K. M. Aumann et al. / Tetrahedron Letters 52 (2011) 1070–1073
1073
Representative procedure for the sulfonylation of spiroacetal
enol ethers: 5-(phenylsulfonyl)-5,6,7,8-tetra hydrochroman
(13a)
spectra for all new compounds) associated with this article can
References and notes
Benzenesulfinic acid was prepared by stirring sodium benzene-
sulfinate (2.05 g, 12.5 mmol) with HCl (10% aq, 40 mL), then
extracting with CH2Cl2 (3 Â 40 mL), drying (MgSO4), and concen-
trating under reduced pressure. Benzenesulfinic acid (1.779 g,
12.5 mmol) was added to a solution of spiroacetal enol ether 8a
(1.54 g, 10.0 mmol) in CH2Cl2 (40 mL) and the solution was stirred
for 45 min. Satd NaHCO3 (50 mL) was added and the mixture ex-
tracted with CH2Cl2 (3 Â 80 mL). The combined organic phases
were washed with satd NaCl (40 mL), dried (MgSO4), and the sol-
vent was removed in vacuo to afford a white solid, which was
recrystallised (Et2O/Pet. Spirits) to yield the title compound 13a
as white prisms (2.25 g, 8.1 mmol, 81%), requiring no further puri-
fication. Rf 0.18 (20% EtOAc in Pet. Spirits); IR (thin film) 2944,
2875, 1665, 1446, 1302, 1138 cmÀ1; mp 104 °C (decomp.); 1H
NMR (500 MHz, CDCl3) d 7.89 (d, J = 7.5 Hz, 2H), 7.63 (app. t,
J = 7.4 Hz, 1H), 7.55 (app. t, J = 7.7 Hz, 2H), 4.06 (m, 1H), 3.97 (m,
1H), 3.67 (m, 1H), 2.64 (m, 1H), 1.89 (m, 7H), 1.70 (m, 1H), 1.49
(m, 1H); 13C NMR (126 MHz, CDCl3) d 155.2, 139.1, 133.5, 129.1,
128.9, 97.2, 67.4, 66.1, 27.0, 25.8, 24.4, 22.8, 18.2; MS (EI) m/z
278 [M]Å+; HRMS (EI) calcd for C15H18O3S [M]Å+ 278.0977, found
278.0926.
1. Spiroacetals are often referred to as a spiroketals. In accordance with IUPAC
nomenclature guidelines, this structural motif will be referred to exclusively as
a spiroacetal throughout this article.
2. For reviews on spiroacetal-containing natural products, see: (a) Franke, W.;
Kitching, W. Curr. Org. Chem. 2001, 5, 233–251; (b) Jacobs, M. F.; Kitching, W.
Curr. Org. Chem. 1998, 2, 395–436; (c) Fletcher, M. T.; Kitching, W. Chem. Rev.
1995, 95, 789–828; (d) Perron, F.; Albizati, K. F. Chem. Rev. 1989, 89, 1617–
1661; (e) Boivin, T. L. B. Tetrahedron 1987, 43, 3309–3362.
3. For selected examples, see: (a) William, D. E.; Roberge, M.; Soest, V. R.;
Anderson, R. J. Am. Chem. Soc. 2003, 125, 5296–5297; (b) Singh, S. B.; Zink, D. L.;
Heimbach, B.; Genilloud, O.; Teran, A.; Silverman, K. C.; Lingham, R. B.; Felock,
P.; Hazuda, D. J. Org. Lett. 2002, 4, 1123–1126; (c) Landini, P.; Corti, E.;
Goldstein, B. P.; Denaro, M. Biochem. J. 1992, 284, 47–52; (d) Osada, H.; Koshino,
H.; Isono, K.; Takahashi, H.; Kawanishi, G. J. Antibiot. 1991, 44, 259–261.
4. Dictionary of Natural Products on DVD, Chapman & Hall/CRC Press, 2009, Version
17:2, July 2008–June 2009.
