Hydrogenation of five-membered heteroaromatic compounds catalyzed by a rhodium-phosphine complex

Article abstract of DOI:10.1246/cl.2000.428

The rhodium complex generated in situ from Rh(acac)(cod) and 2 equivalents of triphenylphosphine is an effective catalyst for hydrogenation of various five-membered heteroaromatic compounds.

Full text of DOI:10.1246/cl.2000.428

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28
Chemistry Letters 2000
Hydrogenation of Five-Membered Heteroaromatic Compounds
Catalyzed by a Rhodium-Phosphine Complex
Ryoichi Kuwano, Koji Sato, and Yoshihiko Ito*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University,
Sakyo-ku, Kyoto 606-8501
(Received January 11, 2000; CL-000029)
The rhodium complex generated in situ from Rh(acac)(cod)
and 2 equivalents of triphenylphosphine is an effective catalyst
for hydrogenation of various five-membered heteroaromatic
compounds.
Hydrogenation of heteroaromatic compounds is a useful
reaction to provide saturated or partially unsaturated heterocyclic
1
compounds, whose skeletons are found in many biologically
active natural products and medicines.2 As well, the hydrogena-
tion, which includes hydrodenitrogenation, hydrodeoxygenation,
and hydrodesulfurization from petroleum and coal, offers an
industrially important process. Although many efforts have been
made toward development of the hydrogenation of heteroaromat-
3–5
ic compounds using homogeneous catalysis which is advanta-
6
geous to pursuit of stereoselectivity, many shortcomings of the
indoles using homogeneous catalyst to our knowledge.9,10
Molar equivalent of phosphine to rhodium atom was a cru-
cial factor for the catalytic activity (entries 7 and 8). Lower
ratio of phosphine ligand to rhodium (1:1) induced complete
hydrogenation of the aryl ring of 1a to give 3 (17%). On the
other hand, higher phosphine ratio caused significant deteriora-
tion of the catalytic activity. Bisphosphine ligand, 1,1'-
bis(diphenylphosphino)ferrocene (DPPF), can be used instead of
triphenylphosphine, exhibiting comparable catalytic activity
(entry 9). Active species for the catalytic hydrogenation may be
a rhodium(I)–hydride complex generated in situ from reaction of
catalysts have thwarted their utilization for organic synthesis, e.g.
limitation of substrate, low catalytic activity, and difficulty in the
availability and modification of the catalysts. Herein, we report
that a rhodium–phosphine complex provided high catalytic activ-
ity for hydrogenations of various five-membered heteroaromatic
compounds. The rhodium catalyst is readily prepared in situ by
mixing commercially available Rh(acac)(cod) and triphenyl-
phosphine.
First of all, we examined several transition metal–phos-
phine complexes for hydrogenation of 1-tert-butoxycarbonylin-
dole (1a) (eq 1). The reactions were carried out in 2-propanol
11
(
acetylacetonato)rhodium(I) with hydrogen. RhH(PPh ) pro-
3 4
vided the same catalytic activity as Rh(acac)(cod)–4PPh (entry
3
1
0). However, RhH(CO)(PPh ) did not promote the hydro-
3 3
genation of 1a at all, indicating that the carbonyl ligand on the
rhodium atom inhibited the catalysis completely (entry 11).
Carbonyl substituent on the nitrogen atom is necessary for
the regioselective hydrogenation. N-Acetylindole was also con-
verted into N-acetylindoline in 100% GC yield, while the
hydrogenation of N-methylindole using the Rh(acac)(cod)–
2
(
0.5 M) at 80 ˚C under 50 kg/cm of hydrogen for 2 h. The
results are shown in Table 1. Wilkinson complex RhCl(PPh ) ,
3
3
which is well-known as a catalyst for hydrogenation of various
unsaturated compounds, exhibited some catalytic activity for
the hydrogenation of 1a (entry 1). Iridium and ruthenium com-
plexes were also possible to promote the hydrogenation, but
much less effective than rhodium catalyst (entries 2 and 3). On
further screening of some rhodium complexes, a rhodium com-
plex (1 mol%) generated in situ from Rh(acac)(cod) and 2
equivalents of triphenylphosphine was found to be the most
effective catalyst, which completes the regioselective hydro-
genation within 2 h to give N-Boc-indoline 2a selectively in
quantitative GC yield (91% isolated yield) with no detectable
2PPh catalyst gave a mixture of several compounds.
3
A variety of substituted indoles were reduced selectively to
yield the corresponding indolines by the hydrogenation using
Rh(acac)(cod)–2PPh catalyst (Table 2). N-Boc-indoles 1b–d,
3
bearing a substituent at the 2-position, were hydrogenated
smoothly to give 2b–d in high yield (entries 1–3). On the other
