4422
J. S. Yadav et al. / Tetrahedron Letters 49 (2008) 4420–4423
H
6
1
Me
Me
1
2
3
Me
4
O
2
3
H
O
O
Me
6
H
8
O
4
5
Me
9
5
H
7
H
H
H
H
H
Figure 1. Characteristic NOE’s of 3i.
Figure 2. Characteristic NOE’s of 3n.
I2
Paraformaldehyde
HCHO
H
H
_
O
+
O
O
O
O
H
H
+
Scheme 3. A plausible reaction mechanism.
by comparison with authentic samples.7 A plausible reaction
mechanism is depicted in Scheme 3.
11. (a) Togo, H.; Iida, S. Synlett 2006, 2159; (b) Lin, X.-F.; Cui, S.-L.; Wang, Y.-G.
Tetrahedron Lett. 2006, 47, 4509; (c) Chen, W.-Y.; Lu, J. Synlett 2005, 1337; (d)
Royer, L.; De, S. K.; Gibbs, R. A. Tetrahedron Lett. 2005, 46, 4595; (e) Banik, B. K.;
Fernandez, M.; Alvarez, C. Tetrahedron Lett. 2005, 46, 2479; (f) Wang, S.-Y.
Synlett 2004, 2642; (g) Ko, S.; Sastry, M. N. V.; Lin, C.; Yao, C.-F. Tetrahedron Lett.
2005, 46, 5771.
12. (a) Yadav, J. S.; Reddy, B. V. S.; Hashim, S. R. J. Chem. Soc., Perkin Trans. 1 2000,
3025; (b) Yadav, J. S.; Reddy, B. V. S.; Premalatha, K.; Swamy, T. Tetrahedron
Lett. 2005, 46, 2687; (c) Kumar, H. M. S.; Reddy, B. V. S.; Reddy, E. J.; Yadav, J. S.
Chem. Lett. 1999, 857; (d) Yadav, J. S.; Reddy, B. V. S.; Rao, C. V.; Chand, P. K.;
Prasad, A. R. Synlett 2001, 1638.
13. (a) Yadav, J. S.; Reddy, B. V. S.; Reddy, U. V. S.; Krishna, A. D. Tetrahedron Lett.
2007, 48, 5243; (b) Yadav, J. S.; Reddy, B. V. S.; Narayana Kumar, G. G. K. S.;
Swamy, T. Tetrahedron Lett. 2007, 48, 2205; (c) Yadav, J. S.; Balanarsaiah, E.;
Raghavendra, S.; Satyanarayana, M. Tetrahedron Lett. 2006, 47, 4921; (d) Yadav,
J. S.; Satyanarayana, M.; Raghavendra, S.; Balanarsaiah, E. Tetrahedron Lett.
2005, 46, 8745.
14. General procedure: A mixture of olefin (1 mmol), aldehyde (2 mmol) and iodine
(1 mmol) in dichloromethane (5 mL) was stirred at 23 °C for the specified
amount of time (Table 1). After completion of the reaction as indicated by TLC,
the reaction mixture was quenched with water and extracted with ether
(2 ꢀ 10 mL). The combined organic layers were washed with aqueous sodium
thiosulfate, brine and dried over anhydrous Na2SO4. Removal of the solvent
followed by purification on silica gel (Merck, 100–200 mesh, ethyl acetate–
hexane, 0.5–9.5) gave the pure 4-iodotetrahydropyran. The products thus
obtained were characterized by IR, NMR and mass spectroscopy. The spectral
data were found to be consistent with authentic samples.9,10 Compound 3d:
It should be noted that the reactions were faster with parafor-
maldehyde compared to aliphatic aldehydes. In addition, styrene
derivatives gave higher yields of products when compared to ali-
phatic olefins. The reaction was sluggish when a catalytic amount
of iodine was used and thus a stoichiometric amount of iodine to
achieve high conversions. The scope and generality of this process
is illustrated with respect to various aldehydes and alkenes, and
the results are presented in Table 1.14
In summary, molecular iodine has proved to be a useful and
novel reagent for the Prins reaction to produce 4-substituted
1,3-dioxanes in excellent yields and in short reaction times. The
experimental procedure is simple, convenient and the reaction
conditions are amenable to scale-up. This method provides an easy
access to a wide range of 1,3-dioxanes with diverse chemical
structures.
Acknowledgement
A.V.H.G. and G.G.K.S.N.K. thank CSIR, New Delhi, for the award
of the fellowships.
4a,5,6,10b-tetrahydro-4H-naphtho[1,2-d][1,3]dioxane: Liquid, IR (KBr):
m
.
3434, 3320, 2926, 2860, 1645, 1543, 1446, 1375, 1078, 971, 759, 701 cmꢁ1
1H NMR (300 MHz, CDCl3): d 1.66–1.78 (m, 2 H), 2.43 (m, 1H), 2.94 (ddd, 1H,
J = 3.0, 6.0, 16.6 Hz), 3.90–4.04 (m, 2H), 4.61 (d, 1H, J = 3.0 Hz), 4.86 (d, 1H,
J = 6.0 Hz), 4.99 (d, 1H, J = 6.0 Hz), 7.06–7.26 (m, 5H). 13C NMR (75 MHz,
CDCl3): d 28.1, 35.1, 40.9, 77.2, 80.7, 99.7, 132.2, 134.4, 134.9, 136.5, 140.7,
143.4. LCMS: m/z (%): (M++Na) 213. HRMS calcd for C12H14O2Na: 213.0891.
Found: 213.0897. Compound 3g: 4,5-diphenyl-1,3-dioxane: Solid, mp 70–
72 °C. IR (KBr): m 3434, 3320, 2926, 2860, 1645, 1543, 1446, 1375, 1078, 971,
References and notes
1. Aubele, D. L.; Wan, S.; Floreancig, P. E. Angew. Chem., Int. Ed. 2005, 44, 3485–
3488.
