Polymer-supported indium lewis acid: Highly versatile catalyst for regio- and stereoselective ring-opening of epoxides

Article abstract of DOI:10.1002/adsc.200303236

The first example of a polymer-supported indium Lewis acid is presented. This new heterogeneous Amberlyst 15/indium complex effectively catalyses (20 mol % based on indium) the formation of new C-C as well as C-S bonds through the highly regio- and stereo

Full text of DOI:10.1002/adsc.200303236

FULL PAPERS
Polymer-Supported Indium Lewis Acid: Highly Versatile Catalyst
for Regio- and Stereoselective Ring-Opening of Epoxides
Marco Bandini,* Matteo Fagioli, Alfonso Melloni, Achille Umani-Ronchi*
Dipartimento di Chimica ™G. Ciamician∫, University of Bologna Via Selmi 2, 40126, Bologna, Italy
Fax: þ39 (0)51/2099456, e-mail: marco.bandini@unibo.it, achille.umanironchi@unibo.it
Received: December 18, 2003; Accepted: March 11, 2004
Abstract: The first example of a polymer-supported Amberlyst 15/indium Lewis acid does not require in-
indium Lewis acid is presented. This new heterogene- ert atmosphere conditions or anhydrous media and
ous Amberlyst 15/indium complex effectively cataly- can be easily recovered and recycled for several times
ses (20 mol % based on indium) the formation of without loss of activity.
À
À
new C C as well as C S bonds through the highly re-
gio- and stereoselective ring-opening reaction of Keywords: asymmetric catalysis; heterogeneous catal-
enantiomerically pure epoxides. The easily prepared ysis; immobilization; indium; ring-opening
Introduction
tions.[5] Then, encouraged by the remarkable functional
group tolerance showed by indium salts in homogene-
Lewis acid-catalyzed reactions continue to attract in- ous catalysis, we planned to synthesize an unprecedent-
creasing attention in the modern organic synthesis sce- ed polymer-supported indium(III) Lewis acid.[6] To this
nario.[1] Nowadays, studies focused on the development aim, Amberlyst-Na[4c] (2 g) and In(OTf)3 (2 mmol) were
of highly efficient, selective and safe Lewis acid-based shaken at room temperature in EtOH under nitrogen
promoting systems are a research topic for numerous for 16 h to give, after filtration and drying under vac-
chemists. In this context, immobilized green Lewis acid uum, the Amberlyst-In (Amb-In) polymer
A
catalysts are receiving a great deal of attention due to (Scheme 1).
environmental, practical and economical concerns. Of
The present resin-In shows one of the highest contents
particular relevance are the resin-supported metal cata- of metal (estimated 0.92 mmol/g) so far described re-
lysts that, due to the fine tuning of their physico-chemi- garding organic polymer-supported Lewis acids with
cal properties, are emerging as alternative promoting an exchange percentage (EP) of 59%.[7] On the other
agents for several challenging organic transformations.
hand, previously reported Sc(III)- and lanthanide(III)-
After the pioneering study of Neckers and co-workers supported catalysts are generally characterized by load-
on syntheses and applications of organic polymer-sup- ing levels of less than 0.8 mmol/g.
ported AlCl3 and BF3 species,[2] numerous heterogene-
As a continuation of our recent findings focused on
ously catalyzed organic transformations involving met- the InBr3-catalyzed ring-opening of epoxides,[8] we start-
als anchored to acid ion-exchange resins have been de- ed testing the catalytic properties of this novel support-
scribed.[3] In particular, heterogeneous Lewis acids ed In catalyst in the ring-opening of enantiomerically
based on metals with high coordination numbers, such pure epoxides[9] by using indoles as nucleophiles.[10] In
as Sc, Yb and Ln, proved to be highly effective in pro- our initial evaluations, we used as the model reaction
moting several organic reactions. Among them, Diels
Alder reactions, Friedel Crafts reactions, allylations of
carbonyls, Michael additions and Mukaiyama reactions
have been studied in anhydrous as well as aqueous me-
dia.[4]
the addition of N-methylindole (2a, 1.5 equivs.) to (R)-
Results and Discussion
In the field of Lewis acid catalysis, indium(III) halides
and triflate have emerged as highly effective promoting
agents for numerous chemoselective organic reac- A.
