Syntheses and fluoride-ion-mediated hydrolysis of Phosphoroselenoic acid ester and amides

Article abstract of DOI:10.1002/hc.20544

Phosphoroselenoic acid ester and amides containing binaphthoxy moiety were prepared by reacting phosphoroselenoyl chloride with alcohols and secondary amines. The resulting amides underwent fluoride-ion-mediated hydrolysis with a THF solution of tetrabuty

Full text of DOI:10.1002/hc.20544

Heteroatom Chemistry
Volume 20, Number 5, 2009
Syntheses and Fluoride-Ion-Mediated
Hydrolysis of Phosphoroselenoic Acid Ester
and Amides
Toshiaki Murai, Shinsuke Inaji, and Tohru Takenaka
Department of Chemistry, Faculty of Engineering, Gifu University, Yanagido, Gifu 501-1193, Japan
Received 6 May 2009; revised 17 June 2009
phorus compounds, chlorine atom and oxygen-
ABSTRACT: Phosphoroselenoic acid ester and
containing substituents have usually been used as
amides containing binaphthoxy moiety were prepared
leaving groups [1–6]. A variety of pentavalent phos-
by reacting phosphoroselenoyl chloride with alco-
phorus compounds bearing a phosphorus–fluorine
hols and secondary amines. The resulting amides
bond, many of which are of interest from the per-
underwent fluoride-ion-mediated hydrolysis with a
spective of biological activity [7–11], have been pre-
THF solution of tetrabutylammonium fluoride to
pared by these methods. In this regard, we identified
give two types of phosphoroselenoic acid ammonium
the fluoride-ion-mediated hydrolysis of phosphoric
salts: one with a fluorine atom and another with a
acid esters and amides leading to phosphorofluoridic
binaphthoxy group on the phosphorus atom. The
and phosphoramidofluoridic acid salt monoesters as
ratio of these products depended on the substituents
products [12] (Scheme 1), during our studies on the
on the nitrogen atom of the amides. A similar reaction
synthesis and properties of compounds with P Se
of the ester with tetrabutylammonium fluoride gave
bonds [13–22]. Then, we turned back our atten-
two types of ammonium salts. The formation of these
tion to the reaction mode of phosphoroselenoic acid
products was confirmed by converting them to the
esters and amides. As readily available O,O-diaryl
ꢀ
C
corresponding methyl esters. 2009 Wiley Periodicals,
O-alkyl phosphoroselenoic acid esters and amides,
Inc. Heteroatom Chem 20:255–261, 2009; Published on-
those containing binaphthoxy moiety were chosen.
line in Wiley InterScience (www.interscience.wiley.com).
We herein report their fluorine-mediated hydrolysis.
DOI 10.1002/hc.20544
RESULTS AND DISCUSSION
INTRODUCTION
Initially, the starting phosphoroselenoic acid ester
and amides were synthesized (Scheme 2). The chlo-
ride 1, which was readily prepared from PCl3, Se,
and 1,1ꢁ-bi-2-naphthol, was stirred with 2 in the pres-
ence of Et3N (2 equiv) for 3.5 h under reflux in THF
to give the desired ester 3 quantitatively [19]. Like-
wise, the reaction of 1 with amines 4 proceeded
smoothly to give the corresponding amides 5 in high
yields, but the reaction time and the use of extra
amines depended on the substituents in amines 4.
In the synthesis of amides 5a and 5d, amines 4a and
4d (2 equiv) were used, and the reaction was com-
pleted within 2 h under reflux in toluene, whereas
The high affinity of the fluorine atom toward the
phosphorus atom has been used as a driving force
to promote the substitution reaction at the phos-
phorus atom. In the reaction of pentavalent phos-
Correspondence to: Toshiaki Murai; e-mail: mtoshi@gifu-u.ac.
jp.
Contract grant sponsor: Grant-in-Aid for Scientific Research on
Priority Area from the Ministry of Education, Culture, Sports,
Science and Technology, Japan.
Contract grant number: 20036020, “Synergy of Elements.”
2009 Wiley Periodicals, Inc.
c
ꢀ
255

256 Murai, Inaji, and Takenaka
O
P
O
P
O
P
Bu4N+
–O
Bu4N+
–Se
TBAF
THF
ArO
ArO
N
Ph
R
R
Se
P
TBAF
F
O
O
F
(4.0 equiv)
R = OR', NR"2
SCHEME 1
Ph
Ph
6a
N
Ph
THF
rt, 2 h
+
5a
Bu4N+
Ph
O
P
–Se
(6a:7a = 28:72)
N
O
7a
45%
Ph
OH
the reaction with amine 4c required a longer reac-
tion time. For the reaction with diphenylamine (4b),
DMAP was necessary to complete the reaction. Sim-
ilarly to reduce the amount of amine 4e, DMAP was
used as an additive.
MeI
THF
rt, 2 h
O
P
MeSe
O
N
Ph
9a
92%
Second,
fluoride-ion-mediated
hydrolysis
Ph
of phosphoroselenoic amides was carried out
(Scheme 3). Phosphoroselenoic amide 5a was re-
acted with a THF solution of tetrabutylammonium
fluoride (TBAF) at room temperature. The starting
material 5a disappeared within 2 h. In the 31P NMR
spectra of the crude products, two types of signals
were observed at 54.0 and 55.1 ppm with satellite
signals due to coupling with 77Se atom. One of them
was observed as a doublet signal due to coupling
with 19F atom (JP1-F = 1083 Hz). Based on these
spectra and those of the products described later,
the two products were identified as salts 6a and
7a, and they were formed in a ratio of 28:72. These
products could be purified by column chromatog-
raphy on silica gel. In this case, the product 7a
was isolated in 45% yield as a stable compound.
