A one-pot synthesis of a branched tertiary phosphine oxide from red phosphorus and 1-(tert-butyl)-4-vinylbenzene in KOH-DMSO: an unusually facile addition of P-centered nucleophiles to a weakly electrophilic double bond

Article abstract of DOI:10.1016/j.tetlet.2008.03.097

Red phosphorus reacts with 1-(tert-butyl)-4-vinylbenzene in a superbase media (KOH-DMSO, 90-100 °C, 3 h) to give tris[4-(tert-butyl)phenethyl]phosphine oxide in 77% yield. Microwave activation of the reaction affords the phosphine oxide in 82% yield in 6 min.

Full text of DOI:10.1016/j.tetlet.2008.03.097

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3480–3483
A one-pot synthesis of a branched tertiary phosphine oxide from
red phosphorus and 1-(tert-butyl)-4-vinylbenzene in KOH–DMSO:
an unusually facile addition of P-centered nucleophiles to
a weakly electrophilic double bond
Boris A. Trofimov *, Svetlana F. Malysheva, Nina K. Gusarova, Vladimir A. Kuimov,
Nataliya A. Belogorlova, Boris G. Sukhov
A.E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 1 Favorsky St., Irkutsk 664033, Russian Federation
Received 15 February 2008; revised 12 March 2008; accepted 19 March 2008
Available online 23 March 2008
Abstract
Red phosphorus reacts with 1-(tert-butyl)-4-vinylbenzene in a superbase media (KOH–DMSO, 90–100 °C, 3 h) to give tris[4-(tert-
butyl)phenethyl]phosphine oxide in 77% yield. Microwave activation of the reaction affords the phosphine oxide in 82% yield in 6 min.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Red phosphorus; Styrene; 1-(tert-Butyl)-4-vinylbenzene; Superbases; Nucleophilic addition; Tris[4-(tert-butyl)phenethyl]phosphine oxide;
Microwave activation
The easy addition of phosphorus-centered nucleophiles,
generated in situ from red phosphorus (Pn) in a superbasic
KOH–DMSO system, to styrenes 11 yielding secondary 2
and tertiary 3 phosphine oxides (Scheme 1) remains fasci-
nating from a mechanistic point of view.2 Indeed, styrenes
are unusual electrophiles. To the best of our knowledge,
there are no explicit examples of nucleophilic addition to
their double bond except for the reaction of the CH-acid,
2-methylpropanoic acid, with styrene under special forced
superbasic conditions (sodium naphthalenide–TMEDA–
THF).3 Meanwhile the nucleophilic character of the above
reaction is strongly supported by the fact that it does not
proceed without alkali metal hydroxides and in the pres-
ence of radical initiators, being also unaffected by typical
inhibitors of radical processes.1b,2
R
KOH/DMSO(H2O)
Pn
+
1a,b
R
O
H
P
O
P
+
R
2a,b
yield up to 20%
a R =H, b R = Me
Scheme 1.
3
yield up to 58%
Until now, tris(phenethyl)phosphine oxide 3 is still the
only representative of the family of tris(arylethyl)phos-
phine oxides.
Tertiary phosphine oxides are used widely as Wittig–
Horner building blocks or for tertiary phosphine genera-
tion,4 ligands for metal complexes (particularly those phos-
phine oxides having bulky and branched substituents5),
intermediates for the design of nano-electronic materials,6
*
Corresponding author. Tel.: +7 395 2511926; fax: +7 3952 419346.
E-mail address: boris_trofimov@irioch.irk.ru (B. A. Trofimov).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.03.097