Scheme 1. Synthesis of the resin-supported indium Lewis acid
Adv. Synth. Catal. 2004, 346, 573 578
DOI: 10.1002/adsc.200303236
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573

Marco Bandini et al.
FULL PAPERS
Table 1. Reaction conditions optimization.
current homogeneous catalysis, we ran a probe reaction
between 1a and 2a in the presence of Amb-In
1
(20 mol %) for 7 h (44% conversion by H NMR, ee>
98%). Then the catalyst was removed by filtration and
the mixture was allowed to react again. However, after
48 h reaction time 3aa was obtained as 47% conversion
and ee>99%. This finding suggested that no significant
leaching is operating under our reaction conditions.
The catalyst A can be easily recovered by filtration af-
ter each reaction and reused without further treatments
(Figure 1). In particular, the same amount of Amb-In
was employed in 5 cycles of the reaction 1a/2a without
a remarkable loss of activity.[13]
Then, several indoles were tested in the ring-opening
reaction of enantiomerically pure epoxides (1a, b, Ta-
ble 2). All the attempts furnished chemoselectively the
alcohol derived from the attack at the benzylic carbon
(a position) in moderate to good yields (up to 62%, en-
try 5) and without detectable racemization (ee>98%).
Only 1H-indole gave rise the b-aryl alcohol 3ah in
90% ee.
Entry
Catalyst
[%]
t
[h]
Solvent
3aa
ee
[%][a]
[%][b]
1
2
3
4
5
6
7
A (20)
A (5)
A (20)
A (20)
A (20)
Amb-Na
Amb-15
24
24
24
24
24
24
24
CH2Cl2 (dry)
CH2Cl2 (dry)
Toluene (dry)
Et2O (dry)
Et2O (wet)
Et2O (wet)
Et2O (wet)
40
40
47
62
64
96
91
>98
>98
>98
11[c]
72
[a]
After flash chromatography.
[b] Determined by HPLC analysis with a chiral column (Chir-
alcel-OD).
[c]
A mixture of regioisomers was obtained.
(þ)-styrene oxide (1a, 1 equiv.). The choice of the sol-
It is noteworthy that while the yields with indole (2 h)
vent appeared crucial in order to maximize yield, to min- and alkyl-substituted indoles (2f, 2 g) were only slightly
imize side rearrangements and to avoid racemization.[11] lower than those of homogeneous counterpart,[8] indoles
Particularly promising proved to be the use of reagent bearing sterically demanding groups such as 2-Ph- and 5-
grade Et2O that, among the various solvents surveyed Br-indoles (2c and 2e) furnished the desired alcohols in
and in the presence of 20 mol % of A (based on the lower yields (40 42%, entries 2 and 4). This phenomen-
amount of In3þ), led to the desired b-indolyl alcohol on can be rationalized by taking into account the poor
(R)-(À)-3aa in good yield (64%) and>98% enantiomer- accessibility of the interior catalytic particles for bulky
ic excess (entry 5, Table 1). The highest yield obtained organic molecules with the consequent drop in activity
by using Et2O as the solvent can be ascribed to the fruit- of the catalytic sites. Interestingly, a different behaviour
ful swelling of the polymer network of the catalyst in this was recorded for 5-BnO-indole (2b) that underwent the
media, allowing the metal particles located inside the reaction with 1a in good yield (60%) and without racemi-
polymer matrix to effect the catalysis.
The key role played by the Lewis acidity of the heter-
zation (entry 1, Table 2).