To further confirm the formation of 7a, it was
methylated with MeI in THF. This methylation
OH
SCHEME 3
took place selectively at the selenium atom of 7a
to give phosphoramidoselenoic acid Se-ester 9a in
high yield. This fluoride-ion-mediated hydrolysis
was then applied to a variety of amides 5b–5e
(Table 1). In all cases, a mixture of salts containing
a fluorine atom 6 and salts with a binaphthoxy
group 7 was formed, and their ratio was affected
by the substituents on the amino groups. Products
6 are rare examples of phosphorus(V) compounds
that possess fluorine and selenium atoms [23,24].
The use of N,N-diphenyl amide 5b gave mainly the
salt 6b (entry 1), which was successfully methylated
with MeI to give Se-methyl ester 8b. In contrast, the
reaction of 5c with a THF solution of TBAF gave two
salts 6c and 7c in a nearly equal ratio (entry 2). Both
salts were isolated as major products, although they
could not be completely separated. Nevertheless,
methylation of the mixture of 6c and 7c followed
by purification by column chromatography led to
pure esters 8c and 9c. For the reaction of amides 5d
and 5e, the salts 7 were formed as major products
(entries 3 and 4), and methylation led to Se-methyl
esters 9d and 9e.
A plausible reaction pathway for the present re-
action is shown in Scheme 4. Initially, the substitu-
tion reaction at the phosphorus atom in 5 with F− in
TBAF may take place with cleavage of one of the
binaphthyloxy-phosphorus bonds to give the salts
10, followed by protonation with H2O in a THF so-
lution of TBAF, to give intermediates 11. Hydroxide
ion (OH−) then nucleophilically attacks the phospho-
rus atom in 11. Cleavage of the other binaphthyloxy-
phosphorus bond (path A) may lead to 6 via 12. In
contrast, fluorine atom acts as a leaving group in the
substitution reaction with OH− (path B) to give the
L-menthol (2)
Se
O
P
Et3N (2 equiv)
THF, reflux, 3.5 h
O
O
3
Se
P
99%
O
O
Cl
Se
P
1
O
O
HNR2
4
NR2
5
Toluene, reflux
1.5–22 h
5a NR2 = NBn2 94%
5b NR2 = NPh2 73%
5c NR2 = NPhBn 89%
O
O
O
O
=
5d NR2 =N[CH2(2-pyridyl)]2 92%
OMe
5e NR =
N
2
91%
SCHEME 2
Heteroatom Chemistry DOI 10.1002/hc

Syntheses and Fluoride-Ion-Mediated Hydrolysis of Phosphoroselenoic Acid Ester and Amides 257
TABLE 1 Fluoride-Ion Mediated Hydrolysis of Phosphorose-
Se
P
H OH
lenoic Amides 5
O
O
Se
Bu4N+
Bu4N+
O–
O
R2
5
O
P
O
P
Se
O
TBAF
N
+
NR2
P
F
R2
–Se
O
–Se
F
P
N
F–
THF
rt
2 h
R1
NR2
O
NR2
10
Bu4N+
R1
6
7
5
OH
Se
Se
Bu4N+
R2
OH–
Path B
OH
O
Ratio of 6 and 7
Isolated Yield
Entry
1
5
P
F
F–
Bu4N+
P
R2
in Crude Products
H O
O
N
N
Se
P
11
R1
R1
O
O
100%a
13
OH
Ph
6b
87:13
N
Path A
5b
Ph
6c + 7c (86:14)
Se
P
Se
51%
O
O
OH
O–
N
Ph
O
2
3
4
60:40
34:64
22:78
P
Bu4N+
R2
H O
F
6c + 7c (23:77)
5c
Se
P
N
Ph
P
–Se
O
27%
R2
Bu4N+
R1
N
12
O
O
R1
7
N
2-pyridyl
OH
7d
7e
64%
72%
5d
2-pyridyl
OMe
O
P
Bu4N+
Se
P
–Se
R2
O
O
N
F
N
R1
5e
6
a Yield of the crude product 6 contaminated with
unreacted TBAF.
SCHEME 4
O
P
O
P
Bu4N+
–Se
O
P
O
Bu4N+
–Se
Ph
Se
TBAF
THF
MeSe
F
MeSe
F
Ph
N
N
+
O
O
P
P
OH
OR
Ph
Ph
OR
8b
8c
O
F
0°C––rt
3
14
15
3.0 h
OH
O
P
O
P
MeSe
O
MeSe
O
MeI
THF, rt, 1.0 h
N
2-pyridyl
N
Ph
9c
OR =
Ph
2-pyridyl
OH
OH
9d
O
O
O
P
OMe
60%
dr = 51 : 49
P
MeSe
O
MeSe
O
N
F
16
OH
9e
SCHEME 5
guished in 31P NMR spectra. To confirm the diastere-
omeric ratio of 14, methylation of 14 with MeI was
carried out. As a result, two diastereomers of 16 were
formed in a nearly equal ratio.
salts 7 via 13. While the factors that control the se-
lectivity for path A or B are currently unclear, the
Lewis basicity of the amino groups in 11 may play
an important role since the amides 5b and 5c, in
which the phenyl group is attached to the nitrogen
atom, are predominantly converted to salts 6.
