Synthesis of dialkyl(aryl)cyclobutenylphosphine oxides

Article abstract of DOI:10.1016/j.tetlet.2012.02.042

Dialkyl(aryl)cyclobutenylphosphine oxides are obtained via two routes: from the corresponding cyclobutenylphosphonic dichlorides using organomagnesium chemistry and from 1,3-dienylphosphine oxides by thermal electrocyclic ring closure.

Full text of DOI:10.1016/j.tetlet.2012.02.042

Tetrahedron Letters 53 (2012) 2100–2102
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Tetrahedron Letters
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Synthesis of dialkyl(aryl)cyclobutenylphosphine oxides
⇑
Alexander S. Bogachenkov, Mariya M. Efremova, Boris I. Ionin
Department of Organic Chemistry, St. Petersburg State Technological Institute (Technical University), 190013 St. Petersburg, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
Dialkyl(aryl)cyclobutenylphosphine oxides are obtained via two routes: from the corresponding cyclob-
utenylphosphonic dichlorides using organomagnesium chemistry and from 1,3-dienylphosphine oxides
by thermal electrocyclic ring closure.
Received 21 October 2011
Revised 31 January 2012
Accepted 10 February 2012
Available online 17 February 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Cyclobutenes
Phosphine oxides
Organomagnesium synthesis
Thermal isomerization
Ring closure
Cyclobutene derivatives are difficult to prepare and their prop-
erties remain vastly underexplored. Methods for the synthesis of
cyclobutenes are based mainly on catalytic [2+2] cycloaddition
reactions between alkenes and acetylenes,1–3 and expansion of
cyclopropane rings with subsequent transformations.4,5 Substi-
tuted cyclobutenes have been obtained by intramolecular Wittig
reaction using the vinyltriphenylphosphonium salt.6 It was
reported7,8 that in some cases, 1-substituted 2-chloro-3-tert-bu-
tyl-1,3-butadiene-1-phosphonic dichlorides readily undergo
butadiene-cyclobutene thermal isomerization. This approach has
allowed the synthesis of a variety of cyclobutenyl dichlorophosph-
onates and can be used as a generic pathway to phosphorus-con-
taining cyclobutenes.9
However, cyclobutenylphosphine oxides, which are interesting
compounds for the study of their subsequent transformations
and for practical applications, are not readily available. Herein,
we report the synthesis of several previously undescribed 1,3-
dienyl- and cyclobutenylphosphine oxides. The cyclobutenylphos-
phine oxides were prepared in two ways: (1) by the replacement of
a halogen with an alkyl(aryl) group in the corresponding cyclob-
utenyl dichlorophosphonates, and (2) through thermal, solvent-
free 1,3-butadiene-cyclobutene isomerization of 1,3-dienylphos-
phine oxides. These general routes to the synthesis of substituted
dialkyl(aryl)cylobutenylphosphine oxides are described in
Scheme 1.
argyl ether with pinacolone in the presence of freshly prepared
potassium tert-butoxide similar to the method described by
Miyamoto et al.11 Alcohol 1 was reacted with phosphorus trichlo-
ride to form intermediate 2, which underwent spontaneous isom-
erization to allene 3.12 Hydrogen chloride formed during this
reaction was efficiently removed with a stream of nitrogen. Next,
allene 3 was chlorinated with a solution of chlorine in carbon tet-
rachloride to give unstable salt 4, which liberated hydrogen chlo-
ride upon heating to form 1,3-diene 5. This isomerized on
Cl2,
CCl4
PCl3,
MeO
O
CH2Cl2
95%
OH
O PCl2
Cl
MeO
PCl2
MeO
3
1
2
Cl
MeO
MeO
Cl
95%
Δ 95%
Cl
Cl
Cl-
P+
MeO
PCl2
PCl2
O
O
O
4
5
6
RMgHal
Et2O
RMgHal
Et2O
Cl
MeO
Cl
Δ
MeO PR2
O
PR2
O
Methyl propargyl ether was prepared by the reaction of propar-
gyl alcohol with dimethyl sulfate using a known method.10 The
acetylenic alcohol 1 was prepared by the reaction of methyl prop-
7-9
10-12
7, 10 R= Me; Hal = I
8, 11 R= Et; Hal = Br
9, 12 R= Ph; Hal = Br
⇑
Corresponding author.
