2855, 1584, 1480, 1438, 1254, 1191, 1090, 1011, 982, 910, 856,
838, 777, 736, 690; δH (600 MHz; CDCl3) 7.40–7.14 (15H, m,
Ar), 4.89 (1H, d, J 8.8, PhCH), 4.24 (1H, dd, J 8.8, 4.1, 14-H),
4.16–4.12 (1H, m, 2-H), 4.06–4.02 (1H, m, CHAHBOH), 3.92–
3.89 (2H, m, CHAHBOH, 15-H), 3.82 (1H, d, J 10.3, OH), 3.22
(1H, dd, J 13.3, 3.9, PhSCHAHB), 2.94 (1H, dd, J 13.3, 7.9,
PhSCHAHB), 2.88 (1H, dd, J 13.2, 6.8, PhSCHЈAHЈB), 2.75
(1H, dd, J 13.2, 5.1, PhSCHЈAHЈB), 2.66–2.62 (1H, m, 9-H),
1.90–1.00 (12H, m), 0.88 (9H, s, But), 0.09 (3H, s, Me), Ϫ0.32
(3H, s, Me); δC (50 MHz; CDCl3) 142.1, 137.7, 136.4, 128.8,
128.7, 128.7, 127.6, 127.6, 127.5, 125.8, 125.5 (Ar), 97.6, 95.8
(6-C, 7-C), 74.5, 72.0, 71.6, 70.1, 69.1 (2-C, 9-C, 14-C, 15-C,
PhCH), 63.0 (CH2OH), 39.3 (CH2SPh), 38.7 (CH2SPh),
29.5, 29.4, 29.2, 28.1, 17.9, 17.8 (3-C, 4-C, 5-C, 10-C, 11-C,
12-C), 25.7 (But), 17.9 (But), Ϫ4.0 (Me), Ϫ5.4 (Me); m/z (CI)
740 (MNH4ϩ, 10%), 723 (MHϩ, 16), 705 (32), 411 (100), 303
(47) [Found (MHϩ) 723.3210. C40H55O6SiS2 requires MH,
723.3209].
492 (95), 475 (100) [Found (MHϩ) 787.3010. C40H55O10SiS2
requires MH, 787.3006].
(2R,3R,4S)-4-(tert-Butyldimethylsilyloxy)-4-phenylbutane-
1,2,3-triol 30
To a stirred solution of 29 (35.3 mg, 0.045 mmol) in THF (1.0
ml) under argon was added a solution of lithium bis(trimethyl-
silyl)amide (1.0 M in THF, 0.12 ml, 0.12 mmol, 2.5 eq.) at 0 ЊC,
and the resulting mixture was stirred for 30 min at room tem-
perature. The reaction mixture was quenched with saturated
NH4Cl aquous solution and then extracted with ether (×3). The
combined organic extracts were dried (Na2SO4) and concen-
trated in vacuo. The resulting residue was purified by flash
chromatography (eluent: ether–petrol 1:1→neat ether; gradi-
ent) to give the title compound 30 (7.5 mg, 0.024 mmol, 53%) as
a colourless oil; [α]D23 ϩ32.0 (c 0.75, CHCl3); νmax(film)/cmϪ1 3415,
2954, 2929, 2857, 1635, 1472, 1389, 1306, 1254, 1085, 910, 838,
779, 734; δH (600 MHz; CDCl3) 7.39–7.29 (5H, m, Ar), 4.79
(1H, d, J 6.2, 4-H), 3.84–3.78 (3H, m, 2 × H-1, 3-H), 3.60 (1H,
td, J 6.7, 4.2, 2-H), 2.99 (1H, br, OH), 2.27 (1H, br, OH), 1.60
(1H, br, OH), 0.89 (9H, s, But), 0.06 (3H, s, Me), Ϫ0.19 (3H, s,
Me); δC (50 MHz; CDCl3) 140.4, 128.3, 128.1, 127.3 (Ar), 77.2,
76.4, 71.9 (2-C, 3-C, 4-C), 63.9 (1-C), 25.7 (But), 18.0 (But),
Ϫ4.6 (Me), Ϫ5.2 (Me); m/z (CI) 330 (MNH4ϩ, 10%), 313
(MHϩ, 19%), 198 (100) [Found (MHϩ) 313.1835. C16H29O4Si
requires MH, 313.1835].