Finally, ester 3 was treated with TBAF in THF
(Scheme 5). The reaction went to completion within
3 h, and two types of signals were observed at 41.3
and 45.1 ppm, analogous to those in the reaction of
amides 5. Therefore, the products were tentatively
considered to be fluoridate 14 and acid salt 15, which
were formed in a ratio of 60:40. These products may
be diastereomeric mixtures but could not be distin-
CONCLUSION
We have demonstrated the synthesis and fluoride-
ion-mediated hydrolysis of phosphoroselenoic acid
ester and amides with a 1,1ꢁ-bi-2-naphthyl group.
These syntheses were achieved by reacting phospho-
roselenoyl chloride with alcohol or amines in the
presence or absence of extra amines as an addi-
tive. The reaction of ester with a THF solution of
Heteroatom Chemistry DOI 10.1002/hc

258 Murai, Inaji, and Takenaka
TBAF was complete within 3 h to give phosphoroflu-
oridoselenoic acid salt and phosphoroselenoic acid
salt. A similar reaction with amides gave phospho-
ramidofluoridoselenoic acid salts and phosphorami-
doselenoic acid salts, and the ratio of these salts de-
pended on the substituents on the amino groups.
The methylation of the resulting salts with MeI
proceeded smoothly at the selenium atom to give
Se-methyl esters.
mp: 272–284◦C; IR (KBr): 3063, 1590, 1487,
1318, 1222, 1200, 1069, 1037, 952, 887, 839, 813,
1
755, 699, 629, 577, 563, 476 cm−1; H NMR (CDCl3)
δ: 5.19–7.94 (m, 22H, Ar); 13C NMR (CDCl3) δ: 120.5,
121.9, 122.0, 122.5, 125.6, 126.3, 126.5, 127.0, 127.2,
127.6, 128.2, 128.6, 129.0, 130.3, 130.8, 131.3, 132.0,
132.3, 132.5, 143.1, 146.3, 146.4, 148.8, 148.9 (Ar);
31P NMR (CDCl3) δ: 76.7 (1 JP-Se = 989 Hz); 77Se NMR
1
(CDCl3) δ: −215.6 (d, JSe-P = 989 Hz); MS (EI) m/z:
563 (M+); HRMS Calcd for C32H22NO2PSe: 563.0553.
Found: 563.0544.
EXPERIMENTAL
(R )-N-Phenyl-N-phenylmethyl-dinaphtho[2,1-d:
ax
1ꢁ,2ꢁ -f][1,3,2]dioxaphosphepine-4-amine-4-selenide
(5c). mp: 88–93◦C; IR (KBr): 3435, 3059, 1734,
1591, 1507, 1492, 1462, 1433, 1361, 1323, 1223,
1155, 1096, 1065, 1029, 980, 953, 915, 855, 836,
813, 772, 750, 720, 695, 652, 625, 599, 565, 549, 522
Typical Procedure for the Synthesis of Amides
A
Method Using Excess Amines: Synthesis
of (Rax)-N,N-Dibenzyl-dinaphtho[2,1-d:1ꢁ,2ꢁ-f][1,3,2]-
dioxaphosphepine-4-amine-4-selenide (5a). To
a
toluene solution (10 mL) of the chloride (R )-1a
ax
1
2
cm−1; H NMR (CDCl3) δ: 4.68dd, JH-H = 14.8 Hz,
(2.15 g, 5.0 mmol) was added dibenzylamine (1.92
mL, 10 mmol) at room temperature under an Ar at-
mosphere. The resulting solution was stirred at re-
flux in toluene for 2 h and concentrated in vacuo.
The reaction mixture was purified by column chro-
matography on silica gel (hexane:CH2Cl2 = 1:1,
Rf = 0.55) to give the corresponding selenide 5a
(2.76 g, 94%) as a colorless solid. mp: 216–218◦C;
IR (KBr): 3455, 3025, 2921, 2792, 2596, 1588, 1495,
1455, 1360, 1321, 1221, 1201, 1157, 1108, 1065, 1028,
978, 943, 913, 859, 833, 808, 785, 745, 693, 651, 624,
3 JH-P = 11.2, 1H, CH2Ph), 4.78dd, JH-H = 14.8 Hz,
2
3 JH-P = 11.2, 1H, CH2Ph), 7.02–8.07 (m, 22H, Ar);
13C NMR (CDCl3) δ: 57.8 (d, JC-P = 5.8 Hz, CH2Ph),
2
120.7, 121.5, 122.1, 122.4, 125.6, 125.6, 126.5, 126.5,
127.0, 127.2, 127.6, 128.2, 128.5, 128.7, 128.8, 129.2,
129.2, 130.4, 130.8, 131.1, 132.0, 132.2, 137.1, 141.5,
146.7, 146.8, 149.1, 149.3 (Ar); 31P NMR (CDCl3) δ:
82.7 (1 JP-Se = 981.2 Hz); 77Se NMR (CDCl3) δ: −256.9
(1 JSe-P = 981.2 Hz); MS (EI) m/z: 577 (M+); Anal.
Calcd for. C33H24NO2PSe (577.07): C, 68.75; H, 4.20;
N, 2.43. Found: C, 68.95; H, 4.44; N, 2.45.
