Syntheses of symmetric and unsymmetric 2,6-bis(phosphino)phenols

Article abstract of DOI:10.1002/hc.20251

Compounds bearing the structural motif of 2,6-bis(phosphino)phenol have been synthesized via two general methods. Double lithium-halogen exchange occurred in low-temperature reactions of O-protected (by methyl- or tetrahydropyranyl groups) 2,6-dibromo-4-m

Full text of DOI:10.1002/hc.20251

Heteroatom Chemistry
Volume 17, Number 7, 2006
Syntheses of Symmetric and Unsymmetric
2,6-Bis(phosphino)phenols
Aldona Beganskiene, Nicolai I. Nikishkin, Rudy L. Luck,
and Eugenijus Urnezius
Department of Chemistry, Michigan Technological University, 1400 Townsend Drive, Houghton,
MI 49931, USA
Received 14 September 2005; revised 27 November 2005
characterized via single crystal X-ray diffraction exper-
ABSTRACT: Compounds bearing the structural mo-
ꢀ
C
iments.
2006 Wiley Periodicals, Inc. Heteroatom Chem
tif of 2,6-bis(phosphino)phenol have been synthesized
via two general methods. Double lithium-halogen ex-
change occurred in low-temperature reactions of
O-protected (by methyl- or tetrahydropyranyl groups)
2,6-dibromo-4-methylphenol derivatives with BuLi
(2 equivalents); quenching the reaction mixtures with
chlorophosphines ClPR2 (R = Ph, iPr) and correspond-
ing O-deprotection yielded symmetrically substituted
2,6-bis(phosphino)phenols. Sequential incorporation
of PR2 functionalities was accomplished via single
lithium-halogen exchange (1 eq. of BuLi) of tetrahydr-
opyranyl-protected 2,6-dibromo-4-methylphenol follo-
wed by ClPR2 quenches, thus enabling the syntheses
of unsymmetric 2,6-bis(phosphino)phenols. Such
compounds were also obtained via sequential ortho-
lithiations of tetrahydropyranyl-protected 4-tert-but
ylphenol, followed by ClPR2 quenches. All of the new
compounds have been characterized by spectrometric
methods (1H and 31P NMR, and mass spectrometry).
In addition, two of the compounds, 1-(diphenylphos-
phino)-3-(diphenylphosphoryl)-2-methoxy-5-methyl-
benzene (3a-ox) and 1,3-bis(diphenylphosphino)-
2-methoxy-5-methylbenzene (6a) have also been
17:656–663, 2006; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.20251
INTRODUCTION
Various derivatives of ortho-phosphinophenol (1,
Fig. 1) have found extensive use recently as mono-
nucleating, monoanionic, bidentate [P,O] chelating
ligands in transition metal chemistry [1–8]. Quite
surprisingly, phenols featuring PR2 groups at both
ortho positions (e.g., 2,6-bis(phosphino)phenol 2,
Fig. 1) have not yet been reported. Two [P,O] chelat-
ing sites possessed by such compounds may pro-
vide interesting platforms for bimetallic, O-bridged
metal complexes, especially since a structurally sim-
ilar ligand, 2,6-bis(diphenylphosphino)-N-methyl-
aniline has been used to support the formation
of an N-bridged dinuclear molybdenum complexes
[9]. Herein we report the syntheses of 2,6-bis(phos-
phino)phenol derivatives, featuring symmetric (3a,
b, 4a) or unsymmetric (3c, 4b) phosphine substitu-
tion patterns.
Aldona Beganskiene is a Fulbrigth visiting scholar.
Permanent address of Aldona Beganskiene: Department of Gen-
eral and Inorganic Chemistry, Vilnius University, Naugarduko 24,
03255 Vilnius, Lithuania.
Correspondence to: Eugenijus Urnezius; e-mail: urnezius@
mtu.edu.