E-mail address: borisionin@mail.ru (B.I. Ionin).
Scheme 1. Synthesis of dialkyl(aryl)cyclobutenylphosphine oxides.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2012.02.042

A. S. Bogachenkov et al. / Tetrahedron Letters 53 (2012) 2100–2102
2101
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2012.02.042. These data
include MOL files and InChiKeys of the most important compounds
described in this article.
References and notes
1. López-Carrillo, V.; Echavarren, A. M. J. Am. Chem. Soc. 2010, 132, 9292–9294.
2. Hilt, G.; Paul, A.; Treutwein, J. Org. Lett. 2010, 12, 1536–1539.
3. Ito, H.; Hasegawa, M.; Takenaka, Y.; Kobayashi, T.; Iguchi, K. J. Am. Chem. Soc.
2004, 126, 4520–4521.
4. Xu, H.-D.; Zhang, W.; Shu, D.; Werness, J. B.; Tang, W. Angew. Chem., Int. Ed.
2008, 47, 8933–8936.
5. Salaün, J.; Fadel, A. Org. Synth. 1986, 64, 50–56.
6. Yavari, I.; Bayat, M. Monatsh. Chem. 2003, 134, 1221–1227.
7. Ionin, B. I.; Brel’, V. K.; Prudnikova, O. G.; Struchkov, Yu. T.; Chernega, A. N.;
Petrov, A. A. Doklady Akad. Nauk SSSR 1985, 284, 359–362.
8. Prudnikova, O. G.; Brel’, V. K.; Ionin, B. I.; Petrov, A. A. Zh. Obshch. Khim. 1987,
57, 1472–1481.
9. Brel‘, V. K., Doctorate dissertation, Chemistry, St-Petersburg, 1993. http://
www.dissercat.com/content/funktsionalno-zameshchennye-12-i-13-alkadieni
lphomsphonaty.
10. Lee, W. C.; Huh, M. W.; Gal, Y. S.; Choi, S.-K. Polymer 1989, 13, 520–528.
11. Miyamoto, H.; Yasaka, S.; Tanaka, K. Bull. Chem. Soc. Jpn. 2001, 74, 185–186.
12. Macomber, R. S.; Kennedy, E. R. J. Org. Chem. 1976, 41, 3191–3197.
13. General procedure for the synthesis of phosphine oxides 7–12 (method A): To a
stirred solution of phosphonic dichloride 5 or 6 (7.64 g, 25 mmol) in Et2O
(25 ml) was added dropwise at À10 °C
a solution of the corresponding
Figure 1. X-ray crystal structure (ORTEP) of 10.
Grignard reagent (0.05 M) in Et2O over 1 h. The mixture was allowed to
warm to room temperature over 1 h with stirring. Formation of a white
precipitate was observed. The mixture was refluxed for another 2 h, then
cooled and treated with a saturated solution of NH4Cl. The ethereal layer was
separated, the aqueous layer extracted with CHCl3 (2 Â 10 ml), and the
combined extracts dried over Na2SO4. The solvent was removed by rotary
evaporation. The crude product was purified either by flash chromatography
(SiO2, CH2Cl2/MeOH, 97:3; compounds 7–9, 12) or by distillation under
vacuum (compounds 10 and 11). Method B (for 10–12 only). Compounds 10–12
were obtained from corresponding 1,3-dienes 7–9 by thermal, solvent-free
electrocyclic ring closure. The products were separated from the starting
compounds by flash chromatography (SiO2, CH2Cl2/MeOH, 97:3). See Table 1
for details. 3-tert-Butyl-2-chloro-1-methoxymethyl-1-dimethylphosphoryl-1,3-
butadiene (7): Yield 3.85 g (58%), pale yellow oil, Rf = 0.37 (CH2Cl2/MeOH,
95:5). IR (KBr, cmÀ1): 3415, 2965, 2890, 2820, 1590, 1460, 1358, 1175, 1100,
955, 906, 758, 710. 1H NMR (400 MHz, CDCl3): d 1.26 (s, 9H, C(CH3)3), 1.63 (d,
6H, CH3P, 2JHP 12.0 Hz), 3.36 (s, 3H, CH3O), 4.21 (dd, 1H, CH3OCH2, 2JHH 12.0 Hz,
Table 1
Synthesis of cyclobutene derivatives 10–12 by cyclization of 1,3-dienes 7–9
1,3-Diene
Time (h)
T (°C)
Ratioa
Isolated yieldb
7
8
9
2
2
2.5
150
150
150
200
13:87
17:83
20:80
25:75
10 (84%)
11 (79%)
12 (70%)
0.5
2
a
Ratio of diene/cyclobutene, determined by 1H NMR spectroscopy.
