Addition of tris(trimethylsilyl) phosphite to quinuclidin-3-one and its carbocyclic analogs

Article abstract of DOI:10.1134/S1070363217080382

Convenient methods of synthesis of functionalized phosphonic acids and their trimethylsilyl esters containing quinuclidine, adamantine, and bornane (camphane) moieties, involving reactions of tris(trimethylsilyl) phosphite with quinuclidin-3-one and its c

Full text of DOI:10.1134/S1070363217080382

ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 8, pp. 1879–1881. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © A.A. Prishchenko, M.V. Livantsov, O.P. Novikova, N.N. Meleshonkova, L.I. Livantsova, V.S. Petrosyan, 2017, published in Zhurnal
Obshchei Khimii, 2017, Vol. 87, No. 8, pp. 1393–1395.
LETTERS
TO THE EDITOR
Addition of Tris(trimethylsilyl) Phosphite to Quinuclidin-3-one
and Its Carbocyclic Analogs
A. A. Prishchenko*, M. V. Livantsov, O. P. Novikova,
N. N. Meleshonkova, L. I. Livantsova, and V. S. Petrosyan
Lomonosov Moscow State University, Moscow, 119991 Russia
*
е-mail: aprishchenko@yandex.ru
Received June 15, 2017
Abstract—Convenient methods of synthesis of functionalized phosphonic acids and their trimethylsilyl esters
containing quinuclidine, adamantine, and bornane (camphane) moieties, involving reactions of tris(trimethyl-
silyl) phosphite with quinuclidin-3-one and its carbocyclic analogs.
Keywords: tris(trimethlsilyl) phosphite, quinuclidin-3-one, adamantan-2-one, camphor, trimethylsilyl trifluoro-
methanesulfonate
DOI: 10.1134/S1070363217080382
Functionalized hydroxymethylphosphonates have
found wide application as polydentate ligands and
biologically active substances with diverse properties
present work we developed convenient methods of
synthesis of polycyclic trimethylsilyl phosphonates
containing quinuclidine, adamantane, and bornane
moieties, involving reactions of tris(trimethylsilyl) phos-
phite with quinuclidin-3-one and its carbocyclic analogs.
[
1, 2]. Of particular interest are hydroxymethylphos-
phonates containing polycyclic moieties, for example,
quinuclidine, adamantane, and bornane (camphane),
which are quite popular in pharmaceutical synthesis
It was found that quinuclidin-3-one 1, adamantan-
2-one 2, and camphor 3 rapidly reacted with excess tris-
(trimethylsilyl) phosphite only in the presence of a
trimethylsilyl trifluoromethanesulfonate catalyst (cf.
[3, 4]. Earlier we synthesized a series of hydroxyme-
thylphosphonates containing piperidine moieties, using
tris(trimethlsilyl) phosphite as a convenient [5]. In the
Scheme 1.
5
6
3
OSiMe3
1
O
4
N
N
P(OSiMe3)2
O
7
2
1
4
2
OSiMe3
O
1
3
(
Me SiO) P, CF SO SiMe
3 3 3 3 3
3
4
P(OSiMe3)2
O
3
2
5
4
3
2
3
5
3
2
OSiMe3
1
O
6
P(OSiMe3)2
7
4
6
5
O
1
879

