Work-up-free deprotection of borane complexes of phosphines, phosphites, and phosphinites with polymer-supported amines

Article abstract of DOI:10.1055/s-2006-950439

Borane complexes of phosphorus compounds, a very common oxidation-free relay for catalytic ligands (phosphines, phosphites, and phosphinites), can be easily deprotected by treatment with polymer-supported piperazine or N-methylpiperazine. Deprotection conditions have been optimized for the different types of phosphorus compounds, and the resulting solutions can be used without any intermediate work-up or purification process. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-950439

LETTER
2585
Work-Up-Free Deprotection of Borane Complexes of Phosphines, Phosphites,
and Phosphinites with Polymer-Supported Amines
W
ork-Up-Free
o
D
eprotectio
n
n of Borane
i
C
omple
a
xes Sayalero,a Miquel A. Pericàs*a,b
a
Institute of Chemical Research of Catalonia (ICIQ), Avda. Països Catalans 16, 43007 Tarragona, Spain
b
Departament de Química Orgànica, Universitat de Barcelona, 08028 Barcelona, Spain
Fax +34(977)920222; E-mail: mapericas@iciq.es
Received 25 July 2006
In this paper we report a very efficient and facile new
method for the deprotection of organophosphorus–borane
complexes using strongly nucleophilic amines anchored
to polystyrene resins. From a practical perspective, attach-
Abstract: Borane complexes of phosphorus compounds, a very
common oxidation-free relay for catalytic ligands (phosphines,
phosphites, and phosphinites), can be easily deprotected by treat-
ment with polymer-supported piperazine or N-methylpiperazine.
Deprotection conditions have been optimized for the different types ing the amine onto a polymer support offers several
of phosphorus compounds, and the resulting solutions can be used
without any intermediate work-up or purification process.
advantages over its use in solution. These advantages in-
clude the separation of the phosphines from the resin-sup-
Key words: deprotection, ligands, phosphorus, boron, supported
reagents
ported amine–borane complex by a simple filtration or
cannulation and the easy recovery and recycling of the
deboronation agent.
The design and preparation of functionalized phosphines
is an area of great interest mainly due to their application
as ligands in transition-metal catalysis.1 In most cases,
however, the use of phosphines is laborious due to the
special precautions required in order to avoid their oxida-
tion. In this respect their preparation and manipulation
requires strict oxygen exclusion or, alternatively, their
protection against oxidation. Phosphine–borane complex-
es should solve these problems since they are very stable,
not sensitive to the usual oxidizing reagents, and can be
handled and stored without special requirements.2 These
borane adducts are easily accessible and represent versa-
tile precursors for the synthesis of free phosphines for
application in catalysis.3
N
1.
N
R
R1
P
R1
P
R = H, Me
R2
R3
R2
R3
BH3
2. filtration or cannulation
Scheme 1 Decomplexation of organophosphorus–borane
complexes.
According to previously reported results on deboronation
and polymer swelling properties, toluene or THF could be
suitable solvents for our purposes.3 Moreover, commer-
cially available piperazinomethyl polystyrene resin 1
[0.80–1.50 mmol/g resin, styrene, 1% divinyl benzene
(DVB)] and homemade N-methylpiperazine-functional-
ized polystyrene prepared from a Merrifield resin (final
functionalization: 1.93 mmol/g resin; 1% DVB), seemed
to be appropriate, as they readily form gels which swell in
these solvents. Supporting N-methylpiperazine on a
Merrifield resin was easily achieved in one step.8 Deter-
mination of the level of functionalization of the final resin
Decomplexation of these adducts must therefore be
effected as simply as possible. The first examples of such
a process were reported by Imamoto4 and involved the use
of a large excess of diethylamine or morpholine as
competitor Lewis bases. Nevertheless, after the results
reported by Le Corre5 the amine most frequently used for
this purpose is DABCO, and toluene is commonly chosen
as the solvent for this deboronation procedure. Also protic
acids such as MsOH, TfOH, and HBF4 have been
efficiently used for deprotecting phosphine–borane com-
plexes.6
O
N
PPh2
Ph
BH3
In all these cases, once the decomplexation is complete
either aqueous treatment involving phase-separation or
purification by short-path column chromatography is re-
quired.7 If the tendency of the free phosphines to undergo
oxidation is considered, it becomes clear that this final
treatment is not desirable.