590, 563, 513, 485, 452 cm−1; H NMR (CDCl3) δ:
1
3.62 (dd, J = 11.3 Hz, 15.4 Hz, 2H, NCH2), 4.64 (dd,
J = 11.2 Hz, 15.1 Hz, 2H, NCH2), 6.87–8.10 (m, 22H,
Ar); 13C NMR (CDCl3) δ: 50.2 (NCH2), 50.3 (NCH2),
120.5, 122.0, 122.1, 122.3, 125.7, 126.5, 126.7, 127.1,
127.2, 127.9, 128.3, 128.6, 128.8, 130.9, 131.3, 132.0,
132.3, 132.4, 147.0, 147.0, 148.9 149.0 (Ar); 31P NMR
(CDCl3) δ: 88.4 (1 JP-Se = 975.7 Hz); 77Se NMR (CDCl3)
δ: −304.1 (1 JSe-P = 975.7 Hz); MS (EI) m/z: 590 (M+);
Anal. Calcd for C34H26NO2PSe: C, 69.16; H, 4.44; N,
2.37. Found: C, 69.22; H, 4.65; N, 2.53.
(R )-N,N-Bis[2-pyridinylmethyl]-dinaphtho[2,1-
ax
d:1ꢁ,2ꢁ -f][1,3,2]dioxaphosphepine-4-amine-4-selenide
(5d). Colorless solid; mp: 261–264◦C; IR (KBr):
3056, 2923, 1620, 1589, 1570, 1508, 1462, 1432,
1361, 1324, 1290, 1255, 1223, 1192, 1134, 1113,
1088, 1068, 1050, 994, 956, 939, 841, 812, 788, 762,
749, 711, 696, 652, 627, 614, 574, 564, 520, 501,
1
488, 455, 418 cm−1; H NMR (CDCl3) δ: 4.15 (t, J =
16.1 Hz, 2H, CH2Py), 4.72 (dd, 3 JH-P = 16.0 Hz, 2 JH-H
= 10.4 Hz, 2H, CH2Py), 7.03–8.55 (m, 20H, Ar); 13C
NMR (CDCl3) δ: 53.2 (CH2Py), 120.6, 121.7, 121.9,
122.3, 122.5, 125.7, 126.5, 126.7, 127.0, 128.5, 130.8,
131.0, 131.4, 131.9, 132.2, 132.4, 136.8, 146.8, 146.9,
148.7, 148.8, 149.3, 157.0 (Ar); 31P NMR (CDCl3) δ:
88.1 (1 JP-Se = 976.4 Hz); 77Se NMR (CDCl3) δ: −300.8
(1 JP-Se = 976.4 Hz); MS (EI) m/z: 593 (M+); Anal
Calcd for C32H24N3O2PSe (593.08): C, 64.87; H, 4.08;
N, 7.09. Found: C, 64.73; H, 4.18; N, 6.99.
A Method Using DMAP: Synthesis of (Rax)-N,N-
Diphenyl-dinaphtho[2,1-d:1ꢁ,2ꢁ-f][1,3,2]dioxaphosph-
epin-4-amine-4-selenide (5b). To a dry toluene
solution (5 mL) of the chloride (R )-1a (1.08 g,
ax
2.5 mmol) and DMAP (366 mg, 3.0 mmol) was
added diphenylamine (510 mg, 3.0 mmol) at room
temperature under an Ar atmosphere. The resulting
solution was stirred at reflux in toluene for 22 h
and concentrated in vacuo. The reaction mixture
was purified by column chromatography on silica
gel (hexane:CH2Cl2 = 1:1, Rf = 0.53) to give the
corresponding selenide 5b (1.02 mg, 73%) as a
colorless solid.
(R )-1(4-Selenidodinaphtho[2,1-d:1ꢁ,2ꢁ-f][1,3,2]-
ax
dioxaphosphepin-4-yl)-2-methoxymethyl-(2S)-pyrro-
lidine ((Rax,S) (5e). Colorless solid; mp: 112–118◦C;
IR (KBr): 3054, 2925, 2874, 1619, 1588, 1507, 1461,
1323, 1102, 1067, 952, 834, 811, 750, 696, 624, 584,
Heteroatom Chemistry DOI 10.1002/hc

Syntheses and Fluoride-Ion-Mediated Hydrolysis of Phosphoroselenoic Acid Ester and Amides 259
566, 523 cm−1; 1H NMR (CDCl3) δ: 1.73 (m, 2H,
NCH2CH2), 1.89 (m, 2H, NCHCH2), 2.58 (m, 1H,
NCH2), 3.20 (m, 1H, NCH2), 3.43 (s, 3H, OCH3), 3.53
and concentrated in vacuo. The reaction mixture
was purified by column chromatography on silica
gel (EtOAc:hexane = 1:1, Rf = 0.80) to give the cor-
responding esters.
2
(dd, J = 7.2 Hz, JH-H = 9.6 Hz, 1H, OCH2), 3.65
2
(dd, J = 4.4 Hz, JH-H = 9.6 Hz, 1H, OCH2), 4.15
(m, 1H, NCH), 7.24–8.04 (m, 12H, Ar); 13C NMR
(CDCl3) δ: 25.3 (d, 3 JC-P = 7.2 Hz, NCH2CH2), 28.1 (d,
3 JC-P = 10.2 Hz, NCH2CH2CH2), 49.4 (NCH2), 59.0,
60.5 (d, J = 7.3 Hz, NCH or OCH2), 75.1 (OCH3),
120.8, 120.9, 121.7, 122.2, 122.3, 125.5, 125.6, 126.4,
126.6, 127.1, 128.4, 128.5, 130.6, 130.7, 131.4, 131.8,
132.2, 132.3, 132.4, 146.8, 146.9, 148.5, 148.7 (Ar);
31P NMR (CDCl3) δ: 80.6 (1 JP-Se = 962.9 Hz); 77Se
N,N-Bis(phenylmethyl)phosphoramidoselenoic
Acid O-(1R)-2ꢁ-Hydroxy[1,1ꢁ-binaphthalene]-2-yl Se-
methyl Ester (9a). A colorless solid; mp: 75–82◦C;
IR (KBr): 3244, 3060, 2923, 1621, 1592, 1506, 1455,
1347, 1275, 1207, 1066, 993, 946, 815, 746, 698, 605,
1
2
496, 446 cm−1; H NMR (CDCl3) δ: 1.91 (d, JH-P
=
14.0 Hz, 3H, SeCH3), 3.51 (dd, 2 JH-H = 15.6 Hz, 3 JH-P
2
= 11.6 Hz, 2H, CH2Ph), 3.65 (dd, JH-H = 15.6 Hz,
1
3 JH-P = 11.6 Hz, 2H, CH2Ph), 6.04 (m, 1H, OH),
NMR (CDCl3) δ: −277.8 (d, JSe-P = 962.9 Hz); MS
(EI) m/z: 509 (M+); HRMS Calcd for C26H24NO3PSe:
