TPAP,9 and PCC10 oxidants have been developed. Al-
though these methods work well for simple primary
alcohols, the chemoselective homologation of a primary
alcohol in the presence of a free secondary or tertiary
alcohol has not been reported.11 We decided to explore
the SO3‚pyridine complex12 as a mild, selective, cheap,
safe, and easily handled oxidant to achieve this chemo-
selective transformation. We report herein on our results
utilizing this complex and ethyl triphenylphosphora-
nylidene acetate as the stabilized ylide for the chemo-
selective one-pot C2-homologation of carbohydrate-de-
rived glycols 1, 3, and 5 and its extension to other
systems.
A Convenient and Chemoselective One-Pot
Oxidation/Wittig Reaction for the
C2-Homologation of Carbohydrate-Derived
Glycols
Fernando R. Pinacho Criso´stomo,† Romen Carrillo,†
Toma´s Mart´ın,†,‡ Fernando Garc´ıa-Tellado,*,‡ and
V´ıctor S. Mart´ın*,†
Instituto Universitario de Bioorga´nica “Antonio Gonza´lez”,
Universidad de La Laguna, Astrofı´sico Francisco Sa´nchez 2,
38206 La Laguna, Tenerife, Islas Canarias, Spain, and
Instituto de Productos Naturales y Agrobiologı´a, Consejo
Superior de Investigaciones Cientı´ficas, Astrofı´sico Francisco
Sa´nchez 3, 38206 La Laguna, Tenerife, Islas Canarias,
Spain
Received July 27, 2005
Carbohydrate chain C2-homologation (eq 1) is a very
common synthetic operation that normally requires the
selective protection of the secondary alcohol in the
presence of the primary hydroxyl group.13 This selective
transformation requires a tedious protecting group ma-
nipulation chemistry that involves at least three syn-
thetic steps: selective primary hydroxyl group protection,
secondary hydroxyl group protection, and finally, selec-
tive primary hydroxyl group cleavage. Once the primary
hydroxyl group is liberated, then oxidation to the corre-
sponding aldehyde and Wittig olefination introduce the
homologation chain. Cleavage of the protecting group at
the secondary alcohol prepares the molecule for further
transformation on this center. In terms of chemical
efficiency and synthetic step economy, it would be desir-
able to reduce this methodology to a simple, one-pot
protocol without protecting groups. The protocol should
be facile, using widely available, cheap, stable, easily
handled, and safe reagents. SO3‚pyridine complex fulfills
all of these requirements, and it appeared to us to be the
ideal candidate to achieve the chemoselective oxidation
of the primary alcohol group.
A simple and convenient one-pot protocol for the chemo-
selective C2-homologation of carbohydrate-derived glycols is
described. The method comprises the chemoselective oxida-
tion of the glycol to the corresponding hydroxyaldehyde and
the subsequent Wittig alkenylation. In addition, the method
does not need selective protective group manipulation, and
it is safe, economical, fast (5 to 6 h), and bench-friendly. Its
general utility is discussed.
In a wide research program aimed at the efficient
transformation of commercial carbohydrates in high
added value synthetic scaffolds1 and chiral molecular
receptors,2 we were interested in the selective C2-Wittig
homologation3 shown in eq 1. The transformation re-
quires the selective oxidation of the primary hydroxyl
group to the corresponding aldehyde and the subsequent
Wittig olefination. One-pot oxidation/Wittig sequences
including Swern,4 Dess-Martin,5 BaMnO4,6 MnO2,7 IBX,8
After some experimental work, we were pleased to find
that the treatment of 1,2-isopropyliden glucose derivative
1 with SO3‚Py (3 equiv) and Ph3PdCHCO2Me (1.5 equiv)
in dichloromethane/dimethyl sulfoxide (2.5:1) cleanly
afforded the homologated derivative 2 in 70% overall
* Corresponding authors. (Garc´ıa-Tellado) Phone: +34-922-256847
ext. 248/9. Fax: +34-922-260135. (Mart´ın) Phone: +34-922-318579.
Fax: +34-922-318571.
† Universidad de La Laguna.
‡ Consejo Superior de Investigaciones Cient´ıficas.
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Chem., Int. Ed. 2000, 39, 2727-2729. (b) Garc´ıa-Tellado, F.; Armas,
P.; Marrero-Tellado, J. J. Eur. J. Org. Chem. 2001, 2, 4423-4429. (c)
Garc´ıa-Tellado, F.; Armas, P.; Marrero-Tellado, J. J. Org. Lett. 2000,
2, 3513-3515. (d) Armas, P.; Garc´ıa-Tellado, F.; Marrero-Tellado, J.
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3923-3925.
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2005, 61, 8177-8191. (b) Carrillo, R.; Martin, V. S.; Martin, T.
Tetrahedron Lett. 2004, 45, 5215-5219.
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10.1021/jo051566e CCC: $30.25 © 2005 American Chemical Society
Published on Web 10/22/2005
J. Org. Chem. 2005, 70, 10099-10101
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