RESULTS AND DISCUSSION
A number of synthetic methods are known for the
syntheses of ortho-phosphinophenols. Such meth-
ods typically involve metallations of o-bromophenols
or O-protected phenols, followed by the reac-
tions with dialkyl/diaryl chlorophosphines [10–13].
Contract grant sponsor: ACS Petroleum Research Fund.
Contract grant sponsor: Michigan Technological University.
2006 Wiley Periodicals, Inc.
c
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656

Syntheses of Symmetric and Unsymmetric 2,6-Bis(phosphino)phenols 657
FIGURE 1 Generic structural drawings of o-phosphinophenol (1) and 2,6-bis(phosphino)phenol (2); Structural formulas of our
synthesized compounds (3a-c and 4a-b) bearing the structural motif of 2,6-bis(phosphino)phenol.
Following
a similar strategy, we have estab-
lished conditions for (1) one-step dilithiations
of O-protected 2,6-dibromophenols via BuLi/Br
exchange, leading to the syntheses of symmetric
2,6-bis(phosphino)phenol derivatives 3a,b; (2) se-
quential single ortho-lithiations of suitable phenol
precursors, leading to the syntheses of symmetric
2,6-bis(phosphino)phenol 4a and unsymmetric phe-
nols 3c and 4b.
Methyl-protected dibromophenol 5a (obtained
via reactions of 2,6-dibromo-4-methylphenol
with dimethylsulfate) readily undergoes double
lithium-halogen exchange upon exposure to 2
equivalents of butyl lithium at low temperature
(−80◦C); generation of a similar organodilithium
intermediate has been reported earlier [14].
Quenching of the reaction mixture with ClPPh2
produces 1,3-bis(diphenylphosphino)-2-methoxy-5-
methylbenzene 6a in 73% yield (Eq. (1)).
FIGURE 2 Thermal ellipsoid plot of 6a. Selected data:
˚
˚
˚
C1-O1 1.394(4) A; C2-P1 1.838(2) A; O1-C11 1.440(4) A;
C1-C2-P1 116.79(17)◦; C3-C2-P1 125.79(16)◦; C2-C1-O1
118.60(14)◦; C1-O1-C11 112.2(3)◦.
for the syntheses of o-phosphinophenols [17]. Our
attempts to obtain X-ray quality crystals of 3a were
only partially successful. The presence of adventi-
tious oxygen in the system resulted in partial oxida-
tion at one of the phosphorus centers of 3a. The
crystals deposited from THF/hexane (1:25) solution
were composed of 3a (37(1)%) and the mono ox-
idation product, 3a-ox (63(1)%), according to the
analysis of the X-ray diffraction data. Such data are
supported by 31P NMR (CDCl3; 3a-ox: δ 38.8, −14.6;
3a: δ −21.0; the approximate ratios of peak intensi-
ties ∼1:1:1) and GC/MS (3a: m/z = 476 (M+); 3a-ox:
m/z = 492 (M+)) analyses of the crystals.
(1)
Compound 6a is an air-stable, crystalline sub-
stance, and we have been able to obtain X-ray
quality crystals and characterize it via single-
crystal X-ray diffraction methods (Fig. 2). Most of
the structural parameters of 6a are similar to
those determined for related compounds featur-
ing (ortho-methoxyphenyl)diphenylphosphine frag-
ments [15,16]. Some notable differences observed
The structural features displayed by 3a-ox
(Fig. 3) are somewhat different from the ones re-
ported for related o-(diphenylphosphoryl)phenols;
...
˚
the main difference being the nature of P O H O
for 6a are the longer C1–O1 distance (by ∼0.02 A)
and the smaller C1–O1–C11 angle (by ∼5◦), with both
probably resulting from steric pressure from the two
PPh2 groups.
hydrogen bond. While predominately intermolecu-
lar hydrogen bonding has been determined for (2-
hydroxyphenyl)diphenylphosphine oxide [18] and
(2-hydroxy-5-methylphenyl)diphenylphosphine ox-
ide [19], an exclusively intramolecular P O· · ·H O
interaction is present in 3a-ox. Other structural pa-
rameters are not exceptional.
