Functional-Group-Directed Diastereoselective Hydrogenation of Aromatic Compounds

Article abstract of DOI:10.1021/jo991091p

Diastereoselective liquid phase hydrogenation of a series of monosubstituted indane and tetralin substrates was studied on supported rhodium catalysts. Predominantly the cis-cis diastereomer, obtained by hydrogenation from the diastereoface opposite the substituent (at the stereogenic center), and the cis-trans diastereomer, obtained by hydrogenation from the diastereoface on the same side as the substituent, were formed. The diastereoselectivity between the two isomers was dependent on the steric repulsion or the electronic attraction of the substituent with the surface of the catalyst. The hydroxyl group did not exhibit a strong attraction (haptophilicity), and the cis-cis diastereomer was obtained as the major product. The amino group exhibited a very high haptophilicity, yielding primarily the cis-trans diastereomer. The diastereoselectivity obtained in the hydrogenation of all the substrates was influenced on addition of bases to the reaction mixture. In the case of alcoholic substrates, the selectivity to the cis-trans diastereomer could be substantially increased with alkaline hydroxide additives.

Full text of DOI:10.1021/jo991091p

8862
J . Org. Chem. 1999, 64, 8862-8867
F u n ction a l-Gr ou p -Dir ected Dia ster eoselective Hyd r ogen a tion of
Ar om a tic Com p ou n d s. 1
Vidyadhar S. Ranade, Giambattista Consiglio, and Roel Prins*
Laboratory for Technical Chemistry, Swiss Federal Institute of Technology (ETH),
CH 8092 Zurich, Switzerland
Received J uly 7, 1999
Diastereoselective liquid phase hydrogenation of a series of monosubstituted indane and tetralin
substrates was studied on supported rhodium catalysts. Predominantly the cis-cis diastereomer,
obtained by hydrogenation from the diastereoface opposite the substituent (at the stereogenic center),
and the cis-trans diastereomer, obtained by hydrogenation from the diastereoface on the same
side as the substituent, were formed. The diastereoselectivity between the two isomers was
dependent on the steric repulsion or the electronic attraction of the substituent with the surface of
the catalyst. The hydroxyl group did not exhibit a strong attraction (haptophilicity), and the cis-
cis diastereomer was obtained as the major product. The amino group exhibited a very high
haptophilicity, yielding primarily the cis-trans diastereomer. The diastereoselectivity obtained in
the hydrogenation of all the substrates was influenced on addition of bases to the reaction mixture.
In the case of alcoholic substrates, the selectivity to the cis-trans diastereomer could be substantially
increased with alkaline hydroxide additives.
In tr od u ction
aromatic ring. Thus a series of indane and tetralin
substrates, substituted at a carbon atom in the saturated
ring, were hydrogenated. The present article (part 1)
elucidates the results of hydrogenation of such substrates
bearing the hydroxyl, amino, and alkyl functional groups
(Figure 1). Results pertaining to the hydrogenation of
substrates bearing the carboxylic acid, amide, ester, and
alkoxy groups will be presented in part 2. The molecules
shown in Figure 1 can adopt only two conformations on
the surface of the noble metal, depending on which face
of the aromatic ring they adsorb. Since the chosen
substrates can be considered approximately planar, the
induction obtained in their hydrogenation is directed by
the functional group substituent present on the saturated
ring. Also, since rotation of the bonds connecting the
carbon atom bearing the functional group to the aromatic
ring is impossible, an unambiguous and direct correlation
can be established between a functional group of a
substrate and the configuration of its hydrogenation
product.
It is well-known that substituents can direct the
stereoselectivity in a multitude of homogeneously cata-
lyzed reactions.5 Directing effects have also been observed
in alkene hydrogenation catalyzed particularly by homo-
geneous rhodium and iridium complexes.5,6 However,
since homogeneous catalysts often show a low activity
in aromatic hydrogenation, studies pertaining to directing
effects in these hydrogenation reactions have not been
conducted. Directing effects of substituents are also
known in heterogeneous hydrogenation albeit restricted
primarily to cyclic olefinic substrates.5,7,8 Heterogeneous
rhodium catalysts excel in their ability to hydrogenate
aromatic substrates under relatively mild reaction condi-
Stereoselective synthesis of substituted cyclohexane
compounds is of interest because the cyclohexane ring is
a constituent of many naturally occurring compounds
such as terpenoids, steroids, and alkaloids. These com-
pounds can be synthesized by catalytic hydrogenation of
the corresponding substituted aromatic compounds, ei-
ther enantioselectively or diastereoselectively. In dias-
tereoselective hydrogenation an auxiliary carrying chiral
information is bonded temporarily to one of the substit-
uents of the aromatic compound before its hydrogenation.
Earlier investigations revealed that the diastereoselec-
tivity obtained during hydrogenation depended strongly
on the structure of the aromatic compound-auxiliary
system and, to some extent, on the catalyst support.1-4
Because these investigations were limited to only two
auxiliaries, namely pyroglutamic acid and proline, the
induction by these auxiliaries eluded qualitative predic-
tion let alone quantification. The primary difficulty in
rationalization of the induction is the large number of
conformations that the aromatic compound-auxiliary
moiety can adopt on the catalyst surface depending on
the interaction of various functional groups of the moiety.