B. A. Trofimov et al. / Tetrahedron Letters 49 (2008) 3480–3483
3481
extractants of noble, rare-earth and transuranic elements,7
OH
Pm OH
Pn
Pk
+
and flame retardants.8
Therefore, evaluation of the generality of the above syn-
thesis (Scheme 1) is timely. Since electron-donating substit-
uents on the benzene ring should slow down the
nucleophilic addition to the double bond of vinylbenzene,
we chose ‘a difficult’ case: 1-(tert-butyl)-4-vinylbenzene,
as a substrate. Our purpose was threefold. Firstly, if the
reaction occurs with good preparative results, other alkyl
substituted vinyl benzenes should also undergo the addi-
tion. Secondly, the syntheses of strongly branched bulky
triarylethylphosphine oxides would probably be realized.
Thirdly, valuable information concerning the substituent
effect on the nucleophilic addition would be obtained
allowing better understanding of the mechanism.
OH
Pm OH
Pm
O
8
4/H2O
P
O
8
5
OH
4/H2O
OH
O
P
4/H2O
We have found that red phosphorus reacts with tert-
butylstyrene 4 in a KOH–DMSO suspension (including
ꢀ1.1 mass% H2O as
a proton transfer agent and
Scheme 3.
ꢀ0.1 mass% of hydroquinone as a radical inhibitor) under
an argon blanket at 90–100 °C for 3 h to give tris[4-(tert-
butyl)phenethyl]phosphine oxide 5 and 4-(tert-butyl)phen-
ethylphosphinic acid 6 in 77% and 17% yields, respectively
(Scheme 2).9 The corresponding secondary phosphine
oxide 7 (traces) was also detected (31P NMR) in the
reaction mixture.9
styrene to give the corresponding secondary11a or ter-
tiary11b phosphines (but not phosphine oxides).
Apparently, the polyphosphinite anion clusters 8 thus
formed (Scheme 3) possess much higher nucleophilicity
compared to simple phosphinite anions (O@PÀ). This
inference is experimentally supported by the fact that the
model reaction of tert-butylstyrene 4 with KH2PO2 (the
latter and PH3 are the products of the redox reaction of
red phosphorus with KOH)2a under the same conditions
gave only traces of the organophosphorus compounds
(31P NMR).
A microwave irradiation promoted version of the reac-
tion (with the same reactants ratio) delivered (in 6 min)
phosphine oxide 5 as the only product in 82% yield (neither
phosphine oxide 7 nor acid 6 was detected in the reaction
mixture). Thus, the reaction was more effective, as well as
chemospecific and rapid (30 times faster).10
In spite of the branched structure and reduced electro-
philicity of the starting tert-butylstyrene 4, the reaction
did not stop during the initial steps of the intermediate pri-
mary and secondary adduct formation. This proves that
the rate-determining steps include the cleavage of the
elemental phosphorus P–P bond (probably occurring in
phosphorus nanoparticles) by hydroxide anions to form
highly active P-centered nucleophiles and their further
addition to the tert-butylstyrene 4 double bond affording
the mono-adducts. As far as the reaction proceeds under
oxygen-free conditions, it is obvious that the initial nucleo-
philes are polyphosphinite type anions 8 (Scheme 3).
In this case, DMSO does not act as an oxidant since
under the conditions studied, phosphine (PH3) adds to
Despite the comparable preparative yields of the corres-
ponding tertiary phosphine oxides from styrene12 and tert-
butylstyrene 4, a competitive reaction13 (Fig. 1) indicates
that 4 is, as expected, much lower in reactivity than unsub-
stituted styrene. Indeed, the conversions of styrenes 1a and
4 (equimolar ratio) in the phosphorylation with red phos-
phorus were 89% and 40%, respectively (Fig. 1).
Consequently, according to 31P NMR monitoring
(Fig. 2), the rates of formation of the adducts 2a and 3 in
the case of styrene are considerably higher than those of
adduct 7 formed from tert-butylstyrene 4. The mixed sec-
ondary phosphine oxide 9 (31P NMR: 32.04 ppm, JP,H
1
452 Hz) was also detected in the reaction mixture (Fig. 2).13
In conclusion, a one-pot chemoselective synthesis of
novel tertiary phosphine oxide 5 in up to 82% yield directly
O
OH
H
KOH/DMSO(H2O)
P
Pn
+
+
+
P
P
90-100 oC
O
O
H
5
6
7
4
Scheme 2.