BH3
4
BH3
BH3
PPh2
OPPh2
Ph
O
O
PPh2
BH3
5
6
SYNLETT 2006, No. 16, pp 2585–2588
0
4
.1
0
.2
0
0
6
Advanced online publication: 22.09.2006
Figure 1 Phosphine–borane and phosphinite–borane complexes
DOI: 10.1055/s-2006-950439; Art ID: G24506ST
© Georg Thieme Verlag Stuttgart · New York
synthesized.

2586
S. Sayalero, M. A. Pericàs
LETTER
29 (mmol piperazine groups/g resin) was calculated by a complexes 5 and 6 (Figure 1) were prepared from the cor-
previously reported procedure.10
responding alcohols in two steps without isolation of the
intermediate phosphinites. Reaction of (+)-(1S,2R)-2-
phenylcyclohexanol in THF with two equivalents of chlo-
rodiphenylphosphine for one hour in the presence of Et3N
and DMAP afforded the desired phosphinite, which was
directly treated with BH3·THF to obtain 5 in 67% total
yield.13 With regard to compound 6,14 (S)-2,2¢-bis(diphen-
ylphosphinooxy)-1,1¢-binaphthyl was synthesized from
(S)-BINOL according to the literature procedure,15 and
Except for triphenylphosphine borane which was ob-
tained from commercial sources, the phosphite–borane
and phosphine–borane complexes were prepared by the
reaction of readily available phosphines with BH3·THF
complex (1 M).11 Thus, treating S-(+)-2-[(2-diphen-
ylphosphino)phenyl]-4-phenyl-2-oxazoline with 2.2
equivalents of the borane solution in THF overnight pro-
vided, after solvent removal in vacuo, the diborane adduct
412 (Figure 1). On the other hand, the phosphinite–borane
Table 1 Deprotection of Phosphorus–Borane Complexes with Piperazine or N-Methylpiperazine Anchored to Polystyrene Resins
Entry Substrate
d (31P{1H})a Resin
ppm
Solvent
Temp
(°C)
Time
(h)
Conversion d( 31P{1H})c
(equiv)
1 (4)
1 (2)
1 (2)
1d (2)
2 (3)
2 (4)
2 (3)
2d (4)
1 (2)
1 (2)
1 (4)
1 (5)
1 (5)
1 (2)
1d (2)
1 (4)
1 (2)
1 (2)
1 (2)
1 (2.5)
1 (2.5)
2 (4)
2d (4)
1 (2)
1 (4)
(%)b
ppm
1
2
Ph3P→BH3
Ph3P→BH3
Ph3P→BH3
Ph3P→BH3
Ph3P→BH3
Ph3P→BH3
Ph3P→BH3
Ph3P→BH3
PhMe2P→BH3
PhMe2P→BH3
Ph2PCH2CH2PPh2
Ph2PCH2CH2PPh2
Ph2PCH2CH2PPh2
(PhO)3P→BH3
(PhO)3P→BH3
(–)-DIOP→BH3
CamPHOS→BH3
PuPHOS→BH3
PuPHOS→BH3
4
23.9
THF
reflux
60
4.5
4.5
4.5
4.5
16
4.5
4.5
4.5
17
17
4
99
–2.3
THF
95
3
toluene
toluene
THF
60
99
4
60
99
5
45
93
6
THF
reflux
60
99
7
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
THF
88
8
60
99
9
5.9
60
4
–42.4
–9.5
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
115e
60
68
21.2
90
60
6
93
60
16
1.5
1.5
22
4
100
100
100
100
99
110.2
60
131
60
17.7
28.3
26.5
60
–20.3
–6.2
–2.2
60
60
2
95
60
4
93
26.9
THF
60
4.5
2
100
98
–2.3
4
toluene
THF
60
4
reflux
reflux
reflux
60
4.5
4.5
16
16
100
100
99
4
THF
5
105.5
111
toluene
toluene
112
6
99
113.5
a 31P{1H} NMR spectra were recorded at 162 MHz (CDCl3) for phosphorus–borane complexes.
b Determined by integration of the residual borane complex signals and the free phosphorus product signals in the 1H NMR and 31P NMR spectra
of the reaction mixture after filtration and solvent removal.
c 31P{1H} NMR spectra were recorded at 162 MHz (CDCl3) for free phosphorus compounds.
d Experiment performed with a recovered sample of resin.
e In a sealed tube.