In all aromatic compound-auxiliary combinations inves-
tigated so far,1-4 the chiral center on the auxiliary was
at least three covalent bonds away from the nearest
substituted position on the aromatic ring, thus complicat-
ing the correlation of the configuration of the hydrogena-
tion product with the chirality of the auxiliary.
To clarify the interaction of the individual functional
groups, we have studied the hydrogenation of a series of
disubstituted aromatic compounds, differing only in the
functional group attached to a carbon atom near the
(5) Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. Rev. 1993, 93,
1307-1370.
(6) Brown, J . M. Angew. Chem., Int. Ed. Engl. 1987, 26, 190-203.
(7) Bartok, M.; Czombos, J .; Felfoldi, K.; Gera, L.; Gondos, G.;
Molnar, A.; Notheisz, F.; Palinko, I.; Wittmann, G.; Zsigmond, A. G.
Stereoselectivity of Heterogeneous Metal Catalysis; J ohn Wiley &
Sons: New York, 1985.
* Corresponding author. Fax: +41 (1) 6321162. Tel: +41 (1)
6325490. E-mail: prins@tech.chem.ethz.ch.
(1) Besson, M.; Gallezot, P.; Neto, S.; Pinel, C. Chem. Commun.
1998, 14, 1432-1433.
(2) Besson, M.; Pinel, C. Top. Catal. 1998, 5, 25-38.
(3) Ranade, V. S.; Consiglio, G.; Prins, R. Catal. Lett. 1999, 58, 71-
74.
(8) Augustine, R. L. Heterogeneous Catalysis for the Synthetic
Chemist; Marcel Dekker: New York, 1996.
(4) Ranade, V. S.; Prins, R. J . Catal. 1999, 185, 479-486.
10.1021/jo991091p CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/09/1999

Hydrogenation of Aromatic Compounds
J . Org. Chem., Vol. 64, No. 24, 1999 8863
Sch em e 1
F igu r e 1. Aromatic substrates hydrogenated.
tions.9,10 Therefore using these catalysts, we have shown
in the present study that useful directing effects occur
during hydrogenation of aromatic substrates.
In addition, we investigated the hydrogenation of these
relatively simple aromatic substrates to understand the
intriguing effect of the addition of organic bases on
stereoselectivity, reported in earlier diastereoselective
aromatic hydrogenation reactions.3,11 A complementary
study investigating the influence of the addition of
inorganic bases on the stereoselectivity was also con-
ducted. The present article focuses on stereoselectivity
rather than activity obtained in the hydrogenation of
various aromatic substrates under different process
conditions.
Ta ble 1. Hyd r ogen a tion of 1-In d a n ol
yield of cis
and trans
yield of cis
perhydro-1-
catalyst
solvent perhydroindaneb indanol isomersb
drb
Rh/Ca
EtOH
hexane
EtOH
EtOH
hexane
77
42
10
6
19
55
88
93
96
59:41
47:53
65:35
67:33
57:43
Rh/Ca
a
c
a
Rh/Al2O3
Rh/Al2O3
Rh/Al2O3
Resu lts
3
a
b
Substrate to rhodium molar ratio ) 154. Determined by
analyses over HP-1 and R-DEX capillary columns. c Substrate to
rhodium molar ratio ) 72.
Hydrogenation of all the substrates yielded predomi-
nantly cis diastereomers (usually cis to trans ratio > 10)
with respect to the substituents on the six-membered ring
(for example see Scheme 1 for hydrogenation of 1-in-
danol). Different methods were employed for identifica-
tion of the relative configuration of the cis diastereomers
(cis-cis and cis-trans), depending upon the substrate
hydrogenated, and they are described in the Experimen-
tal Section. The chemoselectivity to the hydrogenated cis
products is defined as the percentage yield of the two cis
isomers at 100% conversion of the substrate. The selec-
tivity between the two cis isomers is reported as the
diastereomeric ratio (dr) at 100% conversion of the
substrate and is defined as dr ) [cis-cis]/ [cis-trans].
For presentation of the diastereomeric ratio, the sum of
the yield of the two diastereomers is normalized to 100.
In the case of alcoholic substrates significant to substan-
tial amounts of hydrogenolysis-hydrogenation byprod-
ucts (cis and trans) were obtained. The percentage yield
of the hydrogenolysis-hydrogenation products is also
reported for these substrates at 100% conversion of the
substrates.
in the diastereoselectivity, the magnitude of which
depended on the substrate hydrogenated. The position
of the double bond in the cyclohexene intermediates was
not identified rigorously. However from steric consider-
ations it is likely that the double bond is situated between
the two junction carbon atoms.
