O-Methyl-bis-O-(4-nitrophenyl)phosphite: a novel chemoselective O-phosphitylating reagent

Article abstract of DOI:10.1016/j.tetlet.2009.06.102

A novel chemoselective O-phosphitylating reagent containing two aryloxy leaving groups at a P(III) center is developed for selective formation of P(III) esters from amino alcohols without the need to protect the amino group. The reagent proved to be highl

Full text of DOI:10.1016/j.tetlet.2009.06.102

Tetrahedron Letters 50 (2009) 5035–5039
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O-Methyl-bis-O-(4-nitrophenyl)phosphite: a novel chemoselective
O-phosphitylating reagent
*
Wojciech Dabkowski , Łucja Kazimierczak
Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel chemoselective O-phosphitylating reagent containing two aryloxy leaving groups at a P(III) cen-
ter is developed for selective formation of P(III) esters from amino alcohols without the need to protect
the amino group. The reagent proved to be highly convenient for the synthesis of dinucleotides, P(III)–F
structures, and cyclic P(III) nucleotides.
Received 22 April 2009
Revised 5 June 2009
Accepted 19 June 2009
Available online 25 June 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Synthetically available analogues of biological phosphates are of
importance for molecular biology, enzymology, and medicine.1 In
contrast to pentavalent phosphorus compounds which are in-
volved in mechanisms of life, trivalent phosphorus compounds
have not been found in Nature. However, the introduction of
P(III)–X (X = leaving group) type compounds as phosphitylating re-
agents was a central point in the synthetic chemistry of biophos-
phates. In comparison to P(O)–X compounds, they are
considerably more reactive in nucleophilic displacements at the
phosphorus center.2 The early preference for P(V) reagents was
based on their relative stability. Phosphoramidites ˜P–N— are the
most frequently used reagents in the synthesis of various biomol-
ecules.3 The phosphoroamidite strategy is an extension of the Let-
singer4a phosphate method and was introduced in nucleotide
chemistry by Caruthers,4b and later improved by Köster.4c This
class of compounds react poorly with alcohols unless specifically
activated: tetrazole is by far the most commonly used activator
in coupling reactions of phosphoroamidite with alcohols and other
nucleophiles.4b,5 This activator suffers from several drawbacks.
Tetrazole is expensive, explosive, hygroscopic, and sparingly
soluble in acetonitrile, the solvent most often used in coupling
reactions.6 It may also induce transesterification of trialkylphosph-
ites.7 Tetrazole is ineffective or must be used in large excess when
strongly electronegative ligands are attached to the P(III) center.8
To render the phosphoroamidite approach even more useful,
several other activators have been investigated. Examples include
substituted 1H-azoles such as 5-(4-nitrophenyl)-1H-tetra-
zole,9a,b,e,g 5-ethylthio-1H-tetrazole,9c,d,f 4,5-dicyanoimidazole,9f,j
trimethylchlorosilane,9e and 2,4-dinitrophenol.9i Several acid salts
have been proposed to replace tetrazole as the activator for phosp-
horoamidite coupling with alcohols.10 Our recent efforts were di-
rected toward replacement of phosphoroamidites with suitable
phosphitylating reagents which do not require activation by tetra-
zole or other similar acidic activators.11 Therefore P(III) compounds
containing one or two 4-nitrophenoxy leaving groups attracted our
attention.12
Aryloxy groups attached to the P(III) center have been em-
ployed as leaving groups in phosphitylation processes. Reagents
containing the ˜POAr moiety are relatively stable, and easy to
manipulate. They are activated by strong bases such as DBU and
NaH and react rapidly with alcohols in very high yield at ambient
temperature. Formation of an ArOꢀ anion, if necessary, may poten-
tially serve to indicate reaction progress.
In this Letter, we describe a new phosphitylating reagent:
O-methyl-bis-(O-4-nitrophenyl)phosphite 1, which can readily be
prepared in excellent yield from commercially available methoxydi-
chlorophosphine using a standard procedure (Scheme 1).13
Phosphite 1 is a crystalline, stable compound which can be used
and stored without any special precautions. Each of its two aryloxy
groups can be replaced by alcohols in a stepwise manner with
excellent chemoselectivity. The most important chemical property
of phosphite 1 is its O-chemoselectivity. Therefore, as shown in
this study, 1 is the phosphitylating reagent of choice for O-phosph-
itylation of amino alcohols, without the necessity of protecting the
amino group. Another advantage of 1 is that the rate of exchange of
the second aryloxy group is slow enough for efficient preparation
of P(III) esters containing one aryloxy group. This type of com-
pound can be used for further exchange thus allowing syntheses
of (di)nucleotide systems containing a ˜P–F moiety.8b,14
O
O
NO2
NO2
H3C
Cl
Cl
H3C
O
P
O
P
2 HO
+
NO2
Et3N
1
* Corresponding author. Fax: +48 42 6847126.
E-mail address: wdabkow@bilbo.cbmm.lodz.pl (W. Dabkowski).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.06.102

