5038
W. Dabkowski, Ł. Kazimierczak / Tetrahedron Letters 50 (2009) 5035–5039
P. Tetrahedron 1993, 49, 1925; (d) Beaucage, S. L.; Iyer, R. P. Tetrahedron 1993,
RO
O
P
CH3
49, 6123; (e) Beaucage, S. L.; Iyer, R. P. Tetrahedron 1993, 49, 10441; (f)
Nifantiev, E. E.; Grachev, M. K.; Burmistrov, S. Y. Chem. Rev. 2000, 100, 3755; (g)
Strömberg, R.; Stawinski, J. In Current Protocols in Nucleic Acid Chemistry;
Beaucage, S. L., Bergstrom, D. E., Glick, G. D., Jones, R. A., Eds.; John Wiley &
Sons: New York, 2000. Chapter 3.41–3.4.11; (h) Hayakawa, Y. Bull. Chem. Soc.
Jpn. 2001, 74, 1547; (i) Michalski, J.; Dabkowski, W. Top Curr. Chem. 2004, 232,
93.
RO
O
TBAF
O
P
CH3
F 7
2
NO2
O
O
Th
H2N
e)
4. (a) Letsinger, R. L.; Lunsford, W. B. J. Am. Chem. Soc. 1976, 98, 3655; (b)
Beaucage, S. L.; Caruthers, M. H. Tetrahedron Lett. 1981, 22, 1859; (c) Sinha, N.
D.; Biernat, J.; McManus, J.; Köster, H. Nucleic Acids Res. 1984, 12, 4539.
5. Matteucci, M. D.; Caruthers, M. H. J. Am. Chem. Soc. 1981, 103, 3185.
6. Stull, D. R. Fundamentals of Fire and Explosion; AICh Monograph Series, No 10;
American Institute of Chemical Engineers: New York 1977; See MSDS for T-
7641 in the Sigma database. The bulk price for 1-H-tetrazole is $700/kg from
ChemImpex International Chicago, IL.
DMTrO
a)
O
RO:
,
,
d)
O
CH3
O
O
CH3
Entry Product 31P NMR (81 MHz, CDCl3) Yield (%)
(ppm)
δ
7. Watanabe, Y.; Maehara, S-i.; Ozaki, S. J. Chem. Soc., Perkin Trans. 1 1992, 1879.
8. (a) Karl, R. M.; Richter, W.; Klösel, R.; Mayer, M.; Ugi, I. Nucleotides, Nucleosides
1996, 15, 379; (b) Dabkowski, W.; Tworowska, I.; Michalski, J.; Cramer, F. J.
Chem. Soc., Chem. Commun. 1995, 1435; (c) Sanghvi, Y. S.; Guo, Z.; Pfundheller,
H. M.; Converso, A. Org. Process Res. Dev. 2000, 4, 175.
1
2
3
7a
7d
7e
131.7; JP-F = 1212.2 Hz
131.3; JP-F = 1208.6 Hz
132.4; JP-F = 1207.3 Hz
132.3; JP-F = 1199.2 Hz
136.2; JP-F = 1200.2 Hz
95
95
90
9. (a) Froehler, B. C.; Matteucci, M. D. Tetrahedron Lett. 1983, 24, 3171; (b)
Hayakawa, Y.; Kataoka, M. J. Am. Chem. Soc. 1997, 119, 11758; (c) Wright, P.;
Lloyd, D.; Rapp, W.; Andrus, A. Tetrahedron Lett. 1997, 34, 3373; (d) Wincott, F.;
DiRenzo, A.; Schaffer, C.; Grimm, S.; Tracz, D.; Workman, C.; Sweedler, D.;
Gonzales, C.; Scaringe, S.; Usman, N. Nucleic Acids Res. 1997, 23, 2677; (e)
Dabkowski, W.; Tworowska, I.; Michalski, J.; Cramer, F. Chem. Commun. 1997,
877; (f) Vargeese, C.; Carter, J.; Yegge, J.; Krivjansky, S.; Settle, A.; Kropp, E.;
Peterson, K.; Pieken, W. Nucleic Acids Res. 1998, 26, 1046; (g) Graham, S. M.;
Pope, S. C. Org. Lett. 1999, 1, 733; (h) Moriguchi, T.; Yanagi, T.; Kunimori, M.;
Wada, T.; Sekine, M. J. Org. Chem. 2000, 65, 8229; (i) Dabkowski, W.;
Tworowska, I.; Michalski, J.; Cramer, F. Tetrahedron Lett. 2000, 41, 7535; (j)
van der Heden, G. J.; Verhagen, C. P.; van der Horst, M. G.; Overkleeft, H. S.; van
der Marel, G. A.; Filipov, D. V. Org. Lett. 2008, 10, 4461.