Interestingly, while the homogeneous indium(III)
ogeneous catalyst A was proved by employing the Am- bromide-catalyzed ring-opening of epoxides by indoles
berlyst-Na resin (entry 6) and Amberlyst-15 dry (en- needed strictly anhydrous conditions to isolate the prod-
try 7) as catalysts. In fact, while in the former case no re- ucts in high chemical as well as optical yields,[8] the pres-
action occurred, in the latter, 3 was isolated in low yield ent indium-supported protocol did not show this re-
(11%) as a mixture of regioisomers with a significant rac- quirement. The water-tolerance enhancement of the
emization of the benzylic stereocenter (ee¼72%).[12] heterogeneous catalyst may be ascribed to the different
The leaching of active sites in the organic products is a and more lipophilic microenvironment of the metal par-
crucial issue that must be always considered in metal- ticles in the resin-supported catalyst in comparison to
lo-supported catalysis. To rule out the presence of con- the bulk liquid phase.[14]
The thiolysis of epoxides is a powerful route to the syn-
thesis of b-hydroxy sulfides that are widely employed for
the synthesis ofbiologicallyandpharmacologically active
compounds.[15] Numerous catalytic strategies have been
effectively applied to the ring-opening of aryl and alkyl-
epoxides with thiols by using acidic as well as basic condi-
tions.[16] Among them, indium-based Lewis acids also
proved to be remarkably active in aqueous media.[17]
However, to the best of our knowledge no examples of
the catalytic regio- and stereoselective thiolysis of enan-
tiomerically pure epoxides have been described.[18]
To probe the effectiveness of A in this process we re-
Figure 1. Testing the reusability of the In-supported catalyst. acted enantiomerically pure 1a with 2-naphthalenethiol
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Adv. Synth. Catal. 2004, 346, 573 578

Polymer-Supported Indium Lewis Acid
FULL PAPERS
Table 2. Screening of various indoles in the Amb-In cata-
Table 3. Thiolysis of enantiomerically pure epoxides medi-
ated by Amb-In.
lyzed ring-opening of enantiomerically pure epoxides.[a]
Entry[a] Epoxide Yield [%][b] 5: 5’[c]
ee of 5 [%][d]
Entry
Epoxide
Indole
Product Yield
[%][b]
ee
À
75[e]
[%][c]
1
2
3
4
5
6
7
1a
1a
1a
1a
1a
1b
1c
(5a)<10
(5a) 13[f]
(5a) 54[g]
(5a) 50[h]
(5a) 63
(5b) 65
(5c) 67
1: 1
1
2
3
4
5
6
7
1a
1a
1a
1a
1a
1a
1a
3ab (60)
3ac (40)
3ad (54)
3ae (42)
3af (62)
3ag (58)
3ah (54)
>98
>98
97
>49: 1 60
>49: 1 50
>49: 1 81
>11: 1 82
>49: 1 90
[a]
All the reactions were carried out at room temperature in
Et2O for 24 h reaction time, in the presence of 20 mol % of
catalyst A unless otherwise specified.
>98
>98
>98[d]
90
[b]
[c]
[d]
After flash chromatography.
1
Determined by H NMR of the crude mixtures.
Determined by HPLC analysis with a chiral column (Chir-
alcel-OD).
Reaction in the absence of catalyst.
In the presence of Amb-Na (20 mol %).
Toluene was used as the solvent.
[e]
[f]
[g]
[h]
Anhydrous CH2Cl2 was used as the solvent.
8
9
1b
1b
2 g
2 h
3bg (58)
3ch (57)
>98
>98
[a]
All the reactions were carried out at room temperature for
24 h reaction time, in the presence of 20 mol % of catalyst A.
After flash chromatography. Only one regioisomer was ob-
tained.
[b]
[c]
[d]
Determined by HPLC analysis with a chiral column (Chir-
alcel-OD).
1
Scheme 2. Regioselective ring-opening of cis-limonene 1,2-
epoxide mediated by Amb-In with 4.
Determined by H NMR with Eu(hfc)3 shift reagent.
4 in the presence of Amb-In (20 mol %) in a series of re-
agent grade solvents.