Hydrogenation of 1-indanol gave cis and trans isomers
of the hydrogenation product perhydro-1-indanol and of
the hydrogenolysis-hydrogenation product perhydroin-
dane (Scheme 1). We confirmed that perhydroindane was
formed directly from 1-indanol and not by hydrogenolysis
of perhydro-1-indanol. The results of the hydrogenation
in ethanol and hexane using the Rh/C and Rh/Al2O3
catalysts are presented in Table 1. With ethanol as the
solvent, the Rh/C catalyst yielded predominantly perhy-
droindane, while the Rh/Al2O3 catalyst yielded predomi-
nantly perhydro-1-indanol. With hexane as the solvent,
the yield of perhydroindane was lowered with both
catalysts. Low dr values were obtained for both catalysts,
and the value was lower in hexane than in ethanol.
Halving the substrate to metal ratio in the case of Rh/
Al2O3 had a negligible influence on the dr and the
chemoselectivity.
The results obtained in the hydrogenation of 1-tetralol
are reported in Table 2. The yield of the two cis perhydro-
1-tetralol (1-decalol) isomers as well as the dr of the two
cis isomers depended on the catalyst support. As for
1-indanol, severe hydrogenolysis was observed on Rh/C
in ethanol. The dr as well as the yield of 1-decalol was
higher on Rh/Al2O3 than Rh/C. With the Rh/Al2O3 and
Small to significant amounts (up to 10%) of cyclohexene
intermediates were observed (and identified by GC-MS
analysis) depending on the substrate hydrogenated and
the reaction conditions. In most of the substrates the
hydrogenation of cyclohexene intermediate proceeded
much slower than the substrate, and it caused a change
(9) Rylander, P. N. Catalytic Hydrogenation over Platinum Metals;
Academic Press: New York, 1967.
(10) Freifelder, M. Practical Catalytic Hydrogenation: Techniques
& Application; J ohn Wiley and Sons: New York, 1971.
(11) Besson, M.; Blanc, B.; Champelet, M.; Gallezot, P.; Nasar, K.;
Pinel, C. J . Catal. 1997, 170, 254-264.

8864 J . Org. Chem., Vol. 64, No. 24, 1999
Ranade et al.
Ta ble 5. Hyd r ogen a tion of 1-Meth ylin d a n e
Ta ble 2. Hyd r ogen a tion of 1-Tetr a lol
yield of cis and yield of cis 1-decalol
yield of cis perhydro-1-
catalysta solvent trans decalinb
isomersb
drb
catalyst
solvent
methylindane isomersb
drb
a
Rh/C
Rh/C
Rh/Al2O3 EtOH
Rh/Al2O3 hexane
EtOH
hexane
76
53
12
3
16
43
81
91
53:47
45:55
69:31
55:45
Rh/Al2O3
Rh/Ca
EtOH
EtOH
EtOH
EtOH
92
93
92
92
64:36
63:37
62:38
64:36
Rh/Cc
Rh/Ca,d
a
b
a
b
Substrate to rhodium molar ratio ) 139. Determined by
analyses over HP-1 and R-DEX capillary columns.
Substrate to rhodium molar ratio ) 156. Determined by
analyses over HP-1 and R-DEX capillary columns. c Substrate to
metal molar ratio ) 312. H2 pressure ) 15 bar.
d
Ta ble 3. Hyd r ogen a tion of 1-In d a n ylm eth a n ol
Ta ble 6. Hyd r ogen a tion of 1-Am in oin d a n e
yield of cis
yield of cis and
perhydro-1-
yield of cis perhydro-1-
trans perhydro-1- indanylmethanol
catalyst
solvent
aminoindane isomersb
drb
2:98
1.5:98.5
32:68
catalysta solvent
methylindaneb
isomersb
drb
Rh/Ca
Rh/Al2O3
Rh/Al2O3
EtOH
EtOH
EtOH
100
100
90
a
c
Rh/C
Rh/C
EtOH
hexane
30
16
5
70
82
92
97
45:55
47:53
52:48
47:53
Rh/Al2O3 EtOH
Rh/Al2O3 hexane
a
Reaction conducted at 70 °C with substrate to rhodium molar
1
b
ratio ) 77. Determined by analyses over RTX-200 capillary
a
b
Substrate to rhodium molar ratio ) 139. Determined by
analyses over HP-1 and R-DEX capillary columns.
column after derivatization of product with MBTFA. c Hydroge-
nation of 1-aminoindane, hydrochloride salt at room temperature
with substrate to rhodium molar ratio ) 122.
Ta ble 4. Hyd r ogen a tion of 2-Tetr a lol
Ta ble 7. Hyd r ogen a tion in Eth a n ol w ith Tr ieth yla m in e
Ad d itive
yield of cis and yield of cis 2-decalol
catalysta solvent trans decalinb
isomersb
drb
substrate to
rhodium
molar ratio
Rh/C
EtOH
25
8
68
85
89
83c
95
63:37
76:24
64:36
65:35c
49:51
yield of cis
isomers
Rh/Al2O3 EtOH
Rh/Al2O3 hexane
Pt/Al2O3 EtOH
Pt/Al2O3 hexane
substrate
1-indanol
1-methylindane Rh/C
1-methylindane Rh/Al2O3
catalysta
Rh/C
dr
3
5c
154
156
156
97
86
90
50:50
56:44
59:41
1
a
Reaction conducted at 70 °C with Pt/Al2O3. Substrate to metal
molar ratio ) 139. b Determined by analyses over HP-1 and â-DEX
capillary columns. c At 85% conversion of 2-tetralol.
a
Triethylamine to rhodium molar ratio ) 10.