28: [α]D23 Ϫ16.4 (c 1.22, CDCl3); νmax(film)/cmϪ1 3424, 2927,
2855, 1584, 1480, 1438, 1258, 1200, 1104, 1036, 836, 777, 737,
690; δH (600 MHz; CDCl3) 7.34–7.14 (15H, m, Ar), 4.67–4.65
(1H, m, PhCH), 3.94–3.91 (2H, m, 14-H, 15-H), 3.84–3.80 (1H,
m, 2-H), 3.60–3.55 (1H, m, CHAHBOH), 3.48–3.42 (1H, m,
CHAHBOH), 3.37–3.32 (1H, m, 9-H), 3.06 (1H, dd, J 13.4, 6.0,
PhSCHAHB), 3.01 (1H, dd, J 13.5, 7.2, PhSCHЈAHЈB), 2.93
(1H, dd, J 13.4, 6.0, PhSCHAHB), 2.85 (1H, dd, J 13.5, 5.0,
PhSCHЈAHЈB), 1.91 (1H, dd, J 7.9, 5.1, OH), 1.75–1.06 (12H,
m), 0.90 (9H, s, But), 0.08 (3H, s, Me), Ϫ0.16 (3H, s, Me); δC (50
MHz; CDCl3) 142.0, 137.6, 137.3, 129.0, 128.7, 128.7, 128.4,
127.6, 127.1, 127.0, 125.7, 125.4 (Ar), 96.6, 96.3 (6-C, 7-C),
75.9, 72.0, 69.8, 69.7, 69.3 (2-C, 9-C, 14-C, 15-C, PhCH), 62.6
(CH2OH), 39.3 (CH2SPh), 39.1 (CH2SPh), 30.1, 29.6, 27.6,
27.6, 18.3, 18.0 (3-C, 4-C, 5-C, 10-C, 11-C, 12-C), 25.9 (But),
18.2 (But), Ϫ4.7 (Me); m/z (CI) 740 (MNH4ϩ, 12%), 411 (11),
132 (53), 126 (56), 52 (100) [Found (MNH4ϩ) 740.3480.
C40H58O6NSiS2 requires MNH4, 740.3475].
Acknowledgements
We acknowledge financial support from the BP Endowment
(to S. V. L.), the Novartis Research Fellowship (to S. V. L. and
D. L.), the Japan Society for the Promotion of Science (to
M. F.) and Pfizer Limited (to D. L.). We are also grateful to the
EPSRC mass spectrometry service at Swansea.
References and notes
1 Dispiroketals in synthesis. Part 24: D. Lainé, M. Fujita and S. V.
Ley, J. Chem. Soc., Perkin Trans. 1, 1999, 1639.
2 P. M. Collins and R. J. Ferrier, Monosaccharides, John Wiley &
Sons, Chichester, 1995.
(2R,6S,7S,9R,14R,15R)-14-[(S)-(tert-Butyldimethylsilyloxy)-
phenylmethyl]-15-hydroxymethyl-2,9-bis(phenylsulfonylmethyl)-
1,8,13,16-tetraoxadispiro[5.0.5.4]hexadecane 29
To a solution of 27 (37.9 mg, 0.0524 mmol) in CH2Cl2 (2 ml),
was added MCBPA (50–60% purity, 90 mg, 0.26 mmol) at 0 ЊC.
