Synthesis of functionalized 2-trimethylsiloxy-substituted O-trimethylsilyl alkylphosphonites, their analogues, and derivatives

Article abstract of DOI:10.1002/hc.20453

Nucleophilic addition of trimethylsilyl esters of tricoordinate organophosphorus acids to several functionalized alkylene oxides is proposed as convenient methods for the synthesis of new 2-trimethylsiloxysubstituted alkylphosphonites, their analogues, an

Full text of DOI:10.1002/hc.20453

Heteroatom Chemistry
Volume 19, Number 5, 2008
Synthesis of Functionalized
2-Trimethylsiloxy-Substituted O-Trimethylsilyl
Alkylphosphonites, Their Analogues,
and Derivatives
Andrey A. Prishchenko, Mikhail V. Livantsov, Olga P. Novikova,
Ludmila I. Livantsova, and Valery S. Petrosyan
Department of Chemistry, M. V. Lomonosov Moscow State University, Moscow 119992, Russia
Received 11 October 2007; revised 10 March 2008
available O,O-diethyl-2,3-epoxypropylphosphonate
ABSTRACT: Nucleophilic addition of trimethylsi-
[2], as well as cyclohexene oxide are promising com-
lyl esters of tricoordinate organophosphorus acids
pounds for organic synthesis [3,4]. Recently, we have
to several functionalized alkylene oxides is proposed
synthesized the new 1-trimethylsiloxysubstituted
as convenient methods for the synthesis of new
alkylphosphonites and their derivatives with aryl,
2-trimethylsiloxysubstituted alkylphosphonites, their
heterocyclic, and organoelement fragments in high
analogues, and derivatives. Also the new function-
yields via nucleophilic addition of trimethylsilyl es-
alized derivatives of these phosphonites, including
ters of trivalent organophosphorus acids to various
amino, carboxy, or sulfo groups as well as cer-
functionalized aldehydes [5]. Also the functional-
tain properties of these compounds, which may
ized derivatives of 2-hydroxyalkylorganophosphorus
be the important precursors of new functional-
acids containing aryl and heterocyclic fragments
ized 2-hydroxyalkylorganophosphorus acids, are pre-
and various hydroxyl, amino, or amido groups
ꢀ
C
sented. 2008 Wiley Periodicals, Inc. Heteroatom Chem
present great interest as promising-polydentate
ligands and biologically active compounds as
organophosphorus biomimetics of hydroxyl and
19:450–454, 2008; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.20453
amino acids [6,7]. In the present work, with
purpose of synthesis new functionalized 2-
INTRODUCTION
trimethylsiloxyalkylphosphonates and phosphinates
including 3-heteropropyl or cyclohexene fragments,
we have studied reaction of trimethylsilyl esters
of trivalent phosphorus acids with epichlorohydrin,
2,3-epoxypropylphosphonate, and cyclohexene ox-
ide. These reactions provide a convenient synthetic
route to new precursors of interesting functionalized
2-hydroxyalkylorganophosphorus acids (cf. [5]).
There are only a few reported examples of the re-
action of trimethylsilyl phosphites with epoxides,
involving phosphorus-carbon formation [1]. Het-
erosubstituted derivatives of propylene oxide, es-
pecially a well-known epichlorohydrin and readily
Correspondence to: Andrey A. Prishchenko; e-mail: liv@org.
chem.msu.ru.
RESULTS AND DISCUSSION
Contract grant sponsor: Russian Foundation for Basic
Research.
In the present work, we have shown that esters
of trivalent phosphorus acids containing POSiMe3
Contract grant number: 08-03-00282.
2008 Wiley Periodicals, Inc.
c
ꢀ
450