70 °C and with approximately half the normal substrate
to rhodium molar ratio (∼77). Irrespective of the catalyst
support, a very low dr (i.e., high selectivity to the cis-
trans diastereomer of perhydro-1-aminoindane) was ob-
tained (Table 6). A small amount of 1-aminoindane was
converted to 1-aminoindane hydrochloride in a diethyl
ether solution by bubbling dry hydrogen chloride gas.
After isolation of the salt, 0.5 g of it was hydrogenated
at the standard temperature and pressure on the Rh/
Al2O3 catalyst in ethanol. The yield of the cis-trans
isomer decreased, and the dr increased to 32:68. The
relative configuration of the other diastereomer formed
was not identified rigorously but in analogy with the
results of hydrogenation of all other substrates was
assumed to be cis-cis.
Addition of amines has been used before to influence
the diastereoselectivity in aromatic hydrogenation reac-
tions.3,11 We studied the effect of the addition of triethyl-
amine to reaction mixtures of the different substrates
before their hydrogenation in ethanol. The results of the
experiments are reported in Table 7. Addition of amine
resulted in a substantial decrease in the activity of the
rhodium catalysts for all the substrates. Very little
activity was detected for hydrogenation of 1-tetralol and
1-indanylmethanol. The hydrogenolysis activity of Rh/C
catalyst in the hydrogenation of 1-indanol was almost
completely suppressed, thus increasing the yield of the
cis perhydro-1-indanol isomers. The value of dr decreased
on addition of amine for both 1-indanol and 1-methylin-
dane.
Rh/C catalysts, changing the solvent from ethanol to
hexane increased the yield to 1-decalol but decreased the
dr.
Results of hydrogenation of 1-indanylmethanol on
carbon- and alumina-supported rhodium catalysts in
ethanol and hexane are shown in Table 3. Significant
hydrogenolysis was observed on Rh/C catalyst. The value
of dr was almost unity and changed only slightly with
either the catalyst support or the solvent.
The results obtained in the hydrogenation of 2-tetralol
are shown in Table 4. As in the case of hydrogenation of
1-indanylmethanol significant hydrogenolysis was ob-
served during the hydrogenation of 2-tetralol on Rh/C
catalyst. Reactions with the Pt/Al2O3 catalyst were
conducted at 70 °C because of lower activity. As observed
for 1-indanol and 1-tetralol, using hexane as the solvent
instead of ethanol lowered the dr for Rh/Al2O3 as well as
Pt/Al2O3 catalysts.
1-Methylindane was prepared in ethanol by hydro-
genolysis of 3-methyl-1-oxoindane and was contaminated
with the water formed during its preparation. The
separation of 1-methylindane from ethanol and water
was difficult because of its low boiling point and azeotrope
formation with ethanol. Hence, its solution in the ethanol/
water mixture was directly used in the hydrogenation
experiments. Table 5 reports the results obtained at
different process conditions and on the Rh/C catalyst and
at one condition on the Rh/Al2O3 catalyst. The difference
in the performance of Rh/C and Rh/Al2O3 is negligible.
The yield of the cis isomers and the dr were almost
unaffected by a change in hydrogen pressure and the
substrate to rhodium molar ratio.
Addition of an aqueous solution (0.3 mL of 0.5 N) of
inorganic bases to the reaction mixture with ethanol and
Rh/C resulted in a decrease in the activity of the catalyst
by an order of magnitude. The activity decreased with
The hydrogenation of 1-aminoindane proceeded very
slowly at room temperature and hence was conducted at

Hydrogenation of Aromatic Compounds
J . Org. Chem., Vol. 64, No. 24, 1999 8865
Ta ble 8. Hyd r ogen a tion on Rh /C in Eth a n ol w ith
In or ga n ic Ba se Ad d itives
from that obtained in the direct hydrogenation of the
parent aromatic substrate. A rigorous examination of the
diastereoselectivity-functional group relationship in the
aromatic substrates should include a separate investiga-
tion of a similar relationship in the corresponding cyclo-
hexene intermediates. Since the latter investigation was
not done, we are unable to separate the directing effect
of the functional group in the aromatic compound from
that in the corresponding cyclohexene intermediates.
However, the influence on the final diastereoselectivity
is relatively small since only a small percentage of the
aromatic compound desorbs as the cyclohexene interme-
diate after its partial hydrogenation. For example, in the
hydrogenation of 1-tetralol in hexane over the Rh/Al2O3
catalyst, the dr changed from 56:44 at 12% conversion
to 55:45 at 100% conversion.
