Chiral hybrid silica: Sol-gel heterogenisation of trans-(1R,2R)- diaminocyclohexane ligands for the rhodium catalysed enantioselective reduction of acetophenone

Article abstract of DOI:10.1016/j.tetasy.2003.11.005

The synthesis of derivatives of trans-(1R,2R)-diaminocyclohexane with different substituents on the nitrogen atoms has been achieved. Rhodium complexes of these chiral ligands were evaluated as homogeneous catalysts for the asymmetric hydride transfer red

Full text of DOI:10.1016/j.tetasy.2003.11.005

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 495–502
Chiral hybrid silica: sol–gel heterogenisation of trans-(1R,2R)-
diaminocyclohexane ligands for the rhodium catalysed
enantioselective reduction of acetophenone
*
€
Anne Brethon, Joel J. E. Moreau and Michel Wong Chi Man
Laboratoire Hꢀetꢀerochimie Molꢀeculaire et Macromolꢀeculaire (UMR-CNRS 5076), Ecole Nationale Supꢀerieure de Chimie de
Montpellier, 8, rue de l’ꢀecole normale, 34296 Montpellier Cedex 05, France
Received 28 October 2003;accepted 10 November 2003
Abstract—The synthesis of derivatives of trans-(1R,2R)-diaminocyclohexane with different substituents on the nitrogen atoms has
been achieved. Rhodium complexes of these chiral ligands were evaluated as homogeneous catalysts for the asymmetric hydride
transfer reduction (HTR) of acetophenone leading to moderate selectivities (ee ¼ 0–57%). The silylation of a bromo-aryl derivative
was successfully performed by a HeckÕs coupling reaction with vinyltriethoxysilane in the presence of a palladium catalyst. The
immobilisation of this catalyst was then achieved by the sol–gel hydrolysis condensation. The resulting hybrid catalytic materials
showed moderate selectivity, although much higher than the related homogeneous catalytic species.
Ó 2003 Elsevier Ltd. All rights reserved.
1. Introduction
tivities higher than those observed with the
corresponding homogeneous catalysts. Lemaire et al.
have developed a series of diamine–metal complexes
(rhodium, iridium and cobalt) for the reduction of
prochiral ketones.18;19 These catalysts were hetero-
genized by means of in situ generated polymeric species
and revealed even more interesting features with not
only inherent selectivities but also for their potential
re-use.20 Herein, we investigated several rhodium com-
plexes of trans-(1R,2R)-diaminocyclohexane derivatives.
We investigated the sol–gel hydrolysis of one silylated
compound to give new chiral hybrid silica, containing
covalently bonded trans-(1R,2R)-diaminocyclohexane
bridging units. The complexation of the rhodium species
afforded hybrid materials, which were used as hetero-
geneous asymmetric catalysts.
An increase in demand for the preparation of recover-
able catalysts has drawn synthetic chemistsÕ attention to
the need to produce heterogeneous catalysts in different
ways.1 The main advantages of heterogeneous catalysts
consist in easy separation, simple handling and possible
recycling.2;3 Our current interest in creating new hybrid
silicas via the sol–gel process4 has led us to study the
immobilization of catalytic species. Bridged silses-
quioxanes prepared by the hydrolysis of organo-bistri-
alkoxysilanes, (RO)3Si–R0–Si(OR)3,5;6 represent a new
class of material with a high potential for applications.7;8
The design of appropriate molecular precursors and
their hydrolysis can lead to hybrid materials with spe-
cific properties.9–11 Silica-based materials with catalytic
properties have also been prepared by the hydrolysis of
organo-trialkoxysilanes.12–15 Supported chiral catalysts
are of particular interest for enantioselective synthesis.16
We recently reported the incorporation of chiral organic
moieties in hybrid silicas and showed that they can be
used as chiral heterogeneous catalysts for hydride
transfer reduction (HTR) of prochiral ketones.17 Inter-
estingly the solid heterogeneous catalysts showed selec-
2. Results and discussion
2.1. Synthesis of substituted diaminocyclohexane ligands
for catalytic hydrogen transfer reduction
The synthesis of the trans-(1R,2R)-diaminocyclohexane
derivatives was achieved in two steps (Scheme 1). The
reaction of trans-(1R,2R)-diaminocyclohexane (DACH)
with two molar equivalents of the carbonyl com-
pounds gave the corresponding diimines which were
* Corresponding author. Tel.: +33-04-6714-7211;fax: +33-04-6714-
7212;e-mail: jmoreau@cit.enscm.fr
0957-4166/$ - see front matter Ó 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2003.11.005

496
A. Brethon et al. / Tetrahedron: Asymmetry 15 (2004) 495–502
N
NHR'
NHR'
CHR
CHR
NH2
NH2
NaBH4, MeOH
RCHO, toluene
N
1a-6a
1-6
CH
CH
CH
CH
CH
2
2
2
2
2
R' =
N
H C
2
F
5
Br
1
2
3
4
5
6
Scheme 1.
subsequently treated with NaBH4 to produce the cor-
responding benzylic diamines, ligands 1–6.21–24 The
overall yields varied from 50% to 95%.
The aromatic diamine, ligand 7, was prepared by
nucleophilic substitution of p-nitrofluorobenzene
(Scheme 2).25
We then studied the use of these diamine ligands in the
rhodium catalysed asymmetric reduction by hydrogen
transfer. Although an excess of ligand was shown to
increase selectivity in the case of phenanthroline
ligands,26;27 the X-ray crystal structure of a bidentate
diamine ruthenium complex showed that only one
ligand was necessary for this reaction.28 Moreover,
mechanistic investigations suggested that the active
catalytic species was a 1 to 1 diamine/rhodium com-
plex.18d;e Based on these observations, we studied the
reduction reaction with a 1:1 diamine/rhodium ratio.