Yield obtainted via method B.13
b
heating to give cyclobutene 6, which was purified by distillation
under reduced pressure.7,8
2
3
3JHP 8.0 Hz), 4.43 (dd, 1H, CH3OCH2, JHH 12.0 Hz, JHP 16.0 Hz), 5.22 (s, 1H,
1
@CH2), 5.29 (s, 1H, @CH2). 13C NMR (50 MHz, CDCl3): d 18.2 (d, CH3P, JCP
115.7 Hz), 19.7 (d, CH3P, 1JCP 124.3 Hz), 30.7 (s, C(CH3)3), 35.0 (s, C(CH3)3), 57.9
(s, CH3O), 70.6 (s, CH3OCH2), 116.5 (s, @CH2), 129.0 (d, @CP, 1JCP 83.1 Hz), 150.4
(d, C@CP, 11.6 Hz), 157.0 (s, C@CH2). 31P NMR (81 MHz, CDCl3): d 33.8. HRMS
m/z: 265.1115 found (calcd for C12H23ClO2P, (M+H)+ requires 265.1124). 3-tert-
Butyl-2-chloro-1-methoxymethyl-1-diethylphosphoryl-1,3-butadiene (8): Yield
3.34 g (46%), pale yellow oil, Rf = 0.41 (CH2Cl2/MeOH, 95:5). IR (KBr, cmÀ1):
3410, 2963, 2889, 2824, 1593, 1458, 1362, 1177, 1099, 957, 907, 760, 710. 1H
NMR (400 MHz, CDCl3): d 1.08 (dt, 3H, CH3CH2P, 3JHH 7.9 Hz, 3JHP 17.2 Hz), 1.10
Typically, phosphine oxides 7–1213 were prepared by organo-
magnesium synthesis from 6. The crude products were purified
either by flash chromatography on silica gel (dichloromethane/
methanol 97/3; compounds 7–9, 12) or by distillation under vac-
uum (compounds 10 and 11). The structure of compound 10 was
confirmed by X-ray crystal structure analysis (Fig. 1).14
Successful butadiene-cyclobutene isomerization of phosphine
oxides on heating (conversions of 5 into 6 and 7–9 in 10–12) shows
that the formation of the cyclobutene isomer is determined mainly
by steric requirements (Table 1), rather than the polarization of the
parent 1,3-diene molecule.
3
3
(dt, 3H, CH3CH2P, JHH 7.9 Hz, JHP 15.6 Hz), 1.20 (s, 9H, C(CH3)3), 1.75 (q, 2H,
3
2
3
2
CH3CH2P, JHH 7.9 Hz, JHP 11.2 Hz), 1.78 (q, 2H, CH3CH2P, JHH 7.9 Hz, JHP
10.0 Hz), 3.29 (s, 3H, CH3O), 4.04 (dd, 1H, CH3OCH2, JHH 12.0 Hz, JHP 9.8 Hz),
2
3
2
3
4.26 (dd, 1H, CH3OCH2, JHH 12.0 Hz, JHP 14.6 Hz), 5.07 (s, 1H, @CH2), 5.18 (s,
1H, @CH2). 13C NMR (50 MHz, CDCl3): d 5.70 (s, CH3CH2P), 22.0 (d, CH3CH2P,
1JCP 135.2 Hz), 23.4 (d, CH3CH2P, JCP 135.9 Hz), 30.8 (s, C(CH3)3), 34.9 (s,
1
C(CH3)3), 58.1 (s, CH3O), 70.8 (s, CH3OCH2), 116.0 (s, @CH2), 127.4 (d, @CP, 1JCP
75.9 Hz), 151.5 (d, C@CP, JCP 14.2 Hz), 156.6 (s, C@CH2). 31P NMR (81 MHz,
In conclusion, we have reported the synthesis of several previ-
ously undescribed cyclobutenylphosphine oxides, obtained by the
cyclization of the corresponding 1,3-dienyl-phosphine oxides.