Results shown in Table 1 indicate that the haptophi-
licity of the hydroxyl group to the rhodium catalyst, if at
all present, is definitely not high, since the cis-cis instead
of the cis-trans isomer is obtained in excess with Rh/C
and Rh/Al2O3 catalysts. The Rh/C catalyst showed con-
siderably more hydrogenolysis selectivity than the Rh/
Al2O3 catalyst. Labeling experiments indicated that
hydrogenolysis on Rh/C occurs by elimination of the
protonated hydroxyl group followed by hydrogenation by
spillover hydrogen on the mildly acidic carbon support.16
Hydrogenation was also investigated in hexane because
the ethanol hydroxyl groups could compete with and/or
solvate the 1-indanol hydroxyl groups, thus masking its
haptophilicity. The selectivity to perhydroindane is lower
in hexane than in ethanol, because of lower stability of
the intermediate in the hydrogenolysis reaction. In
hexane the selectivity to the cis-cis isomer is reduced,
indicating that the hydroxyl group in 1-indanol probably
interacts mildly with the catalyst surface. Results of
hydrogenation of 1-tetralol are qualitatively similar to
those obtained with 1-indanol (Table 2). The influence
of the nature of the catalyst support on the diastereose-
lectivity could be due to the difference in the magnitude
of interaction of the hydroxyl group of the substrate with
the catalyst support and/or a contribution of hydrogena-
tion with spillover hydrogen in some supports. Since the
adsorption of an aromatic ring is much stronger than that
of a double bond, on rhodium,17 the difference in energy
between the two adsorbed structures leading to the two
different cis diastereomers is probably smaller than that
for the highly hindered olefinic substrates investigated
by Thompson and co-workers. This can explain why the
interaction of the hydroxyl group with the rhodium
catalyst is much weaker than that in their investigation.
We were unable to study hydrogenation of the benzylic
aromatic substrates with platinum or palladium cata-
lysts, because of even more hydrogenolysis than with
rhodium.
substrate
yield
to rhodium
time conver- of cis
substrate
1-indanol
1-indanol
1-indanol
1-indanol
1-tetralol
1-methylindane
molar ratio basea (days) sion isomersb drb
154
154
154
154
139
156
LiOH
1
1
1
4
3
100
91
92
81
100
96
95
96
89
84
88
41:59
19:81
31:69
15:85
28:72
53:47
NaOH
Na2CO3
KOH
NaOH
NaOH
a
b
Alkali metal to rhodium molar ratio ) 6. At 81% conversion
of 1-indanol in experiment with KOH additive and at 100%
conversion of substrates in all other experiments.
increasing concentration of the base and with increasing
size of the cation. The results are shown in Table 8. A
drastic suppression of hydrogenolysis activity was ob-
served on addition of inorganic bases, as observed with
triethylamine. In the case of 1-indanol and 1-tetralol, the
cis-trans diastereomer was the major product. The dr
depended on the base added and increased with the size
of cation in the case of alkaline hydroxide additives. On
increasing the amount of NaOH solution from 0.3 mL to
1 mL in the hydrogenation of 1-indanol, the dr decreased
further from 19:81 to 12:88 and was accompanied by a
further decrease in the activity.
Discu ssion
The aromatic substrates undergoing hydrogenation can
adsorb in two ways on the catalyst surface depending on
the interaction of the functional group present on the
neighboring saturated ring. The interaction of a func-
tional group with the catalyst surface depends on steric
and electronic factors. When the electronic interaction
dominates, hydrogenation of the aromatic ring takes
place from the side of the substituent leading to the cis-
trans diastereomer. Contrarily, when the steric repulsion
dominates, hydrogenation occurs from the side opposite
the substituent, leading to the cis-cis diastereomer.
Similar studies correlating various functional groups with
their ability to influence the adsorption of olefinic sub-
strates in hydrogenation reactions on noble metal cata-
lysts have been conducted by Thompson et al.12-14 and
more recently by MaGee et al.15 In their studies, Thomp-
son and co-workers found that some functional groups
had a strong affinity (also termed as haptophilicity) for
the catalyst, resulting in hydrogenation products with a
configuration opposite of that expected when considering
only steric repulsion of the functional group. While their
study was conducted on the hydrogenation of olefinic
substrates over platinum- and palladium-based catalysts,
our study was conducted on the hydrogenation of aro-
matic substrates over rhodium-based catalysts.
In the hydrogenation of the aromatic substrates, cy-
clohexene intermediates were often observed. The formed
cyclohexene intermediates hydrogenated further only
after the complete conversion of substrate or when the
substrate concentration was very low. The diastereose-
lectivity obtained in their hydrogenation was different
In 1-indanol and 1-tetralol the hydroxyl group is
attached to a carbon at the R position with respect to the
aromatic ring. The effect on the selectivities on shifting
the location of the hydroxyl group to the â carbon was
studied by hydrogenating 1-indanylmethanol and 2-te-
tralol (Tables 3 and 4). The values of dr as well as the
variation of the dr with catalyst support and solvent are
considerably different in 1-indanylmethanol and 2-te-
(12) Thompson, H. W.; Naipawer, R. E. J . Am. Chem. Soc. 1973,
95, 6379-6386.
