Facile synthesis of chelating bisphosphine oxides and bisphosphines via palladium-catalyzed bishydrophosphinylation reactions

Article abstract of DOI:10.1016/S0040-4039(02)00609-3

A series of functional bisphosphosphine oxides were synthesized in good yields via new Pd-catalyzed bis-hydrophosphinylation reactions of terminal alkynes and diphenylphosphine oxide. The resulting bisphosphine oxides were reduced to their corresponding b

Full text of DOI:10.1016/S0040-4039(02)00609-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3707–3710
Facile synthesis of chelating bisphosphine oxides and
bisphosphines via palladium-catalyzed bishydrophosphinylation
reactions
Aberdeen Allen, Jr., Ling Ma and Wenbin Lin*
Department of Chemistry, CBc3290, University of North Carolina, Chapel Hill, NC 27599, USA
Received 27 February 2002; accepted 25 March 2002
Abstract—A series of functional bisphosphosphine oxides were synthesized in good yields via new Pd-catalyzed bis-hydrophosphiny-
lation reactions of terminal alkynes and diphenylphosphine oxide. The resulting bisphosphine oxides were reduced to their
corresponding bisphosphines in quantitative yields via a Ti(OiPr)4-mediated process. © 2002 Elsevier Science Ltd. All rights reserved.
Bisphosphineoxides are an important class of materials
because of their applications as organoextractants in
hydrometallurgy and as fire retardants.1 Their reduced
products, bisphosphines, are important ancillary lig-
ands in organometallic chemistry and homogeneous
catalysis.2 In particular, chiral phosphines have been
successfully employed in many enantioselective catalytic
processes including asymmetric hydrogenation, hydrosi-
lation, hydroformylation and hydrovinylation reac-
tions.3 Most chiral bisphosphines have been derived
from naturally occurring chiral pools with the notable
exception of 2,2%-bis(diphenylphosphino)-1,1%-binaph-
thyl.4 Synthetic elaboration from naturally occurring
chiral pools is limited in scope, and it would be desir-
able to develop alternative methodologies for the facile
and economical synthesis of a wide variety of chiral
chelating bisphosphines as ancillary ligands for transi-
tion-metal mediated asymmetric catalysis. Herein we
wish to report a new Pd-catalyzed bis-hydrophosphinyl-
ation reaction of terminal alkynes to afford chelating
bisphosphineoxides and their reduction to bisphosphi-
nes via a Ti-mediated process.
mol% Pd(PPh3)4 in refluxing toluene over a period of
24 h afforded the vicinal-bisphosphosphine oxide 1 in
90% yield (Scheme 1).6 This new bis-hydrophosphinyla-
tion reaction can be applied to various aliphatic and
aromatic terminal alkynes containing electronically
neutral, electron-withdrawing, and electron-donating
functionalities. The resulting bis-diphenylphosphine
oxides 1–11 have been characterized by H, H{31P},
13C{1H}, and 31P{1H} NMR spectroscopy and high
resolution mass spectrometry.7 The characteristic sig-
nals for the protons on the alkane backbone of 1
appear as three distinct multiplets at ꢀl 4.6–2.8, which
collapse into a doublet, a doublet of doublets, and a
doublet upon decoupling the 31P nuclei. The fact that
the other vicinal 3JHꢀH is negligible is consistent with the
anti conformation of the two vicinal diphenylphosphine
oxide groups. The aromatic protons on the phenyl ring
appear as several complex multiplets because of their
diastereotopic nature. The 31P{1H} NMR spectra of
these vicinal bis-diphenylphosphine oxides appear as
1
1
3
two doublets at ꢀl 33 and ꢀl 30 with a JPꢀP of ꢀ44
Hz. The carbons of the alkane backbone appear as two
sets of doublets of doublets in the 13C{1H} NMR
spectrum.