From the data of Table 3 we see that also for the thiol- 82%) although the 5:5’ ratio slightly decreased to 11:1.
with (R)-(þ)-3-chlorostyrene oxide (1b) (entry 6, ee¼
ysis the use of Amb-In in Et2O provided the highest
Interestingly, also more hindered 1,2-disubstituted
chemical and optical yield. In particular, (R)-(þ)-styr- and 1,2-trisubstituted aryl- as well as alkyloxiranes,
ene oxide (1a) smoothly reacted with 4 yielding regiose- namely (1R,2R)-(þ)-1-phenylpropylene oxide (1c) and
lectively (a attack>98%) the (S)-b-hydroxy sulfide 5a (þ)-cis-limonene-1,2-epoxide[20] (6, Scheme 2), smooth-
in optimal 63% yield and 81% ee.[19]
ly reacted with 2-naphthalenethiol. Thus, under not
Although a partial racemization of the starting epox- strictly anhydrous conditions, a catalytic amount of
ides was observed, the present protocol represents the Amb-In (20 mol %) did afford the corresponding hy-
first example of regiolective thiolysis of enantiomerical- droxy thiols 5c and 7 in good optical (ee¼90%, de>
ly pure epoxides in the presence of heterogeneous cata- 98:2, respectively) and chemical yields (67%, 50%).
lysts. Again the role of indium in the regio- and stereo-
selectivity was demonstrated by running the model reac-
tion both in the absence of catalyst (entry 1: product in Conclusion
traces) and in the presence of 20 mol % of Amb-Na (en-
try 2, 1:1 regioselectivity, 13% yield). Comparable re- In summary, a new green indium-supported Lewis acid
sults in terms of stereoselection were also obtained is presented. Its effectiveness in promoting regio- and
Adv. Synth. Catal. 2004, 346, 573 578
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Marco Bandini et al.
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stereoselective ring-opening reactions of internal as well General Procedure for the Ring-Opening of Epoxides
as terminal epoxides is discussed. In particular, optically
active b-indolyl alcohols and b-hydroxy sulfides can be
A sample vial containing 2 mL of reagent grade Et2O was
charged with 0.2 mmol of epoxide, 0.3 mmol of nucleophile
isolated in good yields after the reaction in the presence
of 20 mol % of catalyst without a strict nitrogen atmos-
phere. This new heterogeneous catalyst, due to the mild
operating conditions and to the possible reusability
without reactivation, could represent a valuable candi-
date for environmentally benign stereoselective flow
processes.
and 44 mg (20 mol % based on indium content) of Amb-In.
The mixture was shaken for 24 h with a basic orbital mixer
and then the catalyst was recovered by filtration. Evaporation
of the solvent and subsequent purification by flash chromatog-
raphy furnished the desired indolyl alcohols 3 or b-hydroxy sul-
fide 5.
(R)-2-(5-Phenylmethoxy-1H-indol-3-yl)-2-
phenylethan-1-ol (3ab)
Experimental Section
Colourless oil; yield: 60%; M. W.¼343.43 g/mol; Rf ¼0.2 (cy-
clohexane/AcOEt, 7:3); [a]2D5: þ64.9 (c 1.3, CHCl3); ee 98%
by HPLC: OD, isocratic 85:15 n-hexane/i-PrOH, flow
0.5 mL/min, acquisition wavelength 225 nm, tR ¼41.0 min, tS ¼
47.1 min; 1H NMR (300 MHz, CDCl3): d¼8.02 (1H, br), 7.47
7.14 (13H, m), 7.00 6.94 (1H, m), 5.03 (2H, s), 4.46 (1H, t, J¼
6.6 Hz), 4.44 4.22 (2H, m), 1.30 (1H, br); 13C NMR (75 MHz,
CDCl3): d¼153.1, 141.5, 137.5, 131.8, 128.6, 128.5, 128.2, 127.8,
127.6, 127.4, 126.7, 122.7, 115.7, 113.1, 111.8, 102.9, 70.9, 66.3,
45.6; IR (nujol): n¼3552, 3272, 1618, 1582, 1184, 1046, 1012,
934, 819, 798, 711 cmÀ1; anal. calcd. for C23H21NO2: C 80.44,
H 6.16, N 4.08; found: C 80.39, H 6.11, N 4.06.