Synthesis of Functionalized 2-Trimethylsiloxy-Substituted O-Trimethylsilyl Alkylphosphonites 451
fragment add to epichlorohydrin and O,O-diethyl-
with bis(trimethylsilyl)amine in the presence of
chlorotrimethylsilane gave no more than traces of
phosphonite 11 detected by 31P NMR in the reaction
mixture (Eq. (3)).
2,3-epoxypropylphosphonate A at 130◦C in the pres-
ence of zinc chloride, with selective opening of the
epoxide ring and formation of 3-heterosubstituted
2-trimethylsiloxypropylphosphonites 1,2; phospho-
nates 3–6, and phosphinates 7,8 in high yields
(Eq. (1)), (cf. [3]).
Me3SiO
(Me3Si)2NNa
Me3SiCl
9
P
(3)
(Me3SiO)2P
Me3SiO
(Me3Si)2NH
NaO
Me3SiO
11
Me3SiO
(RO)2POSiMe3
(Me3SiO)2PH
XCH2
XCH2CHCH2P(OR)2
PCH2CHCH2X
OSiMe3
O
H
O
Me3SiO
O
1,2
A
3,4,5,6
Me
POSiMe3
EtO
(1)
Me
XCH2CHCH2P
OEt
O
O
Me3Si
7, 8
R = Et (3,4), Me3Si (5,6);
X = Cl(1,3,5,7), (EtO)2P(O) (2,4,6,8)
Phosphonites 9,11 are the convenient synthons
Under the same conditions, cyclohexene oxide
easily reacts with bis(trimethylsilyloxy)phosphine
and diethyl trimethylsilyl phosphite to give 2-
trimethylsilyloxycyclohexylphosphonite 9 or phos-
phonate 10, respectively (Eq. (2)).
for preparing functionalized phosphinates including
cyclohexane fragments that attract attention as po-
tential ligands and biologically active compounds.
Thus, the aminomethylation of phosphonite 9 with
Me3SiO
(Me3SiO)2PH
(EtO)2POSiMe3
(EtO)2P
O
(2)
P
H
O
Me3SiO
O
Me3SiO
9
10
aminals at 130◦C in the presence of zinc chloride
(cf. [8]) gives aminomethylphosphinates 12,13 and
the addition of phosphonite 9 to trimethylsilyl acry-
late proceeds to form phosphinate 14 with propi-
onate fragment (Eq. (4); cf. [9]).
Using phosphonite 9, we have devised a con-
venient method for preparing bis(trimethylsilyl)2-
trimethylsiloxycyclohexylphosphonite 11, which
was obtained in high yield by successive treatment of
phosphonite 9 with sodium bis(trimethylsilyl)amide
and chlorotrimethylsilane. Contrary to that, pro-
longed boiling of a mixture of phosphonite 9
CH2NR2
CH2CH2COOSiMe3
Me3SiOP
O
CH2(NR2)2
HNR2
CH2=CHCOOX
Me3SiOP
O
9
(4)
Me3SiO
12,13
Me3SiO
14
NR2=
N
(12)
O (13)
, N
Heteroatom Chemistry DOI 10.1002/hc

