LETTER
Protection of Alcohols as 1,4-Dioxan-2-yl Ethers
C
J = 9.2 Hz), 4.57–4.48 (m, 4 H), 4.21–4.19 (m, 2 H), 4.05–
3.81 (m, 4 H), 3.79 (s, 3 H), 3.76 (s, 3 H), 3.73–3.44 (m, 10
H), 1.45 (s, 18 H). 13C NMR (50 MHz, CDCl3): d = 170.9,
170.7, 155.4 (2 C), 96.1, 95.7, 79.9, 79.8, 68.5, 68.4, 68.2,
67.8, 60.0 (4 C), 61.6, 61.2, 53.8, 53.6, 52.4, 52.3, 28.2 (6 C).
GC-MS (EI): m/z (%, first diastereomer) = 246 (2) [M – 59]+,
189 (21), 146 (100), 133 (59), 101 (15), 87 (63), 57 (46);
m/z (%, second diastereomer) = 246 (3) [M – 59]+, 189 (30),
146 (100), 133 (69), 101 (18), 87 (62), 57 (48). Anal. Calcd
for C13H23NO7: C, 51.14; H, 7.59; N, 4.59. Found: C, 51.47;
H, 7.87; N, 4.33.
References and Notes
(1) (a) Adlington, R. M.; Baldwin, J. E.; Basak, A.; Kozyrod,
R. P. J. Chem. Soc., Chem. Commun. 1983, 944.
(b) Dupuis, J.; Giese, B.; Ruegge, D.; Fischer, H.; Korth, H.-
G.; Sustmann, R. Angew. Chem., Int. Ed. Engl. 1984, 23,
896. (c) Nishiyama, Y.; Yamamoto, H.; Nakata, S.; Ishii, S.
Chem. Lett. 1993, 841. (d) Rawal, V. H.; Singh, S. P.;
Dufour, C.; Michoud, C. J. Org. Chem. 1993, 58, 7718.
(e) Abazi, S.; Rapado, L. P.; Schenk, K.; Renaud, P. Eur. J.
Org. Chem. 1999, 477.
(2) Yoshimatsu, M.; Sato, T.; Shimizu, H.; Hori, M.; Kataoka,
T. J. Org. Chem. 1994, 59, 1011.
(3) (a) Hoffmann, R.; Ruckert, T.; Brückner, R. Tetrahedron
Lett. 1993, 34, 297. (b) Krief, A.; Nazih, A. Tetrahedron
Lett. 1995, 36, 8115.
(4) Uehlin, L.; Wirth, T. Org. Lett. 2001, 3, 2931.
(5) (a) Mehta, S.; Pinto, M. Tetrahedron Lett. 1991, 32, 4435.
(b) Zuurmond, H. R.; van der Klein, P. A. M.; van der Meer,
P. H.; van der Marel, G. A.; van Boom, J. H. Recl. Trav.
Chim. Pay-Bas 1992, 111, 365. (c) Tingoli, M.; Tiecco, M.;
Testaferri, L.; Temperini, A. J. Chem. Soc., Chem. Commun.
1994, 1883.
(13) Selective protection of phenolic alcohols 10a–c was
obtained as described above for substrates 8. Physical and
spectral data of compounds 11a–c are reported below.
4-[(1,4-Dioxan-2-yloxy)methyl]phenol (11a)
Yield 80%; oil. FT-IR (KBr): 3341, 2919, 1615, 1595, 1266,
1143, 1079, 1036, 903, 877 cm–1. 1H NMR (200 MHz,
CDCl3): d = 8.05 (s, 1 H), 7.25 (d, 2 H, J = 8.1 Hz), 6.84 (d,
2 H, J = 8.1 Hz), 4.80 (d, 1 H, J = 11.5 Hz), 4.67 (t, 1 H,
J = 2.6 Hz), 4.52 (d, 1 H, J = 11.5 Hz), 4.24–4.11 (m, 1 H),
3.83–3.72 (m, 3 H), 3.70–3.56 (m, 2 H). 13C NMR (50 MHz,
CDCl3): d = 155.8, 129.9 (2 C), 128.8, 115.3 (2 C), 94.2,
69.1, 68.9, 66.2, 61.2. GC-MS (EI): m/z (%) = 210 (2) [M+],
120 (20), 107 (100), 87 (2), 77 (7). Anal. Calcd for C11H14O4:
C, 62.85; H, 6.71. Found: C, 63.07; H, 6.97.
5-[(1,4-Dioxan-2-yloxy)methyl]benzene-1,3-diol (11b)
Yield 76%; mp 116–119 °C. FT-IR (KBr): 3294, 2859,
1630, 1600, 1497, 1366, 1303, 1173, 1139, 1056, 978, 902,
863, 834 cm–1. 1H NMR (200 MHz, acetone-d6): d = 8.20 (s,
2 H), 6.38–6.30 (m, 2 H), 6.29–6.20 (m, 1 H), 4.61(d, 1 H,
J = 12.1 Hz), 4.58 (t, 1 H, J = 3.1 Hz), 4.38 (d, 1 H, J = 12.1
Hz), 4.04–3.90 (m, 1 H), 3.69–3.40 (m, 5 H). 13C NMR (50
MHz, acetone-d6): d = 159.6 (2 C), 141.6, 106.9 (2 C),
102.6, 95.9, 69.6, 66.9, 62.3. Anal. Calcd for C11H14O5: C,
58.42; H, 6.24. Found: C, 58.68; H, 6.51.