10. (a) Fourrey, J. L.; Varenne, J. Tetrahedron Lett. 1984, 25, 4511; (b) Hostomsky, Z.;
Smrt, J.; Arnold, L.; Tocik, Z.; Paces, V. Nucleic Acids Res. 1987, 15, 4849; (c) Brill,
W. K.-D.; Nielsen, J.; Caruthers, M. H. J. Am. Chem. Soc. 1991, 113, 3972; (d)
Gryaznov, S. M.; Letsinger, R. L. Nucleic Acids Res. 1992, 20, 1879; (e) Hayakawa,
Y.; Kataoka, M.; Noyori, R. J. Org. Chem. 1996, 61, 7996; (f) Hayakawa, Y.;
Kataoka, M. J. Am. Chem. Soc. 1998, 120, 12395; (g) Beier, M.; Pfleiderer, W.
Helv. Chim. Acta 1999, 82, 879; (h) Eluteri, A.; Capaldi, D. C.; Krotz, A. H.; Cole, D.
L.; Ravikumar, V. T. Org. Process Res. Dev. 2000, 4, 182; (i) Hayakawa, Y.; Kawai,
Y.; Hirata, A.; Sugimoto, J.; Kataoka, M.; Sakakura, A.; Hirose, M.; Noyori, R. J.
Am. Chem. Soc. 2001, 123, 8165; (j) Salamon´ czyk, G.; Kuznikowski, M.;
Poniatowska, E. Tetrahedron Lett. 2002, 43, 1747.
Scheme 6.
O
Thy
O
O
HO
P
CH3
O
Thy
O
O
HO
P
O
O2N
H3C
O
DBU
NO2
8
1
Scheme 7.
Products 7a–c, after flash silica gel chromatography, can be used
for further transformations such as selective exchange of the fluo-
rine group with organometallic reagents to give P(III)–R
structures.22
11. (a) Dabkowski, W.; Cramer, F.; Michalski, J. Tetrahedron Lett. 1988, 29, 330; (b)
Dabkowski, W.; Michalski, J.; Wang, Q. Angew. Chem., Int. Ed. Engl. 1990, 29,
522; Dabkowski, W.; Cramer, F.; Michalski, J. J. Chem. Soc., Perkin Trans. 1 1992,
1447.
12. (a) Helinski, J.; Dabkowski, W.; Michalski, J. Nucleosides Nucleotides 1993, 12,
596; (b) Helinski, J.; Dabkowski, W.; Michalski, J. Tetrahedron Lett. 1993, 34,
6451; (c) Dabkowski, W.; Tworowska, I.; Michalski, J. New J. Chem. 2005, 29,
1396.
An additional example of the utility of phosphitylating reagent
1 is its application in the synthesis of cyclic phosphate tries-
ters,23,24 for example, thymidine nucleoside 30,50-cyclic methyl
phosphite 825,26 (Scheme 7).
In summary, we have developed O-methyl-bis-O-(4-nitro-
phenyl)phosphate as an efficient reagent for the preparation of
P(III) esters of amino alcohols without the necessity of protecting
the amino group, and for the preparation of P(III)–F systems.
13. O-Methyl-bis-O-(4-nitrophenyl)phosphate:
(20 mmol) and triethylamine (20 mmol) in dry THF (10 ml) was added
dropwise at rt under nitrogen atmosphere to solution of
A
solution of 4-nitrophenol
a
a
methoxydichlorophosphine (10 mmol) in dry THF (20 ml). After 2 h,
triethylamine hydrochloride was removed by filtration. The filtrate was
evaporated to dryness to give O-methyl-bis-(O-4-nitrophenyl)phosphite. [31P
NMR (121.49 MHz, CDCl3) d: 150.19 ppm; yield 95%].