452 Prishchenko et al.
Phosphonite 11 is a key compound for prepar-
ing various aminomethyl 2-trimethylsiloxycyclo-
hexylphosphinates 12,13,15,16 by aminomethyla-
tion with various N-chloromethylamines under mild
conditions (Eq. (5); cf, [8]).
logues and derivatives 1–18 are presented in Tables 1
and 2. The elemental analysis data of synthesized
compounds are summarized in Table 3.
EXPERIMENTAL
The 1H, 13C, and 31P NMR spectra were registered on
the Varian VXR-400 and Bruker Avance-400 spec-
trometers (400, 100, and 162 MHz, respectively) in
CDCl3 (1–18) against TMS (1H, 13C) and 85% H3PO4
in D2O (31P). All reactions were carried out under dry
argon in anhydrous solvents.
CH2NR2
ClCH2NR2
Me3SiCl
Me3SiOP
O
11
(5)
Me3SiO
12,13,15,16
O-Trimethylsilyl-3-chloro-2-trimethylsiloxypropyl-
phosphonite (1). A mixture of 16 g bis(trimethyl-
siloxy)phosphine, 5 g of epichlorohydrin, and 0.2 g
of zinc chloride was heated at 110–130◦C for 2 h and
then distilled in a vacuum to give 13.3 g phosphonite
1.
The compounds 2–10 were prepared similarly.
O,O-Bis(trimethylsilyl)-2-trimethylsiloxycyclohex-
ylphosphonite (11). To a solution of 15.4 g of
phosphonite 9 in 50 mL of diethyl ether, a solution
of 10.1 g of sodium bis(trimethylsilyl)amide in
15 mL of ether was added dropwise, with stirring,
at 10◦C. The mixture was stirred for 0.5 h, and then
a solution of 6.5 g of chlorotrimethylsilane in 20 mL
of ether was added. The mixture was left to stand
NR2=
N
O (13), N(Et)Ac (15), N(Me)SO2Me (16)
(12), N
Phosphinates 12,13,15 were prepared in high
yields, and the yield of phosphinate 16 was as low
as 35%. The second reaction product in the latter
case was phosphonate 17 isolated in 40% yield. This
reaction’s result is explained by the decomposition
of intermediate quasiphosphonium adduct B in two
directions. The usual Arbuzov reaction leads to phos-
phinate 16, whereas 1,2-elimination in adduct B pro-
ceeds with liberation of cyclohexene and subsequent
formation of phosphonate 17, which was obtained
by us earlier (Eq. (6)).
Phosphonite 11 under mild conditions readily
reacts with benzaldehyde to give unsymmetrical
phosphinate 18 as a promising precursor of in-
teresting substituted 1-hydroxymethyl (2-hydroxy-
cyclohexyl) phosphinic acid (Eq. (7); cf. [5]).
for 24 h, the precipitate that formed was filtered
off, the solvent was removed, and the residue was
distilled in a vacuum to give 14.9 g of phosphonite
11.
O-Trimethylsilyl(N-piperidinomethyl) 2-trimeth-
ylsiloxycyclohexylphosphinate (12)
a. A mixture of 10 g of phosphonite 9, 5.5 g of bis(N-
piperidino)methane, and 0.2 g of zinc chloride
was heated at 130◦C for 1 h and then distilled to
obtain 10.8 g of phosphinate 12.
(7)
Phosphinate 13 was prepared similarly.
b. To a solution of 9.4 g of phosphonite 11 in 50 mL
of methylene chloride, a solution of 3.3 g of
N-(chloromethyl)piperidine in 20 mL of methy-
lene chloride was added dropwise with stirring
at 10◦C. The solvent was then removed, and the
The constants and NMR data of new functional-
ized 2-trimethylsiloxyalkylphosphonites, their ana-
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of Functionalized 2-Trimethylsiloxy-Substituted O-Trimethylsilyl Alkylphosphonites 453
TABLE 1 Yields, Product Constants and NMR Spectral Data for the P1C1H2C2HC3H2X fragmentsa (δ, ppm; J, Hz) of Com-
pounds 1–8a
Yield
(%)
Bp (◦C)
(p, mmHg)
No
1c
nD20
δ(C1) d/d. d 1JPC 3JPC δ(C2) s δ(C3) d/d. d 1JPC 3JPC δ(P1) sb δ(P2) sb
81
78
115 (1)
150 (1)
1.4468
1.4435
37.66
37.77
40.71
40.07
32.67
35.34
34.66
37.87
34.46
34.71
36.87
36.57
96.1
93.9
95.6
—
—
68.69
68.89
49.77
49.25
36.38
35.45
49.72
35.34
48.36
36.06
47.93
48.33
33.28
34.45
—
—
14.8
10.3
18.89
18.11
19.40
19.05
24.14
25.07
5.51
—
—
23.89
24.16
—
25.07
—
25.27
—
2c
4.1 64.48
4.9 64.53
135.0 12.1
134.2
—
136.4
—
137.5
—
—
134.9
135.2 11.1
93.7
7.8
9.6
7.9
6.9
4.4
9.1
12.5
7.3
3
76
83
81
80
85
142 (4)
165 (1)
136 (4)
142 (0.5)
160 (6)
1.4410
1.4415
1.4372
1.4421
1.4528
137.9
136.4
143.1
—
68.72
7.9 64.32
— 67.63
4
5
6
141.1 10.6 63.48d
5.96
7e
93.5
92.0
92.4
90.8
—
—
67.40d
47.93
48.80
48.60
48.34
67.52d
—
24.30
23.84
8e
72
155 (1)
1.4520
4.0 62.69
4.9 62.64
aAll signals of alkyl and trimethylsilyl groups are in the standard area. The 1H NMR signals of the protons of the groups C1H2C2HC3H2 are
multiplets. According to the NMR spectra, compounds 1,2,7.8 are mixtures of two stereoisomers. Their ratio was determined from the 1H NMR
and 31P NMR spectra as 70:30 for 1 and as 55:45 for 2,7,8. The spectral parameters of the major isomer are given first.
1
bData of 31P{ H} spectra.
cIn 1H NMR spectra, PH fragments, d, 1JPH, 1: 7.12, 553.2 and 7.15, 553.4; 2: 7.17, 549.6 and 7.24, 552.4.
dd, 2JPC, 6, 3.8; 7, 3.0 and 3.8.
2
1
eFragments PCH3. In 1H NMR spectra, d, JPH, 7: 1.06, 14.4, and 1.07, 14.4; 8: 0.86, 14.4, and 0.88, 14.8. In 13C NMR spectra, d, JPC, 7:
15.13, 93.6 and 15.19, 94.2; 8: 15.08, 92.5 and 15.19, 92.7.
TABLE 2 Yields, Product Constants, and NMR Spectral Data for the PC1HC2(C3H2)C2 HO, PC4H2 N, PC4H2C5H2C6 O,
and PC4 HO fragmentsa (δ, ppm; J, Hz) of Compounds 9–18a
Bp (◦C)
Yield (p, mmHg),
Ratio
(%)
No
9c
(%)
(mp, ◦C)
105 (1)
110 (2)
nD20
δ(C1)d 1JPC δ(C2)s/d 2JPC δ(C3)s/d 2JPC δ(C4)d 1JPC
δ(P)sb
78
1.4512
1.4548
80
20
85
15
100
60
40
60
40
70
30
70
30
55
45
70
30
46.75 101.3
45.93 100.3
45.50 137.7
43.86 136.5
70.64
71.01
70.31
68.98
70.54
71.11
71.95
70.79
71.80
70.95
72.04
71.13
71.73
70.81
71.47
71.67
72.40
—
—
35.97
35.86
35.97
35.47
35.68
36.13
36.27
35.79
36.05
35.96
36.29
35.89
35.99
34.45
33.45
36.00
36.57
—
—
11.6
15.2
—
—
—
—
—
—
—
—
—
—
—
24.52
24.27
28.01
29.43
158.82
42.85
40.61
42.02
39.93
46.11
45.34
40.10
39.65
38.54
38.20
39.01
40.95
10
83
4.2
5.7
13.3
3.9
4.9
3.8
5.6
3.6
5.5
4.2
5.3
—
11
12
78
89
93 (1)
160 (1),
(42)
1.4497
—
54.54
44.15
43.91
43.86
43.28
44.90
44.68
45.57
45.79
45.11
45.01
41.72
40.48
27.3
94.0
91.7
95.1
92.9
97.2
94.6
97.6
93.0
94.4
96.6
92.7
93.5
11.8 59.91 109.2
15.3 59.51 109.2
11.9 59.18 107.8
15.5 58.80 109.8
13
86
83
68
35
87
164 (1)
1.4705
1.4565
1.4698
1.4675
—
14d
15e
16
164 (2)
158 (2)
175 (1)
11.8 27.52
15.4 27.09
96.3
96.6
11.6 43.47 101.7
9.9 44.38 102.2
4.2 50.07 102.3
5.8 50.01 102.3
11.8 74.64 105.7
12.1 74.30 109.6
—
—
—
18f
148 (0.5)
(34)
aAll signals of alkyl, phenyl, and trimethylsilyl groups are in the standard area. The 1H NMR spectra of products fragments show expected
signals that look like as overlapping multiplets. According to the NMR spectra, all compounds except 11 are mixtures of two stereoisomers.
Their ratio was determined from the 1H and 31P NMR spectra. The spectral parameters of the major isomer are given first. Phosphonate 17,
yield 40%, bp 152◦C (2 mmHg), mp 49◦C. Fragment PCH2 N: δH 3.12d, 2JPH10.8; δC 46.52d, 2JPC 169.8; δH –0.05 s (cf. [10]).
1
bData of 31P{ H} spectra.
cIn 1H NMR, PH fragments, d, 1JPH: 7.08, 557.6, and 7.07, 558.1.
dIn 13C NMR, C5, s; C6 O, d, 3JPC: 29.26 and 29.08; 172.91, 15.6, and 172.73, 15.3.
eIn 13C NMR, NC O, s: 169.18 and 169.82.
f In 1H NMR, C4 H, d, 2JPH, 5.03, 6.4 and 5.14, 7.2.
Heteroatom Chemistry DOI 10.1002/hc