5. Wang, L.; Floreancig, P. E. Org. Lett. 2004, 6, 569–572.
6. Dineen, T. A.; Roush, W. R. Org. Lett. 2005, 7, 1355–1358.
7. For reviews on the Heck reaction, see: (a) Alonso, F.; Beletskaya, I. P.; Yus, M.
Tetrahedron 2005, 61, 11771–11835; (b) Dounay, A. B.; Overman, L. E. Chem.
Rev. 2003, 103, 2945–2963; (c) Shibasaki, M.; Boden, C. D. J.; Kojima, A.
Tetrahedron 1997, 53, 7371–7393; (d) de Meijere, A.; Meyer, F. E. Angew. Chem.,
Int. Ed. Engl. 1994, 33, 2379–2411.
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Brown, D. S.; Bruno, M.; Davenport, R. J.; Ley, S. V. Tetrahedron 1989, 45, 4293–
4308.
9. For a review on the HDA approach to spiroacetals, see: Rizzacasa, M. A.; Pollex,
A. Org. Biomol. Chem. 2009, 7, 1053–1059.
10. Neokosmidi, A.; Ragoussis, V.; Zikos, C.; Paravatou-Petsotas, M.; Livaniou, E.;
Ragoussis, N.; Evangelatos, G. J. Agric. Food. Chem. 2004, 52, 4368–4374.
11. Cuzzupe, A. N.; Hutton, C. A.; Lilly, M. J.; Mann, R. K.; McRae, K. J.; Zammit, S. C.;
Rizzacasa, M. A. J. Org. Chem. 2001, 66, 2382–2393.
12. Ireland, R. E.; Häbich, D. Tetrahedron Lett. 1980, 21, 1389–1392.
13. (a) Loiseleur, O.; Hayashi, M.; Schmees, N.; Pfaltz, A. Synthesis 1997, 1338–
1345; (b) Kwok, D. I.; Farr, R. N.; Daves, G. D., Jr. J. Org. Chem. 1991, 56, 3711–
3713.
Representative procedure for the arylation of 5-(phenylsulfo-
nyl)-5,6,7,8-tetrahydrochromans: 5-phenyl-5, 6,7,8-tetrahyd-
rochroman (21a)
Anhydrous zinc bromide (1.0 M in THF, 510
lL, 0.51 mmol)
14. (a) Shi, G.-Q.; Huang, X.-H.; Hong, F. J. Chem. Soc., Perkin Trans. 1 1996, 8, 763–
765; (b) Sakamoto, T.; Kondo, Y.; Kashiwagi, Y.; Yamanaka, H. Heterocycles
1988, 27, 257–260; (c) Andersson, C. M.; Hallberg, A.; Daves, G. D., Jr. J. Org.
Chem. 1987, 52, 3529–3536.
15. (a) Jarusiewicz, J.; Yoo, K. S.; Jung, K. W. Synlett 2009, 482–486; (b) Holzapfel, C.
W.; Williams, D. B. G. Synth. Commun. 1994, 24, 2139–2146; (c) Ozawa, F.;
Kubo, F.; Matsumoto, Y.; Hayashi, T.; Nishioka, E.; Yanagi, K.; Moriguchi, K.
Organometallics 1993, 12, 4188–4196.
was added to a stirred solution of phenylmagnesium bromide
(1.0 M in THF, 1.6 mL, 1.36 mmol) in THF (7 mL) and the result-
ing suspension was stirred for 30 min. Phenylsulfone 13a (91 mg,
0.34 mmol) was added and the cloudy mixture was stirred for
18 h. Satd NH4Cl (50 mL) was added and the biphasic mixture
extracted with Et2O (3 Â 40 mL). The combined organic phases
were washed with satd NaCl (20 mL), dried (MgSO4), and the
solvent was removed in vacuo to afford the crude product,
which was purified by flash chromatography (1% Et2O in Pet.
16. (a) Cabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28, 2–7; (b) Larock, R. C.; Gong,
W. H.; Baker, B. E. Tetrahedron Lett. 1989, 20, 2603–2606.
17. A range of conditions were explored. Palladium sources include Pd(OAc)2,
Pd(PPh3)4, Pd2(dba)3; arylating agents include PhI, PhBr, PhOTf, 3,5-
(OMe)2C6H3Br; bases include Ag2CO3, NEt3, Cy2NMe, K2CO3, Cs2CO3;
phosphines include PPh3, tBu3P, tBu3PHÁBF4; solvents include 1,4-dioxane,
CH3CN, DMF, THF. For selected references, see: (a) Netherton, M. R.; Fu, G. C.