Terminal alkynes were either obtained from commercial
sources or synthesized in excellent yields by Heck reac-
tions between aryl halides and trimethysilylacetylene
followed by removal of trimethylsilyl group under basic
conditions.5 Treatment of 2-ethynyl pyridine with 3
equiv. of diphenylphosphine oxide in the presence of 5
When the hydrophosphinylation reactions were carried
out with 1 equiv. of diphenylphosphine oxide under
milder conditions and shorter reaction times, both gem-
inal alkenyl diphenylphosphine oxide and terminal
alkenyl diphenylphosphine oxide were isolated. Both
geminal- and terminal-alkenyl diphenylphosphine
oxides readily undergo the second hydrophosphinyla-
tion reaction to result in vicinal-bisphosphineoxides.
Keywords: catalysis; palladium; titanium; phosphine oxides; phosphi-
nes.
* Corresponding author. Tel.: +1 (919)962-6320; fax: +1 (919)962-
2388; e-mail: wlin@unc.edu
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00609-3

3708
A. Allen, Jr. et al. / Tetrahedron Letters 43 (2002) 3707–3710
Scheme 1.
We thus believe that the bis-hydrophosphinylation reac-
tion proceeds via oxidative addition of diphenylphos-
phine oxide to a Pd(0) catalyst followed by insertion of
alkynes into the PdꢀH bond to afford both regioisomers
of alkenylpalladium intermediates,8 which undergo
reductive elimination to afford both geminal- and termi-
nal-alkenyl diphenylphosphine oxides and regenerate the
active Pd(0) catalyst. Subsequent hydrophosphinylation
with alkenyl diphenylphosphine oxides as the substrates
lead to bis-diphenylphosphine oxides 1–11.
In summary, we have developed an efficient method for
the synthesis of functional bis-diphenylphosphine
oxides via Pd-catalyzed bis-hydrophosphinylation reac-
tions of alkynes with diphenylphosphine oxide. We
have also shown the facile reduction of the bisphosphine-
oxides to the corresponding bisphosphines using
triethoxysilane/Ti(OiPr)4.
Acknowledgements
Reduction of phosphine oxides is typically carried out
with a metal hydride system or with HSiCl3 in the
presence of a base. We have tried both procedures and
only obtained products resulting from PꢀC bond cleav-
age. We have successfully reduced bis-diphenylphos-
phine oxides to their corresponding b2isphosphines by
employing the triethoxysilane and Ti(OiPr)4 system first
developed by Lawrence et. al.9 and Buchwald et al.10
We acknowledge NSF (DMR-9875544) for financial
support. W.L. is an Alfred P. Sloan Fellow, an Arnold
and Mabel Beckman Young Investigator, a Cottrell
Scholar of Research Corp, and a Camille Dreyfus
Teacher-Scholar.
References
Treatment of vicinal-bisphosphineoxides 3, 6, and 8–11
with 6 equiv. of triethoxysilane and a catalytic amount
of Ti(OiPr)4 in refluxing toluene afforded their corre-
sponding bisphosphines in quantitative yields after
column chromatography. The reaction proceeds rapidly
and is complete in 5–20 min for the substrates
studied.11,12
1. Turanov, A. N.; Karandashev, V. K.; Kharitonov, A. V.;
Yarkevich, A. N.; Safronova, Z. V. Solvent Extr. Ion
Exch. 2000, 18, 1109–1134.
2. Parshall, G. W.; Ittel, S. D. Homogeneous Catalysis;
Wiley: New York, 1992.
3. Noyori, R. Asymmetric Catalysis in Organic Synthesis;
Wiley: New York, 1994.
The characteristic signals for the protons on the alkane
backbone of 11a appear as three distinct multiplets at l
3.22–2.44. Upon decoupling the 31P nuclei, these three
proton signals collapse into a doublet at l 3.21 and a
multiplet at ꢀl 2.5. As expected, the 31P{1H} NMR
spectra of these vicinal bis-diphenylphosphines appear as
two sets of doublets. The 13C{1H} NMR spectrum of 11a
shows the aromatic carbons as a complex series of
multiplets between l 150–115. The carbons of the alkane
backbone appear as a triplet and two sets of doublets of
doublets.
4. Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito,
T.; Souchi, T.; Noyori, R. J. Am. Chem. Soc. 1980, 102,
7932–7934.