Treatment of 6a with BBr3 followed by
amine results in demethylation, yielding 2,6-
bis(diphenylphosphino)-4-methylphenol 3a in excel-
lent yield (95%); similar procedures have been used
Heteroatom Chemistry DOI 10.1002/hc

658 Beganskiene et al.
unwanted phosphine-BBr3 adducts [22]. Thus, we
found that 1-[(2-tetrahydropyranyl)oxy]-2,6-dibr-
omo-4-methylphenol (5b) readily undergoes a dou-
ble lithium-halogen exchange upon reaction with
2 equivalents of n-BuLi or sec-BuLi.
Quench-
ing of the reaction mixtures with ClPR2 (R = Ph
or iPr) yields the THP-protected symmetric 2,6-
bis(phosphino)phenols 8a,b as moderately air-
sensitive solids (Eq. (3)). The deprotection of the
phenol group proceeds smoothly for 8a, with only
catalytic quantities of H+ (TsOH as H+ donor) re-
quired. Higher than stoichiometric quantities of
stronger H+ donors (anhydrous HCl) were required
for the deprotection of 8b, resulting in the for-
mation of a phosphonium salt, as judged by the
new 31P NMR signal at δ 29.1; the formation of
phosphonium salts under such conditions has been
reported earlier [23,24]. Treatment of this phos-
phonium salt with NEt3 led to the isolation of 2,6-
bis(diisopropylphosphino)-4-methylphenol 3b as an
extremely air-sensitive colorless oil.
FIGURE 3 Thermal ellipsoid plot of 3a-ox. Selected data:
˚
˚
˚
P2-O2 1.420(8) A; P2-C2 1.818(7) A; P6-C6 1.816(7) A;
◦
◦
˚
O1-C1 1.358(8) A; O2-P2-C2 109.8(4) ; O1-C1-C2 123.6(7) ;
O1-C1-C6 114.9(8)◦; C1-C2-P2 118.1(6)◦; C1-C6-P6
118.0(6)◦.
Reactions of 5a with 1 equivalent of BuLi
followed by
a ClPPh2 quench were expected
to produce (3-bromo-2-methoxy-5-methylphenyl)-
diphenylphosphine 7a (Eq. (2)). However, selective
mono BuLi/Br exchange followed by a clean forma-
tion of 7a could not be achieved, and only moderate
yields (∼40–50%) of the desired product were ob-
served by GC/MS (M+ = 384) and 31P NMR (δ –13.9)
analyses of the reaction mixtures. We were not able
to separate 7a from the other components of the
reaction mixtures via crystallization or extractions
by various solvents. Changing the reaction media
to Et2O or hexane did not result in significant im-
provements. Yet, 7a or its analogues may serve as
starting materials for the entire family of unsymmet-
ric 2,6-bis(phosphino)phenols, or other related com-
pounds. Thus we examined different approaches to
such compounds.
(3)
(4)
Reactions of 5b with 1 equivalent of BuLi pro-
ceed differently from those of 5a. We observed rela-
tively clean lithium-halogen exchange involving only
one of the bromines (Eq. (4)), and quenching of the
reaction mixture with ClPPh2 followed by a workup
yields the (3-bromo-5-methyl-2-(tetrahydro-2H-py-
ran-2-yloxy)phenyl)diphenylphosphine 7b in 51%
isolated yield. The presence of bromine in 7b
makes it an attractive starting material for further
syntheses. We briefly investigated this by synthesiz-
ing unsymmetric 2,6-bis(phosphino)phenol deriva-
tives 8c and 3c via repeating the BuLi/ClPR2 steps
on 7b (Eq. (4)). Deprotection of the phenol group
(8c →3c) also requires higher than stoichiometric
quantities of HCl, but only the PiPr2 group is be-
lieved to form phosphonium salt under such condi-
tions, as judged by the presence of two peaks in the
31P NMR (δ 37.4, −21.8) spectrum of the reaction
mixture.
