Indium-bipyridine-catalyzed, enantioselective thiolysis of meso-epoxides

Article abstract of DOI:10.1039/b703625f

The indium-bipyridine-catalyzed, enantioselective ring-opening of meso-epoxides with aliphatic and aromatic thiols furnished 1,2-mercapto alcohols in good yields and excellent enantioselectivities; the crystal structure of the chiral catalyst reveals a pe

Full text of DOI:10.1039/b703625f

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Indium–bipyridine-catalyzed, enantioselective thiolysis of meso-
epoxides{
a
Mecheril Valsan Nandakumar, Andreas Tsch o¨ p, Harald Krautscheid and Christoph Schneider*
a
b
a
Received (in Cambridge, UK) 12th March 2007, Accepted 3rd April 2007
First published as an Advance Article on the web 24th April 2007
DOI: 10.1039/b703625f
The indium–bipyridine-catalyzed, enantioselective ring-opening
Lewis acids and Lewis acid–chiral ligand combinations as catalysts
for this reaction (Table 1). Eventually, we identified indium(III)
halide–bipyridine 1a complexes as the most suitable chiral catalysts
which not only possessed sufficient Lewis acidity to activate the
epoxide towards nucleophilic ring-opening but also readily
tolerated the Lewis basic thiol. Thus, 10 mol% of InCl3 and
of meso-epoxides with aliphatic and aromatic thiols furnished
1,2-mercapto alcohols in good yields and excellent enantio-
selectivities; the crystal structure of the chiral catalyst reveals a
pentagonal-bipyramidal coordination geometry around the
indium center.
1
1 mol% of bipyridine 1a afforded 1,2-mercapto alcohol 4a in 60%
yield and 95% ee after 6 days at rt (entry 4). The reaction was
markedly accelerated by employing 10 mol% of InBr and 11 mol%
The catalytic asymmetric ring-opening of meso-epoxides has
proven to be a valuable tool for the straightforward synthesis of
enantiomerically highly enriched 1,2-difunctionalized fine chemi-
3
bipyridine 1a, which furnished 4a in 80% yield and 92% ee after
just 16 h at rt (entry 5). Interestingly, no product formation was
observed in the absence of the chiral ligand or when the
unsubstituted 2,29-bipyridine, which lacks the additional hydroxyl
groups, was employed as the ligand (entries 1–3). Also, the bis-
O-methylated bipyridine 1b failed to give a reactive indium(III)
catalyst (entry 6). These results clearly indicate the combined effect
of the metal center and the hydroxyl protons for the epoxide
opening reaction, similar to what we had observed in the
scandium–bipyridine-catalyzed alcoholysis and aminolysis of
1
2
cals. In particular, chiral 1,2-amino alcohols and 1,2-azido
3
4
5
alcohols, 1,2-diol derivatives, 1,2-cyano alcohols and 1,2-
6
halohydrins have become available in excellent optical purities
using this strategy. Among the processes reported for the addition
7
of thiols to meso-epoxides, a heterobimetallic gallium–lithium–
BINOL complex has been established by Shibasaki et al. as the
7a
most enantioselective catalyst currently known for this reaction.
Unfortunately, the use of tert-butyl thiol is mandatory here to
avoid undesired ligand exchange on the metal center which
significantly limits the applicability of this process.
8
a
meso-epoxides.
3
Employing 10 mol% of InBr –bipyridine 1a as catalyst, cis-
We have reported recently a highly enantioselective catalyst for
the alcoholysis and aminolysis of meso-epoxides composed of
stilbene oxide (2a) was ring-opened with various aromatic as well
as aliphatic thiols, furnishing 1,2-mercapto alcohols 4a–f in
typically good to very good yields and excellent enantioselectivities
of up to 96% ee (Table 2, entries 1–6). There appears to be no
structural or electronic limitation in the thiol component and
straight-chain aliphatic thiols even give rise to some of the most
enantioselective reactions included in this study (entries 4–6). Other
aromatic meso-epoxides were subsequently ring-opened with
thiophenol and benzylthiol, and furnished the corresponding 1,2-
mercapto alcohols 4g–m in generally good yields and high
8a,b
scandium triflate and bipyridine 1a (Fig. 1).
With just 5 mol%
of the metal–ligand complex formed in situ, meso-epoxides were
ring-opened with anilines and aliphatic alcohols to furnish 1,2-
8c
8d
amino alcohols and 1,2-diol monoethers, respectively, in good
yields and up to 97% ee. We have now extended this protocol to
the enantioselective thiolysis of meso-epoxides and show here that
an indium–bipyridine complex formed in situ from InBr3 and
9,10
bipyridine 1a is an effective chiral catalyst for this endeavour.
We started our investigations with the reaction of cis-stilbene
oxide (2a) and benzylthiol (3a) and screened a broad range of
Table 1 Optimization studies
3
Fig. 1 1a R = H, 1b R = CH .
a
b
Entry Lewis acid Ligand
Time Yield (%)
ee (%)
a
Institut f u¨ r Organische Chemie, Universit a¨ t Leipzig, Johannisallee 29,
4103 Leipzig, Germany. E-mail: schneider@chemie.uni-leipzig.de;
Fax: +49 341 9736599; Tel: +49 341 9736529
1
2
3
4
5
6
a
InCl
InBr
InBr
3
—
—
48 h
48 h
—
—
—
60
80
—
—
—
—
95
92
—
0
3
3
2,29-Bipyridyl 48 h
b
Institut f u¨ r Anorganische Chemie, Universit a¨ t Leipzig, Johannisallee
InCl
3
1a
1a
1b
6 d
16 h
6 d
2
9, 04103 Leipzig, Germany. E-mail: krautscheid@rz.uni-leipzig.de;
Fax: +49 341 36199; Tel: +49 341 9736172