2. Marucci, G.; Piero, A.; Brasili, L.; Buccioni, M.; Giardina, D.; Gulini, U.;
Piergentili, A.; Sagratini, G. Med. Chem. Res. 2005, 14, 274–296.
3. Chan, K.; Ling, Y. H.; Loh, T. Chem. Commun. 2007, 939–941.
4. Schmidt, M.; Ungvari, J.; Glode, J.; Dobner, B.; Langner, A. Bioorg. Med. Chem.
2007, 15, 2283–2297.
5. Yang, N. C.; Yang, D. H.; Ross, C. B. J. Am. Chem. Soc. 1959, 81, 133–136.
6. (a) Fuson, R. C.; Ross, W. E.; McKeever, C. H. J. Am. Chem. Soc. 1938, 60, 2935–
2936; (b) Lumma, W. C.; Ma, O. H. J. Org. Chem. 1970, 35, 2391–2393.
7. (a) Prins, H. J. Chem. Weekbl. 1919, 16, 1072; (b) Adams, D. R.; Bhatnagar, S. P.
Synthesis 1977, 661–672; (c) Arundale, E.; Mikeska, L. A. Chem. Rev. 1952, 51,
505.
8. (a) Snider, B. B. The Prins and Carbonyl Ene Reactions. In Comprehensive Organic
Synthesis; Trost, B. M., Ed.; Pergamon Press: Oxford, UK, 1991; Vol. 2, pp 527–
561; (b) Delmas, M.; Gaset, A. Synthesis 1980, 871; (c) Gharbi, R. E.; Delmas, M.;
Gaset, A. Synthesis 1981, 361.
9. (a) Kobzar, E. A.; Korchagina, D. V.; Salakhutdinov, N. F.; Ione, K. G.; Barkhash,
V. A. J. Org. Chem. USSR (Engl. Transl.) 1992, 28, 1030; (b) Tateiwa, J.; Hashimoto,
K.; Yamauchi, T.; Uemura, S. Bull. Chem. Soc. Jpn. 1996, 69, 2361; (c)
Chandrasekhar, S.; Reddy, B. V. S. Synlett 1998, 851.
759, 701 cmꢁ1 1H NMR (300 MHz, CDCl3): d 3.11 (dt, 1H, J = 4.5, 11.3 Hz), 3.90
.
(t, 1H, J = 11.3 Hz), 4.18 (dd, 1H, J = 4.5, 11.3 Hz), 4.64 (d, 1H, J = 9.8 Hz), 4.95 (d,
1H, J = 6.0 Hz), 5.26 (d, 1H, J = 6.0 Hz), 6.92–6.98 (m, 2H), 7.02–7.08 (m, 2H),
7.10–7.21 (m, 6H). 13C NMR (75 MHz, CDCl3): d 49.1, 71.8, 84.1, 94.0, 126.9,
127.1, 127.7, 127.9, 128.3, 128.4, 137.1, 139.0. LCMS: m/z (%): (M++Na) 263.
HRMS calcd for C16H16O2Na: 263.1047. Found: 263.1054. Compound 3i: 1H
NMR (500 MHz, CDCl3): d 7.37(m, 2H, Ar), 7.34 (m, 2H, Ar), 7.27 (tt, J = 1.9,
6.3 Hz, 1H, para), 4.91 (q, J = 5.2 Hz, 1H, H5), 4.65 (dd, J = 2.6, 11.2 Hz, 1H, H4),
3.89 (ddq, J = 2.6, 12.6, 6.3 Hz, 1H, H2), 1.75 (dt, J = 13.3, 2.6 Hz, 1H, H3e), 1.57
(q,J ꢂ 12.4 Hz, 1H, H3a), 1.43 (d, J = 5.2 Hz, 1H, Me-6), 1.27 (d, J = 6.3 Hz, 1H,
Me-1). Compound 3k: 4-(4-chlorophenyl)-2,6-dimethyl-1,3-dioxane: Solid,
mp 77–79 °C. IR (KBr): m 3434, 3320, 2926, 2860, 1645, 1543, 1446, 1375,
1078, 971, 759, 701 cmꢁ1 1H NMR (300 MHz, CDCl3): d 1.24 (d, 3H, J = 6.0 Hz),
.
1.38 (d, 3H, J = 5.2 Hz), 1.43–1.48 (m, 1H), 1.69 (td, 1H, J = 2.2, 13.6 Hz), 3.82
(m, 1H), 4.57 (dd, 1H, J = 3.0, 11.3 Hz), 4.83 (q, 1H, J = 5.3 Hz), 7.22–7.32 (m,
4H). 13C NMR (75 MHz, CDCl3): d 21.1, 21.4, 40.3, 72.3, 77.5, 98.7, 127.1, 128.4,
133.2, 140.2. LCMS: m/z (%): (M++Na) 249. HRMS calcd for C12H15ClO2Na:
249.0658. Found: 249.0653. Compound 3o: 2,4-dicyclohexyl-6-phenyl-1,3-
dioxane: Solid, mp 94–96 °C. IR (KBr): m 3434, 3320, 2926, 2860, 1645, 1543,
10. (a) Bach, T.; Lobel, J. Synthesis 2002, 2521; (b) Gu, Y.; Karam, A.; Jerome, F.;
Barrault, J. Org. Lett. 2007, 9, 3145–3148 and references cited therein.
1446, 1375, 1078, 971, 759, 701 cmꢁ1 1H NMR (300 MHz, CDCl3): d 0.82–2.02
.