(2)
The dual usage of tetrahydropyranyl (THP)
group as an O-protector and an ortho-lithiation
facilitator has been well documented in the chem-
istry of phenols [20] and in the syntheses of
o-phosphinophenols [2,6]. More importantly, the
O-protecting THP group can be easily removed
under mild acidic conditions [21], whereas the
demethylation of 6a with BBr3 takes several
days, and sometimes results in the formation of
Since phenols protected by the THP group read-
ily undergo ortho-lithiations via deprotonation
Heteroatom Chemistry DOI 10.1002/hc

Syntheses of Symmetric and Unsymmetric 2,6-Bis(phosphino)phenols 659
by organolithium bases [2,6,20,25],
com-
genated (by bubbling N2 for at least 1 h) methanol
was used where dry solvent was not required. Com-
mercially available chlorophosphines ClPR2 were
purified prior to use: ClPPh2 was vacuum distilled,
and ClPiPr2 was frozen and degassed while thawing
under vacuum (repeated three times). Diisopropy-
lamine and triethylamine were distilled from CaH2
under nitrogen atmosphere. Other reagents were ob-
tained from commercial suppliers and were used as
received. 1H and 31P NMR measurements were ob-
tained on Varian INOVA spectrometer operating at
400 and 161.85 MHz, respectively. Spectra are ref-
erenced to tetramethylsilane (1H) and 85% H3PO4
(31P) (external reference). Low-resolution mass
spectrometric measurements were performed on a
Shimadzu QP5050A instrument; high-resolution
measurements were performed at Mass Spectro-
metric Facility of Michigan State University (East
Lansing, MI).
pounds containing the structural motif of 2,6-
bis(phosphino)phenol can also be constructed
via a different synthetic approach, avoiding 2,6-
dibromophenol derivatives as starting materials.
We have successfully implemented this feature for
the syntheses of symmetric and unsymmetric 2,6-
bis(phosphino)phenols 4a,b (Eq. (5)). Thus, pro-
longed exposure of the THP-protected p-tert-
butylphenol (9) to 1 equivalent of sec-BuLi followed
by a ClPPh2 quench yields the THP-protected ortho-
phosphinophenol 10 in >70% yield. Repeating the
BuLi/ClPR2 reaction sequence on 10 allows the
introduction of the second PR2 group, form-
ing symmetric (11a) and unsymmetric (11b)
2,6-bis(phosphino)phenol cores.
SYNTHESES
O-Protected Phenols
(5)
2,6-Dibromo-4-methylanisole (5a). The com-
pound was synthesized according to the previously
published synthetic procedure [26] (with minor
modifications); identical spectroscopic characteriza-
tions were observed.
1-[2-Tetrahydropyranyl)oxy]-2,6-dibromo-4-me-
thylbenzene (5b) and 1-[2-Tetrahydropyranyl) oxy]-
4-tert-butylbenzene (9) were synthesized via the
same general procedure; thus only one (for 5b) is
described in detail.
The deprotection of 11a,b proceeds similarly to
those described for 8a–c. Thus, only catalytic quan-
tities of H+ are required for the synthesis of powdery
4a. Higher than stoichiometric quantities of HCl
were used for the deprotection of 11b; the phospho-
nium salt formed (31P NMR δ 38.4, −20.7) under such
conditions is probably analogous to the one observed
in the synthesis of 3c.
The yields of the products containing 2,6-
bis(phosphino)phenol fragments obtained via the
latter synthetic method are comparable to those ob-
tained starting from the 2,6-dibromophenol deriva-
tive. The synthetic utility of the latter method can
be significantly expanded, as a large number of phe-
nols are readily available commercially, and an entire
family of 2,6-bis(phosphino)phenols or other related
compounds can be envisioned.