3482
B. A. Trofimov et al. / Tetrahedron Letters 49 (2008) 3480–3483
N. K.; Malysheva, S. F.; Brandsma, L.; Albanov, A. I.; Trofimov, B.
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˜
Fig. 1. Change in the conversion of styrenes 1a and 4 during phosphor-
ylation with red phosphorus.13
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2a
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9
7
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Time / min
Fig. 2. Dynamics of phosphine oxides 2a, 3, 7, and 9 formation.13
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from red phosphorus and tert-butylstyrene 4 in the system
KOH–DMSO has been developed thus implying the valid-
ity of the reaction for diverse alkylvinylbenzenes. It has
also been shown that this approach opens a straightfor-
ward route to highly branched, previously inaccessible
phosphine oxides and hence, the corresponding phos-
phines. Evidence for the generation of highly nucleophilic
polyphosphinite anion clusters as key intermediate species
complementary to weakly electrophilic vinylbenzenes has
been obtained.
9. Experimental procedure: All the reaction steps were carried out under
an inert atmosphere (argon). A solution of 4 (4.7 g, 29.3 mmol)
in DMSO (10 mL) was added dropwise over 40 min to a heated
(90–95 °C) suspension of red phosphorus (1 g, 32.3 mmol), KOH
(2.5 g, 44.6 mmol), water (0.38 mL), DMSO (15 mL), and hydroqui-
none (0.03 g) with stirring. The reaction mixture was stirred for 2 h
20 min at 99–100 °C, then diluted with water and extracted with
benzene (3 Â 25 mL). The benzene extract was washed with a 10% aq
solution of KCl (3 Â 20 mL), dried over K2CO3, and the benzene
removed. The residue was dried under vacuum to give 4.38 g of mixed
product, containing (31D NMR) 5 (47.61 ppm) and 7 (32.08 ppm,
1JP,H 452 Hz) in the ratio 10:1. The latter was removed as (4-t-
BuC6H4CH2CH2)2P(O)OK by consecutive treatment of the product
with 35% aq H2O2 and aq KOH.12 This procedure gave 4 g (77%) of
5. The aqueous layer was acidified with a 35% aq solution of HCl up
to pH 4, and extracted with benzene14 (2Â 20 mL). The benzene
extract was washed with water (2 Â 10 mL), dried over CaCl2, the
solvent removed, and the residue dried under vacuum to give 1.15 g
(17%) of 6 as a colorless powder, mp 106–108 °C (benzene). 1H NMR
(400.13 MHz, CDCl3, ppm) d: 1.28 (s, 9H, CH3), 2.08 (m, 2H, CH2P),
Acknowledgment
Financial support from the Russian Foundation for Ba-
sic Research (Grant no. 07-03-00562) is gratefully
acknowledged.
References and notes
1. (a) Gusarova, N. K.; Trofimov, B. A.; Rakhmatulina, T. N.;
Malysheva, S. F.; Arbuzova, S. N.; Shaikhudinova, S. I.; Albanov,
A. I. Russ. Chem. Bull. 1994, 43, 1591; (b) Arbuzova, S. N.; Gusarova,
1
2.87 (m, 2H, CH2C6H4), 7.10 (d, 1H, JP,H = 544.0 Hz, PH),

