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was diluted with ether (50 mL), then quenched by the addition
of water (5 mL). The organic phase was separated, washed with
aqueous hydrochloric acid solution (3 M, 2 × 15 mL) and
saturated sodium chloride solution (20 mL), dried (MgSO4)
and the volatiles removed in vacuo to yield a yellow oil that was
purified by silica gel chromatography (petroleum ether : ethyl
acetate 50 : 1) to give alkyne 43 (0.28 g, 85%); νmax(film)/cmϪ1
1
3312, 2925, 2856, 1460, 1091, 1034, 950; H NMR (400 MHz,
CDCl3) δ (isomer a) = 5.28 (1 H, d, J 8.7, OCHO), 4.22 (1 H, d,
J 2.2, OCHHCCH), 4.18 (1 H, d, J 2.2, OCHHCCH), 4.02
(1 H, m, C7H15CHO), 2.38 (1 H, t, J 2.2, CCH ), 2.12–1.83
(3 H, m, CH2C(O)O, C7H15C(O)CHH), 1.75–1.52 (1 H, m,
C7H15CH(O)CHH ), 1.52–1.20 (12 H, m, 5 × CH2), 0.88 (3 H, t,
J 6.5, CH3); δ (isomer b) = 5.21 (1 H, d, J 8.9, OCHO), 4.22
(1 H, d, J 2.2, OCHHCCH), 4.18 (1 H, d, J 2.2, OCHHCCH),
4.02 (1 H, m, C7H15CHO), 2.38 (1 H, t, J 2.2, CCH ), 2.12–1.83
(3 H, m, CH2C(O)O, C7H15C(O)CHH), 1.75–1.52 (1 H, m,
C7H15CH(O)CHH ), 1.52–1.20 (12 H, m, 5 × CH2), 0.88 (3 H, t,
J 6.5, CH3); 13C NMR (100 MHz) δ (mix of isomers) = 102.4,
102.0, 81.3, 80.0, 78.4, 73.6, 53.8, 53.4, 37.5, 35.4, 32.1, 31.8,
29.6, 29.2, 29.1, 26.1, 22.63, 22.62, 14.05, 14.04; m/z (ESI)
found 247.1674 ([M ϩ Na]ϩ C12H24O2Na requires 247.1674).
19 D. J. Dixon, S. V. Ley and E. W. Tate, J. Chem. Soc., Perkin Trans. 1,
2000, 2385.
20 D. J. Dixon, S. V. Ley and D. J. Reynolds, Angew. Chem., Int. Ed.,
2000, 39, 3622.
2-(3-Hydroxy-propyn-1-yl)-6-n-hexyl tetrahydropyran ether
45. The same procedure was used as for compound 2 to give
stannane 44 from alkyne 43 as a pale yellow oil. This was used
in the subsequent reaction without further purification. The
same procedure was used as for compound 3 to give alkynol
45 from stannane 44 as a colourless oil (0.34 g, 78%, 2 steps
from alkyne 43), obtained after repeated flash column chrom-
atography on silica gel (petroleum ether : ether 10 : 1, then 5 : 1,
then 2 : 1); νmax(film)/cmϪ1 3384, 2926, 2857, 2342, 1458, 1331,
1019; 1H NMR (400 MHz, CDCl3) δ (isomer a) = 4.53 (1 H, dd,
J 7.0 5.9, OCHCC), 4.29 (2 H, s, CH2OH), 3.84–3.80 (1 H, m,
C7H15CHO), 2.23–2.08 (1 H, m, CHHCHOCC), 2.01–1.94
(2 H, m, CHHCHOCC, C7H15CHOCHH), 1.81 (1 H, s, OH ),
1.70–1.51 (1 H, m, C7H15CHOCHH ), 1.50–1.40 (1 H, m,
CH3(CH2)5CHH), 1.38–1.29 (1 H, m, CH3(CH2)5CHH ), 1.28
(10 H, m, 5 × CH2), 0.87 (3 H, t, J 6.5, CH3); (isomer b) = 4.68
(1 H, dd, J 6.8 6.2, OCHCC), 4.29 (2 H, s, CH2OH), 4.07–4.03
(1 H, m, C7H15CHO), 2.23–2.08 (2 H, m, CHHCHOCC,
C7H15CHOCHH), 2.01–1.94 (1 H, m, CHHCHOCC), 1.81
(1 H, s, OH ), 1.70–1.51 (1 H, m, C7H15CHOCHH ), 1.50–1.40
(1 H, m, CH3(CH2)5CHH), 1.38–1.29 (1 H, m, CH3(CH2)5-
21 D. J. Dixon, S. V. Ley, D. J. Reynolds and M. S. Chorghade, Synth.
Commun., 2000, 30, 1955.