There is reason to suppose that similar cyclizations can be carried
out using a variety of sterically hindered 1,3-dienes, and not neces-
sarily bearing a phosphorus-containing group.
2
CDCl3): d 43.2. HRMS m/z: 293.1429 found (calcd for C14H27ClO2P, (M+H)+
requires
293.1437).
3-tert-Butyl-2-chloro-1-methoxymethyl-1-diphenyl-
phosphoryl-1,3-butadiene (9): Yield 2.5 g (26%), colorless crystals, mp 110–
112 °C, Rf = 0.46 (CH2Cl2/MeOH, 95:5). IR (KBr, cmÀ1): 3059, 2963, 2889, 2824,
1651, 1589, 1474, 1458, 1439, 1366, 1188, 1111, 988, 961, 725, 702, 552. 1H
NMR (400 MHz, CDCl3): d 1.27 (s, 9H, C(CH3)3), 2.98 (s, 3H, CH3O), 4.04 (dd, 1H,
2
3
2
3
CH3OCH2, JHH 12.0 Hz, JHP 9.8 Hz), 4.26 (dd, 1H, CH3OCH2, JHH 12.0 Hz, JHP
14.6 Hz), 4.71 (s, 1H, @CH2), 4.98 (s, 1H, @CH2), 7.40–7.53 (m, 6H, 4m-H, 2p-H),
3
3
3
3
Acknowledgements
7.65 (dd, 2o-H, JHH 7.26 Hz, JHP 11.65 Hz), 7.90 (dd, 2o-H, JHH 6.54 Hz, JHP
12.37 Hz). 13C NMR (100 MHz, CDCl3): d 30.7 (s, C(CH3)3), 35.0 (s, C(CH3)3), 58.1
2
3
(s, CH3O), 70.4 (d, CH3OCH2, JCP 9.6 Hz), 117.6 (s, @CH2), 128.0 (d, 2m-C, JCP
12.1 Hz), 128.3 (d, 2m-C, 3JCP 12.8 Hz), 128.5 (d, @CP, 1JCP 92.2 Hz), 131.5 (d, 2p-
C, JCP 8.10 Hz), 131.8 (d, 4o-C, JCP 9.4 Hz), 133.5 (d, ipso-C, JCP 106.4 Hz),
The authors would like to thank DSc Yuriy E. Zevatsky (NOV-
BYTCHIM) for financial support. The authors also gratefully
acknowledge the assistance of Ph.Ds. Valentine I. Zaharov and Albi-
na V. Dogadina (SPbSTI; Department of Organic Chemistry; Labora-
tory of Organophosphorus Compounds) for NMR spectral analyses
and also And rey A. Shchipalkin for XRD data.
