9-Fluorenemethyl H-phosphonoselenoate - A versatile reagent for transferring an H-phosphonoselenoate group

Article abstract of DOI:10.1081/NCN-120023011

This paper expands the available methods for preparation of H-phosphono-selenoate using a new reagent, 9-fluorenemethyl H-phosphonoselenoate.

Full text of DOI:10.1081/NCN-120023011

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9-Fluorenemethyl H-Phosphonoselenoate—A Versatile
Reagent for Transferring an H-Phosphonoselenoate
Group
Martin Kullberg a & Jacek Stawinski a b c
a Department of Organic Chemistry , Arrhenius Laboratory , Stockholm University ,
Stockholm, Sweden
b Institute of Bioorganic Chemistry , Polish Academy of Sciences , Poznan, Poland
c Department of Organic Chemistry , Arrhenius Laboratory , Stockholm University , S-10691,
Stockholm, Sweden
Published online: 31 Aug 2006.
To cite this article: Martin Kullberg & Jacek Stawinski (2003) 9-Fluorenemethyl H-Phosphonoselenoate—A Versatile Reagent
for Transferring an H-Phosphonoselenoate Group, Nucleosides, Nucleotides and Nucleic Acids, 22:5-8, 1463-1465, DOI:
10.1081/NCN-120023011
To link to this article: http://dx.doi.org/10.1081/NCN-120023011
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NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS
Vol. 22, Nos. 5–8, pp. 1463–1465, 2003
9-Fluorenemethyl H-Phosphonoselenoate—
A Versatile Reagent for Transferring an
H-Phosphonoselenoate Group
Martin Kullberg1 and Jacek Stawinski1,2,
*
1Department of Organic Chemistry, Arrhenius Laboratory,
Stockholm University, Stockholm, Sweden
2Institute of Bioorganic Chemistry, Polish Academy of Sciences,
Poznan, Poland
ABSTRACT
This paper expands the available methods for preparation of H-phosphono-
selenoate using a new reagent, 9-fluorenemethyl H-phosphonoselenoate.
Key Words: H-Phosphonates; H-Phosphonoselenoates; Reagent.
To expand synthetic methodologies available for the preparation of H-phospho-
noselenoates, we have developed a new reagent for transferring an H-phosphono-
selenoate moiety, 9-fluorenemethyl H-phosphonoselenoate 1. The previous method
for the preparation of H-phosponoselenoate monoesters,[1] although efficient in gen-
eral sense, required excess of a hydroxylic component and this can be considered a
drawback, especially for alcohols that are expensive and difficult to prepare.
*Correspondence: Jacek Stawinski, Department of Organic Chemistry, Arrhenius Laboratory,
Stockholm University, S-10691 Stockholm, Sweden; Fax: þ46 8 154 908; E-mail: js@
organ.su.se.
1463
DOI: 10.1081/NCN-120023011
Copyright # 2003 by Marcel Dekker, Inc.
1525-7770 (Print); 1532-2335 (Online)
www.dekker.com

1464
Kullberg and Stawinski
Chemistry of reagent 1 is based on the same principle as that for other reagents
previously developed for transferring of H-phosphonate[2] and H-phosphonothioate
groups[3] to various hydroxylic components, however, the presence of selenium
required some cautions during handling.
9-Fluorenemethyl H-phosphonoselenoate monoester 1 can easily be prepared
using standard phosphinate approach previously developed for synthesis H-phos-
phonothioate monoesters.[4] Treatment of 9-fluorenemethanol with triethylammo-
nium phosphinate in the presence of pivaloyl chloride, followed by selenization of
the produced phosphinate intermediate with elemental selenium for 2 hours afforded
1 as a major product, which was isolated by silica gel chromatography as an oily,
triethylammonium salt. A crystalline, stable, white solid was obtained in 88% overall
yield upon replacement of the triethylammonium cation by S-(p-chlorobenzyl)-iso-
thiuronium cation.
Utility of 1 has an H-phosponoselenoate group transferring reagent was assessed
by reacting 50-protected thymidine with a slight excess of 1 in acetonitrile containing
pyridine (5 equiv.) in the presence of diphenyl chlorophosphate (2.5 equiv).[1] 31P
NMR spectroscopy indicated clean formation of H-phoshonoselenoate diester 2
( > 90%). Crude product 2 upon treatment with triethylamine in methylene chloride
could be directly converted into H-phosphonoselenoate monoester 3 that was iso-
lated as triethylammonium salt by precipitation (yield 83%).
It is worth noting that 9-fluorenemethyl H-phosphonoselenoate 2 can be easily
separated into individual diastereoisomers by silica gel column chromatography, and
after removal of the 9-fluorenemethyl group, diastereomerically pure H-phosphono-
selenoate monoesters 3 can be obtained. Alternatively, diastereomerically pure H-phos-
phonoselenoate diesters 2 can be subjected to various oxidative transformations
prior to deprotection. Further studies are in progress in this laboratory.
ACKNOWLEDGEMENT
Financial support from the Swedish Research Council is gratefully acknow-
ledged.
REFERENCES
1. Bollmark, M.; Kullberg, M.; Stawinski, J. Nucleoside H-phosphonates. Part
XIX. Novel nucleotide analogues – H-phosphonoselenoate mono- and diesters.
Tetrahedron Lett. 2002, 43, 515–518.

9-Fluorenemethyl H-Phosphonoselenoate
1465
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for the synthesis of nucleoside H-phosphonates using a novel phosphonylating
agent. Nucleosides & Nucleotides 1995, 14, 167–173.
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thioate, phosphorothioate, and phosphorodithioate monoesters. Tetrahedron
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