The diaminocyclohexane ligands 1–7 were treated with
[Rh(cod)Cl]2 in ethanol (ligand/Rh ¼ 1:1). The forma-
tion of the rhodium–ligand complexes was monitored by
UV–vis absorption measurements. The UV–vis spec-
trum of [Rh(cod)Cl]2 exhibited an absorption maximum
at 350 nm. A clear shift of this band was observed at
380 nm for the diamine–Rh complexes obtained from
compounds 1, 2 and 4. Evidence for the formation of
complexes 3, 6 and 7 was not obtained in solution owing
to the high absorption of these ligands around 380 nm
which masked that of the corresponding Rh complexes.
Finally, with the same 1:1 ligand/rhodium ratio, the
complexation of ligand 5 in solution was not complete
since the absorption band at 350 nm of the starting
rhodium dimer persisted in the spectra. This absorption
band at 350 nm disappeared upon addition of an excess
of ligand. The UV–vis spectra of rhodium complexes of
2 and 5 are given as examples in Figure 1.
Figure 1. UV–vis spectra of [Rh(cod)Cl]2 (black); 2 complexed with
[Rh(cod)Cl]2 (red); 5 complexed with [Rh(cod)Cl]2 (blue).
O
OH
*
"Rh" 3 mol %, Ligand 3 mol %,
°
[KOH]/["Rh"] = 6, iPrOH, 25 C
Scheme 3.
in order to evaluate their efficiency and to determine the
effect of the presence of substituents at the nitrogen
atoms on the enantioselectivities of the reduction reac-
tion.
The results are summarised in Table 1.
The simple trans-(1R,2R)-diaminocyclohexane rhodium
complex (DACH–Rh) was shown to give a low effi-
ciency (conversion ¼ 5% after 6 days) and selectivity
(ee ¼ 12%).29 In our studies, the yields were appreciably
higher (53–96%) with the ee up to 57%. Substituting one
hydrogen atom with a benzylic group on the nitrogen
atom (ligand 1) increased both the selectivity (ee ¼ 47%)
and the conversion (89%). Compared to the trans-
(1R,2R)-diaminocyclohexane containing primary amino
groups (DACH), the nitrogen atoms became stereogenic
centres when bound to rhodium in ligands 1–7. This
may account for the higher selectivity as well as higher
activity as already observed for the related N,N0-di-
methyl-1,2-diphenyl-1,2-ethanediamine.18d Compared to
alkyl substituents,17c the bulky benzylic group led to
higher ee values. The presence of a bromine atom on the
benzylic group 2 increased the selectivity (ee ¼ 57%).
However, bulkier aromatic substituents 3–6, decreased
both the selectivity and activity. Although a high
The resulting solutions of chiral rhodium complexes
were then tested as homogeneous catalysts for the
hydride transfer reduction of acetophenone (Scheme 3)
NH2
p-nitrofluorobenzene,
N
N
°
DMSO, 70 C
H
H
NH2
O2N
NO2
7
Scheme 2.

A. Brethon et al. / Tetrahedron: Asymmetry 15 (2004) 495–502
Table 1. Catalytic activity of the homogeneous catalysts (ligand/Rh
497
SiO1.5
SiO1.5
1:1) in the hydrogen transfer reduction of acetophenone by isopro-
panol (according to Scheme 3)
Entry
Liganda
Reaction
timeb (d)
Conversion Eec
NH
NH
[Rh(cod)Cl]2,
NH
Rh(cod)Cl
NH
(%)
(%)
°
Toluene, 25 C
1
2
3
4
5
6
7
1
2
3
4
5
6
7
6
11
2
89
85
53
62
96
84
92
47
57
7
6
0
SiO1.5
SiO1.5
n
n
0.5
6
9
BS
BS-Rh
0
56
6
Scheme 5.
a Ligands derived from trans-(1R,2R)-diaminocyclohexane (cf.
Schemes 1 and 2).
b The reaction was monitored by capillary gas chromatography.
c The ees [(S)-configuration] were determined by HPLC on a Daicel
chiracel OD column.
leading to the in situ Rh-complexed hybrid catalyst, Rh-
BS (Scheme 6). In this case, the rhodium species was
only partially embedded in the chiral matrix.
The chiral hybrid materials BS, Rh-BS and BS-Rh were
analysed by NMR spectroscopy. In all cases, the solid
state 29Si NMR spectra showed only T substructures
with a predominant T3 substructure [CSi–(OSi)3] at )75
to )78 ppm indicating that no Si–C bond cleavage
occurred during the hydrolysis–condensation step and
the formation of a highly condensed siloxane network.
The 29Si spectrum of BS is given as an example in
Figure 2.
activity was observed for the perfluorinated aromatic
compound 5 (96% in 0.5 day) a low selectivity was
found. A phenyl substituent on the nitrogen atom 7 led
to activity and selectivity values (ee ¼ 56%) comparable
to those already observed for the benzyl derivatives 1
and 2.