General Remarks
1H NMR spectra were recorded on Varian 200 (200 MHz) or
Varian 300 (300 MHz) spectrometers. Chemical shifts are re-
ported in ppm from tetramethylsilane with the solvent reso-
nance as the internal standard (deuterochloroform: d¼
7.27 ppm). Data are reported as follows: chemical shift, multi-
plicity (s¼singlet, d¼doublet, t¼triplet, q¼quartet, br¼
broad, m¼multiplet), coupling constants (J, Hz). 13C NMR
spectra were recorded on Varian 200 (50 MHz) or Varian 300
(75 MHz) spectrometers with complete proton decoupling.
Chemical shifts are reported in ppm from tetramethylsilane
with the solvent as the internal standard (deuterochloroform:
d¼77.0 ppm). Mass spectra were performed at an ionizing
voltage of 70 eV. Chromatographic purification was done
with 240 400 mesh silica gel. Analytical gas chromatography
(GC) was performed on a Hewlett-Packard HP 6890 gas chro-
matograph with a flame ionization detector and split mode ca-
pillary injection system, using a cross-linked 5% PH ME silox-
ane (30 m) column or a Megadex-5 chiral (25 m) column (flow
rate 15 mL/min, method: 508C for 2 min, ramp at 108C/min to
2508C for 15 min). Analytical high performance liquid chro-
matography (HPLC) was performed on an HP 1090 liquid
chromatograph equipped with a variable wavelength UV de-
tector (deuterium lamp 190 600 nm) and using a Daicel Chir-
alcelTM OD column (0.46 cm I. D.Â25 cm) (Daicel Inc.).
HPLC grade isopropyl alcohol and n-hexane were used as
the eluting solvents. Elemental analyses were carried out using
an EACE 1110 CHNOS analyzer. All the commercially avail-
able reagents were used without further purification. Com-
pounds 3aa, 3ad, 3ae, 3ag, 3bg and 3bh have already been re-
ported and analytically characterized.[8]
(R)-2-(2-Phenyl-1H-indol-3-yl)-2-phenylethan-1-ol
(3ac)
Yellow oil; yield: 40%; M. W.¼313.40 g/mol; Rf ¼0.25 (cyclo-
hexane/AcOEt, 8:2); [a]2D5: þ31.7 (c 0.78, CHCl3); ee 98%
by HPLC: OD, isocratic 85:15 n-hexane/i-PrOH, flow
0.5 mL/min, acquisition wavelength 225 nm, tS ¼21.5 min, tR ¼
30.9 min; 1H NMR (300 MHz, CDCl3): d¼8.26 (1H, br), 7.65
7.09 (14H, m), 4.72 (1H, t, J¼8.4 Hz), 4.39 (2H, m), 1.30 (1H,
br); 13C NMR (75 MHz, CDCl3): d¼141.8, 137.7, 136.2,
132.6, 128.8, 128.5, 128.2, 128.1, 127.6, 127.4, 126.5, 126.4,
122.3, 120.8, 120.1, 111.2, 65.5, 45.2; IR (nujol): n¼34547,
3404, 1600, 1027, 907, 737, 697 cmÀ1; anal. calcd. for C22H19
NO: C 84.31, H 6.11, N 4.47; found: C 84.25, H 6.06, N 4.46.