5. (a) Allen, A., Jr.; Manke, D. R.; Lin, W. Tetrahedron
Lett. 2000, 41, 151–154; (b) Takahashi, S.; Kuroyama,
Y.; Sonogashira, K.; Hagihara, N. Synthesis 1980, 627.
6. A typical procedure for bis-hydrophosphinylation reactions
of terminal alkynes: To a mixture of 2-ethynyl pyridine
(100 mg, 0.97 mmol), diphenylphosphine oxide (490 mg,
2.4 mmol), and Pd(PPh3)4 (39 mg, 5 mol%) was added 3
mL of anhydrous toluene under nitrogen. The dark

A. Allen, Jr. et al. / Tetrahedron Letters 43 (2002) 3707–3710
3709
(m, 5H), 7.24–7.14 (m, 4H), 7.09–7.05 (m, 1H), 4.60–4.51
(m, 1H), 3.28–3.18 (m, 1H), 2.85–2.75 (m, 1H); 13C
NMR: l 132.7, 132.5, 132.4, 132.2, 132.0 (d, JCꢀP=3.1
Hz), 131.7, 131.6, 131.1 (d, JCꢀP=3.1 Hz), 131.0 (d,
brown solution was heated to reflux and a solid began to
precipitate out of solution about 30 min later. The reac-
tion was stopped after 20 h, cooled to rt, and the solvent
was removed under reduced pressure. The resulting solid
was washed with diethyl ether (3×15 mL) to afford 390
mg of pure 1-(2%-pyridyl)-1,2-bis(diphenylphosphinyl)-
ethane, 1 as a white solid (yield: 79%).
JCꢀP=3.1 Hz), 130.8 (d, JCꢀP=9.2 Hz), 129.9 (d, JCꢀP=
11.4 Hz), 129.0 (d, JCꢀP=11.4 Hz), 128.5 (d, JCꢀP=12.2
Hz), 128.3 (d, JCꢀP=12.2 Hz), 127.6, 117.7, 37.9 (d,
J
CꢀP=63.3 Hz), 30.3 (d, JCꢀP=68.7 Hz); 31P NMR: l
7. Selected data for new vicinal bis-diphenylphosphine
oxides: All the spectra were taken in CDCl3 at 400 MHz
34.9 (d, JPꢀP=45.4 Hz), 29.1 (d, JPꢀP=46.1 Hz). HRM-
S(EI) calcd for C33H28NO2P2 (MH+), 532.1595; found,
532.1589.
1
for H, 125 MHz for 13C, and 161 MHz for 31P nucleus,
respectively. 3, 8, 9, and 11 are known compounds.
Compound 1: mp 219–221°C; 1H NMR: l 8.16 (d, 1H,
J=4.3 Hz), 7.94–7.89 (m, 2H), 7.59–7.31 (m, 12H), 7.27–
7.23 (m, 1H), 7.17–7.13 (m, 3H), 7.08–7.02 (m, 2H), 6.80
(d, 1H, J=7.9 Hz), 6.73–6.70 (m, 1H), 4.51–4.43 (m, 1H),
3.36–3.54 (m, 1H), 2.90–2.75 (m, 1H); 13C NMR: l 154.3,
148.9, 135.3, 132.0 131.7–131.4 (m), 131.2–130.7 (m),
130.4 (d, JCꢀP=9.2 Hz), 128.9 (d, JCꢀP=11.4 Hz), 128.6
(d, JCꢀP=11.4 Hz), 127.9 (t, JCꢀP=10.7 Hz), 41.9 (d,
1
Compound 7: mp 197–199°C; H NMR: l 7.99–7.94 (m,
2H), 7.63–7.51 (m, 11H), 7.49–7.34 (m, 4H), 7.30–7.24
(m, 2H), 7.21–7.17 (m, 2H), 6.85 (d, 1H, J=3.1 Hz),
4.92–4.84 (m, 1H), 3.54–3.46 (m, 1H), 2.96–2.86 (m, 1H);
13C NMR: l 165.2, 142.4 (d, JCꢀP=2.3 Hz), 132.6 (d,
J
CꢀP=2.3 Hz), 132.1 (t, JCꢀP=3.1 Hz), 131.8 (d, JCꢀP
=
=
8.4 Hz), 131.5 (d, JCꢀP=9.2 Hz), 131.4, 131.2 (d, JCꢀP
9.9 Hz), 130.6 (d, JCꢀP=9.9 Hz), 129.3 (d, JCꢀP=12.3
Hz), 128.9 (d, JCꢀP=11.4 Hz), 128.5 (d, JCꢀP=12.2 Hz),
128.3 (d, JCꢀP=12.2 Hz), 120.2, 38.8 (d, JCꢀP=62.2 Hz),
30.1 (d, JCꢀP=67.9 Hz); 31P NMR: l 33.6 (d, JPꢀP=41.0
Hz), 30.3 (d, JPꢀP=41.0 Hz). HRMS(EI) calcd for
C29H25NO2P2S (M+), 513.1081; found, 513.1075.