1
880
PRISHCHENKO et al.
Scheme 2.
5
6
4
3
OH
1
4
5
N
P(OH)2
7
2
O
3
MeOH
7
2
_3
MeOSiMe3
OH
1
3
3
4
P(OH)2
O
3
2
5
4
3
8
Scheme 3.
3
2
3
MeOH
OH
MeOH
OH
1
6
O
6
_3
MeOSiMe3
_HP(O)(OH)2
_MeOH
P(OH)2
OMe
7
4
5
O
9
9a
3
[
5]). In this case, the reactions occurred in mild
the other to a solution of 4.0 g (0.025 mol) of
quinuclidin-3-one in 10 mL of methylene chloride. The
mixture was heated on a boiling water bath to remove
conditions to form functionalized phosphonates 4–6 in
high yields (Scheme 1).
all volatile compounds and then distilled. Yield 78%
Trimethylsilyl esters 4 and 5 readily react with
methanol under mild conditions to give functionalized
phosphonic acids 7 and 8 as white hygroscopic crystals
1
(
11.0 g), bp 144°С (1 mmHg). H NMR spectrum, δ,
ppm: –0.26 s (9Н, Me Si), –0.12 s (9Н, Me Si), 0.11 s
3
3
5
(
(
9Н, Me Si), 0.85–1.02 m (2Н, С Н ), 1.45–1.65 m
3
2
(
Scheme 2). The reaction of phosphonate 6 with excess
4
3
2Н, С Н ), 1.76–1.87 m (1Н, С Н), 2.25–2.45 m (5Н,
С Н , С Н , С Н ), 2.93–3.02 m (1Н, С Н ).
NMR spectrum, δ , ppm: 0.39 d (2Me Si, J
2
methanol under the same conditions involves Р–С
bond cleavage and forms phosphorous acid and
camphor 3 (Scheme 3). Apparently, the lability of the
Р–С bond in acid 9 is associated with steric effects of
the bulky substituent, and the cleavage of this bond
occurs via the intermediate formation of semiacetal 9а,
which easily dissociates into the starting methanol and
camphor 3.
2
6
7
2
13
С
=
B
2
2
А
3
С
3
PC
4
3
8
2
.2 Hz), 1.44 (Me Si), 20.98 d (С , J = 9.0 Hz),
3 PC
3
5
3
6
2.38 (С ), 28.12 d (С , J = 6.6 Hz), 45.37 (С ),
5.72 (С ), 58.94 d (С , J = 8.7 Hz), 73.36 d (С ,
JPC = 170.8 Hz). Р NMR spectrum: δ 9.81 ppm.
PC
7
2
2
1
4
PC
1
31
Р
Found, %: C 45.26; Н 8.96. C H NO PSi . Calculated,
16
38
4
3
%: C 45.35; Н 9.04.
The resulting quinoclidine, adamantane, and
bornane derivatives 4–8 are promising biomimetics of
hydroxycarboxylic acids and can be used in the
synthesis of previously unknown types of organo-
phosphorus compounds and further search for targeted
polyfunctional drugs, and also present interest as
promising polydentate ligands.
Phosphonates 5 and 6 were prepared in a similar
way.
Bis(trimethylsilyl) [2-(trimethylsiloxy)adamantan-
1
2
-yl]phosphonate (5). Yield 93%, viscous oil. H NMR
spectrum, δ, ppm: 0.04 s (9Н, Me Si), 0.18 s (18Н,
3
4
Me Si), 1.25–1.44 m (4Н, 2С Н ), 1.49–1.60 m (6Н,
3
2
2
3
3
Bis(trimethylsilyl) [3-(trimethylsiloxy)-1-azabi-
cyclo[2.2.2]oct-3-yl]phosphonate (4). Tris(trimethyl-
silyl)phosphite, 30.0 g (0.1 mol), and a solution of 1.6 g
2С Н , С Н ), 1.62–1.75 m (2Н, С Н ), 1.80–1.95 m
2 2 2
3
3
(2Н, С Н ), 1.97–2.10 m (2Н, С Н ), 2.45–2.65 m
2
2
5
13
(2Н, С Н ). С NMR spectrum, δ , ppm: 0.81
(2Me Si), 2.11 (Me Si), 26.46 (С ), 27.07 (С ), 32.91
(С ), 33.02 (С ), 33.28 (С ), 34.39 (С ), 38.29 (С ),
2
С
4
4
(
0.007 mol) of trimethylsilyl trifluoromethanesulfonate
3 3
2
2
3
3
5
in 5 mL of methylene chloride were added one after
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 8 2017