Synlett 2006, No. 16, 2585–2588 © Thieme Stuttgart · New York

LETTER
Work-Up-Free Deprotection of Borane Complexes
2587
protected as the diborane complex without further purifi- under an inert atmosphere. We think that this most
cation (70% total yield).
practical method can greatly facilitate the manipulations
required to convert pre-catalyst into active catalytic spe-
cies in many different types of processes.
Triphenylphosphine–borane complex was used to deter-
mine the optimal conditions for the removal of the borane
group16 (Table 1, entries 1–8). In general, treatment of the
complex with two equivalents of the piperazino resin 1 in
THF or toluene for a few hours at 60 °C is sufficient for
full deprotection (Table 1, entries 1–3). The lower nucleo-
philicity of the supported N-methylpiperazino moiety re-
quires the use of a higher amount of resin 2, but the
removal of borane could be efficiently performed under
the same mild conditions (Table 1, entries 5–7). In addi-
tion, it is worth mentioning that the resins could be simply
recovered for reuse by treatment with Et3N followed by
washing with THF and drying; no decrease in its perfor-
mance is observed after using the same sample three times
(Table 1, entries 4 and 8).
Acknowledgment
We thank the DGI-MEC (CTQ2005-02193/BQU), DURSI
(2005SGR225), and ICIQ Foundation for financial support. We
also thank Prof. Xavier Verdaguer and Prof. Antoni Riera for sam-
ples of the CamPHOS and PuPHOS–borane complexes.
References and Notes
(1) (a) Ojima, I. Catalytic Asymmetric Synthesis; Wiley-VCH:
New York, 2000. (b) Jacobsen, E. N.; Pfaltz, A.;
Yamamoto, H. Comprehensive Asymmetric Catalysis;
Springer: New York, 1999.
(2) Schmidbaur, H. J. Orgamomet. Chem. 1980, 200, 287.
(3) (a) Crepy, K. V. L.; Imamoto, T. Top. Curr. Chem. 2003,
229, 1. (b) Ohff, M.; Holz, J.; Quirmbach, M.; Börner, A.
Synthesis 1998, 1391. (c) Brunel, J. M.; Faure, B.; Maffei,
M. Coord. Chem. Rev. 1998, 178-180, 665.
(4) (a) Imamoto, T.; Kusumoto, T.; Suzuki, N.; Sato, K. J. Am.
Chem. Soc. 1985, 107, 5301. (b) Imamoto, T.; Oshiki, T.;
Onozawa, T.; Kusumoto, T.; Sato, K. J. Am. Chem. Soc.
1990, 112, 5244.
(5) Brisset, H.; Gourdel, Y.; Pellon, P.; Le Corre, M.
Tetrahedron Lett. 1993, 34, 4523.
(6) (a) McKinstry, L.; Livinghouse, T. Tetrahedron Lett. 1994,
35, 9319. (b) McKinstry, L.; Livinghouse, T. Tetrahedron
Lett. 1994, 50, 6145.
(7) For examples see: (a) Williams, D. B. G.; Lombard, H.; van
Niekerk, M.; Coetzee, P. P.; Holzapfel, C. W. Phosphorus,
Sulfur Silicon Relat. Elem. 2002, 177, 2799. (b) Schröder,
M.; Nozaki, K.; Hiyama, T. Bull. Chem. Soc. Jpn. 2004, 77,
1931.
(8) Anchoring N-Methylpiperazine onto a Merrifield Resin: The
amine (1 mmol) was added to a mixture of (chloro-
methyl)polystyrene (10 mmol) and Cs2CO3 (2.5 mmol) in
DMF (10 mL). The mixture was heated for 24 h at 50 °C.
After cooling the suspension was filtered and the resin was
washed with DMF (4 ꢀ 10 mL), H2O (4 ꢀ 10 mL), H2O–
MeOH (1:1; 2 ꢀ 10 mL), MeOH (4 ꢀ 10 mL), toluene
(4 ꢀ 10 mL), and CH2Cl2 (4 ꢀ 10 mL). The solid was dried
in vacuo for 24 h at 40 °C to constant weight.
In the deprotection of dimethylphenylphosphine (Table 1,
entries 8 and 9) a longer reaction time and harsher reaction
conditions were required. After heating resin 1 in toluene
at 115 °C for 17 hours under an argon atmosphere in a
sealed tube, the conversion was over 70%. Unfortunately,
phosphines with higher basicity like tributylphosphine
could not be fully deprotected under these conditions even
in the presence of a large excess of amine.