454 Prishchenko et al.
TABLE 3 Elemental Analyses Data of Synthesized Compoundsa
Calcd. (%)
Found (%)
No
Empirical Formula
Formula Weight
C
H
C
H
1
C9H24ClO3PSi2
C13H34O6P2Si2
C10H24ClO4PSi
C14H34O7 P2Si
C12H32ClO4PSi3
C16H42O7P2Si3
C9H22ClO3PSi
C13H32O6P2Si
302.89
404.53
302.81
404.45
391.07
492.71
272.78
374.42
308.51
308.42
380.69
405.65
407.64
452.74
407.64
429.67
486.81
35.69
38.60
39.67
41.57
36.86
39.00
39.63
41.70
46.72
50.62
47.33
53.29
50.09
47.75
50.09
41.93
54.28
7.99
8.47
7.99
8.47
8.25
8.59
8.13
8.61
9.47
9.48
9.80
9.94
9.40
9.13
9.40
8.44
8.90
35.52
38.41
39.49
41.32
36.54
38.78
39.51
41.53
46.49
50.54
47.12
53.01
49.78
47.59
49.86
41.74
54.01
7.86
8.28
7.83
8.39
8.02
8.47
7.98
8.50
9.39
9.52
9.65
9.87
9.35
8.98
9.28
8.28
8.79
2
3
4
5
6
7
8
9
C
C
12H29O3PSi2
13H29O4PSi
10
11
12
13
14
15
16
18
C15H37O3PSi3
18H40NO3PSi2
C
C17H38NO4PSi2
C18H41O5PSi3
C17H38NO4PSi2
C15H36NO5PSSi2
C22H43O4PSi3
aThe elemental analysis of phosphonate 17 was made in [10].
residue was distilled in a vacuum to give 7.9 g of
phosphinate 12, yield 79%.
The compounds 13 (yield 74%), 15–17 were
prepared similarly.
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Heteroatom Chemistry DOI 10.1002/hc