(13) Thompson, H. W.; McPherson, E.; Lences, B. L. J . Org. Chem.
1976, 41, 2903-2906.
(14) Thompson, H. W.; Wong, J . K. J . Org. Chem. 1985, 50, 4270-
4276.
(16) Ranade, V. S.; Prins, R. Chem. Eur. J ., in press.
(15) MaGee, D. I.; Lee, M. L.; Decken, A. J . Org. Chem. 1999, 64,
2549-2554.
(17) Van Bekkum, H.; Buurmans, H. M. A.; Van Minnen-Pathuis,
G.; Wepster, B. M. Recl. Trav. Chim. Pays-Bas 1969, 88, 779-794.

8866 J . Org. Chem., Vol. 64, No. 24, 1999
Ranade et al.
tralol. In the case of 1-indanylmethanol the haptophilic
effect is stronger than in 1-indanol or 1-tetralol since the
value of dr is almost unity and it does not vary with
catalyst support or the solvent. In contrast, the results
of hydrogenation of 2-tetralol indicate the presence of a
mild haptophilic effect, the magnitude of which changes
with the solvent, as in the cases of 1-indanol and
1-tetralol. The difference in the diastereoselectivities of
hydrogenation of 2-tetralol and 1-indanylmethanol is
probably due to the orientation of the hydroxyl group
when these molecules adsorb on the catalyst surface.
Hydrogenation of 2-tetralol was conducted on Pt/Al2O3
catalyst to compare the haptophilicity of the hydroxyl
group to platinum with that to rhodium. Although a
quantitative comparison between platinum and rhodium
catalysts is not possible because the hydrogenation
reactions were conducted at different temperatures, a
similar trend is observed on changing the solvent from
ethanol to hexane with platinum as with rhodium.
1-Methylindane can interact only sterically with the
surface of the catalyst, and hence both the Rh/C and the
Rh/Al2O3 catalysts give the same results (Table 5). Since
each substrate molecule bears the chiral element neces-
sary for stereoselective hydrogenation, we do not expect
a big effect on diastereoselectivity of the substrate to
rhodium ratio and hydrogen pressure, as observed in
hydrogenation of 1-methylindane. This is confirmed also
in the case of 1-indanol where a change in the substrate
to catalyst ratio by a factor of 2 resulted in hardly any
change in the dr. The purely steric interaction of the
methyl group is unable to prevent the adsorption of the
aromatic substrate from the methyl-group side, and only
a small preference to the cis-cis isomer is observed. The
reason for the low selectivity must be the small size of
the methyl group. The magnitude of the steric hindrance
of the hydroxyl group in 1-indanol is comparable to that
of the methyl group in 1-methylindane in ethanol.
It is a well-known that amines adsorb strongly on noble
metal catalysts.9,10 In some of the diastereoselective
hydrogenation reactions reported earlier, amine additives
were used. These additives decreased the rate of reaction
by strongly adsorbing on the metal and modified the
selectivity. Thus, as expected, strong adsorption of 1-ami-
noindane during reaction resulted in a very low hydro-
genation activity at room temperature, and hence the
reactions had to be conducted at 70 °C. The amino group
showed a strong haptophilic effect, giving an almost
quantitative yield of the cis-trans isomer. The effect is
seen irrespective of whether Rh/C or Rh/Al2O3 is used as
the catalyst because the substrate interacts primarily
with the rhodium metal during hydrogenation. On neu-
tralizing the basicity of the amino group by converting
1-aminoindane to its hydrochloric acid salt before hydro-
genation, the selectivity to the cis-trans isomer was
drastically reduced, clearly demonstrating the haptophi-
licity of the amino group.
aromatic compounds on rhodium catalysts has been
reported before.18 The results in Table 8 show that the
addition of inorganic bases induces a substantial change
in diastereoselectivity of the benzylic aromatic substrates
investigated. The addition of alkali hydroxides in the
hydrogenation of benzylic alcohols not only reduced the
value of the dr below unity but even produced the cis-
trans diastereomer with a moderately high selectivity.
This could be due to the interaction of the hydroxyl group
of the substrate with the alkali metal cations on the
surface of the catalyst. The activity decreases with an
increase in the size of cation, probably because a bigger
cation blocks more surface rhodium atoms than a smaller
cation. The higher dr obtained for Na2CO3 than NaOH
is probably due to a lower extent of dissociation in the
ethanol/water mixture. Addition of NaOH in the hydro-
genation of 1-methylindane also reduced the dr. Reduc-
tion of the dr in the hydrogenation of 1-methylindane by
organic as well as inorganic bases indicates that the
decrease is primarily a result of steric constraints im-
posed on its adsorption on the surface of the catalyst by
the adsorbed bases. It is not clear if the addition of the
inorganic bases also causes an electronic modification of
the rhodium atoms at the surface.