hand, hydrogenation of N-Boc-3-methylindole (1e) proceeded
sluggishly, and prolongation of the reaction time could not
improve the yield of 2e (entry 4). The hydrogenation of 1f,
which has a 5-methyl substituent, gave 2f in 91% GC yield but
was slower than that of 1b (entry 5). 5-Methoxy- (1g) and
methyl indole-5-carboxylate (1h) gave 2g and 2h in high yield,
respectively (entries 6 and 7). The results of entries 5–7 sug-
gest that the reaction rate may be due to the steric effect of the
7
,8
by-product (entry 6). The high catalytic activity of the rhodi-
um catalyst is demonstrated by completion of hydrogenation of
a within 6 h even with 0.1 mol% of the catalyst (92% isolated
1
yield). The catalytic activity is the best in hydrogenations of
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
429
but the reduction of the fused aryl ring was suppressed by use of
DPPF instead of triphenylphosphine. The rhodium catalyst
enabled hydrogenation of benzothiophene (10), but with very
low turnover (entry 12). Sulfur compound produced might have
deactivated the rhodium catalyst.
In conclusion, the rhodium complex prepared in situ from
Rh(acac)(cod) and triphenylphosphine, which are commercially
available, was effective for catalytic hydrogenation of a wide
range of five-membered heteroaromatic compounds. The catalyst
may be readily modified by various chiral phosphine ligands.
Asymmetric version of the hydrogenation is being developed in
our group now.
This work was supported by Grant-in-Aid for Scientific
Research (C) from the Ministry of Education, Science, Sports
and Culture (No. 11650891) and Research Aid of Inoue
Foundation for Science.
References and Notes
1
P. N. Rylander, in “Hydrogenation Methods,” Academic Press,
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(
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2
3
“Comprehensive Natural Products Chemistry,” ed by D. Barton,
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Delgado, J. Am. Chem. Soc., 121, 7071 (1999).
4
5
For reduction of indoles using formic acid with RuCl (PPh ) cat-
2
3 3
alyst, see: Y. Watanabe, T. Ohta, Y. Tsuji, T. Hiyoshi, and Y.
Tsuji, Bull. Chem. Soc. Jpn., 57, 2440 (1984).
For reduction of quinoline and isoquinoline under water gas shift
condition with Rh (CO) catalyst, see: S.-I. Murahashi, Y.
6
16
Imada, and Y. Hirai, Tetrahedron Lett., 28, 77 (1987); S.-I.
Murahashi, Y. Imada, and Y. Hirai, Bull. Chem. Soc. Jpn., 62,
2
968 (1989).
6
7
“Catalytic Asymmetric Synthesis,” ed by I. Ojima, VCH, New
York (1993); “Asymmetric Catalysis in Organic Synthesis,” R.
Noyori, Wiley, New York (1994).
The hydrogenation of 1a by Rh(acac)(cod)–2PPh was carried
3
out as follows: A mixture of Rh(acac)(cod) (1.6 mg, 5.0 µmol)
and triphenylphosphine (2.6 mg, 10.0 µmol) in 2-propanol (1.0
ml) was stirred vigorously at room temperature for 10 min. The
resulting mixture was transferred by a cannula to a nitrogen-filled
stainless steel autoclave, in which 1a (109 mg, 0.50 mmol) was
placed beforehand. Hydrogen was introduced into the reaction
5
-substituent rather than its electronic effect. 5-Chloroindole
(1i) also underwent the selective hydrogenation in the presence
of the rhodium catalyst and molecular hydrogen at 30 ˚C to
give 2i (entry 8). The hydrogenation at 80 ˚C provided 2a with
hydrodechlorination.
Related five-membered heteroaromatic compounds also
underwent the rhodium catalyzed hydrogenation as well. N-
Protected pyrrole 4 was completely hydrogenated under similar
conditions, giving N-tert-butoxycarbonylpyrrolidine (5) in 91%
isolated yield (entry 9). Partial reduction of 4 was not detected
by GLC analysis during the hydrogenation. Rh(acac)(cod)–
2
vessel until the pressure gauge indicated 50 kg/cm . The reaction
mixture was stirred at 80 ˚C for 2 h. After the solvent was evapo-
rated, the residue was purified by a flash column chromatography
on silica gel (hexane/EtOAc = 20/1) to give 2a (100 mg, 91%
yield).
2
8
The hydrogenation of 1a proceeded at 10 kg/cm of hydrogen
(88% GC yield, for 2 h).
9
1
C. S. Chin, Y. Park, and B. Lee, Catal. Lett., 31, 239 (1995).
An efficient heterogeneous hydrogenation of N-Boc-indoles was
reported, see: S. Coulton, T. L. Gilchrist, and K. Graham,
Tetrahedron, 53, 791 (1997).
0
2PPh catalyst promoted the hydrogenations of furan 6 and ben-
3
zofuran 8, giving 7 and 9, respectively (entries 10, 11). In the lat-
ter case, octahydrobenzofuran was obtained in 38% GC yield,
11 A. M. Trzeciak, J. J. Ziolkowski, S. Aygen, and R. van Eldik, J.
Mol. Cat., 34, 337 (1986).