22 D. J. Dixon, S. V. Ley, D. J. Reynolds and M. S. Chorghade,
Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem., 2001, 40,
1043 and references therein.
23 D. J. Dixon, S. V. Ley and D. J. Reynolds, Chem. Eur. J., 2002, 8,
1621 and references therein.
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1988, 110, 2501.
25 P. Deslongchamps, Pure Appl. Chem., 1993, 65, 1161.
26 F. Perron and K. F. Albizati, Chem. Rev., 1989, 89, 1617.
27 E. Fischer, Chem. Ber., 1893, 26, 2400.
28 A. F. Bockov and G. E. Zaikov, Chemistry of the O-Glycoside Bond,
Pergamon Press, Oxford, 1979, 11.
29 R. S. Mann and T. R. Lien, J. Catal., 1969, 15, 1.
30 M. L. Mihailovic, S. Gojokovic and S. Konstantinovic, Tetrahedron,
1973, 29, 3675.
31 I. T. Kay and E. G. Williams, Tetrahedron Lett., 1983, 24, 5915.
32 NMR analysis confirmed that the spiroketals were present as single
diastereoisomers, although unambiguous assignment of the
stereochemistry could not be achieved by NOE studies due to
coincidental signals for important protons. The predicted most
thermodynamically stable diastereoisomer is shown in each case.
33 E. J. Corey and P. L. Fuchs, Tetrahedron Lett., 1972, 3769.
34 G. Shi, Z. M. Gu, K. He, K. V. Wood, L. Zeng, Q. Ye, J. M.
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1281.
CHH ), 1.28 (10 H, m, 5 × CH2), 0.87 (3 H, t, J 6.5, CH3); 13
C
NMR (100 MHz) δ (mix of isomers) = 86.1, 86.0, 82.7, 82.6,
80.5, 79.3, 67.8, 67.6, 51.2, 51.1, 35.9, 35.5, 33.4, 33.2, 31.8,
31.7, 31.2, 31.1, 29.6, 29.6, 29.2, 29.2, 26.2, 26.1, 22.6, 14.0;
m/z (ESI) found 247.1666 [M ϩ Na]ϩ C12H24O2Na requires
247.1674).
35 X. Cai, M. S. Chorghade, A. Fura, G. S. Grewal, K. A. Jauregui,
H. A. Lounsbury, R. T. Scannell, C. G. Yeh, M. A. Young, S. X. Yu,
L. Guo, R. M. Moriarty, R. Penmasta, M. S. Rao, R. K. Singhal,
Z. Z. Song, J. P. Staszewski, S. M. Tuladhar and S. M. Yang, Org.
Process Res. Dev., 1999, 3, 73.
36 O. Mitsunobu, Synthesis, 1981, 1.
Acknowledgements
37 We are grateful to Dr Neil Feeder and Dr John Davies of the
Department of Chemistry, Cambridge, UK for the determination of
the single crystal X-ray structure. Single crystals of 65 were
recystallised from ethyl acetate, mounted in inert oil and transferred
to the cold gas stream of the diffractometer. Crystal data.
C15H17F1O3, M = 264.29, orthorhombic, a = 6.8956(2), b = 8.0263(2),
c = 25.0635(7) Å, U = 1387.17(7) Å3, T = 250(2) K, space group
P212121, Z = 4, µ(Mo–Ka) = 0.096 mmϪ1, 3124 reflections measured.
The final wR(F2) was 0.1868 (all data). The Flack parameter was
suppdata/ob/b3/b316858a/ for crystallographic data in.cif or other
electronic format.
38 Q. H. Huang, J. A. Hunter and R. C. Larock, J. Org. Chem., 2002,
67, 3437.
39 Y. Kita, R. Okunaka, T. Honda, M. Shindo, M. Taniguchi,
M. Kondo and M. Sasho, J. Org. Chem., 1991, 56, 119.
40 M. E. Fox, A. B. Holmes, I. T. Forbes and M. Thompson, J. Chem.
Soc., Perkin Trans. 1, 1994, 3379.
The authors would like to thank the EPSRC (to D.J.D. and
D.J.R.), the University of Cambridge (to R.I.S.), the Novartis
Research Fellowship (to S.V.L.), the BP Research Endowment
(to S.V.L.) and Pfizer Global Research and Development,
Groton, USA for generous financial support for this work.
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