2.2. Synthesis of the heterogeneous hybrid catalysts
The 13C NMR spectrum of BS (Fig. 3a) exhibited sig-
nals at chemical shifts characteristic of the organic
fragment at 25.7 and 30.9 (cyclic CH2), 52.6 and 59.4
(NCH, NCH2, residual OCH2) and 120–150 (CPh and
Cvin). An additional signal centred at 68 ppm was found
in the spectra of the hybrid Rh-BS and BS-Rh attrib-
utable to the C sp3 (CH2) of the cyclo-octadiene (Fig.
3b), which remained in the coordination sphere of the
incorporated rhodium atom.18d;e
We next studied the synthesis of the chiral hybrid cat-
alytic material from the readily available benzyl substi-
tuted diaminocyclohexane. The silylation of 2 with
vinyltriethoxysilane via a Heck reaction was achieved
leading to 8 (Scheme 4). The sol–gel hydrolysis–con-
densation of the alkoxy groups on silicon allowed the
formation of a chiral bridged silsesquioxane, BS
(Scheme 4), consisting of a siloxane network with (R,R)-
diaminocyclohexane crosslinking units.
The formation of rhodium complexes within the solid
material was confirmed by solid UV–vis spectroscopy,
with an absorption maximum centred at 380 nm.
Elemental analyses showed that 30% and 40% of the
expected amount of rhodium was incorporated in
Rh-BS and BS-Rh respectively. These hybrid solids
proved to be materials with low porosity; BS and BS-Rh
having specific surface areas quite close to zero whereas
The preparation of the chiral hybrid rhodium catalysts
was envisaged by two routes: (i) The complexation of
rhodium species was performed via treatment of BS
with [Rh(cod)Cl]2 in refluxing toluene to afford the post
Rh-complexed hybrid catalyst BS-Rh (Scheme 5). Using
this approach, rhodium atoms were expected to react
only with accessible diamine ligands in the solid mate-
rial, BS. (ii) 8 was first treated with [Rh(cod)Cl]2 in
ethanol yielding 8-Rh. The latter was then hydrolysed,
Rh-BS exhibited a higher surface area of 5 m2 gÀ1
.
SiO1.5
Si(OEt)3
Br
NH
NH
NH
NH
NH
Si(OEt)3
H2O/cat/EtOH
Pd(OAc) ,TOP,DMF
2
NH
Si(OEt)3
SiO1.5
Br
n
BS
2
8
Scheme 4.

498
A. Brethon et al. / Tetrahedron: Asymmetry 15 (2004) 495–502
Si(OEt)3
Si(OEt)3
SiO1.5
NH
Rh(cod)Cl
NH
NH
Rh(cod)Cl
NH
NH
NH
[Rh(cod)Cl]2,
H2O, cat,
EtOH
n
°
THF, 25 C
Si(OEt)3
SiO1.5
Si(OEt)3
n
8
8-Rh
Rh-BS
Scheme 6.
Table 2. Catalytic activity of 8-Rh and related hybrid materials
(ligand/Rh 1:1) in the hydrogen transfer reduction of acetophenone by
isopropanol (according to Scheme 3)
Entry
Catalyst
Reaction
timea (d)
Conversion Eeb (%)
(%)
1
2
3
4
5
8-Rh
7
2
6
6
6
100
90
91
6
39
Rh-BS
Rh-BSc
BS-Rh
BS-Rhc
37.5
39
94
22
37
a The reaction was monitored by capillary gas chromatography.
b The ees [(S)-configuration] were determined by HPLC on a Daicel
chiracel OD column.
Figure 2. Solid state 29Si CP-MAS NMR of BS.
c Recycled catalyst (2nd run).
The rhodium catalysed hydrogen transfer reduction of
acetophenone was used to evaluate the catalytic mate-
rial. The HTR reactions were performed with the solu-
ble 8-Rh homogeneous catalyst along with the derived
chiral hybrid solids, Rh-BS and BS-Rh. The results are
summarised in Table 2.
surface area of the in situ Rh-complexed catalyst Rh-BS
(5.2 m2 gÀ1) whereas the BS-Rh featured a completely
non porous solid (0.4 m2 gÀ1). The selectivity observed
with the two hybrid solids was higher than that of the
homogeneous catalyst probably due to the 3D chiral
network of the solid support, which contributes to the
chiral environment of the catalytic system. We have al-
ready observed a related chiral matrix effect.17 Interest-
ingly, the two solid catalysts could easily be recovered
by filtration and washing with water and ethanol and
then recycled for a further HTR reaction by adding
KOH again. The in situ Rh-complexed catalyst, Rh-BS,
gave similar activity in the second run (90% vs 91%)
whereas an important loss of activity was observed with
the post Rh-complexed catalyst, BS-Rh, in the second
run (22% vs 94%). This loss in catalytic properties is
probably due to a degradation of the catalytic species,
which are most likely located at the external surface of
The reaction was first performed with 8-Rh in solution.
Complete conversion was attained after 7 days with this
homogeneous catalyst. Surprisingly, the selectivity
proved to be very low (ee ¼ 6%) when compared with
the previously related benzylic ligands 1 and 2 (Table 1).
The use of chiral material as heterogeneous catalysts is
more interesting. A much higher enantioselectivity was
obtained with the two hybrid solids, Rh-BS and BS-Rh,
giving identical enantiomeric excesses (ee ¼ 39%). Fur-
thermore, a higher activity was obtained from Rh-BS
(conversion ¼ 90% in only 2 days) when compared to
that of BS-Rh (conversion ¼ 94% in 6 days). The reac-
tivity difference between these two hybrid catalytic
materials may be due to the higher (although moderate)
Figure 3. Solid state 13C CP-MAS NMR of: (a) BS and (b) Rh-BS.