1-[2-Tetrahydropyranyl)oxy]-2,6-dibromo-4-me-
thylbenzene
(5b). 2,6-Dibromo-4-methylphenol
(26.6 g, 0.1 mol) and 3,4-dihydro-2H-pyran (11.3 g,
0.13 mol) were mixed in a 100-mL flask, kept at
−20◦C. The cooling was removed, 0.15 mL of 37%
HCl (aq.) was added, and the reaction mixture was
stirred for 1 h at 0◦C. After stirring overnight re-
sulting in solution attaining room temperature, the
reaction mixture was extracted with ether (250 mL),
the organic layer was washed with 150 mL of 5%
NaOH (aq.) and dried over K2CO3. All volatiles were
removed on a rotary evaporator, and the remaining
oily residue was crystallized from pentane (50 mL)
at −20◦C, yielding 5b (20.6 g, 59%) as colorless
EXPERIMENTAL
Manipulations requiring inert atmospheres were car-
ried out by using Schlenk techniques or in a dry box
under nitrogen atmosphere. Low-temperature reac-
tions were performed in Schlenk flasks immersed in
hexane/N2 (liq.) or ethanol/N2 (liq.) slush, contained
in a Dewar flask. Solvents were purified before use
by distillation from Na-benzophenone ketyl (ether,
THF, hexane, benzene) or CaH2 (toluene, acetoni-
trile) under nitrogen atmosphere. Methanol was dis-
tilled from magnesium methoxide under N2; deoxy-
1
crystals. Melting point: 38–40◦C; H NMR (CDCl3):
δ 1.64 (m, 3H, THP), 1.85 (m, 2H, THP), 2.10 (m,
1H, THP), 2.44 (s, 3H, CH3), 3.60 (m, 1H, THP),
4.20 (m, 1H, THP), 5.38 (m, 1H, THP), 7.30 (s, 2H,
arom).
Heteroatom Chemistry DOI 10.1002/hc

660 Beganskiene et al.
1H NMR (C6D6): δ 1.18 (m, 3H, THP), 1.68 (s, 3H,
CH3), 1.70 (m, 2H, THP), 2.10 (m, 1H, THP), 3.47
(m, 1H, THP), 4.20 (m, 1H, THP), 5.85 (m, 1H,
THP), 6.90–7.44 (m, 22H, arom). 31P NMR (C6D6):
δ −13.9 (s). HRMS (FAB): 561.2110 (MH+) (Calcd
for C36H35O2P2: 561.2112).
1-[2-Tetrahydropyranyl)oxy]-4-tert-butylbenzene
(9). Same procedure as described for 5b was used.
Protected phenol 9 was isolated as a colorless liquid
after distillation of the crude reaction mixture under
reduced pressure (yield: 22.0 g, 94%). Boiling point:
82–84◦C (0.05 mmHg). 1H NMR (CDCl3): δ 1.05
(s, 9H, tBu), 1.54 (m, 3H, THP), 1.75 (m, 2H,
THP), 1.95 (m, 1H, THP), 3.60 (m, 1H, THP), 3.79
(m, 1H, THP), 5.25 (m, 1H, THP), 6.85 (d, 2H,
2-(2,6-Bis(diisopropylphosphino)-4-methylphen-
oxy)-tetrahydro-2H-pyran (8b). Evaporation of the
benzene yielded 8b as oil. Yield: 2.0 g (82%). 1H
NMR (C6D6): δ 0.82 (m, 12H, CH(CH3)2), 0.98
(m, 12H, CH(CH3)2), 1.18 (m, 3H, THP), 1.70
(m, 2H, THP), 1.67 (s, 3H, CH3), 1.97 (m, 4H,
CH(CH3)2), 2.19 (m, 1H, THP), 3.27(m, 1H, THP),
4.25 (m, 1H, THP), 5.80 (m, 1H, THP), 6.90–7.40
(m, 2H, arom). 31P NMR (C6D6): δ −4.7 (s). HRMS
(FAB): 425.2737 (MH+) (Calcd for C24H43O2P2:
425.2738).
3
3
arom, JHH = 8 Hz), 7.15 (d, 2H, arom, JHH = 8 Hz).