B. A. Trofimov et al. / Tetrahedron Letters 49 (2008) 3480–3483
3483
7.11–7.30 (m, 4H, C6H4),11.74 (s, 1H, OH); 13C NMR (100.62 MHz,
CDCl3, ppm) d: 26.35 (CH2C6H4), 31.27 (d, JP,C = 91.7 Hz, CH2P),
1JP,C = 62.3 Hz, CH2P), 31.40 (CH3), 34.46 (CCH3), 125.66 (C-o),
127.80 (C-m), 137.86 (d, 3JP,C = 12.7 Hz, C-i), 149.48 (C-p); 31P NMR
(161.98 MHz, CDCl3, ppm) d: 47.21. IR (KBr, cmÀ1): 3090, 3050, 3012
(m, @CH of phenyl rings); 2949, 2900, 2855 (m, CH); 1510 (m, C@C of
phenyl rings); 1463, 1390 (d, CH2); 1360, 1270, 1220 (d, CH); 1150 (m,
P@O); 1100, 1010, 990, 930, 910 (d, CH of phenyl rings); 835, 817, 800
(d, CH2), 770, 726, 559 (m, P–C). Anal. Calcd for C36H51OP: C, 81.46;
H, 9.69; P, 5.84. Found: C, 81.57; H, 9.73; P, 5.81.
1
31.34 (CH3), 34.37 (CCH3), 125.51 (C-o), 127.75 (C-m, C6H4), 137.28
1
(d, JP,C = 15.9 Hz, C-i), 149.28 (C-p); 31P NMR (161.98 MHz,
1
CDCl3, ppm) d: 36.73 (d, JP,H = 544 Hz). IR (KBr, cmÀ1): 3030,
3022 (m, @CH of phenyl rings); 2950, 2900, 2860 (m, CH); 2630 (m,
OH); 2370 (m, PH); 2150, 1680 (m, OH); 1506,1450 (m, C@C of phenyl
rings); 1463, 1430, 1390 (d, CH2); 1360, 1350, 1260, 1203 (d, CH);
1190, 1170 (m, P@O); 1098 (d, CH of phenyl rings); 950 (d, OH); 816,
800 (d, CH of phenyl rings); 550 (m, P–C). Anal. Calcd for C12H19O2P:
C, 63.70; H, 8.46; P, 13.69. Found: C, 63.75; H, 8.57; P, 13.47.
10. Tris[4-(tert-butyl)phenethyl]phosphine oxide (5). Under microwave
irradiation: a mixture of red phosphorus (1 g, 32.3 mmol), 4 (4.7 g,
29.3 mmol), hydroquinone (0.03 g), KOH (2.5 g, 44.6 mmol), water
(0.38 mL), and DMSO (25 mL) was irradiated (600 W) for 6 min
(Microwave oven, model: Samsung M181DNR, maximum power level
850 W). The reaction mixture was cooled, diluted with water, and
extracted with benzene (3 Â 25 mL). The benzene extract was washed
with a 10% aq solution of KCl (3 Â 10 mL) and dried over K2CO3. The
benzene and unreacted 4-tert-butylstyrene (0.84 g, 82% conversion)
were removed under vacuum, and the residue was washed with hexane
and dried under vacuum to give 4.26 g (82%) of phosphine oxide 5 as a
11. (a) Trofimov, B. A.; Brandsma, L.; Arbuzova, S. N.; Malysheva, S.
F.; Gusarova, N. K. Tetrahedron Lett. 1994, 35, 7647; (b) Trofimov,
B. A.; Gusarova, N. K.; Brandsma, L. Phosphorus, Sulfur, Silicon
Relat. Elem. 1996, 109–110, 601; (c) Trofimov, B. A.; Brandsma, L.;
Arbuzova, S. N.; Malysheva, S. F.; Belogorlova, N. A.; Gusarova, N.
K. Russ. J. Gen. Chem. 1997, 67, 650.
12. Malysheva, S. F.; Gusarova, N. K.; Kuimov, V. A.; Sukhov, B. G.;
Kudryavtsev, A. A.; Sinyashin, O. G.; Budnikova, Yu. H.; Pai, Z. P.;
Tolstikov, A. G.; Trofimov, B. A. Russ. J. Gen. Chem. 2007, 77, 415.
13. Reaction conditions: 70–75 °C, 1 h; red phosphorus (1 g, 32.3 mmol),
KOH (3.3 g, 59.5 mmol), water (1.4 mL), 1a (1.3 g, 12.5 mmol) and 4
(2 g, 12.5 mmol), hydroquinone (0.03 g), toluene (1 g) (as standard),
and DMSO (25 mL). Conversion of styrenes 1a and 4 was determined
by GLC. The relative content of secondary 2a, 7, and 9 and tertiary 3
phosphine oxides in the reaction mixture was determinated by 31P
NMR using standard samples of 2a,1a 7, and 3.1b,12
1
colorless powder, mp 145–146 °C (benzene). H NMR (400.13 MHz,
CDCl3, ppm) d: 1.31 (s, 27H, CH3), 2.03–2.04 (m, 6H, CH2P), 2.89–
2.91 (m, 6H, CH2C6H4), 7.11–7.34 (m, 12H, C6H4); 13C NMR
(100.62 MHz, CDCl3, ppm) d: 27.31 (CH2C6H4), 30.15 (d,
14. Toluene, CHCl3, and CH2Cl2 can be used as extractants instead of
benzene.