A. Brethon et al. / Tetrahedron: Asymmetry 15 (2004) 495–502
499
BS-Rh. Conversely, the embedded catalytic species in
the porous matrix of the in situ Rh-complexed sol–gel
hybrid Rh-BS appeared stable.
temperature using deuterated chloroform as solvent and
TMS as the internal reference. 13C and 29Si solid state
NMR spectra were obtained from Bruker FT-AM 200
or FT-AM 400 spectrometers using cross-polarization
and magic-angle spinning techniques (CP-MAS) with
TMS as a reference for the chemical shifts. Mass spectra
were measured on
a JEOL MS-DX 300 mass
3. Conclusions
spectrometer. BET measurements for the determination
of the surface areas of the solid hybrids were performed
with a Micromeritics Gemini 2375 apparatus. Enantio-
meric excesses (ee) were determined by HPLC analyses
on a Waters 515 apparatus equipped with a Daicel
chiracel OD column, hexane/isopropanol (9:1) as eluent
with a flow of 0.5 mL/min and the UV detection was
performed at 254 nm.
N,N0-Substituted
trans-(1R,2R)-diaminocyclohexane
derivatives have been synthesised and used as chiral
ligands for the asymmetric hydrogen transfer reduction
of acetophenone. Simple benzylic substituents on nitro-
gen allowed a significant increase in selectivity when
compared to the non-substituted derivative, DACH.
The silylation and the heterogenisation of chiral trans-
(1R,2R)-N,N0 dibenzyl diaminocyclohexane moieties
were successfully achieved. Two routes were used to
form heterogeneous chiral hybrid catalysts, to give
Rh-BS (the in situ Rh-complexed catalyst) where the
catalytic species was embedded within the chiral matrix,
and BS-Rh (the post Rh-complexed catalyst), where the
catalytic species was likely to lie at the outer surface of
the material. Increased selectivity and stability arose
from embedding the catalytic species in a chiral three-
dimensional network. This approach seems particularly
relevant to generating selective, re-usable catalytic
materials.
4.2. (1R,2R)-N,N0-Di(40-bromobenzylidene)-1,2-diamino-
cyclohexane 2a
ꢁ
Molecular sieves 3 A (5 g), trans-(1R,2R)-diaminocyclo-
hexane (4 g, 35 mmol), p-bromobenzaldehyde (13 g,
70 mmol) and CH2Cl2 (80 ml) were introduced in a
Schlenk tube under nitrogen atmosphere. The mixture
was stirred for 20 h, filtered and then washed with
CH2Cl2 (three times). After evaporation of the solvent,
the title compound (14.9 g, 95%) was obtained as a pale
yellow solid. mp ¼ 124–125.5 °C; ½aŠ ¼ À266:5 (c 1.23,
D
CHCl3); mmax (KBr, cmÀ1) 3048, 2936, 2852, 1646, 1587,
1
1483, 1372, 1065, 933, 822; H NMR (CDCl3, d) 1.5
(2H, m), 1.8 (6H, m), 3.4 (2H, m), 7.4 (8H, s), 8.1 (2H,
s); 13C NMR (CDCl3, d) 24.4, 32.8, 73.7, 124.7, 129.3,
131.6, 135.1, 159.7;mass spectrum: m=z [FABþ] (%):
447, 449 (100, Mþ);Anal. Calcd for C 20H20N2Br2: C,
53.6;H, 4.5;N, 6.25;Br, 35.6. Found: C, 53.4;H. 4,5;N,
6.45 Br, 35.1.
4. Experimental
4.1. General
The syntheses of the chiral ligands were carried out
under a nitrogen atmosphere using a vacuum line and
schlenk techniques or round-bottom flasks. Diamine
ligands 1,21 423 and 725 as well as the Schiff bases 3a23
and 6a24 were synthesised as described in literature.
trans-(1R,2R)-Diaminocyclohexane was resolved accord-
ing to literature30 from a commercial cis/trans mixture of
(1,2)-diaminocyclohexane. Commercial acetophenone
was distilled before use and kept at )30 °C. All other
chemicals were purchased from ACROS, Aldrich,
Avocado, Fluka, Gelest, Lancaster and Strem Chemicals
and used without further purification. Molecular sieves
4.3. (1R,2R)-N,N0-di(20,30,40,50,60-pentafluorobenzyl-
idene)-1,2-diaminocyclohexane 5a
trans-(1R,2R)-Diaminocyclohexane (1 g, 8.8 mmol),
pentafluorobenzaldehyde (3.45 g, 17.6 mmol) and dry
toluene (60 mL) were introduced in a 2-neck round
bottom flask (100 mL) equipped with a Dean–StarkÕs
apparatus and reflux condenser. The mixture was stirred
and refluxed in order to eliminate water through the
azeotropic distillation of water–toluene. After 20 h, tol-
uene was removed in vacuo and the resulting crude
product crystallised in cyclohexane affording the title
compound (2 g, 48%) as an off-white solid. mp ¼ 115–
(3 A) were dried under vacuum (10À2 Torr) at 100 °C for
ꢁ
12 h. Solvents were distilled under nitrogen over P2O5
(CH2Cl2), magnesium turnings (ethanol and propan-
2-ol), KOH pellets (triethylamine) and from sodium/
benzophenone (THF, diethylether and toluene). Melting
points were determined on an electrothermal apparatus
(IA9000 series) and are uncorrected. Optical rotations
were measured using a Perkin–Elmer (Norwalk, CT) 241
polarimeter with solutions in a 1 dm cell in CHCl3.
