35
F. Rota et al.
Letter
Synlett
give the epoxide 7f in moderate yield (Scheme 5). There are
relatively few methods available for accessing this type of
unfunctionalized 1,2-disubstituted epoxide19 in high enan-
tiopurity, so this approach may prove extremely useful.
(5) (a) List, B.; Lerner, R. A.; Barbas, C. F. III. J. Am. Chem. Soc. 2000,
122, 2395. (b) Northrup, A. B.; MacMillan, D. W. C. J. Am. Chem.
Soc. 2002, 124, 6798. (c) Beeson, T. D.; MacMillan, D. W. C. J. Am.
Chem. Soc. 2005, 127, 8826. (d) Cobb, A. J. A.; Shaw, D. M.; Ley, S.
V. Synlett 2004, 558. (e) Yamamoto, Y.; Momiyama, N.;
Yamamoto, H. J. Am. Chem. Soc. 2004, 126, 5962.
(6) (a) Hayashi, Y.; Gotoh, H.; Hayashi, T.; Shoji, M. Angew. Chem.
Int. Ed. 2005, 44, 4212. (b) Franzén, J.; Marigo, M.; Fielenbach,
D.; Wabnitz, T. C.; Kjærsgaard, A.; Jørgensen, K. A. J. Am. Chem.
Soc. 2005, 127, 18296.
i. Me3OBF4
OH
MeNO2, CH2Cl2
O
Ph
n-Bu
Ph
n-Bu
ii. NaOH, CH2Cl2
SPh
ent-5f
7f 54%
(7) (a) Steiner, D. D.; Mase, N.; Barbas, C. F. III. Angew. Chem. Int. Ed.
2005, 44, 3706. (b) Marigo, M.; Schulte, T.; Franzen, J.;
Jørgensen, K. A. J. Am. Chem. Soc. 2005, 127, 15710.
Scheme 5 Conversion of a β-hydroxysulfide into an enantioenriched
1,2-disubstituted epoxide
(8) (a) Marigo, M.; Wabnitz, T. C.; Fielenbach, D.; Jørgensen, K. A.
Angew. Chem. Int. Ed. 2005, 44, 794. (b) Armstrong, A.; Challinor,
L.; Moir, J. H. Angew. Chem. Int. Ed. 2007, 46, 5369.
(c) Armstrong, A.; Deacon, N.; Donald, C. Synlett 2011, 2347.
(9) (a) Brown, M. D.; Whitham, G. H. J. Chem. Soc., Perkin Trans. 1
1988, 817. (b) Watanabe, M.; Komota, M.; Nishimura, M.; Araki,
S.; Butsugan, Y. J. Chem. Soc., Perkin Trans. 1 1993, 2193.
(c) Enders, D.; Schäfer, T.; Piva, O.; Zamponi, A. Tetrahedron
1994, 50, 3349. (d) Enders, D.; Piva, O.; Burkamp, F. Tetrahedron
1996, 52, 2893.
In conclusion, we have demonstrated that asymmetric
organocatalytic sulfenylation of aldehydes can be employed
in the synthesis of enantioenriched secondary alcohols and
1,2-disubstituted epoxides via short synthetic routes. This
approach can provide access to enantiomerically enriched
chiral building blocks which are difficult to access via exist-
ing approaches.
(10) Dubey, R.; Polaske, N. W.; Nichol, G. S.; Olenyuk, B. Tetrahedron
Lett. 2009, 50, 4310.
(11) (a) Dale, J. A.; Dull, D. A.; Mosher, H. S. J. Org. Chem. 1969, 34,
2543. (b) Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973, 95,
512. (c) Sullivan, G. R.; Dale, J. A.; Mosher, H. S. J. Org. Chem.
1973, 38, 2143.
Acknowledgment
We would like to thank the Leverhulme Trust (studentship to F.R.,
F/00 134/CL) and the Engineering and Physical Sciences Research
Council (PDRA funding to L.B., EP/K001183/1; Advanced Research Fel-
lowship to T.D.S., EP/E052789/1) for supporting this work. We would
also like to acknowledge the EPSRC UK National Mass Spectrometry
Facility at Swansea University for analysis of some of the compounds
prepared in this work.
