Fluoride-ion-mediated hydrolysis of phosphoric acid esters, amides, and phosphorous acid esters leading to phosphorofluoridic, phosphoramide fluoridic, and phosphonic acid monoester salts

Article abstract of DOI:10.1246/cl.2008.1198

Fluoride-ion-promoted hydrolysis of phosphoric acid esters and amides to give phosphorofluoridie and phosphoramide fluoridic acid monoester salts takes place upon treatment with a THF solution of TBAF, whereas a similar treatment of phosphorous acid ester

Full text of DOI:10.1246/cl.2008.1198

1198
Chemistry Letters Vol.37, No.12 (2008)
Fluoride-ion-mediated Hydrolysis of Phosphoric Acid Esters, Amides, and Phosphorous Acid
Esters Leading to Phosphorofluoridic, Phosphoramide Fluoridic,
and Phosphonic Acid Monoester Salts
Toshiaki Murai,ꢀ Tohru Takenaka, Shinsuke Inaji, and Yusuke Tonomura
Department of Chemistry, Faculty of Engineering, Gifu University, Yanagido, Gifu 501-1193
(Received September 12, 2008; CL-080877; E-mail: mtoshi@gifu-u.ac.jp)
Fluoride-ion-promoted hydrolysis of phosphoric acid esters
and amides to give phosphorofluoridic and phosphoramide fluo-
ridic acid monoester salts takes place upon treatment with a THF
solution of TBAF, whereas a similar treatment of phosphorous
acid esters generates phosphonic acid monoester salts selectively
without introduction of fluorine.
Table 1. Fluoride-ion-mediated hydrolysis of phosphoric esters
1 and 6a
TBAF
O
P
O
P
1
O
O
O
PhO
PhO
Bu4N+ -
O
F
or
THF
rt, time
P
6
OR
OR
OR
2
Entry
1
1 or 6
Time/h
4.5
Product 2, Yield/%b
O
P
1b
1c
6a
Bu4N+ -
O
F
The introduction of fluorine into organophosphorus com-
pounds is of great importance because phosphoric acid deriva-
tives bearing P–F bonds display a wide range of biologically in-
teresting properties.1 The high affinity2 of fluorine toward phos-
phorus is the driving force for fluoride-ion-promoted substitution
reactions of phosphonic3 and phosphoric acid derivatives4 that
provide P–F bond containing pentavalent organophosphorus
compounds. In addition, oxidative fluorination of dialkyl phos-
phites is known to give dialkyl fluorophosphates.5 However,
air-sensitive and/or less accessible substrates and reagents are
necessary in some cases, and more straightforward methods with
readily available starting materials are desired.
In the course of our current studies with organophosphorus
compounds,6 we observed that site-selective reactions of phos-
phoroselenoic acid O- and Se-2-silylethyl esters bearing the bi-
naphthoxy group take place in THF solutions containing tetrabu-
tylammonium fluoride (TBAF).7 Below, we describe observa-
tions made in studies of fluoride-ion-mediated hydrolysis reac-
tions of phosphoric esters, amides, and phosphorous esters
occurring in THF solutions of TBAF that lead to the formation
of phosphorofluoridate monoester acid and phosphonic acid salts
in a highly selective manner.
O
Ph
2b
2c
87%
O
P
2
3
4.5
5.0
Ph
Bu4N+ -
O
F
O
65%
O
P
Bu4N+ -
O
F
O
2d
86%
O
P
4
5
6b
1d
4.0
4.5
Bu4N+ -
O
F
O
2e
64%
Ph
O
P
Bu4N+ -
O
F
O
2f
86%
6
6c
3.0
O
P
H
H
2g
80%
Bu4N+ -
O
F
O
O
O
7
8
1e
6d
2.5
In our initial efforts in this area, the phosphate triester 1a
was treated with a THF solution of TBAF (Scheme 1). The start-
ing ester 1a was consumed within 4.5 h, and purification of the
reaction mixture gave the phosphorofluoridic acid monoester
salt 2a along with 1,10-bi-2-naphthol. The 31P NMR spectra of
2a contained a doublet at ꢁ5:4 ppm with a characteristic 1J val-
O
O
O
P
Bu4N+ -
O
F
O
O
2h 83%
1.0
O
P
Bu4N+ -
O
F
O
2i
81%
Bu4N+
-O
O
P
TBAF
O
P
aPhosphoric esters 1 and 6 were reacted with THF solution of
TBAF (1.2–2.0 equiv) at rt. Isolated yields.
O
O
O
O
O
O
=
b
THF
rt
3.5 h
O
O
F
1a
2a
68%
ue for coupling between a phosphorus and a fluorine atom. The
two ArO–P bonds in 1a were selectively cleaved, while the
alkylO–P bond in the starting material was retained in the prod-
uct 2a. The reaction pathway for this process (Scheme 1) likely
involves nucleophilic substitution by fluoride at phosphorus to
form intermediate 3, which is protonated by adventitious water
in the THF solution of TBAF8 to give 4 and hydroxide ion.
F–
OH–
O
O
H2O
O
P
O-
O
OH
O
P
P
HO
OR
OR
OR
3
F
F
F
4
5
Scheme 1.
Copyright Ó 2008 The Chemical Society of Japan