UV–vis spectra in solution were obtained from a
Hewlett–Packard 8453 spectrophotometer. IR data were
obtained on a Perkin–Elmer 1000 FT-IR spectropho-
tometer. Elemental analyses were carried out by the
ÔService Central dÕAnalyse du CNRSÕ in Vernaison,
France. 1H, 13C and 29Si NMR in solution were recorded
on Bruker AC-200 and AC-250 spectrometers at room
118 °C; ½aŠ ¼ À172 (c 1.03, CH2Cl2); 1H NMR (CDCl3,
D
d) 1.5 (2H, m), 1.9 (6H, m), 3.5 (2H, m), 8.3 (2H, s); 13C
NMR (CDCl3, d) 24.1, 32.3, 75.3, 112, 135.1, 139.3,
143.1, 148.1, 149;mass spectrum: m=z [FABþ] (%):
471(100, Mþ).
4.4. (1R,2R)-N,N0-Di(quinoline-20-methylidene)-1,2-
diaminocyclohexane 6a
Yield: 77%;mp ¼ 205–208 °C; ½aŠ ¼ þ90:3 (c 1,
D
CH2Cl2); mmax (KBr, cmÀ1) 3062, 2926, 2857, 1640, 1595,

500
A. Brethon et al. / Tetrahedron: Asymmetry 15 (2004) 495–502
1
1560, 1500, 1427, 830, 753; H NMR (CDCl3, d) 1.6
(2H, m), 3.6–3.7 (2H, m), 7.4–7.8 (6H, m), 8–8.1 (6H,
m), 9.5 (2H, s), 1.9 (6H, m); 13C NMR (CDCl3, d) 24.4,
32.7, 73.9, 118.5, 127.1, 127.6, 128.7, 129.4, 136.3, 147.6,
154.9, 161.8;mass spectrum: m=z [FABþ] (%): 393 (100,
Mþ).
[FABþ] (%): 475 (100, Mþ);Anal. Calcd for C 26H28N4:
C, 78.75;H, 7.12;N, 14.13. Found: C, 78.44;H, 7.11;N,
14.1.
4.6. Synthesis of the silylated hybrid catalysts
4.6.1. (1R,2R)-N,N0-bis(40-(Triethoxysilylethenyl)benz-
4.5. General procedure for the synthesis of the diamino
ligands 2, 3, 5, 6
yl)-1,2-diaminocyclohexane 8. Diamine
2
(1 g,
2.2 mmol), Pd(OAc)2 (10 mg, 0.044 mmol) and tris
o-tolylphosphine (82 mg, 0.26 mmol) were introduced in
a Schlenk tube and dried under vacuum for 1 h. Vinyl-
triethoxysilane (0.95 g, 4.95 mmol), NEt3 (1 mL,
6.8 mmol) and DMF (5 mL) were added under nitrogen
atmosphere and the mixture heated overnight at 105 °C.
Cooling resulted in the formation of white needle-like
crystals of NHEt3Br. DMF was then removed in vacuo
and the crude product dissolved in dry toluene. Diami-
nocyclohexane was added to precipitate any further
ammonium bromide salt. The mixture was filtered, tol-
uene was evaporated leading to an orange viscous oil.
Typically, to a cool solution (0 °C) of 2a (14.96 g,
33.4 mmol) in methanol (150 mL), NaBH4 (3 g,
79.3 mmol) was added portionwise over a period of
30 min and the reaction mixture, then left to stir over-
night at room temperature. Water was then added and
the resulting milky solution extracted (three times) with
CH2Cl2. The solution was dried over K2CO3, filtered
and the solvent then removed in vacuo.
4.5.1.
(1R,2R)-N,N0-Di(40-bromobenzyl)-1,2-diamino-
cyclohexane 2. Colourless oil;Yield: 87% (13.1 g);
Yield: 60% (0.92 g); ½aŠ ¼ À30:3 (c 0.33, THF); mmax
D
(film, cmÀ1) 3300, 2970, 2927, 1606, 1567, 1509, 1450,
1390, 1166, 1077, 960, 826, 790; 1H NMR (CDCl3, d) 1.3
(18H, q), 1.7 (4H, m), 2.1–2.2 (4H, m), 3.6 (2H, d), 3.8–
3.9 (12H, q, +2H, d), 6.2 (2H, d), 7.4–7.1 (8H, m); 13C
NMR(CDCl3, d) 18.325, 31.5, 50.6, 58.6, 60.8, 117,
128.6, 126.8, 136.3, 141.8, 148.9;Anal. Calcd for
C36H58N2O6Si2: C, 64.44;H, 8.71;N, 4.17;Si, 8.37.
Found: C, 63.94;H, 8.62;N, 4.3;Si, 8.62.
½aŠ ¼ À39:6 (c 1.12, CHCl3); mmax (KBr, cmÀ1) 3297,
D
3022, 2927, 2853, 1591, 1486, 1457, 1403, 1357, 1240,
1
1116, 1070, 1011, 974, 858, 834, 796; H NMR (CDCl3,
d) 1.2–1.01 (4H, m), 1.7–1.8 (2H, m), 1.8 (2H, s), 2.1–2.2
(4H, m), 3.6 (2H, d), 3.8 (2H, d), 7.2 (4H, d), 7.4 (4H, d);
13C NMR (CDCl3, d) 120, 24.9, 31.5, 50.2, 60.9, 129.7,
131.4, 140.1;mass spectrum: m=z [FABþ] (%): 453,
451(100, Mþ);Anal. Calcd for C 20H24N2Br2: C, 53.1;H,
5.35;N, 6.2;Br, 35.34. Found: C, 53.1;H, 5.59;N, 6.37;
Br, 35.06.