Con clu sion s
The aromatic substrates investigated give very differ-
ent stereoselectivities depending on the functional group
substituent. The hydroxyl group in most of the alcoholic
substrates has a mild haptophilic effect, which becomes
evident on conducting the reaction in hexane. The dr
obtained in the hydrogenation of these substrates de-
pends on the exact location and orientation of the
hydroxyl group and is influenced by the nature of the
catalyst support. Aromatic substrates with a hydroxyl
group at the â position are also significantly hydrogeno-
lyzed on Rh/C catalyst in ethanol. The methyl group in
1-methylindane, because of its relatively small steric
repulsion, leads to only a small preference for the cis-
cis isomer. Since it interacts exclusively sterically with
the catalyst surface, the diastereoselectivity is indepen-
dent of the catalyst support. The amino group in 1-ami-
noindane interacts very strongly (high haptophilicity)
with the catalyst, and the cis-trans isomer is obtained
almost exclusively. The haptophilicity of the amino group
is diminished considerably on converting it to its salt.
The addition of organic and inorganic bases results in a
reduction of the diastereoselectivity to the cis-cis dias-
tereomer in the case of 1-methylindane, primarily by
constraining its adsorption on the surface of the catalyst.
In the case of benzylic alcohols, the magnitude of the dr
decreases to a value significantly below unity, on addition
of inorganic bases because of the interaction of the
hydroxyl group with the alkali metal cations. From a
synthetic point of view, the high haptophilicity of the
amino group and the ability of the inorganic base
additives to influence the selectivity in the hydrogenation
of benzylic alcohols should be of interest.
Addition of triethylamine reduces the activity of the
catalyst due to strong adsorption. The dr decreases on
addition of amine in the hydrogenation of 1-indanol over
Rh/C and somewhat surprisingly also in the hydrogena-
tion of 1-methylindane. The decrease in diastereoselec-
tivity of 1-methylindane indicates that the amine modi-
fies the stereoselectivity not only by an electronic
mechanism but also by a steric mechanism.
Exp er im en ta l Section
Hyd r ogen a tion Exp er im en ts. Hydrogenation reactions
were conducted under efficient mass-transport conditions in
a 60 mL stainless steel autoclave equipped with a gas-inducing
The influence of inorganic base additives on stereose-
lectivity in the hydrogenation of substituted phenolic
(18) Auer, E.; Freund, A.; Panster, P.; Stein, G.; Tacke, T. Stud. Surf.
Sci. Catal. 1997, 108, 223-229.

Hydrogenation of Aromatic Compounds
J . Org. Chem., Vol. 64, No. 24, 1999 8867
impeller at a stirring speed of 1100 rpm. In a typical experi-
ment, a solution of 0.5 g of substrate in 15 mL of ethanol or
hexane (and basic additive, if any) was added to 50 mg of
catalyst in the autoclave. Pt/Al2O3, Rh/Al2O3 (Fluka), and Rh/C
(Aldrich) catalysts (metal loading 5 wt %) were used as
supplied. The autoclave was closed, flushed three times
successively with nitrogen and hydrogen, and then pressurized
to 50 bar with hydrogen. Hydrogenation of 1-aminoindane on
the rhodium catalysts and that of 2-tetralol on the platinum
catalyst were conducted at 70 °C. All other reactions were
conducted at room temperature. Samples could be taken with
a sample tube during the reaction to detect the completion of
the reaction (typically less than 12 h, in experiments without
base addition), but no kinetic measurements were done.
Analysis of samples for determination of conversion and
selectivity was done using a GC equipped with a FID detector
and various capillary columns depending on the substrate
hydrogenated. Although the diastereomeric products in most
cases could be separated on a nonchiral HP-1 column, chiral
columns were also used for GC analyses. In the case of
1-aminoindane, the reaction samples were dried free of etha-
nol, derivatized with N-methyl-bis(trifluoroacetamide) (MB-
TFA) overnight at room temperature and then injected in a
RTX-200 capillary column after redissolving the sample in
dichloromethane.
P r ep a r a tion of 1-In d a n ylm eth a n ol a n d 1-Meth ylin -
d a n e. Racemic 1-indanol, 1-tetralol, 1-aminoindane (all Flu-
ka), and 2-tetralol (Acros) were used as obtained. Racemic
1-indanylmethanol was prepared in two steps from racemic
3-oxoindan-1-carboxylic acid (Aldrich). In the first step the keto
group was hydrogenolyzed over 10 wt % Pd/C catalyst (Fluka).
In the second step the carboxylic acid group was hydrogenated
to the hydroxymethylene group using LiAlH4. The product of
synthesis was identified as 1-indanylmethanol by comparison
of its NMR data with that reported in the literature.19
Hydrogenolysis of racemic 3-methyl-1-oxoindanone (Aldrich)
over Pd/C catalyst in ethanol under 3 bar hydrogen yielded
racemic 1-methylindane quantitatively. It was identified by
comparison of MS data with that reported in the literature.20
The catalyst was filtered off, and the solution of racemic
1-methylindane in ethanol was used in its hydrogenation. The
purity of all substrates exceeded 97% as determined by GC
analysis.