Cleavage of the P–B bond in the dppe–bis(borane) com-
plex was almost complete after stirring with five equiva-
lents of resin 1 in toluene for four to six hours (Table 1,
entries 11 and 12); heating for a longer time provided total
conversion (Table 1, entry 13).
Functional groups like acetals or thioacetals were tolerat-
ed by this mild deprotection method. Thus, (–)-DIOP and
chiral phosphines CamPHOS and PuPHOS were easily
recovered from their borane complexes17 (Table 1, entries
16–19). The bis(borane) complex 4 was also fully depro-
tected in a few hours using polymer-supported piperazine
(2.2 equiv) or N-methylpiperazine (4 equiv) as the nucleo-
phile under the same reaction conditions (Table 1, entries
20–22). Recovered resin 2 also provided total conversion
(Table 1, entry 23).
(9) Resin 2 (1% DVB, fmax = 2.15) from (chloromethyl)poly-
styrene (1% DVB, fo = 2.0–2.5 mmol/g). 13C gel-phase
NMR (100 MHz, CDCl3): d = 40.6, 46.1, 52.9, 55.2, 62.8,
127.7. Anal. Found: N, 5.41; C, 84.82; H, 10.47; f = 1.93
mmol/g.
(10) Vidal-Ferran, A.; Bampos, N.; Moyano, A.; Pericàs, M. A.;
Riera, A.; Sanders, J. K. M. J. Org. Chem. 1998, 63, 6309.
(11) Beres, J.; Dodds, A.; Morabito, A. J.; Adams, R. M. Inorg.
Chem. 1971, 10, 2072.
This deprotection procedure is also suitable for phosphin-
ite and phosphite–borane complexes. Triphenylphosphite
was quantitatively obtained after heating with resin 1 in
toluene for 1.5 hours (Table 1, entry 14). As expected, re-
using the same resin sample for the deprotection leads to
no decrease in its efficiency (Table 1, entry 15).
Longer reaction times were required to achieve complete
deboronation in the decomplexation of the phosphinite–
boranes 5 and 6 (Table 1, entries 24 and 25).
(12) (S)-2-[2-(Diphenylphosphino)phenyl]-4-phenyl-4,5-
dihydrooxazole Diborane Complex (4): White solid; yield:
98%; mp 95–96 °C; [a]D27 +26.6 (c 1.00, CHCl3). IR
(ATR): 3064, 2966, 2864, 2385–2262, 1650, 1478, 1434,
1387, 1321, 1168, 1062, 928, 742, 695 cm–1. 1H NMR (400
MHz, CDCl3): d = 0.95–1.98 (br s, 6 H), 3.86 (dd, J = 10.5,
9.3 Hz, 1 H), 4.17 (dd, J = 9.2, 6.7 Hz, 1 H), 4.58 (dd,
J = 11.0, 6.7 Hz, 1 H), 7.18–7.21 (m, 2 H), 7.32–7.68 (m, 12
H), 7.70–7.76 (m, 2 H), 7.78–7.86 (m, 2 H), 7.94–7.99 (m, 1
In summary, we have developed a straightforward proce-
dure for the in situ deprotection of borane complexes of
different types of phosphorus compounds by simple treat-
ment with resin-supported piperazines. The phosphine so-
lutions resulting from this protocol can be directly used in
a catalytic application without any manipulation or, if
desired, through simple cannulation to a different flask
H). 31P{1H} NMR (162 MHz, CDCl3): d = 26.9 (br m). 11
B
NMR (128 MHz, CDCl3): d = –36.5 (br m, PBH3), –19.42
Synlett 2006, No. 16, 2585–2588 © Thieme Stuttgart · New York

2588
S. Sayalero, M. A. Pericàs
LETTER
(br s, NBH3). HRMS (ESI+): m/z calcd for C27H28B2NOPNa
(M + Na): 458.1992; found: 458.2012.
(d, J = 4.0 Hz), 122.8 (d, J = 5.1 Hz), 125.2, 126.4, 127.0,
127.9, 128.2 (d, J = 10.5 Hz), 128.7 (d, J = 10.5 Hz), 129.6,
130.7, 131.0 (d, J = 4.4 Hz), 131.1 (d, J = 4.4 Hz), 131.7 (d,
J = 2.0 Hz), 131.8 (d, J = 2.0 Hz), 131.9, 132.5, 133.7, 148.7
(d, J = 4.2 Hz). 31P{1H} NMR (162 MHz, CDCl3): d = 111
(br m). 11B NMR (128 MHz, CDCl3): d = –39 (m, BH3).