4.6.2. Synthesis of the hybrid bridged silsesquioxane, BS.
In a schlenk tube, water (69 lL, 3.8 mmol) and NH4F
(6.4 lL of a 1 M solution, 0.5 mol%) were added to a
stirred mixture of 8 (0.85 g, 1.27 mmol) in ethanol
(1.6 mL) and the mixture then left under static condi-
tions. After 3 days, a white gel formed. This was aged for
7 days and then powdered, washed with ethanol and
dried under vacuum for 12 h to give a white powder
(0.4 g). mmax (KBr, cmÀ1) 3627, 3294, 2925, 2853, 1605,
1509, 1450, 1198, 1080, 827, 789; 13C CP-MAS NMR (d,
ppm) 25.7,30.9, 47.8, 52.6, 59.4, 122.2, 127.6, 136.4,
148.4; 29Si CP-MAS NMR (d, ppm) broad signal cen-
4.5.2. (1R,2R)-N,N0-Di(anthracenyl-90-methylene)-1,2-di-
aminocyclohexane 3. Yield: 80%; ½aŠ ¼ þ242:9 (c 1.144,
D
CHCl3); mmax (KBr, cmÀ1) 3280, 3043, 2963, 2852, 1444,
1
1260, 1090, 1019, 799, 724. H NMR (CDCl3, d) 1.7
(10H, m)2.8 (2H, m), 4.3 (2H, d), 4.7 (2H, d), 8.4–6.8
(18H, m); 13C NMR (CDCl3, d) 49, 69.7, 24.7;mass
spectrum: m=z [FABþ] (%): 494 (100, Mþ).
4.5.3. (1R,2R)-N,N0-Di(20,30,40,50,60-pentafluorobenzyl)-
1,2-diaminocyclohexane 5. Yield: 50%; ½aŠ ¼ À55 (c
tred at )75 (T3 unit);N BET surface area: 0.5 m2 gÀ1
.
D
2
1
1.04, CH2Cl2); H NMR (CDCl3, d) 1.0 (2H, m,), 1.2
(2H, m), 1.7–2.2 (8H, m), 3.8 (2H, d), 3.9 (2H, d); 13C
NMR (CDCl3, d) 24.8, 31.4, 37.9, 60.7, 113.8, 134.9,
137.8, 139.8, 142.7, 147.7;mass spectrum: m=z [FABþ]
(%): 475 (100, Mþ);Anal. Calcd for C 20H16N2F10: C,
50.64;H, 3.40;N, 5.91;F, 40.01. Found: C, 50.86;H,
3.42;N, 6.15;F, 39.06.
4.6.3. Synthesis of the post Rh-complexed hybrid catalyst,
BS-Rh. In a Schlenk tube under nitrogen atmosphere,
[Rh(cod)Cl]2 (0.165 g, 0.35 mmol) was added to a sus-
pension of BS (0.3 g) in dry ethanol (5 mL). After stir-
ring for 3 days, the mixture was filtered. The solid was
washed with THF in a soxhlet apparatus and then dried
under vacuum to give a yellow powder (0.195 g). mmax
(KBr, cmÀ1) 3278, 2925, 2854, 1605, 1560, 1509, 1450,
1198, 1108, 828, 790; 13C CP-MAS NMR (d, ppm) 25.7,
30.9, 52.9, 59.3, 68, 128.3, 136.9, 147.5; 29Si CP-MAS
NMR (d, ppm) broad signal centred at )77.9 (T3 unit);
N2 BET surface area: 0.4 m2 gÀ1;Anal. Calcd
C32H40O3N2Si2RhCl: Si, 8.06;N, 4.03;Rh, 14.83;Cl,
5.11. Found: Si, 7.2;N, 4.01;Rh, 5.2;Cl, 2.54.
4.5.4. (1R,2R)-N,N0-Di(quinoline-20-methylene)-1,2-di-
aminocyclohexane 6. Yield: 50% mp ¼ 90.5–92.3 °C;
½aŠ ¼ À42:7 (c 1.1, CH2Cl2); mmax (film, cmÀ1) 3300,
D
3057, 2926, 2853, 1600, 1504, 1450, 1260, 1095, 1019,
1
799; H NMR (CDCl3, d) 2.9 (4H, m), 3.4 (2H, m), 3.9
(2H, m), 4.1 (2H, m), 4.4 (2H, m), 5.7 (2H, d), 5.95 (2H,
d); 13C NMR(CDCl3, d) 25, 31.7, 53.2, 61.7, 120.8,
125.9, 127.5, 128.9, 129.2, 136.2, 147.7, 161.2; m=z

A. Brethon et al. / Tetrahedron: Asymmetry 15 (2004) 495–502
501
5. (a) Shea, K. J.;Loy, D. A.;Webster, O. W. Chem. Mater.
1989, 1, 512–513;(b) Shea, K. J.;Loy, D. A.;Webster,
O. W. J. Am. Chem. Soc. 1992, 114, 6700–6710;(c) Loy,
D. A.;Shea, K. J. Chem. Rev. 1995, 95, 1431–1442;
(d) Shea, K. J.;Loy, D. A. Chem. Mater. 2001, 19, 3306–
3319.