Sch em e 2
Identification of the absolute configuration of the perhydro-
1-methylindane product posed considerable difficulty because
no separate spectral data of the isomers were available in the
literature. Therefore a reference mixture of cis-cis and cis-
trans diastereomers was synthesized starting from perhy-
droindan-1-carboxylic acid (cis-cis to cis-trans ratio of 3:1)
using the route reported by Brewster and Buta.27 The mixture
of perhydroindan-1-carboxylic acid was obtained by hydroge-
nation of indan-1-carboxylic acid on Rh/C catalyst.28 Compari-
son of the gas chromatograms of the reaction product obtained
using a R-DEX capillary column and that of the synthesized
reference sample enabled identification of the relative config-
uration. As shown in Scheme 2, the synthesis of the reference
sample involved reduction of the mixture of cis-cis and cis-
trans diastereomers of perhydroindan-1-carboxylic acid to the
corresponding perhydro-1-indanylmethanol isomers using Li-
AlH4. The isomeric mixture of alcohols was converted into their
tosyl derivatives. These tosyl derivatives were then reduced
using LiAlH4 to give a mixture of cis-cis and cis-trans
perhydro-1-methylindane in approximately the same ratio as
the diastereomeric mixture of the starting acid. The interme-
diate mixture of perhydro-1-indanylmethanol isomers was
used as a reference for identification of the product isomers
obtained in the hydrogenation of 1-indanylmethanol.
The relative configuration of the product perhydro-1-ami-
noindane was identified by converting it to the N-benzoyl
derivative, by treatment of the isolated product with benzoyl
chloride in a dilute NaOH solution. A two-dimensional 1H NOE
NMR spectrum of the resulting amide enabled us to determine
that the proton at the carbon atom bearing the amide group
was trans to the protons attached to both junction carbon
atoms. Further proof of the structure was obtained by X-ray
crystallography (see Supporting Information) on a monoclinic
crystal of the N-benzoyl derivative, obtained by crystallization
from a diisopropyl ether/hexane solvent mixture.
Id en tifica tion of cis-cis a n d cis-tr a n s P r od u ct Iso-
m er s. Isomers of perhydro-1-indanol were identified by com-
parison of a 13C NMR spectrum of the product mixture with
their spectra reported in the literature.21 Isomers of perhydro-
1
1-tetralol were identified by comparison of a H NMR spectrum
of the product mixture to their spectra reported in the
literature.22 The cis-cis perhydro-2-tetralol (2-decalol) isomer
was identified by comparison of a 13C NMR spectrum of the
product mixture to the spectrum reported in the literature.
The identification of the other isomeric product was difficult,
however, because of conflicting 13C NMR data in the literature
for the cis-trans isomer.23,24 The product mixture was there-
fore oxidized to 2-decalone using chromic acid as reported by
Brown and Garg.25 13C NMR of the 2-decalone product showed
only one CdO group, indicating that the hydrogenation
product consisted of cis-cis and cis-trans isomers. The cis
configuration of 2-decalone was also confirmed by comparison
of its 13C NMR spectrum to that reported in the literature.26
Ack n ow led gm en t. We are grateful to F. Bangerter
for the NMR measurements, A. Dutly for the MS
measurements, and Prof. V. Gramlich for the determi-
nation of the crystal structure of the N-benzoyl deriva-
tive of cis-trans perhydro-1-aminoindane.
(19) Lorentzen, R. J .; Brewster, J . H.; Smith, H. E. J . Am. Chem.
Soc. 1992, 114, 2181-2187.
Su p p or tin g In for m a tion Ava ila ble: NMR and MS data
of cis-cis and cis-trans isomers of perhydro-1-indanylmetha-
nol, perhydro-1-methylindane, and perhydro-1-aminoindane
and NMR, MS, and crystal structure data of the N-benzoyl
derivative of cis-trans perhydro-1-aminoindane. This material
is available free of charge via the Internet at http://pubs.acs.org.
(20) Meijs, G. F.; Bunnett, J . F.; Beckwith, A. L. J . J . Am. Chem.
Soc. 1986, 108, 4899-4904.
(21) Schneider, H.-J .; Nghe, N.-B. Org. Magn. Reson. 1982, 18, 38-
41.
(22) Grob, C. A.; Tam, S. W. Helv. Chim. Acta 1965, 48, 1317-1321.
(23) Dodds, D. R.; J ones, J . B. J . Am. Chem. Soc. 1988, 110, 577-
583.
J O991091P
(24) Oritani, T.; Ichimura, M.; Hanyu, Y.; Yamashita, K. Agric. Biol.
Chem. 1983, 47, 2613-2617.
(25) Brown, H. C.; Garg, C. P. J . Am. Chem. Soc. 1961, 83, 2952-
2953.
(26) Rao, H. S. P.; Reddy, S. Magn. Reson. Chem. 1995, 33, 987-
988.
(27) Brewster, J . H.; Buta, J . G. J . Am. Chem. Soc. 1966, 88, 2233-
2240.
(28) Ranade, V. S.; Consiglio, G.; Prins, R. To be published.