6.81–7.98 (m, 22H, Ar); 13C NMR (CDCl3) δ: 5.54
2
2
509.0659. Found: 509.0656.
(d, JC-P = 4.9 Hz, SeCH3), 47.5 (d, JC-P = 4.8 Hz,
CH2Ph), 115.4, 119.3, 120.5, 122.6, 123.5, 124.9,
125.9, 126.6, 127.3, 127.4, 128.0, 128.3, 129.1, 130.0,
130.6, 131.6, 133.5, 133.9, 136.2, 147.5, 147.6, 152.1
Typical Procedure for the Fluoride-Ion-Mediated
Hydrolysis of Amides and Ester
(Ar); 31P NMR (CDCl3) δ: 26.9 (d, JP-Se = 463 Hz);
1
77Se NMR (CDCl3) δ: 89.9 (d, JSe-P = 463 Hz); MS
1
To a dry THF solution (1 mL) of 5a (591 mg,
1.0 mmol) was added TBAF (1 M, THF) (4.0
mL, 4.0 mmol) at room temperature under an Ar
atmosphere. The resulting solution was stirred
at room temperature for 2 h and concentrated
in vacuo. The reaction mixture was purified by
column chromatography on silica gel (CH2Cl2
(EI) m/z: 622 (M+); HRMS Calcd for C35H30NO3PSe:
623.1129. Found: 623.1130.
Tetra-n-butylammonium Salt with N,N-Diphenyl-
phosphoramidofluoridoselenoic Acid (6b). 1H NMR
(CDCl3) δ: 0.91 (t, J = 7.0 Hz, 12H, CH2CH2CH3),
1.32 (m, 8H, CH2CH2Me), 1.48 (m, 8H, CH2Et),
3.09 (m, 9H, CH2Pr), 6.85–7.35 (m, 10H, Ar); 31P
100% and EtOAc 100%, RfCH
= 0.10, RfEtOAc =
Cl
2
2
0.38) to give N,N,N-tributyl-1-butanaminium-O-
(1R)-2ꢁ-hydroxy[1,1ꢁ-binaphthalene]-2-yl-[N,N-bis-
(phenylmethyl)]phosphonoselenoate (7a) (380 mg,
45%) as a colorless solid.
1
1
NMR (CDCl3) δ: 41.9 (dd, JP-F = 1095.4 Hz, JP-Se
=
830.4 Hz).
IR (KBr): 3444, 2960, 1593, 1456, 1377, 1220,
1146, 1069, 948, 821, 792, 745, 698, 591, 563, 494,
445 cm−1; 1H NMR (CDCl3) δ: 0.72 (t, J = 7.2 Hz, 10H,
CH3), 1.07 (sex, J = 7.2 Hz, 6H, CH2CH3), 1.32 (m,
6H, NCH2CH2), 2.92 (m, 6H, NCH2CH2), 3.65 (dd,
Tetra-n-butylammonium Salt with N-Phenyl-N-
phenylmethylphosphoramidofluoridoselenoic Acid
(6c). 1H NMR (CDCl3):
0.85 (m, 15H,
δ
CH2CH2CH3), 1.25 (m, 10H, CH2CH2Me), 1.45
(m, 10H, CH2Et), 3.07 (m, 10H, CH2Pr), 4.82 (dd,
3
2 JH-H = 15.8 Hz, JH-P = 12.4 Hz, 2H, CH2Ph), 4.11
3
2 JH-H = 16.0 Hz, JH-P = 10.0 Hz, 1H, NCH2), 4.94
2
3
(dd, JH-H = 15.8 Hz, JH-P = 11.6 Hz, 2H, CH2Ph),
6.77–7.75 (m, 21H, Ar), 8.51 (d, J = 8.8 Hz, 1H,
Ar); 13C NMR (CDCl3) δ: 13.6 (CH3), 19.5 (CH2CH3),
2
3
(dd, JH-H = 16.0 Hz, JH-P = 10.4 Hz, 1H, NCH2),
6.84–7.30 (m, 10H, Ar); 31P NMR (CDCl3): δ 47.9 (dd,
1 JP-F = 1089.5 Hz, 1 JP-Se = 815.6 Hz).
2
24.0 (NCH2CH2), 48.4 (d, JC-P = 5.3 Hz, CH2Ph),
58.6 (NCH2), 119.6, 121.2, 122.5, 123.0, 124.3, 124.6,
125.4, 125.8, 125.9, 127.6, 127.7, 128.2, 129.1, 129.4,
130.1, 134.2, 134.4, 139.0, 150.5, 150.6, 152.7 (Ar);
31P NMR (CDCl3) δ: 55.1 (1 JP-Se = 761 Hz); 77Se NMR
N,N,N-Tributyl-1-butanaminium-O-(1R)-2ꢁ -hy-
droxy[1,1ꢁ -binaphthalene]-2-yl-[N,N-bis-(2-pyridinyl-
methyl)]phosphonoselenoate (7d). IR (KBr): 3407,
3055, 2959, 1593, 1471, 1436, 1334, 1219, 1148,
1
(CDCl3) δ: −168.4 (d, JSe-P = 761 Hz); MS (FAB−)
1
m/z: 608 (M+ − Bu4).