(R)-2-(1,2-Dimethyl-indol-3-yl)-2-phenylethan-1-ol
(3af)
Yellow oil; yield: 62%; M. W.¼265.15 g/mol; Rf ¼0.3 (cyclo-
hexane/AcOEt, 8:2); [a]2D5: À44.9 (c 1.6, CHCl3); ee 98% by
HPLC: OD, isocratic 85:15 n-hexane/i-PrOH, flow 0.5 mL/
min, acquisition wavelength 225 nm, tS ¼22.7 min, tR ¼
28.1 min; 1H NMR (300 MHz, CDCl3): d¼7.53 7.06 (9H,
m), 4.56 (1H, t, J¼7.8 Hz), 4.38 (2H, dd, J1 ¼7.8 Hz, J2 ¼
1.5 Hz), 3.73 (3H, s), 2.43 (3H, s), 1,30 (1H, br); 13C NMR
(50 MHz, CDCl3): d¼141.8, 136.9, 135.2, 128.4, 127.9, 126.6,
126.2, 120.7, 119.3, 119.1, 109.2, 108.9, 65.1, 45.4, 29.7, 10.7;
GC-MS: m/z (relative intensity)¼265 (11), 247 (2), 234
(100), 218 (11), 204 (3), 176 (2), 158 (6), 144 (2), 115 (4), 109
(3), 77 (3), 56 (4); IR (nujol): n¼3398, 3050, 3026, 1407, 1368,
1333, 1030, 738, 700 cmÀ1; anal. calcd. for C18H19NO: C 81.47,
H 7.22, N 5.28; found: C 81.50, H 7.16, N 5.26.
Preparation of the Amb-In Catalyst (A)
A flamed two-necked flask was charged with 25 mL of EtOH,
2 g of Amb-Na and 1.12 g (2 mmol) of In(OTf)3 under a nitro-
gen atmosphere and the resulting mixture was shaken over-
night (16 h). Then, the resin was collected by filtration, washed
with 50 mL of EtOH and dried under vacuum overnight.
The content of indium in the resin (0.92 mmol/g) was deter-
mined by titration of the remaining amount of In3þ in the sol-
ution following the known procedure (EDTA 0.01 M, xylenol
orange as the indicator, buffer: 20% hexamethylenetetra-
amine).[4c]
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Adv. Synth. Catal. 2004, 346, 573 578

Polymer-Supported Indium Lewis Acid
FULL PAPERS
(3H, s); 13C NMR (75 MHz, CDCl3): d¼149.2, 137.4, 134.2,
133.3, 133.1, 128.5, 127.9, 127.8, 127.6, 126.8, 126.4, 109.2,
76.0; 53.3, 38.0, 33.7, 32.8, 26.6, 25.4, 21.1; GC-MS: m/z (relative
intensity)¼312 (5), 207 (6), 160 (100), 128 (13), 115 (21), 109
(9), 79 (8), 67 (9), 55 (6); IR (neat): n¼3423, 3054, 2928,
2853, 1645, 1450, 1374, 1261, 1184, 1132, 1018, 957, 890, 858,
816, 745 cmÀ1; anal. calcd. for C20H24OS: C 78.88, H 7.74;
found: C 77.82, H 7.78.
(S)-2-(2-Thionaphthalenyl)-2-phenylethan-1-ol (5a)
White solid; mp 99 1038C; yield: 60%; M. W.¼280.39 g/mol,
Rf ¼0.25 (cyclohexane/AcOEt, 85:15); [a]2D5: þ223.8 (c 0.9,
CHCl3); ee 81% by HPLC: OD, isocratic 85:15 n-hexane/i-
PrOH, flow 0.5 mL/min, acquisition wavelength 229 nm, tS ¼
18.0 min, tR ¼23.5 min; 1H NMR (300 MHz, CDCl3): d¼7.83
7.72 (4H, m), 7.49 7.30 (8H, m), 4.45 (1H, t, J¼7.3 Hz), 3.98
(2H, m), 2.06 (1H, br); 13C NMR (50 MHz, CDCl3): d¼138.8,
133.5, 132.4, 131.3, 131.0, 129.6, 128.8, 128.5, 128.1, 127.9,
127.6, 127.4, 126.5, 126.3, 65.3, 55.9; GC-MS: m/z (relative in-
tensity)¼280 (22), 249 (15), 215 (6), 171 (11), 160 (100), 128
(15), 121 (30), 115 (38), 103 (35), 91 (12), 77 (22), 65 (8), 51
(7); IR (nujol): n¼3473, 3057, 1584, 1490, 1132, 1045, 859,
820, 738, 697 cmÀ1; anal. calcd. for C18H16OS: C 77.11, H 5.75;
found: C 77.07, H, 5.71.