Electronic supplementary information (ESI) available: Experimental
InBr
InBr
3
3
{
b
Isolated yields of chromatographed material. Determined from
procedures, HPLC data, and spectral data for all new compounds. See
DOI: 10.1039/b703625f
chiral HPLC analysis (see supplementary information).
2
756 | Chem. Commun., 2007, 2756–2758
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Table 2 Indium–bipyridine-catalyzed ring opening of meso-epoxides
with thiols
a
b
c,d
ee (%)
Entry Ar
R
Yield (%)
1
2
3
4
5
6
7
8
9
0
1
2
3
C
C
C
C
C
C
6
6
6
6
6
6
H
H
H
H
H
H
5
5
5
5
5
5
C
C
6
H
H
5
CH
2
80 (4a)
81 (4b)
79 (4c)
91 (4d)
90 (4e)
89 (4f)
79 (4g)
82 (4h)
67 (4i)
76 (4j)
68 (4k)
92
96
96
.95
95
96
96
96
91
85
92
92
93
6
5
4-Me-C
CH CH
n-Bu
(CH
C
C
C
C
C
C
C
6
H
4
3
2
+
Fig. 2 ORTEP (50% ellipsoid) of the [InBr ?1a?H O] moiety in the
2
2
3
)
2
CH(CH
2
)
2
2 2 2
X-ray crystal structure of [InBr ?1a?H O]Br?THF?4H O.
2-Naphthyl
2-Naphthyl
3-Me-C
4-Me-C
4-Me-C
6
6
6
6
6
6
6
H
H
H
H
H
H
H
5
5
5
5
5
5
5
CH
2
+
6
6
6
H
H
H
4
4
4
a molecular peak at 602.9533 for [M] which further corroborated
the molecular formula InBr
1
1
1
1
a
2 20 28 2 2
C H N O .
CH
2
2
e
Considering the failure of any indium(III)–bipyridine catalyst
lacking the additional hydroxyl groups, it is most likely that the
chiral catalyst exhibits a combined Lewis acid–Brønsted acid
activity, with the Lewis acidic indium center activating the epoxide
and the hydroxyl protons possibly forming a hydrogen bond to the
incoming thiol, thereby guiding it to the epoxide.
4-Cl-C
4-Cl-C
6
H
H
4
84 (4l)
67 (4m)
e
6
4
CH
Reaction conditions: 10 mol% InBr
3
, 11 mol% bipyridine 1a,
2 2
.5 equiv. thiol, CH Cl , rt, 16 h. Isolated yields of chromato-
c
b
1
graphed material. Determined from chiral HPLC analysis (see
d
supplementary information). The absolute configuration of 4b was
proven to be 1R,2R through conversion into the corresponding
known sulfone; the configurations of all other products were
1
1
In conclusion, we have devised a novel chiral catalyst for the
highly enantioselective thiolysis of aromatic meso-epoxides, with
aromatic as well as aliphatic thiols furnishing 1,2-mercapto
alcohols in good yields and excellent enantioselectivities. Most
importantly, there is no restriction to a specific thiol. A crystal
structure analysis of the chiral catalyst reveals a pentagonal-
bipyramidal coordination geometry around the indium center with
both nitrogen and oxygen atoms coordinating to the metal.
Additional hydrogen-bonding between the catalyst and the
incoming nucleophile appears to activate and direct the incoming
nucleophile to the indium-bound epoxide.
e
assigned by analogy. Reaction time: 6 d.
enantioselectivities (entries 7–13). Unfortunately, aliphatic meso-
epoxides currently give rise to only low enantioselectivity in the
indium–bipyridine-catalyzed thiolysis.
The product 1,2-mercapto alcohols 4 may be employed as
substrates for desulfurization reactions, furnishing chiral, highly
12
enantiomerically enriched alcohols. Thus, nickel boride reduction
of 4a afforded alcohol 5 in good yield and almost identical
enantiomeric excess as 4a, proving that the reaction had not
affected the stereochemistry of the adjacent carbinol center
Generous financial support was provided by the Deutsche
Forschungsgemeinschaft (Schn 441/3-2). We thank Wacker AG
for providing chemicals and Dr Claudia Birkemeyer (University of
Leipzig) for recording the ESI-MS spectra of the indium–
bipyridine complex.
(
Scheme 1).
Accordingly, the sequential thiolysis–desulfurization of meso-
epoxides constitutes an elegant alternative to the still elusive
13
enantioselective hydride addition to epoxides.
A single crystal of the indium(III)–bipyridine complex suitable
for X-ray crystallography was obtained from tetrahydrofuran–
Notes and references
14
+
O] complex (the
H
2
O solution. The cationic [InBr ?1a?H
2
2
1 Reviews: (a) C. Schneider, Synthesis, 2006, 3919; (b) I. M. Pastor and
M. Yus, Curr. Org. Chem., 2005, 9, 1; (c) E. N. Jacobsen and M. H. Wu,
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and H. Yamamoto, Springer, Berlin, 1999, vol. 3, p. 1309.
2 (a) X. L. Hou, J. Wu, L. X. Dai, L. J. Xia and M. H. Tang,
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A. Carlone, M. Locatelli, M. Massaccesi, P. Melchiorre and L. Sambri,
Org. Lett., 2004, 6, 2173; (e) F. Carree, R. Gil and J. Collin, Tetrahedron
Lett., 2004, 45, 7749; (f) F. Carree, R. Gil and J. Collin, Org. Lett., 2005,
bromide counter anion is omitted for clarity) depicted in Fig. 2
is characterized with a pentagonal-bipyramidal coordination
geometry around the indium(III) center, which is tetracoordinated
by the bipyridine ligand 1a through both nitrogen and oxygen
atoms. Significantly, both hydroxyl protons are still attached to the
catalyst. The crystal structure very closely resembles the structure
1
5
of the scandium(III)–bipyridine catalyst, and both catalysts also
exhibit the same sense of asymmetric induction in epoxide-opening
7, 1023.
8
reactions. Additional high resolution ESI-MS measurements gave
3
4
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Scheme 1 Desulfurization of 1,2-mercapto alcohol 4a.
This journal is ß The Royal Society of Chemistry 2007
Chem. Commun., 2007, 2756–2758 | 2757