J
CꢀP=63.3 Hz), 28.3 (d, JCꢀP=68.7 Hz); 31P NMR: l
35.5 (d, JPꢀP=46.1 Hz), 31.2 (d, JPꢀP=46.1 Hz). HRMS
(EI) calcd for C31H28NO2P2 (MH+), 508.1595; found,
508.1593.
1
Compound 2: mp 264–266°C; H NMR: l 8.04–8.00 (m,
1
Compound 10: mp 239–241°C; H NMR: l 7.80–7.67 (m,
1H), 7.57–6.95 (m, 23H), 4.26–4.18 (m, 1H), 3.12–3.04
(m, 1H), 2.87–2.77 (m, 1H); 13C NMR: l 141.1, 132.7,
132.2, 132.0, 131.9, 131.7 (d, JCꢀP=8.4 Hz), 131.0–130.8
(m), 130.4 (d, JCꢀP=9.9 Hz), 129.5 (d, JCꢀP=11.4 Hz),
129.0 (d, JCꢀP=11.4 Hz), 128.4 (t, JCꢀP=12.2 Hz), 39.4
(d, JCꢀP=68.8 Hz), 29.8 (d, JCꢀP=68.8 Hz); 31P NMR:
l 35.4 (d, JPꢀP=44.7 Hz), 29.8 (d, JPꢀP=44.7 Hz).
HRMS(EI) calcd for C31H28NO2P2 (MH+), 508.1595;
found, 508.1591.
5H), 7.56–7.26 (m, 15H), 3.08–2.93 (m), 2.68–2.51 (m),
1.68–1.60 (m), 1.55–1.43 (m), 0.88–0.72 (m); 13C NMR: l
131.6 (d, JCꢀP=2.3 Hz), 131.4 (d, JCꢀP=3.1 Hz), 131.3,
130.9 (d, JCꢀP=8.4 Hz), 130.8 (d, JCꢀP=8.4 Hz), 130.6 (d,
J
CꢀP=9.2 Hz), 130.5 (d, JCꢀP=9.2 Hz), 128.6 (d, JCꢀP=
3.8 Hz), 128.5, 128.4, 128.3 (d, JCꢀP=2.3 Hz), 38.2, 36.9,
36.3, 31.7 (d, JCꢀP=9.9 Hz), 30.6, 26.7 (d, JCꢀP=17.5
Hz), 25.7, 25.1, 24.4; 31P NMR: l 37.8 (d, JPꢀP=42.6
Hz), 30.9 (d, JPꢀP=42.6 Hz). HRMS(EI) calcd for
C32H35O2P2 (MH+), 513.2112; found, 513.2110.
8. (a) Han, L. B.; Tanaka, M. Organometallics 1996, 15,
3259; (b) Han, L. B.; Hua, R.; Tanaka, M. Angew.
Chem., Int. Ed. 1998, 37, 94.
9. Coumbe, T.; Lawrence, J. N.; Muhammad, F. Tetra-
hedron Lett. 1992, 35, 625.
10. Berk, S. C.; Buchwald, S. L. J. Org. Chem. 1992, 57,
3751.
