2000
B. R. Raju et al. / Tetrahedron Letters 47 (2006) 1997–2001
References and notes
MeO
+
–
+ I2
+
+ MeOH
+ H2O2
+ I + H
1. (a) House, H. Modern Synthetic Reactions, 2nd ed.; W.A.
Benjamin: Menlo Park, CA, 1972; p 432; (b) March, J.
Advanced Organic Chemistry, 4th ed.; Wiley: New York,
1992, p 815T.W; (c) Eisch, J. J.; Liu, Z. R.; Ma, X.; Zheng,
G. X. J. Org. Chem. 1992, 57, 5140; (d) Ueda, Y.;
Maynard, S. C. Tetrahedron Lett. 1988, 29, 5197; (e)
Konopelski, J. P.; Boehler, M. A.; Tarasow, T. M. J. Org.
Chem. 1989, 54, 4966; (f) Gibson, K. H.; Saxton, J. E. J.
Chem. Soc., Perkin Trans. 1 1972, 2776; (g) Wilson, C. V.
Org. React. 1957, 9, 332.
2. (a) Sasson, Y. Formation of Carbon–Halogen Bonds (Cl,
Br, I). In The Chemistry of Functional Groups, Supplement
D2: The Chemistry of Halides, Pseudo Halides and Azides,
Part 2; Patai, S., Rappoport, Z., Eds.; Wiley: Chichester,
1995; pp 535–620; (b) Diederich, F.; Stang, P. J. Metal-
Catalysed Cross-Coupling Reactions; Wiley-VCH: Wein-
heim, Germany, 1998; (c) Yang, X.; Althammer, A.;
Knochel, P. Org. Lett. 2004, 6, 1665.
3. Maeda, K.; Shinokubo, H.; Oshima, K. J. Org. Chem.
1996, 61, 6770.
4. (a) Bonini, C.; Righi, G. Synthesis 1994, 204; (b) Fenical,
W. In Marine Natural Products; Scheuer, P. J., Ed.;
Academic: New York, 1980; Vol. 2, p 174; (c) Faulkner,
D. J. Nat. Prod. Pep. 1984, 25.
5. Sovak, M. Radiocontrast Agents. Handbook of Experi-
mental Pharmacology; Springer: Berlin, 1993.
6. Glover, S. A.; Gossen, A. Tetrahedron Lett. 1980, 21,
2005.
I
+ 2 H
2I
Scheme 2.
I2 + 2 H2O
2-exo-iodo-7-syn-methoxybicyclo-[2.2.1]heptane, 10c17
in 87% yield along with 2-exo-hydroxy-7-syn-iodobicy-
clo[2.2.1]heptane, 10b in 7% yield. On the other hand
iodohydroxylation of 10a gives 2-exo-hydroxy-7-syn-
iodobicyclo[2.2.1]heptane, 10b as the major product
(78%) and its isomer 2-exo-iodo-7-syn-hydroxybi-
cyclo[2.2.1]heptane, 10d as a minor product (10%).18
Geraniol gives the 6,7-addition products, 15b and
15c, as the major products (74%) with minor 2,3- and
6,7-addition products (5%). Interestingly, when the
same reaction was carried out in the presence of glacial
acetic acid, instead of the acetylated products iodohyd-
rins were obtained. It was also observed that no hydro-
lyzed product was formed under these reaction
conditions. This can be attributed to the reactions
shown in Scheme 2. The product is formed by nucleo-
philic attack of the methanol or water on the iodonium
ion formed from the reaction of the olefin and iodine,
releasing iodide and hydrogen ion. The iodide thus
formed is reoxidized to molecular iodine by hydrogen
peroxide in the presence of hydrogen ion and thereby
consuming the hydrogen iodide formed in the reaction.
As a result the reaction medium becomes neutral and
there is no chance of acid hydrolysis of the iodo com-
pounds. It is important to note that only water is
formed as a byproduct.
7. (a) Barluenga, J.; Gonzalez, J. M.; Campos, P. J.; Asensio,
G. Angew. Chem., Int. Ed. Engl. 1985, 24, 319; (b) Cambie,
R. C.; Noall, W. I.; Potter, G. J.; Rutledge, P. S.;
Woodgate, P. D. J. Chem. Soc., Perkin Trans. 1 1977,
226.
8. Asensio, G.; Andreu, C.; Boix-Bernardini, C.; Mello, R.;
Gonzalez-Nunez, M. E. Org. Lett. 1999, 1, 2125.
9. Georgoulis, C.; Valery, J. M. Synthesis 1978, 402.
10. (a) Wilson, C. V. Org. React. 1957, 9, 332; (b) Woodward,
R. B.; Brutcher, F. V. J. Am. Chem. Soc. 1958, 80,
209.
OR
OH
OH
I
11. (a) Bougault, J. C.R. Acad. Sci. 1900, 130, 1766; (b)
Bougault, J. C.R. Acad. Sci. 1900, 131, 528.
I
I
12. Barluenga, J.; Rodriguez, M. A.; Campos, P. J.; Asensio,
G. J. Chem. Soc., Chem. Commun. 1987, 1491.
13. Iranpoor, N.; Shekarriz, M. Tetrahedron 2000, 56, 5209.
14. Corso, A. R. D.; Panunzi, B.; Tingoli, M. Tetrahedron
Lett. 2001, 42, 7245.
OR
10d
R = H = 15d
R = Me = 15e
15. (a) Clark, J.; Macquarrie, D. Handbook of Green Chem-
istry & Technology; Blackwell Science: London, 2002; (b)
Noyori, R.; Aoki, M.; Sato, K. Chem. Commun. 2003,
1977; (c) Lane, B. S.; Burgess, K. Chem. Rev. 2003, 103,
2457.
In conclusion, an efficient method for methoxy and
hydroxy iodination of olefins using molecular iodine
and hydrogen peroxide under mild conditions has been
developed. This protocol may be extended for the syn-
thesis of other alkoxyiodoalkanes.
16. Typical experimental procedure for the synthesis of an
alkoxyiodoalkane:
A
mixture of styrene (400 mg,
3.8 mmol), acetonitrile (4 ml), iodine (533 mg, 2.1 mmol)
was stirred at room temperature and to this mixture was
added 30% hydrogen peroxide (0.64 ml, 5.7 mmol) and the
mixture allowed to stir for 5 h. The reaction was moni-
tored by TLC using ethyl acetate and hexane as eluents.
After completion of the reaction, the acetonitrile was
removed under vacuum. The residue was extracted with
ethyl acetate and the organic layer was washed with a
solution of sodium thiosulfate, dried (Na2SO4), and
evaporated to get the crude product. Finally, the product
was purified by column chromatography to give 958 mg
(96%) of the pure product. The compound was character-
ized by spectroscopic methods.19 1H NMR (400 MHz,
CDCl3): d 2.52 (br s, 1H, –OH), 3.39 (m, 1H, –CH–), 3.48
Acknowledgments
The authors are grateful to Council of Scientific and
Industrial Research (CSIR), New Delhi, for the financial
assistance.
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