The mixture was allowed to warm up to room temperature and
stirred for 1.5 h. The reaction was quenched with a saturated
Na2SO3 aqueous solution at 0 ЊC, and extracted with CH2Cl2
(×4). The combined organic phases were dried (Na2SO4) and
evaporated in vacuo. The resulting residue was purified by flash
chromatography (eluent: neat ether) to afford the title com-
pound 29 (36.3 mg, 0.0461 mmol, 88%) as a white solid; mp
118 ЊC (ether); [α]D23 Ϫ41.7 (c 1.54, CHCl3); νmax(film)/cmϪ1 3520,
3056, 2933, 1770, 1586, 1447, 1365, 1303, 1261, 1202, 1148,
1087, 1067, 1039, 1006, 970, 909, 860, 838, 780, 735, 688;
δH (600 MHz; CDCl3) 7.93 (2H, d, J 7.6, Ar), 7.89 (2H, d, J 7.6,
Ar), 7.67 (1H, t, J 7.4, Ar), 7.60–7.53 (5H, m, Ar), 7.49 (2H, t,
J 7.7, Ar), 7.35 (2H, t, J 7.6, Ar), 7.26 (1H, t, J 7.3, Ar), 4.81
(1H, d, J 8.5, PhCH), 4.48 (1H, td, J 8.5, 2.8, 2-H), 4.25 (1H,
dd, J 8.5, 3.9, 14-H), 4.02–3.97 (1H, m, CHAHBOH), 3.88–3.85
(1H, m, 15-H), 3.72 (1H, dd, J 12.1, 2.0, CHAHBOH), 3.40 (1H,
br, OH), 3.33 (1H, dd, J 14.1, 3.3, PhSO2CHAHB), 3.29–3.22
(2H, m, PhSCHЈAHЈB, 9-H), 3.15 (1H, dd, J 14.1, 8.3, PhSCHA-
HB), 3.00–2.95 (1H, m, PhSCHЈAHЈB), 1.84 (1H, br d, J 12.7),
1.64–0.87 (10H, m), 0.92 (9H, s, But), 0.59 (1H, br d, J 13.7),
0.08 (3H, s, Me), Ϫ0.25 (3H, s, Me); δC (50 MHz; CDCl3) 141.4,
141.1, 139.8, 133.7, 132.9, 129.3, 128.9, 127.9, 127.8, 127.7,
127.7, 127.6 (Ar), 97.2, 95.6 (6-C, 7-C), 74.7, 72.0, 71.1, 65.8,
64.9 (2-C, 9-C, 14-C, 15-C, PhCH), 61.9, 61.9, 61.6 (CH2OH,
2 × CH2SPh), 30.9, 29.7, 28.6, 27.9, 17.5, 17.0 (3-C, 4-C, 5-C,
10-C, 11-C, 12-C), 25.8 (But) 18.0 (But), Ϫ4.1 (Me), Ϫ5.3 (Me);
m/z (CI) 804 (MNH4ϩ, 45%), 787 (MHϩ, 92), 672 (58), 647 (75),
3 Y. Hirata, D. Uemura, K. Ueda and S. Takano, Pure Appl. Chem.,
1979, 51, 1875; D. Uemura, K. Ueda, Y. Hirata, H. Naoki and
T. Iwashita, Tetrahedron Lett., 1981, 22, 1909, 2781; P. J. Scheuer
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4 N. Minami, S. S. Ko and Y. Kishi, J. Am. Chem. Soc., 1982, 104,
1109; A. W. M. Lee, V. S. Martin, S. Masamune, K. B. Sharpless and
F. J. Walker, J. Am. Chem. Soc., 1982, 104, 3315; S. Y. Ko, A. W. M.
Lee, S. Masamune, L. A. Reed, III, K. B. Sharpless and F. J. Walker,
Science, 1983, 220, 949.
5 For a comprehensive review of dispiroketal chemistry see: S. V. Ley,
R. Downham, P. J. Edwards, J. E. Innes and M. Woods, Contemp.
Org. Synth., 1995, 2, 365.
6 (a) S. V. Ley, S. Mio and B. Meseguer, Synlett, 1996, 787; (b) S. V.
Ley and S. Mio, Synlett, 1996, 789; (c) S. V. Ley, S. Mio and
B. Meseguer, Synlett, 1996, 791.
7 N. L. Douglas, S. V. Ley, U. Lücking and S. L. Warriner, J. Chem.
Soc., Perkin Trans. 1, 1998, 51; G.-J. Boons, P. Grice, R. Leslie,
S. V. Ley and L. L. Yeung, Tetrahedron Lett., 1993, 34, 8523.
8 B. C. B. Bezuidenhoudt, G. H. Castle and S. V. Ley, Tetrahedron
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J. V. Geden and S. V. Ley, Tetrahedron Lett., 1994, 35, 7451; G. H.
Castle and S. V. Ley, Tetrahedron Lett., 1994, 35, 7455.
9 In referring to diastereoisomers obtained from reaction of non-
chiral starting materials, their racemic nature is assumed and only
one enantiomeric form is depicted in their formulae.
10 G.-J. Boons, R. Downham, K. S. Kim, S. V. Ley and M. Woods,
Tetrahedron, 1994, 50, 7157.
11 R. P. Linstead, L. N. Owen and R. F. Webb, J. Chem. Soc., 1953,
1218.
12 J.-N. Denis, A. Correa and A. E. Greene, J. Org. Chem., 1990, 55,
1957; Z.-M. Wang, H. C. Kolb and K. B. Sharpless, J. Org. Chem.,
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J. Chem. Soc., Perkin Trans. 1, 1999, 1647–1656
1655