An efficient one-stage deprotection/reduction of 1,2-O-isopropylidene furanoses to the corresponding tetrahydrofurans

Article abstract of DOI:10.1021/ol9901117

(Matrix presented) Treatment of 1,2-O-isopropylidenefuranose derivatives with triethylsilane/boron trifluoride etherate results in generation of the corresponding tetrahydrofurans. This one-stage process removes the 1,2-O-isopropylidene group with accompa

Full text of DOI:10.1021/ol9901117

ORGANIC
LETTERS
1999
Vol. 1, No. 4
635-636
An Efficient One-Stage Deprotection/
Reduction of 1,2-O-Isopropylidene
Furanoses to the Corresponding
Tetrahydrofurans
Gregory J. Ewing and Morris J. Robins*
Department of Chemistry and Biochemistry, Brigham Young UniVersity,
ProVo, Utah 84602-5700
morris_robins@byu.edu
Received June 5, 1999
ABSTRACT
Treatment of 1,2-O-isopropylidenefuranose derivatives with triethylsilane/boron trifluoride etherate results in generation of the corresponding
tetrahydrofurans. This one-stage process removes the 1,2-O-isopropylidene group with accompanying deoxygenation at the anomeric position
and is compatible with several hydroxyl protecting groups.
Highly functionalized tetrahydrofurans occur frequently in
natural products and have been incorporated into numerous
synthetic biologically active compounds.1,2 A number of
approaches have been developed for their preparation,
including several that use monosaccharides as precursors.
Unfortunately, various procedures that utilize carbohydrates
employ harsh conditions or involve multiple steps.1,2 We now
report an efficient one-step procedure for the reductive
deoxygenation of 1,2-O-isopropylidenefuranose derivatives
into the corresponding tetrahydrofurans.
Gray had used triethylsilane and boron trifluoride etherate
(or trimethylsilyl triflate) to convert methyl furanosides or
pyranosides into 1,4- or 1,5-anhydroalditols, respectively.3
This was extended to the generation of C-glycosides4 from
ulose hemiacetals, but attempted application of the method
for reductive deprotection of 1,2-O-isopropylidenefuranoses
was less successful. Only moderate product yields with the
formation of troublesome byproducts were observed.5 Our
requirement for several 1,4-anhydroalditol derivatives6 led
us to reexamine this method with isopropylidenefuranoses.
Treatment of 1,2-O-isopropylidenefuranose derivatives 1
with Et3SiH/BF3‚Et2O produced the tetrahydrofurans 2 in
high yields (Table 1). However, it is noteworthy that the
replacement of BF3‚Et2O by TMS triflate resulted in the
formation of 2-O-isopropyl ethers5 (10-20%) in addition to
(1) (a) Soltzberg, S. AdV. Carbohydr. Chem. Biochem. 1970, 25, 229.
(b) Hanessian, S. Total Synthesis of Natural Products: The ′Chiron′
Approach; Pergamon: New York, 1983; Chapter 6. (c) Friedrichsen, W.
In ComprehensiVe Heterocyclic Chemistry II; Katritzky, A. R., Rees, C.
W., Scriven, E. F. V., Bird, C. W., Eds.; Pergamon: New York, 1996;
Volume 2, Chapter 2.07.5. (d) Lundt, I. In Glycoscience: Synthesis of
Substrate Analogues and Mimetics; Driguez, H., Thiem, J., Eds.; Topics in
Current Chemistry 187; Springer-Verlag: New York, 1997; Chapter 4.4.
(2) (a) Danishefsky, S. J.; Armistead, D. M.; Wincott, F. E.; Selnick, H.
G.; Hungate, R. J. Am. Chem. Soc. 1989, 111, 2967. (b) Tino, J. A.; Clark,
J. M.; Field, A. K.; Jacobs, G. A.; Lis, K. A.; Michalik, T. L.; McGeever-
Rubin, B.; Slusarchyk, W. A.; Spergel, S. H.; Sundeen, J. E.; Tuomari, A.
V.; Weaver, E. R.; Young, M. G.; Zahler, R. J. Med. Chem. 1993, 36,
1221. (c) Lundt, I.; Frank, H. Tetrahedron 1994, 50, 13285. (d) Shuto, S.;
Tatani, K.; Ueno, Y.; Matsuda, A. J. Org. Chem. 1998, 63, 8815.
(3) (a) Rolf, D.; Gray, G. R. J. Am. Chem. Soc. 1982, 104, 3539. (b)
Rolf, D.; Bennek, J. A.; Gray, G. R. J. Carbohydr. Chem. 1983, 2, 373. (c)
Bennek, J. A.; Gray, G. R. J. Org. Chem. 1987, 52, 892.
(4) Lewis, M. D.; Cha, J. K.; Kishi, Y. J. Am. Chem. Soc. 1982, 104,
4976.
(5) Kakefuda, A.; Shuto, S.; Nagahata, T.; Seki, J.-i.; Sasaki, T.; Matsuda,
A. Tetrahedron 1994, 50, 10167.
(6) Robins, M. J.; Ewing, G. J. J. Am. Chem. Soc. 1999, 121, 5823.
10.1021/ol9901117 CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/21/1999