4
2
1
1
2
134.2 (d, ipso-C, JCP 106.4 Hz), 154.5 (d, C@CP, JCP 16.8 Hz), 155.8 (d, C@CH2,
3JCP 3.4 Hz). 31P NMR (81 MHz, CDCl3): d 28.4. HRMS m/z: 389.1411 found
(calcd for
C
22H27ClO2P, (M+H)+ requires 389.1437). Spin–spin coupling
between germinal protons of terminal methylene group (compounds 7–9) is
not observed. 2-Chloro-1-dimethylphosphoryl-1-methoxymethyl-3-tert-butyl-

2102
A. S. Bogachenkov et al. / Tetrahedron Letters 53 (2012) 2100–2102
cyclobut-2-ene (10): Yield 4.2 g (63%, method A), colorless hygroscopic crystals,
3-tert-butylcyclobut-2-ene (12): Yield 3.3 g (34%, method A), colorless crystals,
mp 113–114.5 °C, Rf = 0.66 (CH2Cl2/MeOH 95:5). IR (KBr, cmÀ1): 3437, 3055,
2963, 2928, 2870, 2827, 1651, 1474, 1458, 1439, 1366, 1281, 1192, 1115, 984,
756, 725, 698, 548. 1H NMR (400 MHz, CDCl3): d 0.78 (s, 9H, C(CH3)3), 2.39 (dd,
mp 62–63 °C, bp 110–112 °C (0.006 Torr). IR (KBr, cmÀ1): 3429, 2963, 2932,
2882, 2824, 1655, 1474, 1366, 1304, 1177, 1103, 934, 868, 745, 718. 1H NMR
(400 MHz, CDCl3): d 1.02 (s, 9H, C(CH3)3), 1.37 (d, 3H, CH3P, 2JHP 12.8 Hz), 1.45
(d, 3H, CH3P, 2JHP 13.2 Hz), 2.22 (dd, 1H, @CCH2, 2JHH 12.4 Hz, 3JHP 2.2 Hz), 2.44
3
2
3
2
1H, @CCH2, JHP 7.0 Hz, JHH 12.2 Hz), 2.61 (dd, 1H, @CCH2, JHP 3.3 Hz, JHH
2
3
2
3
(dd, 1H, @CCH2, JHH 12.4 Hz, JHP 6.2 Hz), 3.27 (s, 3H, CH3O), 3.62 (t, 1H,
12.2 Hz), 3.26 (s, 3H, CH3O), 3.77 (dd, 1H, CH3OCH2, JHH 11.0 Hz, JHP 7.4 Hz),
2 3
2
3
2
3
CH3OCH2, JHH 10.4 Hz, JHP 10.4 Hz), 3.70 (t, 1H, CH3OCH2, JHH 10.4 Hz, JHP
3.82 (dd, 1H, CH3OCH2, JHH 11.0 Hz, JHP 5.4 Hz), 7.40–7.53 (m, 6H, 4m-H, 2p-
3 3
10.4 Hz). 13C NMR (100 MHz, CDCl3): d 14.2 (d, CH3P, JCP 174.8 Hz), 14.9 (d,
H), 7.87 (dd, 4o-H, JHH 11.4 Hz, JHP 19.5 Hz). 13C NMR (100 MHz, CDCl3): d
27.4 (s, C(CH3)3), 31.2 (s, @CCH2), 32.9 (s, C(CH3)3), 53.5 (d, CH2CP, 1JCP 73.4 Hz),
1
CH3P, 1JCP 172.9 Hz), 27.5 (s, C(CH)3), 30.9 (s, @CCH2), 33.0 (s, C(CH3)3), 51.7 (q,
1
3
2
3
CH2CP, JCP 71.6 Hz), 59.2 (s, CH3O), 72.5 (s, CH3OCH2), 117.0 (d, C@CH2, JCP
59.6 (s, CH3O), 69.9 (d, CH3OCH2, JCP 8.1 Hz), 128.2 (d, 4m-C, JCP 11.4 Hz),
5.8 Hz), 152.6 (d, @CCl, JCP 1.12 Hz). 31P NMR (81 MHz, CDCl3): d 44.3. HRMS
130.2 (d, ipso-C, 1JCP 96.9 Hz), 130.8 (d, ipso-C, 1JCP 96.9 Hz), 132.0 (d, 4o-C, 4JCP
2
m/z: 265.1109 found (calcd for C12H23ClO2P, (M+H)+ requires 265.1124). 2-
Chloro-1-diethylphosphoryl-1-methoxymethyl-3-tert-butylcyclobut-2-ene (11):
Yield 3.81 g (52%, method A), pale yellow oil, bp 120–122 °C (0.005 Torr). IR
(KBr, cmÀ1): 3395, 2966, 2882, 2827, 1655, 1458, 1366, 1281, 1173, 1107,
1030, 1003, 980, 949, 764. 1H NMR (400 MHz, CDCl3): d 1.07 (s, 9H, C(CH3)3),
1.1 Hz), 132.1 (d, 2p-C, JCP 10.4 Hz), 152.9 (d, C@CP, JCP 1.1 Hz). 31P NMR
(81 MHz, CDCl3): d 34.3. HRMS m/z: 389.1418 found (calcd for C22H27ClO2P,
(M+H)+ requires 389.1437).
