rh(CO)2acac]/3/
substrate/CF3SO3H (1:10:500:5), c0(substrate)=0.6m, CH2Cl2 (2 mL),
CO/H2 (1:1, 20 bar), 20 h, 408C; b) [Rh(CO)2acac]/3/substrate/
CF3SO3H (1:10:1000:5), c0(substrate)=0.2m, CH2Cl2 (2 mL), CO/H2
(1:1, 20 bar), 3 h, 408C. The yields were determined by GC.
Furthermore, the catalyst is completely selective for aldehyde
reduction in the presence of a ketone functionality (Table 2,
entry 11). In competition experiments between octanal and
several ketones (acetophenone, benzophenone, ethyl aceto-
acetate, and trifluoroacetophenone), the aldehyde was hydro-
genated with complete selectivity (see the Supporting Infor-
mation).
We undertook a number of experiments to clarify the
reaction mechanism. When methanol, which is known to
disturb hydrogen bonding, was used as the solvent, a
significant decrease in the activity of the catalyst was
observed (Table 3, entry 2). No reaction was observed with
Scheme 4. Proposed mechanism for aldehyde hydrogenation catalyzed
by [Rh]/3.
protonated guanidine moiety. This interaction may activate
the aldehyde (decrease its LUMO energy;[13] see the Sup-
porting Information) for the subsequent metal–ligand bifunc-
tional hydrogenation. The catalyst is supposed to provide an
acidic (from guanidine) and a hydridic hydrogen atom (at the
rhodium center) in a concerted manner. In the next step, the
basic guanidine functionality may facilitate the heterolytic
cleavage of hydrogen and regeneration of the active cata-
lyst.[14]
Further support for this mechanism came from DFT
calculations,[15] which enabled the identification of a transition
state for the hydride-transfer reaction (Figure 2). Thus, in the
calculated catalyst–substrate complex, the aldehyde is bound
to the guanidinium unit by two hydrogen bonds. Interestingly,
on the way to the transition state, a third hydrogen bond to
the pyrrole NH group develops. Finally, after proton and
hydride transfer, the alcohol product is bound to one
guanidine N atom and the pyrrole NH functionality. Hence,
participation of the pyrrole NH group in the reaction
mechanism may account for the observed efficiency of
ligand 3 in the hydrogenation reaction.
Table 3: Control experiments.[a]
Entry
Ligand
Solvent
Yield [%]
1
2
3
4
5
3
3
CH2Cl2
MeOH
CH2Cl2
CH2Cl2
CH2Cl2
97
10
0
0
10
no ligand
PPh3/7
8
[a] Reaction conditions: [Rh(CO)2acac]/ligand/5/CF3SO3H (1:10:500:5),
c0(5)=0.6m, CH2Cl2 (2 mL), 408C, CO/H2 (1:1, 20 bar), 20 h.
the unmodified rhodium complex [Rh(CO)2acac] (Table 3,
entry 3) or when a combination of triphenylphosphine and
the acyl guanidine additive 7 was used (Table 3, entry 4). The
use of ligand 8, which incorporates an N-Boc-protected
guanidine moiety, furnished a slow catalyst (Table 3, entry 5).
These results taken together provide strong evidence for an
intramolecular reduction pathway that involves both the
rhodium metal center and the guanidine functionality.
If this hydrogenation reaction occurs through a supra-
molecular mechanism, it should display saturation kinetics.
Indeed, the hydrogenation of octanal at various substrate
concentrations (0.05–0.6m) revealed that the reaction kinetics
With an efficient hydrogenation catalyst that operates
under hydroformylation conditions in hand, we carried out
first investigations of the proposed tandem hydroformyla-
tion–hydrogenation (Table 4). Terminal alkenes 9 (Table 4,
entries 1–3) were converted into the corresponding alcohols
with good regioselectivities (10/11 up to 92:8) under mild
conditions (408C, 40 bar). Interestingly, in the case of the
methyl ketone functionalized alkene (Table 4, entry 3), the
ketone was not touched at all under these reaction conditions.
In the case of styrene, the branched alcohol was formed as the
major regioisomer (Table 4, entry 4). This regiochemical
outcome was also observed for the rhodium-catalyzed hydro-
formylation of aryl-substituted alkenes with a monodentate
phosphine ligand.[16]
obeys the Michaelis–Menten equation (KM = 0.1m and Vmax
=
134 hÀ1, R2 = 0.93; see the Supporting Information for
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2009, 48, 8022 –8026