(A similar synthesis of this compound has been
reported in [27].)
Syntheses of Symmetric 2,6-Bis(phosphino)-
phenols
Syntheses of O-Protected 2,6-Bis(phosphino)-
phenols. 1,3-Bis(diphenylphosphino)-2-methoxy-5-
methylbenzene (6a). To a stirred THF (80 mL)
solution of 2,6-dibromo-4-methylmethoxybenzene
(2.80 g, 10 mmol) at −80◦C was added 12.5 mL
(20 mmol) of n-butyl lithium solution (1.6 M in hex-
ane). The reaction mixture was stirred for 2 h at
−80◦C, then a solution of 3.68 mL (20 mmol) of
ClPPh2 in THF (20 mL) was added. The reaction
mixture was left to stir overnight and slowly warmed
up to room temperature. The resulting yellow so-
lution was filtered, and the volume of the solution
was reduced under vacuo resulting in the precipita-
tion of 6a as a white powder, which was isolated by
filtration; more product was obtained upon adding
hexane to the filtrate. Combined yield: 3.58 g (73%).
1H NMR (CDCl3): δ 2.00 (s, 3H, CH3), 3.84 (s, 3H,
OCH3), 6.53 (s, 2H, arom), 7.29 (m, 20H, arom). 31P
NMR (CDCl3): δ −16.0 (s). HRMS (FAB): 491.1697
(MH+) (Calcd for C32H29OP2: 491.1694).
Compounds 8a,b were obtained by the same gen-
eral procedure, thus only one detailed description
(for 8a) is provided: To a stirred solution of 5b (2.0 g,
5.7 mmol) in THF (80 mL) at −80◦C was added a solu-
tion of 1.6 M n-butyl lithium in hexane (7.81 mL, 12.5
mmol). The reaction mixture was stirred at −80◦C
for 1 h. A solution of corresponding ClPR2 (2 equiv-
alents) in THF (5 mL) was added dropwise over 15
min. The reaction mixture was stirred at −80◦C for
15 min and then allowed to warm up to room tem-
perature overnight. After removal of the volatiles,
benzene (50 mL) was added and the inorganic salt
was removed by filtration.
2-(4-Tert-butyl-2,6-bis(diphenylphosphino)phen-
oxy)-tetrahydro-2H-pyran (11a). To a stirred so-
lution of 10 (1.40 g 3.3 mmol) in THF (60 mL) at
−80◦C was added a solution of 1.6 M n-butyl lithium
in hexane (2.28 mL, 3.6 mmol). The resulting yellow
solution was stirred for 10 min at −80◦C before the
cooling bath was removed, and the reaction mixture
was stirred while warmed up to room temperature
for 1 h. The reaction mixture was then recooled to
−80◦C, and a solution of diphenylchlorophosphine
(0.74 mL, 3.4 mmol) in THF (5 mL) added dropwise
over 20 min. The reaction mixture was stirred at
−80◦C for 15 min and then allowed to warm up to
room temperature overnight. After reducing the
reaction volume by about a half, the solution was
filtered, and the remaining volatiles removed. The
residue was crystallized from THF/hexane (1:10).
Yield: 1.38 g (68%). Melting point: 123–125◦C.
t
1H NMR (C6D6): δ 0.90 (s, 9H, Bu), 1.10 (m, 1H,
THP), 1.30–1.75 (m, 5H, THP), 3.15 (m, 1H, THP),
3.90 (m, 1H, THP), 5.25 (s, 1H, THP), 6.75 (s, 2H,
arom), 7.21–7.32 (m, 20H, arom). 31P NMR (C6D6):
δ –12.9 (s). HRMS (FAB): 603.2577 (MH+) (Calcd
for C39H41O2P2: 603.2582).
O-Deprotection. 2,6-Bis(diphenylphosphino)-4-
methylphenol (3a). The compound was obtained
via two separate routes, thus both preparations are
described.
