(R)-4-(tert-Butyldimethylsilyloxy)cyclohex-2-enone
(+)-19.
4 S. K. Basra, M. G. B. Drew, J. Mann and P. D. Kane, J. Chem. Soc.,
Perkin Trans. 1, 2000, 3592.
The acetoxy adduct (–)-17 (1.00 g, 2.95 mmol, 1 equiv.) was
dissolved in MeOH (20 mL), K2CO3 was added (429 mg,
3.10 mmol, 1.05 equiv.) and stirred for 30 min. The reaction
mixture was diluted with brine (10 mL) and extracted with CHCl3
(3 ¥ 10 mL) and dried over MgSO4, reduced in vacuo and further
dried under reduced pressure for 12 h. The crude alcohol 16
(0.53 g, 1.79 mmol, 1 equiv.) was dissolved in dichloromethane
(6 mL) and TBSCl (539 mg, 3.58 mmol, 2 equiv.) was added
followed by DBU (0.67 mL, 4.48 mmol, 2.5 equiv.) in a dropwise
fashion. The reaction was stirred overnight at room temperature.
The reaction mixture was then diluted with ether (20 mL) washed
with 0.1 M HCl (2 ¥ 12 mL), saturated NaHCO3 (10 mL), then
dried over MgSO4. Filtration followed by solvent removal in vacuo
and flash column chromatography (CH2Cl2) gave (+)-19 (290 mg,
44%) as a colourless oil. Rf 0.15 (CH2Cl2); nmax (neat/cm-1) 3020,
3000, 2942, 2840, 1675, 1377, 1245; dH (400 MHz, CDCl3) 0.12
(3H, s, CH3), 0.13 (3H, s, CH3), 0.91 (9H, s, CH3), 1.95–2.05
(1H, m, CH2), 2.17–2.24 (1H, m, CH2), 2.30–2.39 (1H, m, CH2),
2.54–2.60 (1H, m, CH2), 4.50–4.55 (1H, m, CH), 5.92 (1H, ddd,
J = 1.0, 2.0, 10.0 Hz, CH), 6.83 (1H, ddd, J = 1.5, 2.5, 10.0 Hz,
CH); dC (100 MHz, CDCl3) -4.8 (CH3), -4.6 (CH3), 18.1 (C),
25.7 (CH3), 32.9 (CH2), 35.5 (CH2), 67.0 (CH), 128.7 (CH), 153.9
5 For previous examples in which the advantages of sulfur chemistry have
been linked to studies involving kinetic enzymatic resolution see: (a) B.
Haase and M. P. Schneider, Tetrahedron: Asymmetry, 1993, 4, 1017;
(b) S. Takano, O. Yamada, H. Iida and K. Ogasawara, Synthesis, 1994,
592.
6 For lead references concerning the reversibility of conjugate addition
of thiols to electron poor olefins see: (a) M. Suzuki, M. Mori, T. Niwa,
R. Hirata, K. Furuta, T. Ishikawa and R. Noyori, J. Am. Chem. Soc.,
1997, 119, 2376; (b) N. T. Nashed and E. T. Kaiser, J. Am. Chem. Soc.,
1981, 103, 3611; (c) V. van Axel Castelli, F. Bernardi, A. Della Cort, L.
Mandolini, I. Rossi and L. Schiaffino, J. Org. Chem., 1999, 64, 8122;
(d) B. M. Eschler, R. K. Haynes, M. D. Ironside, S. Kremmydas, D. D.
Ridley and T. W. Hambley, J. Org. Chem., 1991, 56, 4760.
7 R. J. Kazlauskas, A. N. E. Weissfloch, A. T. Rappaport and L. A.
Cuccia, J. Org. Chem., 1991, 56, 2656.
8 (a) U. Goergens and M. P. Schneider, J. Chem. Soc., Chem. Commun.,
1991, 1066; (b) M. J. Kim and Y. K. Choi, J. Org. Chem., 1992, 57,
1605.
9 P. Bayo´n, G. Marjanet, G. Toribio, R. Alibe´s, P. de March, M.
Figueredo and J. Font, J. Org. Chem., 2008, 73, 3486.
10 Z. Cabrera, G. Fernandez-Lorente, R. Fernandez-Lafuente, J. M.
Palomo and J. M. Guisan, J. Mol. Catal. B: Enzym., 2009, 57,
171.
11 (a) M. Matoba, T. Kajimoto and M. Node, Synlett, 2007, 1930; (b) M.
Node, K. Kumar, K. Nishide, S. Ohsugi and T. Miyamoto, Tetrahedron
Lett., 2001, 42, 9207.
12 Crystal structural data for compound (–)-4b: C14H18O4S; M = 282.34;
˚
˚
˚
trigonal, P32; a = 11.6708(9) A, b = 11.6708(9) A, c = 8.9661(14) A;
+
(CH), 198.8 (CO); HRMS (CI) cald. for C12H26O2SiN (MNH4 )
3
˚
U = 1057.6(2) A ; T = 293(2) K; Z = 3; 5382 reflections measured,
requires 244.17791; found 244.17786; [a]2D0 = +101.0 (c = 1.0,
2316 unique (Rint = 0.0168). The final wR2 was 0.0735 (all data). Flack
CHCl3); {lit. [a]2D0 = +107.1 (c = 1.3, CHCl3)}.25
-0.12(7). CCDC reference number 742464.
