A new approach for syntheses of 2′,3′-dideoxy-2′,3′ -dehydronucleosides using 2,2-difluoro-1,3-dimethylimidazolidine (DFI) as a dehydrating reagent

Article abstract of DOI:10.1081/NCN-120022607

We found that 2,2-difluoro-1,3-dimethylimidazolidine (DFI) is useful for not only fluorination but also dehydrating reactions. This dehydrating ability of DFI was applied to the syntheses of dihydrofurans (2) that are possible starting materials for various anticancer or antiviral drugs.

Full text of DOI:10.1081/NCN-120022607

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A New Approach for Syntheses of 2′,3′-Dideoxy-
2′,3′-dehydronucleosides Using 2,2-Difluoro- 1,3-
dimethylimidazolidine (DFI) as a Dehydrating Reagent
Hideki Umetani a c , Hiroshi Sonoda b & Hironori Komatsu a
a Catalysis Science Laboratory , Mitsui Chemicals Inc. , Sodegaura-shi, Chiba, Japan
b Process Technology Laboratory , Mitsui Chemicals Inc. , Omuta-shi, Fukuoka, Japan
c Catalysis Science Laboratory , Mitsui Chemicals Inc. , 580-32 Nagaura, 299-0265,
Sodegaura-shi, Chiba, Japan
Published online: 31 Aug 2006.
To cite this article: Hideki Umetani , Hiroshi Sonoda & Hironori Komatsu (2003) A New Approach for Syntheses of 2′,3′-
Dideoxy- 2′,3′-dehydronucleosides Using 2,2-Difluoro- 1,3-dimethylimidazolidine (DFI) as a Dehydrating Reagent, Nucleosides,
Nucleotides and Nucleic Acids, 22:5-8, 667-669, DOI: 10.1081/NCN-120022607
To link to this article: http://dx.doi.org/10.1081/NCN-120022607
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NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS
Vol. 22, Nos. 5–8, pp. 667–669, 2003
A New Approach for Syntheses of 20,30-Dideoxy-
20,30-dehydronucleosides Using 2,2-Difluoro-
1,3-dimethylimidazolidine (DFI)
as a Dehydrating Reagent
2
1
Hideki Umetani,1, Hiroshi Sonoda, and Hironori Komatsu
*
1Catalysis Science Laboratory, Mitsui Chemicals Inc., Sodegaura-shi,
Chiba, Japan
2Process Technology Laboratory, Mitsui Chemicals Inc., Omuta-shi,
Fukuoka, Japan
ABSTRACT
We found that 2,2-difluoro-1,3-dimethylimidazolidine (DFI) is useful for not only
fluorination but also dehydrating reactions. This dehydrating ability of DFI was
applied to the syntheses of dihydrofurans (2) that are possible starting materials
for various anticancer or antiviral drugs.
Key Words: DFI; Dehydrating reactions; Dihydrofurans.
*Correspondence: Hideki Umetani, Catalysis Science Laboratory, Mitsui Chemicals Inc.,
580-32 Nagaura, 299-0265 Sodegaura-shi, Chiba, Japan; Fax: þ81 43 864 2371; E-mail:
hideki.umetani@mitsui-chem.co.jp.
667
DOI: 10.1081/NCN-120022607
Copyright # 2003 by Marcel Dekker, Inc.
1525-7770 (Print); 1532-2335 (Online)
www.dekker.com

668
Umetani, Sonoda, and Komatsu
INTRODUCTION
We have recently developed a new fluorinating agent, DFI.[1] DFI is commer-
cially available and advantageous with respect to cost, safe handling, accessibility,
and possible to be recycled. In the course of studies on DFI, we have found that
it is useful for not only fluorination but also dehydrating reactions. We have focused
on the dehydrating ability of DFI and applied it to the syntheses of dihydrofurans (2)
that would be possible key compounds for the preparation of various anticancer or
antiviral drugs.
RESULTS AND DISCUSSION
The reaction of sugar[2] (1a) with DFI was performed at rt in DMI or PhMe.
DFI-adduct (4) was unexpectedly observed as a main product. In attempt to enhance
the conversion into 2a, raising the temperature to 85ꢀC in DMI resulted in disappear-
ance of 4 and 2a was obtained as a main product in 77% yield. Fluorinated sugar (3)
derived by inversion at C3-position was also observed as a by-product. Furthermore,
effect of solvents such as DMI, PhMe, CHCl3, CH3CN and THF was examined to
increase the ratio of 2a. Using CH3CN as a solvent resulted in the highest ratio of
2a:3 (84:17). In contrast, the reaction in PhMe ended in the lowest ratio of 2a:3
(64:37). To generate 2a efficiently, the polar solvents such as CH3CN or DMI were
superior to the non-polar solvents such as PhMe or CHCl3. Finally, the reactions
of various stereoisomers of 1 with DFI were examined (Fig. 1). Consequently, a
hydroxyl group of each stereoisomer was dehydrated by DFI regardless of the con-
figuration at the C1- or the C3-position of the substrates (1a-c). However, 2-deoxy-
ribose derivatives (1b,c) demonstrated lower yields than 2-deoxy-xylose derivative
(1a). The low yield was attributable to the formation of 2-deoxy-3-O-(4-phenylben-
zoyl)xylose derivative resulting from the acyl transfer from C5- to C3-position.
We showed a new synthesis for dehydrated sugars using DFI. We will apply this
synthesis to other nucleosides in the future to come.
Figure 1. Reaction of various stereoisomers. aConditions: 2.2 equiv DFI, CH3CN, 4 h, 85ꢀC.
c
bIn the presence of 17 equiv KF. Determined by HPLC.

Syntheses of 20,30-Dideoxy-20,30-dehydronucleosides
REFERENCES
669
1. Hayashi, H.; Sonoda, H.; Fukumura, K.; Nagata, T. 2,2-Difluoro-1,3-dimethyl-
imidazolidine (DFI). A new fluorinating agent. Chem. Commun. 2002,
1618–1619.
2. Motawia, M.S.; Pedersen, E.B. A short route to 30-deoxy-30-fluorothymidine.
Liebigs Ann. Chem. 1990, 1137–1139.