4.6.4. Synthesis of the in situ Rh-complexed hybrid
catalyst, Rh-BS. A mixture of 8 (0.76 g, 1.15 mmol),
[Rh(cod)Cl]2 (0.278 g, 0.565 mmol) and ethanol (3 mL)
was stirred in a schlenk for 2 h. A solution of NH4F
(27 lL of a 1 M solution, 0.1 mol %) and water (35 lL,
1.5 mmol) in ethanol (0.8 mL) was then added and the
mixture kept under static conditions at room tempera-
ture. A gel then appeared after 8 h. After ageing for
7 days, it was crushed, washed with THF for 1 day in a
soxhlet apparatus and then dried under vacuum. A
ꢀ
6. (a) Corriu, R. J. P.;Moreau, J. J. E.;Th epot, P.;Wong
Chi Man, M. Chem. Mater. 1992, 4, 1217–1224;(b)
Corriu, R. J. P.;Leclercq, D. Angew. Chem., Int. Ed. 1996,
35, 1432–1455;(c) Corriu, R. J. P. Angew. Chem., Int. Ed.
2000, 39, 1376–1398.
yellow powder (0.49) was obtained. mmax (KBr, cmÀ1
)
7. Sanchez, C.;Ribot, F. New J. Chem. 1994, 18, 1007–1047.
8. (a) Organic/inorganic HybridMaterials, MRS Symp. ;
Laine, R. M., Sanchez, C., Brinker, C. J., Giannelis, E.,
Eds.;1998;(b) Organic/inorganic HybridMaterials, MRS
Symp.;Laine, R. M., Sanchez, C., Brinker, C. J., Eds.;
2000;(c) Organic/inorganic HybridMaterials, MRS Symp. ;
Laine, R. M., Sanchez, C., Brinker, C. J., Eds.;2002.
9. (a) Moreau, J. J. E.;Wong Chi Man, M. Coord. Rev. 1998,
178–180, 1073–1084;(b) Adima, A.;Moreau, J. J. E.;
Wong Chi Man, M. Chirality 2000, 12, 411–420;(c)
Ameduri, B.;Boutevin, B.;Moreau, J. J. E.;Moutaabbid,
H.;Wong Chi Man, M. J. Fluorine Chem. 2000, 104, 185–
194;(d) Bourg, S.;Broudic, J.-C.;Conocar, O.;Moreau, J.
J. E.;Meyer, D.;Wong Chi Man, M. Chem. Mater. 2001,
13, 491–499.
10. (a) Oviatt, H. W.;Shea, K.;Kalluri, S.;Shi, Y.;Steier, W.
H.;Dalton, L. R. Chem. Mater. 1995, 7, 493;(b) Dalton,
L. R.;Harper, A. W.;Ghosn, R.;Steier, W. H.;Ziari, M.;
Fetterman, H.;Shi, Y.;Mustacich, R. V.;Jen, K.-Y. A.;
Shea, K. Chem. Mater. 1995, 7, 1060.
11. (a) Corriu, R. J. P.;Hesemann, P.;Lanneau, G. F. Chem.
Commun. 1996, 1845–1846;(b) Boury, B.;Ben, F.;Corriu,
R. J. P. Angew. Chem., Int. Ed. 2001, 40, 2853–2856;(c)
Cerveau, G.;Corriu, R. J. P.;Framery, E.;Ghosh, S.;
Nobili, M. Angew. Chem., Int. Ed. 2002, 41, 594–596;(d)
3272, 2927, 2854, 1656, 1606, 1566, 1510, 1450, 1200,
1134, 828, 784; 13C CP-MAS NMR (d, ppm) 25.6, 31.7,
53.1, 59.2, 68, 128, 136.9, 147.9; 29Si CP-MAS NMR (d,
ppm) broad signal centred at )77.0 (T3 unit);N BET
2
surface area: 5.2 m2 gÀ1;Anal. Calcd C 32H40O3N2Si2-
RhCl: Si, 8.06;N, 4.03;Rh, 14.83;Cl, 5.11. Found: Si,
9.9;N, 5.27;Rh, 4.35;Cl, 2.39.
4.7. General procedure for the rhodium-catalysed reduc-
tion of acetophenone with the homogeneous catalysts
The diamine ligand (0.06 mmol), [Rh(cod)Cl]2 (14.8 mg,
0.03 mmol), KOH (20 mg, 0.36 mmol) and freshly dis-
tilled isopropanol were stirred for 1 h in a Schlenk tube
under nitrogen atmosphere. Acetophenone was then
added (0.24 g, 2 mmol) to the mixture and the reaction
monitored by capillary gas chromatography. After the
reaction was complete, the solvent was evaporated. The
ee was measured by HPLC on a Daicel chiracel OD
column, eluent: hexane/i-PrOH 9:1, 0.5 mL minÀ1
.
ꢀ
Corriu, R. J. P.;Lancelle-Beltran, E.;Mehdi, A.;Rey e, C.;
Brandes, S.;Guilard, R. J. Mater. Chem. 2002, 12, 1355–
1362.
ꢂ
4.8. General procedure for the rhodium-catalysed
reduction of acetophenone with the heterogeneous
hybrid catalysts
12. Schubert, U. New J. Chem. 1994, 18, 1049–1958.
13. (a) Lindner, E.;Schneller, T.;Auer, F.;Mayer, H. A.