11. A typical procedure for the reduction of bis-diphenylphos-
phine oxides: To a mixture of 11 (200 mg, 0.36 mmol),
titanium isopropoxide (60 mL, 0.2 mmol) and triethoxy
silane (354 mL, 2.16 mmol) was added 5 mL of anhydrous
benzene under nitrogen. The pale brown slurry was
heated to reflux, and the solid dissolved and the solution
turned gray–green 25 min later. The reaction was
stopped, cooled to rt and the solvent was removed in
vacuo to afford a brown solid. The crude material was
purified by column chromatography under nitrogen
(degassed CHCl3/acetone 2:1) to afford 195 mg (98%) of
1-(4%-N,N-dimethylaminophenyl)-1,2-bis(diphenylphos-
phino)ethane, 11a, as white solid.
1
Compound 4: mp 308–310°C; H NMR: l 8.03–8.01 (m,
2H), 7.57–7.50 (m, 5H), 7.47–7.44 (m, 1H), 7.39–7.35 (m,
2H), 7.33 (m, 6H), 7.20–7.16 (m, 4H), 7.11–7.06 (m, 4H),
4.34–4.28 (m, 1H), 3.14–3.05 (m, 1H), 2.86–2.76 (m, 1H);
13C NMR: l 140.2, 132.5, 132.0, 131.8, 131.7, 131.4,
131.3, 130.8–130.5 (m), 130.1 (d, JCꢀP=9.2 Hz), 129.2 (d,
J
J
CꢀP=12.2 Hz), 129.3 (d, JCꢀP=11.4 Hz), 128.2 (d,
CꢀP=12.2 Hz), 128.1 (d, JCꢀP=11.4 Hz), 118.5, 110.6,
39.8 (d, JCꢀP=65.3 Hz), 29.8 (d, JCꢀP=65.3 Hz); 31P
NMR: l 35.3 (d, JPꢀP=45.4 Hz), 29.9 (d, JPꢀP=45.4 Hz).
HRMS(EI) calcd for C33H28NO2P2 (MH+), 532.1595;
found, 532.1597.
Compound 5: mp 254–255°C; 1H NMR: l 8.93 (d, 1H
J=2.4 Hz), 7.96–7.88 (m, 2H), 7.63–7.42 (m, 15H), 7.40–
7.35 (m, 3H), 7.28–7.12 (m, 2H), 4.70–4.36 (m, 1H),
3.62–3.53 (m, 1H), 2.89–2.79 (m, 1H); 13C NMR: l 144.3,
132.7 (d, JCꢀP=2.4 Hz), 132.3, 131.9, 131.7 (d, JCꢀP=8.4
Hz), 131.6 (d, JCꢀP=2.3 Hz), 131.2 (t, JCꢀP=8.4 Hz),
130.7 (d, JCꢀP=9.2 Hz), 130.3, 129.4 (d, JCꢀP=11.4 Hz),
129.0 (d, JCꢀP=12.2 Hz), 128.6 (d, JCꢀP=11.4 Hz), 128.3
(d, JCꢀP=12.2 Hz), 125.3 (d, JCꢀP=3.8 Hz), 43.0 (d,
J
CꢀP=62.6 Hz), 28.9 (d, JCꢀP=69.4 Hz); 31P NMR:
12. Selected data for new vicinal bis-diphenylphosphines. 8a–
10a are known compounds.
l 33.9 (d, JPꢀP=44.3 Hz), 29.9 (d, JPꢀP=44.3 Hz).
HRMS(EI) calcd for C31H27N2O4P2 (MH+), 553.1446;
found, 553.1447.