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B. M. Cole, C. A. Krueger, K. W. Kuntz, M. L. Snapper and
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10 After the work described herein had been carried out and while the
manuscript was being prepared, a related report about a scandium–
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11 S. Nakamura, R. Nakagawa, Y. Watanabe and T. Toru, J. Am. Chem.
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12 T. G. Back, D. L. Barton and K. Yang, J. Org. Chem., 1993, 58,
2407.
13 For a mechanistically different approach towards formal enantioselec-
tive hydride addition to meso-epoxides, see: A. Gans a¨ uer, T. Lauterbach,
H. Bluhm and M. Noltemeyer, Angew. Chem., 1999, 111, 3112, (Angew.
Chem., Int. Ed., 1999, 38, 2909); A. Gans a¨ uer, H. Bluhm, B. Rinker,
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2003, 9, 531.
7
8
14 Crystallographic data for the complex: single crystal from THF–H
46Br InN , M = 845.18, orthorhombic, a = 8.3069(3), b =
17.0302(6), c = 23.6466(9) A, U = 3345.2(2) A , T = 180(2) K, space
2
O,
24
C H
3
2 8
O
3
˚
˚
21
1 1 1 c
group P2 2 2 (No. 19), Z = 4, m(Mo-Ka) = 4.333 mm , D =
23
1.678 g cm , 26 247 reflections measured, 7293 unique (Rint = 0.0413),
which were used in all calculations. The final R1 = 0.0407 and wR2 =
0.0892 (all data). G. M. Sheldrick, SHELXS-97, SHELXL-97.
Programs for crystal structure determination, University of G o¨ ttingen,
Germany, 1997. CCDC 640641. For crystallographic data in CIF or
other electronic format, see DOI: 10.1039/b703625f.
2
585.
For non-enantioselective indium(III)-catalyzed thiolyses of epoxides, see:
a) J. S. Yadav, B. V. S. Reddy and G. Baishya, Chem. Lett., 2002, 31,
06; (b) F. Fringuelli, F. Pizzo, S. Tortoioli and L. Vaccaro, Adv. Synth.
9
(
9
15 S. Ishikawa, T. Hamada, K. Manabe and S. Kobayashi, J. Am. Chem.
Soc., 2004, 126, 12236.
2
758 | Chem. Commun., 2007, 2756–2758
This journal is ß The Royal Society of Chemistry 2007