14. Dabkowski, W.; Tworowska, I. Tetrahedron Lett. 1995, 36, 1095.
15. General procedure for the preparation of RO-P(OMe)(OC6H4-m-NO2) 2: A solution
of the appropriate alcohol (10 mmol) and DBU (10 mmol) in dry CH3CN was
added at rt under an N2 atmosphere to a solution of O-methyl-bis-(O-4-
nitrophenyl)phosphite (10 mmol) in dry CH3CN. The progress of the reaction
was monitored by 31P NMR and TLC. On completion, the reaction mixture was
evaporated in vacuo. The residue was purified by flash column
chromatography.
Acknowledgments
This work was supported by the State Committee for Scientific
Research, Poland (No. 7 T09A 155 21). We are indebted to Professor
J. Michalski for his interest in this work.
16. W. Dabkowski, unpublished results.
17. General procedure for the preparation of RO-P(OMe)(OR00) 3: To a solution of RO-
P-(OMe)(OAr) (10 mmol) and DBU (10 mmol) in dry CH3CN (20 mL) was added
a solution of 300-O-acetylthymidine (10 mmol) in CH3CN (10 mL). The progress
of the reaction was monitored by 31P NMR and TLC. On completion, the
reaction mixture was evaporated in vacuo. The residue was purified by flash
column chromatography to give 3.
References and notes
1. (a) Hilderbrand, R. L. The Role of Phosphonates in Living Systems; CRC Press: Boca
Raton, FL, 1983; (b) Westheimer, F. H. Sciences 1987, 235, 1173; (c) Kafarski, P.;
Lejczak, B. Curr. Med. Chem.-Anti-Cancer Agents 2001, 1, 301; (d) McMurray, J. S.;
Coleman, D. R., IV; Wang, W.; Campbell, M. L. Biopolymers (Peptide Science)
2001, 60, 3; (e) Engels, J. W.; Parsch, J. Nucleic Acid Drugs. In Molecular Biology
in Medicinal Chemistry; Dingermann, T., Steinhilber, D., Folkers, G., Eds.; Wiley-
VCH: Weinheim, 2004; p 153; (f) Aboul-Fadl, Tarek Expert Opin. Drug Discov.
2006, 1, 285; (g) Guga, P. Curr. Top. Med. Chem. 2007, 7, 695; (h) Nawrot, B.;
Re˛bowska, B.; Michalak, O.; Bulkowski, M.; Błaziak, D.; Guga, P.; Stec, W. J. Pure
Appl. Chem. 2008, 80, 1859.
2. Quin, D. A. Guide to Organophosphorus Chemistry; John Wiley & Sons: New York,
2000.
3. For comprehensive information concerning oligonucleotides and other
biophosphates, see: (a) Uhlman, E.; Peyman, A. Chem. Rev. 1990, 90, 453; (b)
Beaucage, S. L.; Iyer, R. P. Tetrahedron 1992, 48, 2223; (c) Beaucage, S. L.; Iyer, R.
18. General procedure for the preparation of RO-P(S)(OMe)(OR00) 4: To a solution of
ROP(OMe)(OR00) (10 mmol) in dry THF (15 ml) was added a saturated solution
of sulfur in N,N-diisopropylamine (5 ml) and the reaction was stirred for 2 h at
rt. The crude product 4 was chromatographed on silica gel, using a gradient of
0–10% CH3C(O)CH3 in CH2Cl2 as eluent.
19. General procedure for the preparation of RO-P(Se)(OMe)(OR00) 5: To a solution
of ROP(OMe)(OR0) (10 mmol) in dry THF (15 ml) was added
a saturated
solution of selenium in N,N-diisopropylamine (5 ml). The mixture was
stirred for 2 h at rt, and then concentrated in vacuo. Purification by column
chromatography, using a gradient of 0–10% CH3C(O)CH3 in CH2Cl2 as eluent
gave 5.