Org. Lett. 2001, 3, 4295–4298; (b) Littke, A. F.; Fu, G. C. J. Am. Chem. Soc. 2001,
123, 6989–7000; (c) Mo, J.; Xiao, J. Angew. Chem., Int. Ed. 2006, 45, 4152–4157;
(d) Littke, A. F.; Fu, G. C. Org. Synth. 2004, 81, 63–70; (e) Abelman, M. M.; Oh, T.;
Overman, L. E. J. Org. Chem. 1987, 52, 4133–4135; (f) Sakamoto, T.; Kondo, Y.;
Uchiyama, M.; Yamanaka, H. J. Chem. Soc., Perkin Trans. 1 1993, 1941–1942; (g)
Littke, A. F.; Fu, G. C. J. Org. Chem. 1999, 64, 10–11; (h) Overman, L. E. Pure Appl.
Chem. 1994, 66, 1423–1430; (i) Trost, B. M.; Dumas, J.; Villa, M. J. Am. Chem. Soc.
1992, 114, 9836–9845.
Spirits) to give the title compound 21a as
(57 mg, 0.27 mmol, 80%); Rf 0.40 (20% EtOAc in Pet. Spirits); IR
(thin film) 2930, 2858, 1449, 1173 cmÀ1 1H NMR (500 MHz,
a colorless oil
;
C6D6) d 6.91 (m, 4H), 6.81 (app. t, J = 7.0 Hz, 1H), 3.50 (m, 1H),
3.45 (m, 1H), 2.90 (app. t, J = 5.7 Hz, 1H), 1.89 (m, 2H), 1.55
(m, 1H), 1.37 (m, 1H), 1.25 (m, 5H), 1.11 (m, 1H); 13C NMR
(126 MHz, C6D6)
d
150.3, 146.6, 129.0 (2 Â C), 126.6, 105.9,
66.0, 46.4, 33.8, 28.5, 24.6, 23.9, 20.5; MS (EI) m/z 214 [M]Å+;
HRMS (EI) calcd for C15H18O [M]Å+ 214.1358, found 214.1351.
18. The relative configuration was assigned on the basis of NOESY correlations, see
Supplementary data.
19. (a) Ley, S. V.; Lygo, B.; Wonnacott, A. Tetrahedron 1986, 42, 4333–4342; (b) Ley,
S. V.; Lygo, B.; Wonnacott, A. Tetrahedron Lett. 1985, 26, 535–538.
20. Brown, D. S.; Ley, S. V. Tetrahedron Lett. 1988, 29, 4869–4872.
21. Crystallographic data (excluding structure factors) for structure 13b have been
deposited with the Cambridge Crystallographic Data Centre, CCDC 782586.
Copies of the data can be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK, (fax: +44 (0)1223 336033 or e-mail:
deposit@ccdc.cam.ac.uk).
Acknowledgments
We thank the Australian Research Council for funding
(DP556187) and Dr. Natasha Hungerford for NMR assistance.
Supplementary data
22. Horner, L.; Basedow, O. H. Liebigs Ann. 1958, 612, 108–131.
23. Amarego, W. L. F.; Chai, C. L. L. Purification of Laboratory Chemicals, 5th ed.;
Butterworth Heinemann Press, Elsevier Science, 2003. pp 120–121.
24. (a) Bai, Y.; Lin, S.-J.; Qi, G.; Palcic, M. M.; Lowary, T. L. Carbohydr. Res. 2006, 341,
1702–1707; (b) Paul, S.; Jayaraman, N. Carbohydr. Res. 2004, 339, 2197–2204.
Supplementary data (experimental procedures and character-
ization data for compounds not included in the experimental sec-
tion; X-ray crystallographic data (CIF) for 13b; 1H and 13C NMR