5036
W. Dabkowski, Ł. Kazimierczak / Tetrahedron Letters 50 (2009) 5035–5039
RO
O
Compounds 2a, 2b, and 2c were allowed to react with another
nucleoside in the presence of DBU or NaH to give dinucleosidyl
phosphites 3 (Scheme 3).17
DBU
P
CH3
ROH
1 +
O
or NaH
The condensations leading to the dinucleotides 3a–c (Scheme 3)
proceeded in excellent yield in the presence of DBU at 20 °C. The
reaction rates were distinctly lower than the exchange reactions
presented in Scheme 2. The minimum time necessary to complete
the above coupling was ca. 4 h, the reaction being monitored by 31P
NMR.
Phosphites 3 were readily oxidized by adding elemental sulfur
or selenium to give the corresponding thio 418 or seleno 519 dinu-
cleotides (Scheme 4).
Interestingly, compound 1 can be readily transformed, via three
steps (Scheme 5), into the corresponding salts 6 after removal of
the methyl group. In this way we were able to confirm our earlier
discovery that such demethylation occurs via the action of 4-nitro-
phenolate under mild conditions.12a
NO2
2
Scheme 2.
Exchange of the first aryloxy group of 1 by an alcohol proceeds
smoothly in the presence of DBU or NaH in excellent yield within
10 min (Scheme 2).15 Examples of products obtained according to
Scheme 2 are given in Table 1.
Nucleoside 300-phosphites 2a,12a 2b, 2c, and 2d were obtained as
1:1 mixtures of diastereoisomers as determined from 31P NMR
spectroscopy. No signals were found in the region 145–150 ppm,
which could have indicated the formation of N-phosphitylated
products.16
Table 1
Synthesis of phosphites 2a–e
Entry
ROH
Product
31P NMR (81 MHz, CDCl3) d (ppm)
Yield (%)
O
O
N
N
O
DMTrO
O
N
1
134.9, 133.8 (1:1)
98
O
N
O
DMTrO
O
P
O
O2N
HO
HO
HO
O
CH3
2a
N
NH2
O
N
N
DMTrO
NH2
O
N
N
N
2
138.9, 138.0 (1:1)
95
O
DMTrO
N
N
P
O
O2N
O
CH3
2b
N
O
O
N
N
O
O
DMTrO
N
N
N
DMTrO
3
4
5
141.0, 139.2 (1:1)
136.1, 135.6 (1:1)
135.4
95
98
90
O
N
N
NH2
P
O
O2N
NH2
O
CH3
2c
O
P
O
OH
O
H3C
NO2
O
2d
O
H2N
O
O
H2N
HO
CH3
CH3
O
O
P
CH3
CH3
O
O2N
CH3
2e