2
2
14. The X-ray crystal structure for compound 10 has been deposited at the
Cambridge Crystallographic Data Centre and allocated the deposition number
3
3
3
1.13 (dt, 3H, CH3CH2P, JHH 8.4 Hz, JHP 16.8 Hz), 1.15 (dt, 3H, CH3CH2P, JHH
8.4 Hz, JHP 15.6 Hz), 1.77 (q, 2H, CH3CH2P, JHH 8.4 Hz, JHP 15.2 Hz), 1.80 (q,
2H,CH3CH2P, JHH 8.4 Hz, JHP 15.0 Hz), 2.26 (dd, 1H, @CCH2, JHP 2.2 Hz, JHH
CCDC 847993. Formula:
Orthorhombic, Pcab. Unit cell parameters: a = 11.0602(2) Å, b = 13.8647(2) Å,
c = 19.2508(4) Å, = 90°, b = 90°,
= 90°. V = 2952.04(9) Å3; T = 193(2) K; Z = 8;
calc = 1.191 g cmÀ3 = 0.354 mmÀ1 (for MoK
, k = 0.71073 Å); F(000) = 1136;
C12H22ClO2P. Crystal system, space group
3
3
2
3
2
3
2
a
c
3
2
11.9 Hz), 2.57 (dd, 1H, @CCH2, JHP 6.0 Hz, JHH 11.9 Hz), 3.31 (s, 3H, CH3O),
q
;
l
a
3.62 (t, 1H, CH3OCH2, 2JHH 9.9 Hz, 3JHP 9.9 Hz), 3.73 (t, 1H, CH3OCH2, 2JHH 9.9 Hz,
full-matrix least-squares on F2; parameters = 145; restraints = 0; R(all) = 0.083;
wR(all) = 0.341; GooF(all) = 1.889. Key intramolecular bond lengths, Å: C(1)–C(2)
1.332(2); C(2)–C(3) 1.524(2); C(3)–C(4) 1.568(2); C(4)–C(1) 1.515(2); C(1)–
Cl(5) 1.7232(13); C(2)–C(6) 1.496(2); P(10)–C(13) 1.7943(15); P(10)–C(12)
1.794(2); P(10)–O(11) 1.4911(10). Key intramolecular bond angles: Cl(5)–C(1)–
C(2) 134.99(11)°; C(1)–C(2)–C(3) 91.65(10)°; C(2)–C(3)–C(4) 87.57(9)°; C(3)–
C(4)–C(1) 83.50(9)°; C(1)–C(2)–C(6) 138.59(13)°.
3JHP 9.9 Hz). 13C NMR (50 MHz, CDCl3): d 5.8 (d, CH3CH2P, JCP 9.6 Hz), 18.9 (d,
2
CH3CH2P, 1JCP 64.7 Hz), 19.7 (d, CH3CH2P, 1JCP 64.1 Hz), 27.6 (s, C(CH3)3), 31.3 (s,
1
@CCH2), 33.0 (s, C(CH3)3), 52.4 (d, CH2CP, JCP 65.7 Hz), 59.2 (s, CH3O), 72.8 (s,
CH3OCH2), 116.9 (d, C@CH2, 3JCP 6.7 Hz), 152.7 (d, @CCl, 2JCP 9.11 Hz). 31P NMR
(81 MHz, CDCl3): d 50.4. HRMS m/z: 293.1423 found (calcd for C14H27ClO2P,
(M+H)+ requires 293.1437). 2-Chloro-1-diphenylphosphoryl-1-methoxymethyl-