1
Compound 3a. H NMR: l 7.98–7.96 (m, 1H), 7.82–7.80
(m, 1H), 7.92–7.66 (m, 5H), 7.64–7.33 (m, 8H), 7.23–6.97
(m, 10H), 4.27–4.06 (m, 1H), 2.85–2.72 (m, 2H); 13C
NMR: l 132.5, 131.8, 131.62 (d, JCꢀP=19.3 Hz), 131.5,
131.0 130.7–130.6 (m) 130.2 (d, JCꢀP=9.2 Hz), 128.9 (d,
1
Compound 6: mp 258–259°C; H NMR: l 7.94–7.89 (m,
2H), 7.82 (d, 11H J=8.5 Hz), 7.64–7.58 (m, 3H), 7.55–
7.48 (m, 4H), 7.47–7.41 (m, 4H), 7.37 (s, 1H), 7.36–7.26

3710
A. Allen, Jr. et al. / Tetrahedron Letters 43 (2002) 3707–3710
J
CꢀP=10.7 Hz), 128.5 (d, JCꢀP=12.2 Hz), 127.9, 127.8,
7 (d, JCꢀP=6.1 Hz), 41.3 (d, JCꢀP=16.8 Hz), 40.5 (d,
J
CꢀP=16.8 Hz), 29.3 (d, JCꢀP=16.8 Hz); 31P NMR:
40.6, 39.3 (d, JCꢀP=70.0 Hz), 31.3 (d, JCꢀP=70.0 Hz); 31
P
l 35.3 (d, JPꢀP=31.7 Hz), −17.9 (d, JPꢀP=31.7 Hz).
HRMS(EI) calcd for C33H28NP2 (MH+), 500.1697;
found, 500.1688.
NMR: l 29.8 (d, JPꢀP=41.5 Hz), 5.85 (d, JPꢀP=41.5 Hz).
HRMS(EI) calcd for C32H28NO2P2 (MH+), 520.1595;
found, 520.1602.
1
Compound 6a. 1H NMR: l 8.01 (d, 1H, J=7.90 Hz),
7.65–7.51 (m, 5H), 7.45–7.39 (m, 3H), 7.37–7.35 (m, 2H),
7.31–7.27 (m, 2H), 7.25–7.23 (m, 1H), 7.22–7.18 (m, 5H),
7.15–7.12 (m, 5H), 3.95–3.87 (m, 1H), 2 95–2.85 (m, 1H),
Compound 11a: H NMR: l 7.42–7.20 (m, 11H), 7.18 (d,
4H J=3.1 Hz) 7.42–7.23 (m, 8H), 7.16–7.12 (m, 4H),
7.08–7.03 (m, 2H), 6.91 (d, 2H J=7.9 Hz), 6.18 (d, 2H
J=7.9 Hz), 4.20–4.12 (m, 1H), 3.12–3.03 (m, 1H), 2.80–
2.70 (m, 7H); 13C NMR: l 149.6, 131.8, 131.6, 131.5,
131.0, 130.7–130.6 (m) 130.2 (d, JCꢀP=9.2 Hz), 128.9 (d,
2.64–2.57 (m, 1H); 13C NMR: l 139.9, 137.9 (d, JCꢀP
=
12.2 Hz), 136.2 (d, JCꢀP=15.2 Hz), 134.3 (d, JCꢀP=20.6
Hz), 133.0 (d, JCꢀP=2.3 Hz), 132.2, 132.1, 131.7 (d,
JCꢀP=10.7 Hz), 128.5 (d, JCꢀP=12.2 Hz), 127.9, 127.8,
127.7, 40.6, 38.3 (d, JCꢀP=70.0 Hz), 30.3 (d, JCꢀP=70.0
J
CꢀP=17.5 Hz), 131.6 (d, JCꢀP=3.1 Hz), 131.2 (d, JCꢀP
8.5 Hz), 130.7 (d, JCꢀP=9.2 Hz), 129.8, 129.7, 128.8 (t,
CꢀP=11.4 Hz), 128.3, 128.2, 128.0 (d, JCꢀP=12.2 Hz),
127.5 7 (d, JCꢀP=2.3 Hz), 117.6 (d, JCꢀP=1.5 Hz), 114.1
=
Hz); 31P NMR: l 35.9 (d, JPꢀP=48.8 Hz), 30.9 (d,
J
PꢀP=48.8 Hz). HRMS(EI) calcd for C34H34NP2 (MH+),
J
518.2166; found, 518.2162.