ADDITION OF TRIS(TRIMETHYLSILYL) PHOSPHITE
1881
1
1
31
7
1
9.00 d (С , J = 168.3 Hz). Р NMR spectrum: δР
methanol under stirring and cooling to 10°С. The
mixture was heated to reflux, the solvent was distilled
off, and the remaining viscous oil was subjected to a
vacuum (1 mmHg) for 1 h to obtain a mixture of 3.2 g
of phosphorous acid and camphor 3 as a viscous oil,
yield 95%.
PC
1.06 ppm. Found, %: C 50.69; Н 9.12. C H O PSi .
Calculated, %: C 50.85; Н 9.21.
1
9
41
4
3
Bis(trimethylsilyl) [1,7,7-trimethyl-2-(trimethyl-
siloxy)bicyclo[2.2.1]hept-2-yl]phosphonate (6). Yield
9%, viscous oil. H NMR spectrum, δ, ppm: 0.27 s
9Н, Me Si), 0.29 s (18Н, Me Si), 0.68 s (3H, Me),
1
8
(
1
1
Phosphorous acid. H NMR spectrum, δ, ppm:
3
3
1
1
31
.09 c (3H, Me), 1.14 s (3H, Me), 1.25–1.35 m (4Н,
6.60 d (1H, PH , J 675.2 Hz). Р NMR spectrum:
PH
6
7
5
С Н , С Н ), 1.40–1.45 m (2Н, С Н ), 1.58–1.65 m
δР 3.34 ppm.
2
2
13
2
4
(
1Н, С Н). С NMR spectrum, δ , ppm: 0.49 (Me Si),
1
С
3
Camphor 3. H NMR spectrum, δ, ppm: 0.55 s
1
2
4
.67 (2 Me Si), 10.65 (Me), 17.92 (Me), 18.52 (Me),
3
(
3H, Me), 0.60 s (3H, Me), 0.70 s (3H, Me), 1.05–1.60
7
6
5
2
5.88 (С ), 28.75 (С ), 41.92 d (С , J = 9.9 Hz),
3.89 d (С , J = 6.4 Hz), 48.62 d (С , J
5.3 Hz), 52.34 d (С , J = 5.9 Hz), 82.39 d (С ,
JPC = 176.0 Hz). Р NMR spectrum: δ 9.74 ppm.
6
7
4
5
PC
m (4Н, С Н , С Н ), 1.65–2.15 m (3Н, С Н , С Н ).
4
3
3
3
2
2
2
2
=
13
PC
PC
С NMR spectrum, δ , ppm: 9.04 (Me), 18.66 (Me),
2
2
1
С
1
6
7
5
PC
1
(
9.26 (Me), 26.50 (С ), 29.48 (С ), 42.71 (С ), 46.49
С ), 48.87 (С ), 57.34 (С ), 219.89 (С ).
1
31
Р
3
4
2
1
Found, %: C 50.48; Н 9.52. C H O PSi . Calculated,
1
9
43
4
3
%: C 50.62; Н 9.61.
The NMR spectra were obtained on a Bruker
Avance 400 spectrometer; solvents CDCl3 (4–6),
СD СOОD (7), and (CD ) SO (8); references TMS
[
3-Hydroxy-1-azabicyclo[2.2.2]oct-3-yl]phosphonic
3
3 2
acid (7). A solution of phosphonate 1a in 15 mL of
diethyl ether was added to a stirred solution of 30 mL
of methanol under cooling to 10°С. The mixture wa
then heated to reflux, the solvent was distilled off, and
the remaining white crystals were subjected to a
vacuum (1 mmHg) for 1 h. Yield 98% (5.1 g), mp 130–
32°С (decomp.). H NMR spectrum, δ, ppm: 1.70–
.00 m (2Н, С Н ), 2.40–2.67 m (3Н, С Н, С Н ), 3.28–
.50 m (5Н, С Н , С Н , С Н ), 3.80–3.93 m (1Н,
С Н ). С NMR spectrum, δ , ppm: 18.38 d (С ,
JPC = 8.3 Hz), 19.77 (С ), 27.13 (С ), 45.99 (С ),
6.43 (С ), 56.24 d (С , J = 10.1 Hz), 68.49 d (С ,
JPC = 163.6 Hz). Р NMR spectrum: δ 18.49 ppm.
1
13
31
(
H, C) and 85% H PO in D O ( Р).
3 4 2
ACKNOWLEDGMENTS
The work was financially supported by the Russian
foundation for Basic Research (project nos. 15-03-
0002 and 17-03-00169).
1
1
2
3
0
5
3
4
2
2
2
6
7
B
2
2
REFERENCES
2
13
4
А
С
3
3
5
6
1. Kukhar, V.P. and Hudson, H.R., Aminophosphonic and
Aminophosphinic Acids. Chemistry and Biological
Activity, New York: Wiley, 2000.
7
2
2
1
4
PC
1
31
Р
Found, %: C 40.42; Н 6.89. C H NO P. Calculated,
7
14
4
2. Kolodiazhnyi, O.I., Russ. Chem. Rev., 2006, vol. 75,
%
: C 40.58; Н 6.81.
2-Hydroxyadamantan-2-yl]phosphonic acid (8)
was prepared in a similar way. Yield 95%, mp 217–
no. 2, p. 227. doi 10.1070/RC2006v075n03ABEH001193
[
3. Hou, F., Miyakawa, T., Kataoka, M., Takeshita, D.,
Kumashiro, S., Uzura, A., Urano, N., Nagata, K.,
Shimizu, S., and Tanokura, M., Biochem. Biophys. Res.
Commun., 2014, vol. 446, p. 911. doi 10.1016/
j.bbrc.2014.03.030
1
2
19°С (cf. [6]). H NMR spectrum, δ, ppm: 1.25–1.40
4
2
3
m (Н, 2С Н), 1.45–1.75 m (6Н, 2С Н , С Н ), 1.90–
2
3
2
3
2
.05 m (2Н, С Н ), 2.15–2.25 m (2Н, С Н ), 2.30–2.50
2
2
3
5
13
4
. Bagrii, E.I., Adamantany: Poluchenie, svoistva, primene-
nie (Synthesis, Properties, Application), Moscow:
Nauka, 1989.
m (4Н, С Н , С Н ). С NMR spectrum, δ , ppm:
2
2
С
4
4
2
2
2
6.71 (С ), 27.07 (С ), 32.22 (С ), 33.32 (С ), 33.33
3
3
5
1
1
(
С ), 33.52 (С ), 38.28 (С ), 74.19 d (С , J
=
PC
31
5. Prishchenko, A.A., Alekseyev, R.S., Livantsov, M.V.,
Novikova, O.P., Livantsova, L.I., Terenin, V.I., and
Petrosyan, V.S., Russ. J. Gen. Chem., 2017, vol. 87,
no. 2, p. 359. doi 10.1134/S1070363217020360
1
59.9 Hz). Р NMR spectrum: δ 25.07 ppm. Found,
Р
%
: C 51.54; Н 7.29. C H O P. Calculated, %: C
10 17 4
5
1.72; Н 7.38.
Reaction of phosphonate 6 with methanol. A
solution of 6.5 g (0.014 mol) of phosphonate 6 in
0 mL of diethyl ether was added to 20 mL of
6. Gamaleya, V.F., Sorochinskii, A.E., Aleksandrov, A.M.,
Pavlenko, A.F., Kukhar’, V.P., and Terenin, V.I., Zh.
Obshch. Khim., 1980, vol. 50, no. 11, p. 2619.
1
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 8 2017