To a stirred solution of 6a (2.33 g, 4.74 mmol) in
CH2Cl2 (50 mL) at −80◦C, BBr3 was added (1.8 mL,
18.96 mmol). The resulting mixture was stirred
for 12 h, all volatiles were removed under reduced
pressure, and methanol (50 mL) was added to the
residue. After stirring the suspension for 48 h,
all volatiles were removed, and the residue was
2-(2,6-Bis(diphenylphosphino)-4-methylphenoxy)-
tetrahydro-2H-pyran (8a). Benzene was removed,
and the crude product was dissolved in THF
(10 mL). After addition of hexane (50 mL), the white
powdery 8a was filtered off and dried in vacuo.
Yield: 2.26 g (71%). Melting point: 126–128◦C.
Heteroatom Chemistry DOI 10.1002/hc

Syntheses of Symmetric and Unsymmetric 2,6-Bis(phosphino)phenols 661
suspended in toluene and diisopropylamine
Syntheses of Unsymmetric 2,6-Bis(phosphino)-
phenols
(2.65 mL, 18.96 mmol) was added. After stir-
ring for 2 h, the mixture was filtered, and removal
of volatiles precipitated 3a as a white solid. Yield:
Syntheses of Precursors. (3-Bromo-5-methyl-2-
(tetrahydro-2H-pyran-2-yloxy)phenyl)diphenylphos-
phine (7b). To a stirred solution of 5b (2.0 g,
5.7 mmol) in THF (80 mL) at –80◦C was added
a solution of 1.6 M n-butyl lithium in hexane
(3.56 mL, 5.7 mmol). The reaction mixture was
allowed to stir at −80◦C for 1 h, and a solution of
diphenylchlorophosphine (1.0 mL, 5.7 mmol) in
THF (5 mL) was added dropwise over 15 min. The
reaction mixture was stirred at −80◦C for 15 min
and then allowed to warm up to room temperature
overnight. After removal of all the volatiles under
reduced pressure, hexane (30 mL) was added and
the insoluble inorganic salts were removed by
filtration. Cooling of the filtrate afforded 7b as a
yellow solid. Yield: 1.32 g (51%). Melting point:
73–75◦C. 1H NMR (C6D6): δ 1.15 (m, 3H, THP), 1.61
(s, 3H, CH3), 1.70 (m, 2H, THP), 2.10 (m, 1H, THP),
3.47 (m, 1H, THP), 4.28 (m, 1H, THP), 5.7 (m, 1H,
THP), 6.67–7.33 (m, 12H, arom). 31P NMR (C6D6):
δ −13.1 (s). HRMS (FAB): 455.0774 (MH+) (Calcd
for C24H25BrO2P: 455.0776).
1
2.14 g (95%). Melting point: 132–134◦C. H NMR
(C6D6): δ 2.05 (s, 3H, CH3), 6.75 (s, 2H, arom), 7.24–
7.40 (m, 20H, arom). 31P NMR (C6D6): δ –19.5 (s).
HRMS (FAB): 477.1539 (MH+) (Calcd for C31H27OP2:
477.1537).
To a stirred solution of 8a (1.0 g, 1.78 mmol)
in THF (20 mL) and methanol (50 mL) was added
p-TsOH hydrate (0.12 g, 0.65 mmol) at room temper-
ature. The reaction mixture was stirred overnight,
solvents were removed under reduced pressure, and
THF (3 mL) was added. A white solid was obtained
after the solution was allowed to stand overnight
at room temperature; this was recrystallized from
THF/hexane (1:25) to give 3a as white powder. Yield:
0.52 g (61%).
2,6-Bis(diisopropylphosphino)-4-methylphenol
(3b). The solution of 8b (1.0 g, 2.35 mmol)
in deoxygenated methanol (30 mL) was treated
with O2-free anhydrous 2 N HCl solution in ether
(4 mL, 8.0 mmol) at room temperature. The reaction
mixture was stirred overnight, volatiles removed
in vacuo, and the resulting oil dissolved in CH2Cl2
(10 mL). Addition of Et2O (30 mL) precipitated a
phosphonium salt (31P NMR δ 29.1) as a white solid
(isolated by filtration). Stirring of a suspension of
this solid in benzene (20 mL) and NEt3 (2.2 mL,
18.00 mmol) overnight yielded 3b as a colorless
oil after filtration and evaporation of all volatiles.