Acknowledgements
This workwas supported by M. I. U. R. (Rome), National proj-
ect ™Stereoselezione in Sintesi Organica: Metodologie and Ap-
plicazioni∫, FIRB Project (Progettazione, preparazione e valu-
tazione biologica e farmacologica di nuove molecole organiche
quali potenziali farmaci innovativi) and from University of Bo-
logna (Funds for selected research topics). MF thanks Consor-
zio Spinner fellowship and Great Lakes Manufacturing, Italy
for the generous gift of Amberlyst-15.
(S)-2-(2-Thionaphthalenyl)-2-(3-chlorophenyl)-ethan-
1-ol (5b)
Yellow oil; yield (total of the two regioisomers): 65%; M. W.¼
314.84; 5b:5’b ratio¼91:9; Rf ¼0.3 (cyclohexane/AcOEt,
85:15); [a]2D5: þ154.1 (c 1.4, CHCl3); ee 82% by HPLC: OD,
isocratic 85:15 n-hexane/i-PrOH, flow 0.5 mL/min, acquisition
wavelength 229 nm, tS ¼17.9 min, tR ¼25.7 min; 1H NMR
(300 MHz, CDCl3): d¼7.87 7.77 (4H, m), 7.52 7.23 (7H,
m), 4.42 (1H, t, J¼6.9 Hz), 3.98 (2H, m), 1.56 (1H, br);
13C NMR (75 MHz, CDCl3): d¼141.1, 134.5, 133.5, 132.5,
131.7, 130.5, 129.9, 129.7, 128.6, 128.2, 128.0, 127.7, 127.4,
126.6, 126.5, 126.3, 65.0, 55.6; GC-MS: m/z (relative in-
tensity)¼314 (16), 283 (14), 207 (22), 191 (8), 160 (100), 138
(63), 128 (44), 115 (23), 103 (61), 91 (40), 77 (34), 65 (12), 51
(22); IR (nujol): n¼3388, 3169, 3057, 2726, 2660, 1594, 1568,
1303, 1170, 1058, 943, 892, 850, 813, 722 cmÀ1; anal. calcd. for
C18H15ClOS: C 68.67, H 4.80; found: C 68.61, H 4.76.
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85 2986.
(1S,2R)-1-(2-Thionaphthalenyl)-1-phenylpropan-2-ol
(5c)
Colourless oil; yield: 67%; M. W.¼294.42 g/mol; Rf ¼0.3 (cy-
clohexane/AcOEt, 9:1); [a]2D5: þ231.2 (c 1.3, CHCl3); ee
90% by HPLC: OD, isocratic 85:15 n-hexane/i-PrOH, flow
0.5 mL/min, acquisition wavelength 229 nm, t(1R,2S) ¼13.5 min,
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drichimica Acta 2000, 33, 16 22.
1
t(1S,2R) ¼16.4 min; H NMR (200 MHz, CDCl3): d¼7.86 7.65
(4H, m), 7.52 7.23 (8H, m), 4.52 (1H, d, J¼5.5 Hz), 4.14
(1H, m), 1.98 (1H, br), 1.26 (3H, d, J¼6.2 Hz); 13C NMR
(50 MHz, CDCl3): d¼138.2, 133.5, 132.3, 131.7, 130.9, 129.4,
128.9, 128.5, 128.5, 127.7, 127.6, 127.3, 126.5, 126.2, 69.4, 61.4,
20.3; IR (nujol): n¼3457, 3421, 3051, 1719, 1623, 1583, 1489,
1267, 1123, 1066, 943, 907, 815, 735, 699 cmÀ1; anal. calcd. for
C19H18OS: C 77.51, H 6.16; found: C 77.45, H 6.11.