Angew. Chem., Int. Ed. 1999, 38, 2154–2174;(b) Lu, Z.-I.;
Lindner, E.;Mayer, H. A. Chem. Rev. 2002, 102, 3543–
3578.
14. (a) Abu-Reziq, R.;Avnir, D.;Blum, J. Angew. Chem., Int.
Ed. 2002, 41, 4132–4134;(b) Abu-Reziq, R.;Avnir, D.;
Blum, J. J. Mol. Catal. A., Chem. 2002, 187, 277–281.
15. Duchateau, R. Chem. Rev. 2002, 102, 3225–3542.
16. Song, C. E.;Lee, S.-G. Chem. Rev. 2002, 102, 3495–3524.
17. (a) Adima, A.;Moreau, J. J. E.;Wong Chi Man, M. J.
Mater. Chem. 1997, 7, 2331–2333;(b) Adima, A.;Moreau,
J. J. E.;Wong Chi Man, M. Chirality 2000, 12, 411–420;
(c) Hesemann, P.;Moreau, J. J. E. Tetrahedron: Asym-
metry 2000, 11, 2183–2194;(d) Brethon, A.;Hesemann, P.;
The solid catalyst containing 3 mol% of rhodium is
mixed with KOH (20 mg, 0.36 mmol) and freshly dis-
tilled isopropanol (10 mL) in a Schlenk tube. The mix-
ture was then stirred under nitrogen atmosphere for 4 h.
Acetophenone (240 mg, 2 mmol) was then added and the
reaction monitored by capillary gas chromatography. At
the end of the reaction, the heterogeneous mixture was
centrifuged and the solution mixed with pentane and
then filtered on a silica column. The ee was measured by
HPLC technique equipped with a chiral column (Daicel
chiracel OD). The solid catalyst was washed with pen-
tane, dried under vacuum and then re-used for a second
run.
ꢀ
Moreau, J. J. E.;R ejaud, L.;Wong Chi Man, M. J.
Organomet. Chem. 2001, 627, 239–248;(e) Bied, C.;
Gauthier, D.;Moreau, J. J. E.;Wong Chi Man, M. J.
Sol–Gel Sci. Technol. 2001, 20, 313–320.
18. (a) Gamez, P.;Fache, F.;Mangeney, P.;Lemaire, M.
Tetrahedron Lett. 1993, 34, 6897–6898;(b) Gamez, P.;
Fache, F.;Lemaire, M. Tetrahedron: Asymmetry 1995, 6,
References and notes
ꢀ ꢀ
705–718;(c) ter Halle, R.;Br eheret, A.;Schulz, E.;Pinel,
1. Gladysz, J. A. Chem. Rev. 2002, 102, 3215–3216.
2. Rechavi, D.;Lemaire, M. Chem. Rev. 2002, 102, 3467–
3494.
3. Fan, Q.-H.;Li, Y.-M.;Chan, A. S. C. Chem. Rev. 2002,
102, 3385–3466.
C.;Lemaire, M. Tetrahedron: Asymmetry 1997, 8, 2101–
2108;(d) Gamez, P.;Fache, F.;Mangeney, P.;Lemaire,
M. J. Organomet. Chem. 1998, 567, 133–136;(e) Bernard,
M.;Guiral, V.;Delbecq, F.;Fache, F.;Sautet, P.;
Lemaire, M. J. Am. Chem. Soc. 1998, 120, 1441–1446.
19. Zassinovich, G.;Mestroni, G. Chem. Rev. 1992, 92, 1051–
1069.
4. Brinker, C. J.;Scherer, G. W. Sol–Gel Science;Academic:
London, 1990.

502
A. Brethon et al. / Tetrahedron: Asymmetry 15 (2004) 495–502
20. Gamez, P.;Dunjic, B.;Fache, F.;Lemaire, M.
Soc., Chem. Commun. 1994, 1417–1418.
21. Bennani, Y. L.;Hanessian, S. Tetrahedron 1996, 52,
13837–13866.
22. Desimoni, G.;Faita, G.;Righetti, P.;Sardone, N.
Tetrahedron 1996, 52, 12019–12030.
23. Krasik, P.;Alper, H. Tetrahedron 1994, 50, 4347–4354.
24. Abu-Surrah, A. S.;Laine, T.;Repo, T.;Fawzi, R.;
Steimann, M.;Rieger, B. Acta Cryst., Section C 1997,
C53, 1458–1459.
J. Chem.
26. Botteghi, C.;Chelucci, G.;Chessa, G.;Delogu, G.;
Soccolini, F. J. Organomet. Chem. 1986, 304, 217–225.
27. Gladiali, S.;Pinna, L.;Delogu, G.;De Martin, S.;
Zassinovich, G.;Mestroni, G. Tetrahedron: Asymmetry
1990, 1, 635–648.
28. Haack, K. J.;Hashiguchi, S.;Fujii, A.;Ikariya, T.;
Noyori, R. Angew. Chem., Int. Ed. 1997, 36, 285–290.
29. Dunjic, B.;Gamez, P.;Fache, F.;Lemaire, M.
Polym. Sci. 1996, 59, 1255–1262.
J. Appl.
30. (a) Whitney, T. A. J. Org. Chem. 1980, 45, 4214–4219;(b)
Larrow, J. F.;Jacobsen, E. N. J. Org. Chem. 1994, 59,
1939–1942.
25. Smith, H. E.;Cozart, W. I.;de Paulis, T.;Chen, F.-M.
J. Am. Chem. Soc. 1979, 101, 5186–5193.