(6) (a) Goldsmith, D. J.; Liotta, D. C.; Volmer, M.; Hoekstra,
W.; Waykole, L. Tetrahedron 1985, 41, 4873.
(b) Brunetier, A. P.; Lallemand, J. Y. Tetrahedron Lett.
1988, 29, 2179. (c) Deleuze, A.; Sollogoub, M.; Bleriot, Y.;
Marrot, J.; Sinay, P. Eur. J. Org. Chem. 2003, 2678.
(d) Chambers, D. J.; Evans, G. R.; Fairbanks, A.
Tetrahedron Lett. 2003, 44, 5221.
(7) (a) Bonner, W. A.; Robinson, A. J. Am. Chem. Soc. 1950, 72,
354. (b) Tingoli, M.; Temperini, A.; Testaferri, L.; Tiecco,
M.; Resnati, G. Carbohydr. Lett. 1998, 3, 39.
(8) (a) Raucher, S.; Koolpe, G. A. J. Org. Chem. 1978, 43,
3794. (b) Hendra, P. J.; Sadasivan, N. J. Chem. Soc. 1965,
2063.
2-[2-(1,4-Dioxan-2-yloxy)ethyl]phenol (11c)
(9) (a) Wuts, P. G. M.; Greene, T. W. Protective Groups in
Organic Synthesis, 4th ed.; John Wiley and Sons: New York,
2007, 72. (b) Fetizon, M.; Hanna, I. Synthesis 1985, 806.
(c) French, A. N.; Cole, J.; Wirth, T. Synlett 2004, 2291.
(10) Tingoli, M.; Tiecco, M.; Testaferri, L.; Temperini, A. Synlett
1995, 1129.
(11) Other metal salts such as ZnCl2, Zn(OTf)2, CoCl2, NiCl2,
CeCl3, and FeCl3 did not give any trace of product 8a.
Product 8a was also obtained in moderate yield by activation
with silver triflate, NIS, or NBS.
Yield 72%; mp 726–74 °C. FT-IR (KBr): 3267, 2926, 2870,
1594, 1505, 1455, 1265, 1143, 1053, 909, 866, 757 cm–1. 1H
NMR (200 MHz, CDCl3): d = 7.40 (s, 1 H), 7.20–7.02 (m, 2
H), 6.95–6.76 (m, 2 H), 4.57 (t, 1 H, J = 2.6 Hz), 4.12 (ddd,
1 H, J = 9.1, 6.5, 3.9 Hz), 3.98–3.84 (m, 1 H), 3.77–3.60 (m,
5 H), 3.59–3.42 (m, 1 H), 3.01 (ddd, 1 H, J = 14.9, 7.8, 3.7
Hz), 2.87 (ddd, 1 H, J = 14.9, 6.4, 3.6 Hz). 13C NMR (50
MHz, CDCl3): d = 155.2, 130.8, 128.3, 126.2, 120.4, 117.0,
95.8, 69.6, 68.4, 66.0, 61.1, 32.3. GC-MS (EI): m/z (%) =
224 (15) [M+], 138 (100), 121 (96), 107 (29), 91 (32), 87
(48), 77 (29). Anal. Calcd for C12H16O4: C, 64.27; H, 7.19.
Found: C, 64.59; H, 7.41.
(12) Protection of Alcohols; General Procedure
To a mixture of the alcohol 8 (1 mmol), the O,Se-acetal 7
(1.4 mmol) and activated 3 Å MS (0.10 g) in dry EtOAc or
THF (15 mL), dry CuCl2 (2.8 mmol) was added at r.t. The
mixture was stirred under inert atmosphere until the starting
alcohol has completely disappeared (monitored by TLC).
Reaction times ranged from 2–23 h. A 30% NH4OH solution
(0.4 mL) was added and stirring was continued for few
minutes. After addition of anhyd Na2SO4, the reaction
mixture was filtered through a Celite pad and the filtrate
concentrated. After chromatography on silica gel column,
compound 9 were obtained in a pure form. Physical and
spectral data of compound 9d are reported below whereas
compound 9b is described in the Supporting Information.
Methyl N-(tert-Butoxycarbonyl)-O-1,4-dioxan-2-yl-
serinate (9d)
(14) Selective Protection of Diol 10e
To a mixture of the diol 10e (0.12 g. 0.8 mmol), the O,Se-
acetal 7 (0.23 g, 0.96 mmol) and activated 3 Å MS (0.10 g)
in dry THF (12 mL), dry CuCl2 (0.13 g, 0.96 mmol) was
added at r.t. under inert atmosphere. After 9 h a 30% NH4OH
solution (0.3 mL) was added and stirring was continued for
few minutes. After addition of anhyd Na2SO4, the reaction
mixture was filtered through a Celite pad and the filtrate
concentrated. After chromatography on silica gel column,
0.10 g compound 11e and 0.05 g of the starting diol 10e were
obtained in a pure form. Physical and spectral data of 11e are
reported below.
3-(1,4-Dioxan-2-yloxy)-1-phenylpropan-1-ol (11e)
Yield 89%; oil. FT-IR (KBr): 3449, 2880, 1455, 1266, 1147,
1052, 870, 757 cm–1. 1H NMR (200 MHz, CDCl3): d (1:1
Yield 72%; oil; 1:1 mixture of diastereomers. 1H NMR (200
MHz, CDCl3): d = 5.57 (d, 1 H, J = 8.6 Hz), 5.39 (d, 1 H,
Synlett 2009, No. x, A–D © Thieme Stuttgart · New York