Chemistry Letters Vol.37, No.12 (2008)
1199
Hydroxide-initiated hydrolysis of 4 then takes place with elimi-
nation of 1,10-bi-naphtholate to give 2a via 5.
lowed in fluoride-induced reactions of phosphate esters 1 and 6.
In this process, substitution reactions at the phosphorus atom of 9
with fluoride and hydroxide proceed sequentially to form inter-
mediate 11 (Scheme 3). Then, 11 undergoes Arbuzov rearrange-
ment to yield the phosphonofluoridic acid monoester 12, which
upon hydrolysis generates 13, which is deprotonated to give
10.11
In summary, the results of this investigation demonstrate
that fluoride-ion-mediated hydrolyses of phosphoric and phos-
phorous acid esters and amides are efficient reactions that take
place in an highly selectively manner. The findings show that
fluoride-promoted hydrolysis of phosphoric acid esters and
amides produces phosphorofluoridic and phosphoramide fluori-
dic acid monoester salts. In contrast, phosphorous acid esters
are converted to phosphonic acid monoester salts in reactions
with TBAF.12
To demonstrate that this reaction is applicable to the produc-
tion of less accessible phosphorofluoridic acid monoester
salts,9,10 a variety of phosphoric acid esters containing the bi-
naphthyloxy group (1 in Table 1) as well as two phenoxy groups
(6 in Table 1) were reacted with TBAF. In each case, reaction
proceeds to completion within 5 h, and the tetrabutylammonium
salt of the corresponding phosphorofluoridic acid monoester 2 is
generated in good yield. The reactions of esters derived from
secondary and tertiary alcohols (Entries 5–8) proceed with equal
efficiency to provide fluorophosphate monoesters. The presence
of alkenyl groups and acetal moieties does not affect the reaction
(Entries 4, 6, and 7). Owing to the fact that the salts obtained as
products in these processes are soluble in polar solvents, such as
acetone, Et2O, and CH2Cl2, and in water, work up of the reaction
mixtures involves partitioning between Et2O and water. The
organic layers contain 1,10-bi-2-naphthol and phenol, and the
aqueous layers are then extracted with CH2Cl2 to isolate the
fluorophosphate salts 2 except for 2g.
Phosphoramidates 7 also undergo fluoride-promoted hydrol-
ysis when treated with TBAF to produce phosphoramide fluori-
dic acid monoester salts 8 (Scheme 2). Slightly longer reaction
times are required for completion of these reactions. In this pro-
cess, selective elimination of two phenoxy groups takes place
and the N–P bond remains in the products 8.
In this effort we also explored reactions of phosphorous acid
esters 9 with the expectation that selective cleavage of ArO–P
bonds would again occur (Scheme 3).
This work was supported in part by Grant-in-Aid for Scien-
tific Research on Priority Area (No. 20036020, ‘‘Synergy of
Elements’’) from the Ministry of Education, Culture, Sports,
Science and Technology, Japan.
References and Notes
1
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2
3
As a matter of fact, reaction of 9 with TBAF, which pro-
ceeds to completion in 1 h, efficiently produces phosphonic acid
ammonium salts 10 in which two aryloxy moieties of the binaph-
thyloxy group are eliminated, but a fluorine atom is not intro-
duced. This result stands in striking contrast to the pathway fol-
4
a) K. Misiura, D. Szymanowicz, H. Kusnierczyk, Bioorg. Med.
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O
P
Bu4N+
–O
O
P
O
P
Bu4N+
Ph
TBAF
THF, rt
6–8 h
–O
PhO
N
NR1R2
N
Ph
F
F
PhO
7
Ph
8a 75%
8b 90%
Ph
OMe
5
6
A. K. Gupta, J. Acharya, D. Pardasani, D. K. Dubey, Tetrahedron
Lett. 2008, 49, 2232.
O
Bu4N+
–O
O
P
Bu4N+
–O
O
Bu4N+
P
N
P
–O
a) T. Kimura, T. Murai, J. Org. Chem. 2005, 70, 952. b) T. Kimura,
T. Murai, Chem. Commun. 2005, 4077. c) T. Kimura, T. Murai, A.
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N
N
F
F
F
Ph
8c 94%
8d 90%
8e 89%
Scheme 2.
7
8
9
T. Murai, M. Monzaki, F. Shibahara, Chem. Lett. 2007, 36, 852.
THF solution of TBAF (Aldirch) contains 5 wt % water.
For examples of phosphorofluoridic acid monoester ammonium
salts, see: a) C. Sund, J. Chattopadhyaya, Tetrahedron 1989, 45,
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Whiddon, Can. J. Chem. 1998, 76, 946.
O
TBAF (4 equiv)
O
P
P
Bu4N+ -
O
H
OR
O
OR
THF, 0 °C then rt
9
0.5 - 1.0 h
10
Bu4N+
Bu4N+
Bu4N+
O
O
P
O
P
P
–O
H
–O
10 W. Dabkowski, I. Tworowska, Org. Biomol. Chem. 2005, 3, 866.
11 a) M. Sobkowski, A. Kraszewski, J. Stawinski, Tetrahedron:
Asymmetry 2007, 18, 2336. b) P. A. Turhanen, K. D. Demadis,
–O
H
O
O
O
H
25%
10a
10b
10c
87%
73%
S. Peraniemi, J. J. Vepsalainen, J. Org. Chem. 2007, 72, 1468.
¨ ¨
¨
O
P
O
P
HO
c) K. Tram, X. Wang, H. Yan, Org. Lett. 2007, 9, 5103. d) L.
Coudray, I. Abrunhosa-Thomas, J.-L. Montchamp, Tetrahedron
Lett. 2007, 48, 6505.
OR
P
HO
H
F
OR
OR
F
H
11
12
13
12 Supporting Information is available electronically on the CSJ
Journal web site, http://www.csj.jp/journals/chem-lett/.
Scheme 3.
Published on the web (Advance View) November 1, 2008; doi:10.1246/cl.2008.1198