Recently, Breit and co-workers reported the first example
of hydroformylation at 1 atm of CO/H2, using standard lab-
oratory glassware.7 The use of a new catalyst Rh(I) 6-(diphe-
nylphosphino)pyridin-2(1H)-on [6-DPPon)/Rh(I)] operative
in a chelation system gave excellent regioselectivity in the
formation of linear aldehydes from terminal alkenes.8 This
work represents a real breakthrough rendering the hydro-
formylation reaction practical to use in fine organic synthesis.
Following our interest in the use of microwaves9 and
application of hydroformylation in organic synthesis,10 we
were intrigued by the possibility to carry out this reaction
under microwave irradiation. Thus, we adapted a Discover
microwave oven equipped with the 80 mL vial for reaction
under pressure.11 This glass vial, tested for resisting up to
250 psi (17 bar, 1723 KPa), is provided with a tube
connection to an external pressure controlling system equipped
with a valve and an exit tube for venting the vial at the end
of the reaction. When the valve of the pressure controlling
system is closed, the reactor vial is under pressure (registered
by the system), whereas when the valve is open, the vial is
connected with the exit tube.
syngas (CO/H2 1:1) until the internal pressure reached 40
psi (the pressure was registered in real time by the computer
connected to the Discover device).
Finally, tap A was closed, and the vial was inserted in the
MW cavity and irradiated at 150 W of power for 4 min (two
cycles of 2 min each). The internal temperature reached 110
°C, and the power was automatically modified to maintain
this temperature. We observed a decrease of the internal
pressure indicating that the gas was adsorbed by the reaction
(see Supporting Information). The vial was cooled to room
temperature, and the taps A and C were opened to release
the gas contained in the vial inside a fume cupboard. After
GC/MS analysis of the crude reaction mixture, we were
pleased to find that the peak at m/z 112 (1-octene or an
isomer) had disappeared, and instead a single peak at m/z
142 was present, indicating that the hydroformylation was
operating. The formation of 1-nonanal was confirmed by
NMR after purification of the mixture by column chro-
matograhy. To check the influence of the parameters involved
in the reaction, different experiments on 1-octene were
performed. Thus, we found that the reaction worked similarly
with 1 mol % loading of catalyst and ligand and in a scale-
up to 1 g of substrate.14
We connected this exit tube to a cylinder containing the
mixture CO/H2 1:1 (syngas) through a three-way connector
equipped with two taps (Scheme 1). Then, we ran the
The presence of the ionic liquid was crucial for the
reaction. Although the presence of the Rh(I) catalyst allowed
the temperature of the reaction mixture to rise to 60 °C, in
the absence of [bmim][BF4] the conversion of 1-octene was
not complete even after 15 cycles of 2 min each.
Scheme 1. Connections Required to Carry Out MW-Assisted
Hydroformylation in a Discover Microwave Oven12
Several terminal alkenes (3, 5, 7, 9, 11, 13, 15, 17, 18,
21) were submitted to the above reaction conditions and all
gave high conversion into the linear aldehydes (2, 8, 10, 12,
14, 16, 19, 20, 22) without notable formation of the branched
isomers (Table 1) with the exception of the two styrenes 3
and 5 which gave a mixture of products, respectively, 4a/
4b (iso/n 9:1) and 6a/6b (iso/n 15:1). Similar results were
observed under standard hydroformylation conditions using
the Wilkinson catalyst and XANTPHOS.15 These results
suggest that for the hydroformylation reaction no special
effects can be ascribed to the microwaves except for a
tremendous increase of the reaction rate. The compatibility
of the process with different functional groups is demon-
strated by the high-yielding transformations carried out
successfully on alkenes 9, 11, 13, 15, 17, 18, and 21 (see
Table 1). The impact of the microwave effect on the
hydroformylation reaction is impressive in terms of practi-
cability and efficiency.
following preliminary experiment. A solution of 1-octene
in toluene was mixed together with HRh(CO)(PPh)3 and
XANTPHOS12 as the catalyst (4 mol % of a 1:4 mixture) in
the 80 mL vial. The solution contained also ionic liquid
[bmim][BF4] (butylmethylimidazolium tetrafluoroborate), an
additive recommended to enhance heat transfer from the
microwaves toward the reaction mixture.13 Then, while tap
C was closed, taps A and B were opened to fill the vial with
Moreover, when compounds 23 and 24 were submitted
to the microwave hydroformylation under our standard
conditions, we observed the formation of the dehydropip-
eridines 25 and 26, respectively (in relatively low yields),
via a cyclohydrocarbonylation reaction. Most of the starting
material remained unreacted. In the case of the product
protected as Cbz (24), it was possible to monitor the presence
(6) Breit, B. Acc. Chem. Res. 2003, 36, 264.
(7) Seiche, W.; Schuschkowski, A.; Breit, B. AdV. Synth. Catal. 2005,
347, 1488.
(8) Breit, B.; Seiche, W. J. Am. Chem. Soc. 2003, 125, 6608. To our
knowledge, this ligand is not commercially available: search done on
from 20 to 90 h to go to completion.
(9) Minetto, G.; Raveglia, L. F.; Taddei, M. Org. Lett. 2004, 6, 389.
(10) Dessole, G.; Marchetti, M.; Taddei, M. J. Comb. Chem. 2003, 5,
198.
(11) Discover microwave ovens for organic synthesis are produced by
the CEM Corporation. A photograph of the equipment is enclosed in the
Supporting Information.
(12) XANTPHOS: 9,9-dimethyl-4,5-bis(diphenylphosphine)xanthene.
Kranenburg, M.; van der Burgt, Y. E. M.; Kamer, P. C. J.; van Leeuwen,
P. W. N. M. Organometallics 1995, 14, 3081. The ligand is commercially
available from Sigma-Aldrich, Stream, and other chemical suppliers.
(13) Leadbeater, N. E.; Torenius, H. M. J. Org. Chem. 2002, 67, 3145.
(14) Scale applied to alkene 9. For security reasons, we did not fill the
vial. However, the speed of the reaction allowed us to repeat the process 4
times, producing 4.8 g of aldehyde 10 in 30 min.
(15) Marchetti, M.; Botteghi, C.; Paganelli, S.; Taddei, M. AdV. Synth.
Catal. 2003, 345, 1229.
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Org. Lett., Vol. 8, No. 17, 2006