W. Dabkowski, Ł. Kazimierczak / Tetrahedron Letters 50 (2009) 5035–5039
5037
O
B
O
B
DMTrO
DMTrO
H3C
O
Thy
O
CH3
+
DBU
HO
O
O
P
Thy
O
+
O
NO2
O2N
P
O
O
or NaH
AcO
O
AcO
2a, B = Thy
2b, B = Ad
2c, B = Gu
3a, B = Thy
3b, B = Ad
3c, B = Gu
31P NMR (81 MHz,
CDCl3) δ (ppm)
141.5, 140.5
Entry
Product
Yield
(%)
95
1
2
3
3a
3b
3c
140.4, 144.0
90
141.9, 140.1
90
Scheme 3.
O
O
B
B
DMTrO
DMTrO
H3C
S8 or Se
O
O
X
O
Thy
O
Thy
P
O
P
O
H3C
O
O
AcO
AcO
4a X = S, B = Thy
4b X = S, B = Ad
4c X = S, B = Gu
5a X = Se, B = Thy
5b X = Se, B = Ad
5c X = Se, B = Gu
3
Entry
Product
31P NMR (81
MHz, CDCl3) δ
(ppm)
Yield
(%)
Entry
Product
31P NMR (81 MHz, CDCl3) δ
Yield
(%)
(ppm)
1
2
3
4a
4b
4c
69.5, 69.8
90
4
5
6
5a
74.6; JP-Se = 976.3 Hz
74.3; JP-Se = 980.0 Hz
74.3; JP-Se= 976.3 Hz
74.0; JP-Se= 976.3 Hz
74.3; JP-Se= 977.3 Hz
73.9; JP-Se= 975.3 Hz
95
69.9, 68.0
69.8, 68.9
90
95
5b
85
90
5c
Scheme 4.
O
NO2
Thy
NaH
DMTrO
a)
HO
O
Thy
O
DMTrO
O
Thy
P
O
O
O
S
NO2
MeO
Thy
HO
H3C
+
O
P
NaH
O
AcO
O
b)
AcO
6
1
NO2
[ S ]
c)
Scheme 5.
The coupling described in Scheme 3 involves the formation of 4-
nitrophenolate. Therefore, the addition of sulfur (selenium)
(Scheme 4) and demethylation (Scheme 5) can be performed to-
gether efficiently (Scheme 5).20
change of an aryloxy group attached to the P(III) center by a fluo-
rine ligand has been demonstrated previously in this
laboratory.8b,14 This method was successfully applied in the pres-
ent study as shown in Scheme 6.
Compounds 2a,e, as well as that derived from
are excellent substrates for the synthesis of fluorophosphites 7. Ex-
L
-(ꢀ)-menthol 2d
Exchange of an aryloxy group for the fluorine using TBAF pro-
ceeds at room temperature in THF solution in over 90% yield.21

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.

W. Dabkowski, Ł. Kazimierczak / Tetrahedron Letters 50 (2009) 5035–5039
5039
20. 500-O-Dimethoxytritylthymidine-300-O-(500-O-thymidyl-300-O-acetyl)phosphorothioate
6: A solution of 50-O-dimethixytritylthymidine (10 mmol) and NaH (10 mmol)
in dry THF was added, at rt under an N2 atmosphere, to a solution of O-methyl
bis(O-4-nitrophenyl)phosphite (10 mmol) in dry THF. The reaction was
purified by column chromatography using a gradient of 0–15% CH3C(O)CH3
in CH2Cl2 as eluent to give pure fluoridate 7.
22. Dabkowski, W. unpublished results.
23. Amigues, E. J.; Migaud, M. E. Tetrahedron Lett. 2004, 45, 1001.
24. Wenska, M.; Jankowska, J.; Sobkowski, M.; Stawinski, J.; Kraszewski, A.
Tetrahedron Lett. 2001, 42, 8055.
complete within 0.5 h to yield 2b in 95% yield (
31P NMR). This reaction
mixture was allowed to react with 300-O-acetylthymidine (1.1 mmol) and NaH
(2.2 mmol dissolved in dry THF (10 mL). After 10 min, the phosphite 3a had
formed in 90% yield (31P NMR). The reaction mixture was treated with a
saturated solution of sulfur in N,N-diisopropylamine (5 ml). After 2 h, the crude
solution of 6 was purified by silica gel column chromatography [31P NMR
(81 MHz, C5D5N) d: 55.7, 55.0 ppm (1:1); yield 85%].
25. Thymidine 300,500-cyclic methyl phosphite 8. A solution of thymidine (10 mmol)
and DBU (11 mmol) in dry acetonitrile (10 mL) was added dropwise at rt under
a
nitrogen atmosphere to a solution of O-methyl-bis-(O-4-nitrophenyl)
phosphate 1 (5 mmol) in dry acetonitrile (10 mL) with stirring for 10 h. The
mixture was evaporated to dryness and the resulting residue was purified by
column chromatography using CH2Cl2–CH3C(O)CH3 (10:3 v/v) as eluent to give
pure thymidine nucleoside 30,50-cyclic methyl phosphite 8. 31P NMR (81 MHz,
CDCl3) d: 120.2, 128.0 ppm. Yield 84%.
21. General procedure for the preparation of RO-P(OMe)F 7: To a solution of aryl
phosphite 2 (10 mmol) in dry THF (10 mL) was added TBAF (12 mmol) at rt.
After 10 min, tetrabutylammonium 4-nitrophenolate was removed by
filtration. The filtrate was concentrated in vacuo and the residue was
26. Nelson, K. A. A.; Sopchik, E.; Bentrude, W. G. J. Am. Chem. Soc. 1983, 105, 7752.