[6] For the use of InCl3-impregnated zeolite catalysts in rad-
ical acylation of aromatics, see: a) V. R. Choudhary, S. K.
Jana, N. S. Patil, Tetrahedron Lett. 2002, 43, 1105 1107;
b) V. R. Choudhary, S. K. Jana, N. S. Patil, S. K. Bharga-
va, Micropor. Mesopor. Mater. 2003, 57, 21 35.
[7] EP was calculated as: (In contentÂ3)/proton exchange
capacity (ffi4.7 mmol/g).
[8] M. Bandini, P. G. Cozzi, P. Melchiorre, A. Umani-Ron-
chi, J. Org. Chem. 2002, 67, 5386 5389.
(1R,2R,4S)-1-Hydroxy-2-(2-thionaphthalenyl)-
limonene (7)
[9] Enantiomerically pure epoxides are valuable electro-
philes for the synthesis of key synthetic building blocks,
see: a) A. B. Smith III, S. M. Pitram, A. M. Boldi, M. J.
Gaunt, C. Sfouggatakis, W. H. Moser, J. Am. Chem.
Colourless oil; yield: 50%, M. W.¼312.48 g/mol; Rf ¼0.3 (cy-
clohexane/AcOEt, 9:1); [a]2D5: þ88.8 (c 0.5, CHCl3);
1H NMR (300 MHz, CDCl3): d¼8.04 (1H, s), 7.87 7.77 (3H,
m), 7.57 7.51 (3H, m), 4.77 (2H, d, J¼7.8 Hz), 3.89 (1H, br),
2.38 (2H, dd, J1 ¼8.4, J2 ¼4.8 Hz), 1.89 1.65 (8H, m), 1.29
¬
Soc. 2003, 125, 14435 14445; b) M. Pasto, B. RodrÌguez,
¡
A. Riera, M. A. Pericas, Tetrahedron Lett. 2003, 44, 8369
8372.
Adv. Synth. Catal. 2004, 346, 573 578
asc.wiley-vch.de
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
577

Marco Bandini et al.
FULL PAPERS
[10] The ring-opening of functionalized epoxides by N-Me-in-
dole in the presence of a stoichiometric amount of SnCl4
has been recently used as the key step in the synthesis of
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S. Saleh-Hanna, T. Durst, Org. Lett. 2002, 4, 695 697.
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[12] A comparative ring opening reaction between (R)-1a
and 2a in the presence of 10 mol % of In(OTf)3 (wet
Et2O, rt, 24 h) was carried out. Under these optimal con-
ditions the desired b-indolyl alcohol 3aa was isolated
only in traces, 1,1-bisindolyl-2-phenylethane being the
major reaction product (yield: 85%), derived from the
double addition of 2a to phenylacetaldehyde (rearrange-
ment of 1a).
[18] A survey based on the SciFinder database revealed that
the ring opening of enantiomerically pure epoxides with
sulfur nucleophiles was published only by Tang et al. in
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SN2 mechanism. As support to this statement the ring
opening of (R)-1a with thiophenol was carried out using
20 mol % of Amb-In and the optical rotation value of
the corresponding (S)-hydroxy sulfide {ee¼68%, [a]D:
184 (c, 0.9, EtOH)} was compared with the known com-
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8997 9008.
[13] 1st cycle: yield¼53%, ee¼98%; 2nd cycle: yield¼67%,
ee¼98%; 3rd cycle: yield¼57%, ee¼98%; 4th cycle:
yield¼52%, ee¼96%; 5th cycle: yield¼56%, ee¼96%.
œ
[14] A. Biffis, R. Ricoveri, S. Campestrini, M. Kralik, K. Jer-
¡
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Chem. 1999, 35, 44 47.
578
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2004, 346, 573 578