13 We were unable to find a direct precedent for the hydrogen bond-
mediated delivery proposed, however, the thiolate ring-opening of an
epoxide, proceeding with retention of configuration, was ascribed to a
similar interaction: A. Schwartz, P. B. Madan, E. Mohacsi, J. P. O’Brien,
L. J. Todaro and D. L. Coffen, J. Org. Chem., 1992, 57, 851; For a general
reference concerning diastereoselective nucleophilic addition to g-oxy-
a,b-unsaturatedelectrophiles see: Y. Aye, S. G. Davies, A. C. Garner,
P. M. Roberts, A. D. Smith and J. E. Thomson, Org. Biomol. Chem.,
2008, 6, 2195 and references therein.
(S)-4-(tert-Butyldimethylsilyloxy)cyclohex-2-enone
(–)-19.
The hydroxy adduct (+)-16 (1.30 g, 4.39 mmol, 1 equiv.) was
dissolved in dichloromethane (100 mL) and TBSCl (1.32 g,
8.77 mmol, 2 equiv.) was added. DBU (1.64 mL, 10.98 mmol,
2.5 equiv.) was then added dropwise and the mixture was stirred
overnight at room temperature. The reaction mixture was then
diluted with ether (60 mL) washed with 0.1 M HCl (2 ¥ 20 mL),
saturated NaHCO3 (20 mL), then dried over MgSO4. Upon
filtration and solvent removal in vacuo the crude product was
purified by flash column chromatography (CH2Cl2) to afford
(–)-19 (0.57 g, 57%) as a colourless oil with data in accord with
that reported. [a]2D0 = -102.0 (c = 2.0, CHCl3); {lit. [a]D = -115.94
(c = 1.06, CHCl3)}.24a
14 For an example how relative stereochemistry can dramatically influence
the outcome of the EKR of secondary alcohols see: L. M. Levy, I.
Lavandera and V. Gotor, Org. Biomol. Chem., 2004, 2, 2572.
15 X. Verdaguer, J. Va´zquez, G. Fuster, V. Bernardes-Ge´nisson, A. E.
Greene, A. Moyano, M. A. Perica`s and A. Riera, J. Org. Chem., 1998,
63, 7037.
16 B. M. Trost and Y. Tanigawa, J. Am. Chem. Soc., 1979, 101,
4413.
17 M. G. Edwards, M. N. Kenworthy, R. R. A. Kitson, A. Perry, M. S.
Scott, A. C. Whitwood and R. J. K. Taylor, Eur. J. Org. Chem., 2008,
4769.
Acknowledgements
18 M. Pour and E. Negishi, Tetrahedron Lett., 1996, 37, 4679.
19 Crystal structural data for compound (–)-17: C17H22O5S; M = 338.41;
We wish to thank UCD for an Ad Astra scholarship (A. O’B.), the
Pro-Bio Faraday Partnership, UK (B. S. M.), Dr. Jenny Rickerby
(UCD) for HPLC measurements, Dr. Helge Mu¨ller-Bunz (UCD)
for X-ray crystallography and finally Prof. Stan Roberts for helpful
advice.
˚
˚
˚
Triclinic, P1; a = 7.6102(9) A, b = 8.2782(10) A, c = 8.3471(8) A; U =
3
˚
410.05(8) A ; T = 100(2) K; Z = 1; 7913 reflections measured, 3785
unique (Rint = 0.0290). The final wR2 was 0.0826 (all data). Flack–
0.05(5). CCDC reference number 742465.
20 M. C. Carren˜o, J. L. G. Ruano, M. Garrido, M. P. Ruiza and G. Solladie´,
Tetrahedron Lett., 1990, 31, 6653.
21 D. R. Hookins and R. J. K. Taylor, personal communication.
22 (a) B. M. Trost, T. N. Salzman and K. Hiroi, J. Am. Chem. Soc., 1976,
98, 4887; (b) P. de March, M. Escoda, M. Figueredo, J. Font, E. Garc´ıa-
Garc´ıa and S. Rodr´ıguez, Tetrahedron: Asymmetry, 2000, 11, 4473.
23 E. G. Miller, D. R. Rayner, H. T. Thomas and K. Mislow, J. Am. Chem.
Soc., 1968, 90, 4861.
References
1 A. K. Gupta and R. J. Kazlauskas, Tetrahedron: Asymmetry, 1993, 4,
879.
2 (a) B. S. Morgan, D. Hoenner, P. Evans and S. M. Roberts, Tetrahedron:
Asymmetry, 2004, 15, 2807; (b) J. F. Bickley, P. Evans, A. Meek, B. S.
Morgan and S. M. Roberts, Tetrahedron: Asymmetry, 2006, 17, 355;
B. S. Morgan, S. M. Roberts and P. Evans, Tetrahedron Lett., 2006, 47,
5273.
3 S. R. Ghorpade, K. B. Bastawade, D. V. Gokhale, P. D. Shinde,
V. A. Mahajan, U. R. Kalkote and T. Ravindranathan, Tetrahedron:
Asymmetry, 1999, 10, 4115.
24 The synthesis of (S)-19 is frequently performed for target synthesis
and is typically performed from D-quinic acid (6 steps, 32% overall
yield): J. E. Audia, L. Boisvert, A. D. Patten, A. Villalobos and S. J.
Danishefsky, J. Org. Chem., 1989, 54, 3738; Modification of this route
enables the preparation of (R)-15 (6 steps, 18% overall yield): O.
Gebauer and R. Bru¨ckner, Liebigs Ann., 1996, 1559.
25 M. C. Witschel and H. J. Bestmann, Synthesis, 1997, 107.
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