1070, 963, 934, 790, 693, 570 500 cm−1; H NMR
(CDCl3) δ: 0.75 (t, J = 7.2 Hz, 9H, CH3), 1.13 (m,
6H, CH2CH3), 1.39 (m, 6H, NCH2CH2), 3.04 (m,
6H, NCH2CH2), 3.91 (m, 2H, CH2Ph), 4.33 (m, 2H,
CH2Ph), 6.77–7.73 (m, 17H, Ar), 8.15 (d, J = 4.0 Hz,
2H, Ar), 8.48 (d, J = 8.4 Hz, 1H, Ar); 31P NMR
(CDCl3) δ: 56.4 (1 JP-Se = 1086 Hz); MS (FAB−) m/z:
608 (M+–Bu4).
General Procedure for the Methylation of Salts
To dry THF (1 mL) or dry Et2O (1 mL) solutions
of the salts was added MeI (4 equiv) at room tem-
perature under an Ar atmosphere. The resulting so-
lutions were stirred at room temperature for 2 h
Heteroatom Chemistry DOI 10.1002/hc

260 Murai, Inaji, and Takenaka
N,N,N-Tributyl-1-butanaminium-O-(1R)-2ꢁ -hy-
droxy[1,1ꢁ -binaphthalene]-2-yl-1-[2-methoxymethyl-
(2S)-pyrrolidinyl]-phosphonoselenoate
CH2Ph), 116.4, 119.9, 120.2, 123.0, 123.1, 123.6,
124.9, 125.9, 126.5, 126.6, 127.1, 127.4, 128.0, 128.2,
128.3, 128.7, 129.3, 129.5, 130.1, 130.6, 130.8, 131.6,
133.8, 136.7, 140.0, 147.5, 147.6, 152.4 (Ar); 31P
(7e). 1H
NMR (CDCl3) δ: 0.75 (t, J = 7.4 Hz, 20H, CH3),
1.23 (m, 12H, CH2CH3), 1.47 (m, 15H, NCH2CH2),
1.77 (m, 2H, NCHCH2 or CHCH2CH2), 2.56 (m, 1H,
PNCH2), 2.65 (m, 1H, PNCH2), 3.05 (s, 3H, OCH3),
3.10 (m, 15H, CH2NCH2), 3.30 (m, 2H, OCH2), 3.76
(m, 1H, NCH), 6.88–7.33 (m, 6H, Ar), 7.74–7.81
(m, 5H, Ar), 8.52 (d, J = 8.8 Hz, 1H, Ar); 31P NMR
(CDCl3) δ: 53.1 (1 JP-Se = 758 Hz) The signals due
to NCHCH2 were overlapped with those due to
NCH2CH2CH2CH3.
1
NMR (CDCl3) δ: 24.0 (d, JP-Se = 476 Hz); 77Se NMR
(CDCl3) δ: 98.8 (d, 1 JSe-P = 476 Hz); MS (EI) m/z: 609
(M+); HRMS Calcd for C34H28NO3PSe: 609.0972.
Found: 609.0975.
N,N-Bis[2-pyridinylmethyl]phosphoramidoselen-
oic Acid O-(1R)-2ꢁ-Hydroxy[1,1ꢁ-binaphthalene]-2-yl
Se-methyl Ester (9d). A colorless solid; mp: 82–
92◦C; IR (KBr): 3203, 3055, 2931, 1733, 1621, 1592,
1505, 1474, 1435, 1346, 1212, 1146, 1071, 994,
1
N,N-Diphenylphosphoramidofluoridoselenoic
Acid Se-methyl Ester (8b). A yellow oil; IR (neat):
3062, 2940, 1588, 1490, 1287, 1258, 1202, 1075,
1036, 992, 889, 842, 755, 697, 615, 557 499 cm−1;
937, 817, 749, 661, 606, 513, 445 cm−1; H NMR
(CDCl3) δ: 1.73 (d, 3 JH-P = 14.4 Hz, 3H, SeCH3), 3.89
2
3
(dd, JH-H = 15.6 Hz, JH-P = 12.0 Hz, 2H, CH2Py),
2
3
4.30 (dd, JH-H = 15.6 Hz, JH-P = 12.4 Hz, 2H,
1H NMR (CDCl3) δ: 2.25 (dd, JH-P = 15.2 Hz, J =
CH2Py), 6.92–7.94 (m, 20H, Ar); 13C NMR (CDCl3)
3
2
2
1.6 Hz, 3H, SeCH3), 7.15–7.29 (m, 10H, Ar); 13C
δ: 5.04 (d, JC-P = 5.3 Hz, SeCH3), 50.7 (d, JC-P =
2
1
NMR (CDCl3) δ: 5.5 (dd, JC-P = 5.4 Hz, JC-Se
=
4.8 Hz, CH2Ph), 115.1, 119.5, 120.0, 122.3, 123.0,
123.3, 124.9, 125.5, 126.0, 127.1, 127.9, 128.0, 128.8,
0.95 Hz, SeCH3), 126.8, 127.0, 127.1, 129.5, 141.6
(Ar); 19F NMR (CDCl3) δ: −31.4 (dd, 1 JF-P = 1153 Hz,
129.9, 130.0, 131.2, 133.9, 136.7, 148.7, 153.0, 156.2,
1
1
2 JF-Se = 53.2 Hz); 31P NMR (CDCl3) δ: 19.5 (dd, JP-F
156.3 (Ar); 31P NMR (CDCl3) δ: 26.0 (d, JP-Se
=
1
1
= 1153 Hz, JP-Se = 530 Hz); 77Se NMR (CDCl3) δ:
482 Hz); 77Se NMR (CDCl3) δ: 101.9 (d, JSe-P
=
111.2 (dd, JSe-P = 530 Hz, JSe-F = 53.2 Hz); MS
(EI) m/z: 329 (M+); HRMS Calcd for C13H13FNOPSe:
328.9884. Found: 328.9859.
482 Hz); MS (EI) m/z: 626 (M+); Anal. Calcd for.
C33H28N3O3PSe·0.5H2O: C, 62.56; H, 4.61; N, 6.63.
Found: C, 62.76; H, 4.38; N, 6.50.
1
2
N-Phenyl-N-phenylmethylphosphoramidofluorid-
oselenoic Acid Se-methyl Ester (8c). A colorless
solid; IR (neat): 3032, 2939, 1596, 1493, 1455, 1284,
1-[2-Methoxymethyl-(2S)-pyrrolidinyl]-phospho-
noselenoic Acid O-(1R)-2ꢁ-Hydroxy[1,1ꢁ-binaphtha-
lene]-2-yl Se-methyl Ester (9e). A colorless solid;
mp: 62–69◦C; IR (KBr): 3220, 3063, 2934, 1622,
1592, 1506, 1461, 1433, 1346, 1275, 1220, 1105,
1
1251, 1097, 1068, 886, 820, 774, 695, 537 cm−1; H
NMR (CDCl3) δ: 2.20 (d, 3 JH-P = 15.2 Hz, 3H, SeCH3),
4.62 (m, 1H, NCH2), 4.79 (dd, JH-H = 15.2 Hz, JH-P
= 9.2 Hz, 1H, NCH2), 7.03–7.33 (m, 10H, Ar); 13C
1070, 993, 816, 748, 661, 603, 561, 531 cm−1; H
2
3
1
NMR (CDCl3) δ: 1.42–1.68 (m, 4H, NCH2CH2), 1.98
2
3
NMR (CDCl3) δ: 4.8 (d, JC-P = 4.9 Hz, SeCH3), 54.7
(dd, JH-P = 13.4 Hz, J = 1.8 Hz, 3H, SeCH3), 2.45
4
(d, 2 JC-P = 5.8 Hz, NCH2), 127.5, 127.7, 128.3, 128.4,
(m, 1H, NCH2), 2.57 (m, 1H, NCH2), 2.90 (dd, JH-P
2
4
128.6, 129.4, 136.7, 139.3 (Ar); 19F NMR (CDCl3) δ:
= 7.2 Hz, JH-H = 9.6 Hz, 1H, OCH2), 3.05 (dd, JH-P
1
2
2
−30.9 (dd, JF-P = 1152 Hz, JF-Se = 51.3 Hz); 31P
= 4.0 Hz, JH-H = 9.6 Hz, 1H, OCH2), 3.06 (s, 3H,
1
1
NMR (CDCl3) δ: 23.3 (dd, JP-F = 1152 Hz, JP-Se
OCH3), 3.32 (m, 1H, NCH), 7.04–8.02 (m, 12H, Ar);
1
2
= 517 Hz); 77Se NMR (CDCl3) δ: 97.2 (dd, JSe-P
=
13C NMR (CDCl3) δ: 5.01 (d, JC-P = 4.9 Hz, SeCH3),
2
3
3
517 Hz, JSe-F = 51.3 Hz); MS (EI) m/z: 343 (M+);
HRMS Calcd for C14H15FNOP82Se: 345.0042. Found:
345.0020.
2.45 (d, JC-P = 8.3 Hz, NCH2CH2), 28.8 (d, JC-P
2
= 7.8 Hz, N CH2CH2CH2), 47.2 (d, JC-P = 3.9 Hz,
NCH2), 57.5 (d, J = 3.9 Hz, NCH2 or OCH2), 58.7
(NCH2 or OCH2), 74.6 (OCH3), 116.0, 119.5, 120.6,
122.7, 123.5, 124.9, 125.8, 126.5, 127.3, 127.9, 128.2,
129.1, 130.0, 130.5, 131.5, 133.7, 147.4, 147.5, 125.3
(Ar); 31P NMR (CDCl3) δ: 25.5 (1 JP-Se = 464.2 Hz);
N-Phenyl-N-phenylmethylphosphoramidoselenoic
Acid O-(1R)-2ꢁ-Hydroxy[1,1ꢁ-binaphthalene]-2-yl Se-
methyl Ester (9c). A yellow solid; mp: 72–77◦C; IR
(neat): 3238, 3059, 2932, 1621, 1593, 1493, 1455,
1433, 1329, 1276, 1207, 1068, 990, 881, 815, 749,
695, 604, 529 cm−1; 1H NMR (CDCl3) δ: 1.96 (d,
3 JH-P = 13.6 Hz, 3H, SeCH3), 4.10 (m, 2H, CH2Ph),
6.49–7.97 (m, 22H, Ar); 13C NMR (CDCl3) δ: 5.7
77Se NMR (CDCl3) δ: 77.3 (d, JSe-P = 464.2 Hz); MS
1
(EI) m/z: 509 (M+); HRMS Calcd for C27H28NO4PSe:
541.0921. Found: 541.0948.
Tetrabutylammonium L-Methylphosphorofluoro-
selenoic Acid (14). IR (neat): 2925, 2363, 2343,
2
2
(d, JC-P = 4.9 Hz, SeCH3), 53.4 (d, JC-P = 4.8 Hz,
Heteroatom Chemistry DOI 10.1002/hc

Syntheses and Fluoride-Ion-Mediated Hydrolysis of Phosphoroselenoic Acid Ester and Amides 261
2206, 1718, 1637, 1596, 1458, 1384, 1200, 1107, 1019,
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1
481, 471, 445, 433, 419, 406 cm−1; H NMR (CDCl3)
δ: 0.78 (d, J = 6.8 Hz, 3H, CH3), 0.82 (d, J = 7.3 Hz,
3H, CH3), 0.83 (d, J = 6.3 Hz, 3H, CH3), 0.72–0.83
(m, 1H), 0.96 (t, J = 7.3 Hz, 12H, CH2CH3), 0.92–
1.04 (m, 2H), 1.41 (sex, J = 7.3 Hz, 8H, CH2CH3),
1.19–1.66 (m, 4H, CH2 and/or CH), 1.54–1.66 (m, 8H,
CH2CH2CH3), 2.20–2.28 (m, 1H), 2.37–2.40 (m, 1H),
3.26–3.30 (m, 8H, NCH2), 4.21 (ddt, J = 10.9 Hz,
J = 6.3 Hz, J = 4.5 Hz, 1H, OCH); 13C NMR (CDCl3)
δ: 13.7, 16.0, 19.7, 21.2, 22.1, 22.9, 24.1, 25.2, 31.5,
34.5, 43.0, 48.5 (d, J = 6.6 Hz), 58.8, 77.3 (d, 2 JC-P
=
1
8.3 Hz); 19F NMR (CDCl3) δ: −16.8 (d, JP-F
=
2
1109.9 Hz, JF-Se = 136.1 Hz); 31P NMR (CDCl3) δ:
1
1
41.8 (dd, JP-F = 1109.9 Hz, JP-Se = 848.1 Hz); 77Se
1
2
NMR (CDCl3) δ: −247.6 (dd, JP-Se = 848.1 Hz, JF-Se
= 136.1 Hz); MS (FAB−) m/z: 301 (M+–Bu4).
A
Mixture of Diastereomers of L-Menthyl-
phosphorofluoridoselenoic Acid Se-methyl Ester (16).
IR (neat); 3410, 2961, 2929, 2868, 2338, 1701, 1455,
1427, 1388, 1370, 1351, 1290, 1264, 1218, 1081, 1060,
1000, 932, 916, 881, 849, 822, 806, 563, 545, 504,
493, 424, 407 cm−1; 1H NMR (CDCl3) δ :0.806 (d, J =
6.8 Hz, 3H, CH3), 0.809 (d, J = 6.8 Hz, 3H, CH3),
0.89 (m, 6H, CH3, m, 6H, CH3), 0.78–0.92 (m, 1H, m,
1H), 0.94–1.06 (m, 1H, m, 1H), 1.17–1.28 (m, 1H,
m, 1H), 1.36–1.51 (m, 2H, m, 2H), 1.61–1.70 (m, 2H,
m, 2H), 1.98–2.10 (m, 1H, m, 1H), 2.291 (d, J =
16.4 Hz, 3H, SeCH3), 2.294 (d, J = 15.6 Hz, 3H,
SeCH3), 2.17–2.32 (m, 1H, m, 1H), 4.39–4.51 (m, 1H,
OCH, m, 1H, OCH); 13C NMR (CDCl3) δ: 5.0 (d, J =
5.8 Hz, SeCH3), 5.1 (d, J = 5.8 Hz, SeCH3), 15.7, 15.8,
20.8, 20.9, 21.8, 21.9, 23.0, 23.0, 25.7, 25.9, 31.6, 31.7,
33.79, 33.81, 42.4, 42.8, 48.2 (d, J = 7.4 Hz), 48.3 (d,
2
J = 6.6 Hz), 82.3 (d, JC-P = 11.6 Hz, OCH), 82.4
2
(d, JC-P = 9.1 Hz); 19F NMR (CDCl3) δ: −31.6 (dd,
2
1
1 JP-F = 1173.0 Hz, JF-Se = 72.2 Hz), −33.8 (dd, JP-F
= 1173.0 Hz, JF-Se = 72.2 Hz); 31P NMR (CDCl3)
2
1
1
δ: 16.0 (dd, JP-F = 1173.0 Hz, JP-Se = 558.5 Hz),
14.8 (dd, JP-F = 1173.0 Hz, JP-Se = 558.5 Hz); 77Se
1
1
[22] Murai, T. Phosphorus, Sulfur Silicon Relat Elem
2008, 183, 889–896.
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Nucleic Acids 2005, 24, 659–661.
[24] Bollmark, M.; Kullberg, M.; Stawinski, J. Coll Czech
Chem Commun 2006, 71, 832–841.
1
2
NMR (CDCl3) δ: 87.1 (dd, JP-Se = 558.5 Hz , JF-Se
1
2
= 72.2 Hz), 73.4 (dd, JP-Se = 558.5 Hz , JF-Se
=
72.2 Hz); MS (EI) m/z: 316 (M+); HRMS Calcd for
C11H22O2PSe: 316.0507. Found: 316.0513.
Heteroatom Chemistry DOI 10.1002/hc