HRMS (ESI+): m/z calcd for C44H38B2O2P2Na (M + Na):
705.2459; found: 705.2431.
(13) Diphenyl[(1S,2R)-2-phenylcyclohexyloxy]phosphine–
Borane Complex (5): [a]D27 +87.9 (c 0.70, CH2Cl2). IR
(ATR): 3057, 3027, 2931, 2856, 2378, 1739, 1600, 1492,
1437, 1361, 1114, 1063, 1014, 975, 737, 698 cm–1. 1H NMR
(400 MHz, CDCl3): d = 0.55–1.65 (br m, 3 H), 1.20–1.71
(m, 4 H), 1.68–1.83 (m, 2 H), 1.88–1.97 (m, 1 H), 2.13–2.25
(m, 1 H), 2.74 (ddd, J = 12.4, 10.5, 3.8 Hz, 1 H), 4.57–4.66
(m, 1 H), 6.78–6.83 (m, 2 H), 7.04–7.09 (m, 2 H), 7.14–7.28
(m, 6 H), 7.38–7.51 (m, 3 H), 7.64–7.70 (m, 2 H). 13C NMR
(100 MHz, CDCl3): d = 24.8, 25.7, 34.3, 34.9, 52.0 (d,
J = 6.4 Hz), 82.2 (d, J = 2.5 Hz), 126.5, 127.9, 128.0, 128.3,
128.4, 130.7, 130.8, 131.3, 131.4, 131.5 (d, J = 2.9 Hz),
133.6, 143.5. 31P{1H} NMR (162 MHz, CDCl3): d = 105.5
(br m). 11B NMR (128 MHz, CDCl3): d = –39.7 (m, BH3).
HRMS (ESI+): m/z calcd for C24H28BOPNa (M + Na):
397.1869; found: 397.1886.
(14) (S)-2,2¢-Bis(diphenylphosphinooxy)-1,1¢-binaphthyl–
Diborane Complex (6): White solid; mp 190–191 °C;
[a]D26 –2.5 (c 0.83, THF). IR (ATR): 3051, 2372, 2333,
1585, 1500, 1455, 1227, 1114, 975, 830, 730, 664 cm–1. 1H
NMR (400 MHz, CDCl3): d = 0.7–1.6 (br s, 3 H), 6.96–7.02
(m, 4 H), 7.05–7.15 (m, 6 H), 7.16–7.27 (m, 8 H), 7.30–7.41
(m, 4 H), 7.42–7.52 (m, 4 H), 7.55 (d, J = 8.9 Hz, 2 H), 7.81
(t, J = 9.6 Hz, 4 H). 13C NMR (100 MHz, CDCl3): d = 120.3
(15) (a) Zhou, Y.-G.; Tang, W.; Wang, W.-B.; Li, W.; Zhang, X.
J. Am. Chem. Soc. 2002, 124, 4952. (b) Grubbs, R. H.;
DeVries, R. A. Tetrahedron Lett. 1977, 22, 1879.
(16) P–B Bond Cleavage; General Procedure: A solution of the
phosphorus–borane complex (0.025 mmol) in anhyd toluene
(0.5 mL) was added to a smoothly stirred suspension of the
resin (see Table 1, f = 1.93–0.86 mmol/g) in anhyd toluene
(1 mL) placed in a schlenk tube under an argon atmosphere
at 60 °C. The mixture was heated at 60–63 °C to complete
deprotection (see Table 1) and then the solution was filtered
under an argon atmosphere and the resin was washed with
toluene (2 ꢀ 1 mL). Removal of the solvent in vacuo
provided the pure phosphorus compound without further
purification.
(17) (a) Verdaguer, X.; Pericàs, M. A.; Riera, A.; Maestro, M. A.;
Mahia, J. Organometallics 2003, 22, 1868. (b) Verdaguer,
X.; Lledo, A.; Lopez-Mosquera, C.; Maestro, M. A.; Pericàs,
M. A.; Riera, A. J. Org. Chem. 2004, 69, 8053.
Synlett 2006, No. 16, 2585–2588 © Thieme Stuttgart · New York