ORGANIC
LETTERS
1999
Vol. 1, No. 11
1737-1739
Efficient and Chemoselective
Conversion of Carbonyl Compounds to
1,3-Dioxanes Catalyzed with
N-Bromosuccinimide under Almost
Neutral Reaction Conditions
Babak Karimi,* G. Reza Ebrahimian,† and Hassan Seradj†
Department of Chemistry, Institute for AdVanced Studies in Basic Sciences (IASBS),
P.O. Box 45195-159, GaVa Zang, Zanjan, Iran, and Department of Chemistry and
Medicinal Chemistry, School of Pharmacy, Shiraz UniVersity of Medical Sciences,
Shiraz 71345, Iran
Received September 1, 1999
ABSTRACT
Various types of carbonyl compounds were converted to the corresponding 1,3-dioxanes in the presence of ethyl orthoformate, 1,3-propanediol,
and a catalytic amount of NBS via an in situ acetal exchange process. In contrast to conventional acid-catalyzed acetalization reactions,
acid-sensitive substrates such as THP ethers and TBDMS ethers remain intact under described reaction conditions.
Acetals are among the most popular protecting groups for
carbonyl compounds.1 In addition, chiral acetals are particu-
larly important for the preparation of enantiomerically pure
compounds.2 Although the formation of acetals is generally
achieved with protic acid catalysts, it has been shown that
the use of Lewis acids in these transformations may be
advantageous in some cases.3 Very recently, we have shown
that WCl6 and ZrCl4 are highly efficient catalysts for
chemoselective acetalization of various types of carbonyl
compounds.4 However, these two catalysts were not suitable
for the acetalization of carbonyl compounds containing other
acid-sensitive functionalities, such THP ethers. We thus
researched a milder catalytic system that would allow
survival of other acid-sensitive groups.
NBS has already been known as a mild oxidizing reagent
for chemoselective oxidative deprotection of S,S-acetals. A
brief survey of the literature shows that free hydroxyl groups,
disubstituted alkenes, and acid-sensitive functional groups
such as MEM ethers, TBDPS ethers, 1,3-dioxanes, and
phenolic benzyl ethers survive intact in the presence of NBS.5
In our development of new methods for functional group
† Shiraz University of Medical Sciences.
(1) (a) Greene, T. W.; Wuts, P. G. M. ProtectiVe Groups in Organic
Synthesis, 2nd ed.; Wiley: New York, 1991; pp 175-198. (b) Kocienski,
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Thieme: Stuttgart, 1994; Chapter 4.
(2) Seebach, D.; Imwinkelried, R.; Weber, T. Modern Synthetic Methods
1986; Scheffold, R., Ed.; Springer-Verlag: Berlin, 1986; Vol. 4, pp 125-
259.
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M. J. Org. Chem. 1987, 52, 188. (c) Tsunoda, T.; Suzuki, M.; Noyori, R.
Tetrahedron Lett. 1980, 21, 1357. (d) Ott, J.; Ramos Tombo, G. M.; Schmid,
B.; Venanzi, L. M.; Wang, G.; Ward, T. R. Tetrahedron Lett. 1989, 30,
6151. (e) Otera, J.; Mizutani, T.; Nozaki, H. Organometallics 1989, 8, 2063.
(f) Ma, S.; Venanzi, L. M. Synlett 1993, 751. (g) Fukuzawa, S. I.;
Tsuchimoto, T.; Hotaka, T.; Hiyama, T. Synlett 1995, 1077. (h) Ishihara,
K.; Karumi, Y.; Kubota, M.; Yamamoto, H. Synlett 1996, 839.
(4) (a) Firouzabadi, H.; Iranpoor, N.; Karimi, B. Synlett 1999, 321. (b)
Firouzabadi, H.; Iranpoor, N.; Karimi, B. Synth. Commun. 1999, 29, 2255.
10.1021/ol9909987 CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/04/1999