Although ∼10 equiv each of Et3SiH and BF3‚Et2O was
used in our standard conditions, comparable yields were
obtained in recent experiments with 3-5 equiv of each
reagent. No reaction was observed after 1 h at 0 °C, but
conversions were complete (TLC) in 1.5 h at ambient
temperature. The protecting groups on all compounds in
Table 1 were stable under these conditions. However, the
known equilibration of acetyl or benzoyl groups between
O3 and (newly deprotected) O2 in ribofuranose derivatives
and benzoyl migration (O5 to O3) in the reaction with 5-O-
benzoyl-1,2-O-isopropylidene-R-D-xylofuranose did occur
(data not shown). Of particular concern is the mixture of 3-
and 2-O-benzyl ethers (∼2:1) that was obtained by standard
treatment of the 3,5-di-O-benzyl-1,2-O-isopropylidene-R-D-
ribofuranose substrate (not shown).
Table 1. Deprotection/Reduction of
1,2-O-Isopropylidenefuranoses to the Corresponding
Tetrahydrofuransa-c
The only furanose derivative that did not react rapidly with
Et3SiH/BF3‚Et2O was 1f. Reaction was sluggish and did not
proceed to completion within 3 days in the absence of
trifluoroacetic acid (TFA). Possible interactions between the
3-O-benzoyl group and the cationic anomeric center might
be unfavorable.
The utility of this methodology is readily apparent by
comparison with a route used to prepare 2d from 1d. That
five-step sequence2d (55% overall) is much less convenient
and efficient than the present one-stage process (87%).
In summary, treatment of 1,2-O-isopropylidenefuranose
derivatives with triethylsilane and boron trifluoride etherate
provides convenient and efficient one-stage access to the
correspondingly substituted tetrahydrofurans. This is an
appealing route to various 1,4-anhydroalditol derivatives,
because many 1,2-O-isopropylidenefuranose precursors with
different hydroxyl protecting groups can be used. These
furanose derivatives are readily accessible in a few steps from
inexpensive, commercially available carbohydrates. The 1,4-
anhydroalditol products can be modified by standard carbo-
hydrate transformations to provide a variety of functionalized
tetrahydrofurans and other derivatives.7
Acknowledgment. We thank the Brigham Young Uni-
versity development fund for support.
OL9901117
(7) Collins, P. M.; Ferrier, R. J. Monosaccharides; Wiley: New York,
1995; Chapters 4 and 5.
(8) General Procedure for Deprotection/Reduction of 1,2-O-Isopro-
pylidene Furanoses. To a solution of 1g (3.6 g, 11.2 mmol) in CH2Cl2 (45
mL) at 0 °C were added Et3SiH (16.7 mL, 12.1 g, 104 mmol) and BF3‚
Et2O (13.3 mL, 14.9 g, 105 mmol), and the reaction was stirred at ambient
temperature for 2 h. The reaction was quenched by careful addition to
saturated NaHCO3/H2O (50 mL) and CH2Cl2 (100 mL). The aqueous layer
was extracted (CH2Cl2, 3 × 50 mL), and the combined organic phase was
washed (brine) and dried (MgSO4). Purification by flash chromatography
(2.5 f 3% MeOH/CH2Cl2, silica gel) gave 2g (2.83 g, 10.6 mmol, 95%)
as an oil.
the desired products. These boron and silicon Lewis acid
promoters might have different affinities for O1 versus O2.
636
Org. Lett., Vol. 1, No. 4, 1999