(12) General Procedure for the Preparation of β-Hydroxysulfides
5
A solution of aldehyde (1 equiv) and catalyst 2 (0.1 equiv) was
stirred in toluene (1.3 M) for 15 min. A solution of sulfenyltri-
azole 3 (1.3 equiv) in toluene (1.6 M) was added dropwise, and
the resulting mixture was stirred under argon at r.t. for 24 h.
The reaction mixture was then quickly sucked under vacuum
through a pre-wet (toluene) pad of silica (ca. 1.5 g per 100 mg of
aldehyde) and washed with toluene (10 mL per 100 mg of alde-
hyde). The filtrate was added dropwise to a solution of the
organometallic reagent (3–4 equiv) cooled to –78 °C (for Li
reagents) or –10 °C (for Grignard reagents). The reaction was
monitored by TLC and stirred until all the intermediate α-sulfenyl-
aldehyde was consumed. The reaction was then quenched with
sat. NH4Cl and partitioned between H2O and Et2O. The aqueous
layer was extracted with Et2O, and the combined organic layers
were washed with brine, dried over MgSO4, filtered, and evapo-
rated to dryness. The crude β-hydroxysulfide was purified by
column chromatography (PE–Et2O).
Supporting Information
Supporting information for this article is available online at
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References and Notes
(1) Current address: Dr. Filippo Rota, Principal Scientist, Abcam,
Unit 3, Avon Riverside Estate, Victoria Rd, Bristol BS11 9DB, UK.
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Nozaki, K.; Kumobayashi, H.; Sayo, N.; Hori, Y.; Ishizaki, T. J. Org.
Chem. 1994, 59, 3064. (b) Itsuno, S.; Ito, K.; Hirao, A.; Nakahama,
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Wang, Y. M.; Hunziker, D.; Petter, W. Helv. Chim. Acta 1992, 75,
2171. (c) Ishizaki, M.; Fujita, K.-I.; Shimamoto, M.; Hoshino, O.
Tetrahedron: Asymmetry 1994, 5, 411. (d) Dai, Z.; Zhu, C.; Yang,
M.; Zheng, Y.; Pan, Y. Tetrahedron: Asymmetry 2005, 16, 605.
(e) Brown, H. C.; Jadhav, P. K. J. Am. Chem. Soc. 1983, 105, 2092.
(4) (a) Abbasov, M. E.; Romo, D. Nat. Prod. Rep. 2014, 31, 1318.
(b) Scheffler, U.; Mahrwald, R. Chem. Eur. J. 2013, 19, 14346.
(c) Mennino, S.; Lattanzi, A. Chem. Commun. 2013, 49, 3821.
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114, 2390.
(2R,3S)-3-(Phenylthio)octan-2-ol (5a)
25
[α]D –4.2 (c 1.0, CHCl3). IR (film): νmax = 3414, 3060, 2959,
2929, 2858, 1584, 1466, 1439, 1279, 1139 cm–1. Isolated as a
91:9 mixture of diastereoisomers. 1H NMR (600 MHz, CDCl3): δ
(major isomer): 0.88 (3 H, t, J = 6.8 Hz, CH2CH3), 1.19 (3 H, d, J =
6.4 Hz, CHCH3), 1.27–1.71 (8 H, m, 4 × CH2), 2.33 (1 H, br s, OH),
3.16 (1 H, ddd, J = 9.4, 5.8, 3.2 Hz, SCH), 3.89 (1 H, qd, J = 6.4, 3.2
Hz, CHOH), 7.22–7.30 (3 H, m, 3 × ArH), 7.44 (2 H, d, J = 7.7 Hz,
2 × ArH). 13C NMR (150 MHz, CDCl3): δ = 14.2, 19.1, 22.6, 27.5,
30.1, 31.8, 58.7, 68.3, 127.1, 129.2, 132.0, 135.5. 1H NMR (600
MHz, CDCl3): δ (minor isomer): 0.88 (3 H, t, J = 6.8 Hz, CH2CH3),
1.25 (3 H, d, J = 6.1 Hz, CHCH3), 1.27–1.71 (8 H, m, 4 × CH2), 2.91
(1 H, ddd, J = 9.6, 6.5, 3.2 Hz, SCH), 3.72 (1 H, dq, J = 6.5, 6.1 Hz,
CHOH), 7.22–7.30 (3 H, m, 3 × ArH), 7.44 (2 H, d, J = 7.7 Hz,
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 33–36