Yield: 0.45 g (56%). 1H NMR (C6D6): δ 0.95 (m,
12H, CH(CH3)2), 1.05 (m, 12H, CH(CH3)2), 1.75
(s, 3H, CH3), 1.95 m (m, 4H, CH(CH3)2), 7.09–7.21
(m, 2H, arom). 31P NMR (C6D6): δ −4.7 (s (br)).
HRMS (FAB): 341.2162 (MH+) (Calcd for C19H35OP2:
341.2163).
(5-Tert-butyl-2-(tetrahydro-2H-pyran-2-yloxy)-ph-
enyl)diphenylphosphine (10). To a stirred solution
of 9 (4.6 g 19.6 mmol) in THF (150 mL) at −80◦C
was added a solution of 1.3 M sec-butyl lithium in
hexane (17.0 mL, 22.0 mmol). The resulting yellow
solution was stirred for 10 min at −80◦C before the
cooling bath was removed, and the reaction mixture
was stirred while warming up to room temperature
for 1 h. The reaction mixture was recooled to
−80◦C, and a solution of diphenylchlorophosphine
(3.50 mL, 20.0 mmol) in THF (10 mL) was added
dropwise over 20 min. The reaction mixture was
stirred at −80◦C for 15 min and then allowed to
warm up to room temperature overnight. After
removal of the volatiles in vacuo, hexane (50 mL)
was added. The extract was filtered; volatiles were
removed under vacuo to yield an oil. Yield: 6.1 g
2,6-Bis(diphenylphosphino)-4-tert-butylphenol
(4a). To a stirred solution of 11a (1.0 g, 1.66 mmol)
in THF (20 mL) and methanol (50 mL) was added
p-TsOH hydrate (0.17 g, 0.88 mmol). The reac-
tion mixture was stirred overnight, volatiles were
removed under reduced pressure, and the residue
was extracted with benzene (30 mL). Benzene was
removed under reduced pressure and following
crystallization from a THF/hexane mixture (1:30),
white powdery 4a was obtained. Yield: 0.58 g (67%).
t
(74%). 1H NMR (CDCl3): δ 0.99 (s, 9H, Bu), 1.25
(m, 3H, THP), 1.45 (m, 3H, THP), 3.35 (m, 2H,
THP), 5.25 (s, 1H, THP), 6.75 (m, 1H, arom), 6.95
(m, 1H arom), 7.15–7.30 (m, 11H, arom). 31P NMR
(CDCl3): δ –12.2 (s). HRMS (FAB): 419.2138 (MH+)
(Calcd for C27H32O2P: 419.2140).
Syntheses of O-Protected Unsymmetric 2,6-
Bis(phosphino)phenols. 2-(2-(Diisopropylphosphino)-
6-(diphenylphosphino)-4-methylphenoxy)-tetrahydro-
2H-pyran (8c). To a stirred solution of 7b (1.2 g,
2.6 mmol) in THF (40 mL) at −80◦C was added
1
Melting point: 102–104◦C. H NMR (CDCl3): δ 0.91
t
(s, 9H, Bu), 6.88 (s, 2H, arom), 7.19–7.43 (m, 20H,
arom). 31P NMR (CDCl3): δ −19.5 (s). HRMS (FAB):
519.2004 (MH+) (Calcd for C34H33OP2: 519.2007).
Heteroatom Chemistry DOI 10.1002/hc

662 Beganskiene et al.
a solution of 1.6 M n-butyl lithium in hexane
(1.75 mL, 2.8 mmol). The reaction mixture was
allowed to stir at −80◦C for 1 h, and a solution of
diisopropylchlorophoshine (0.42 mL, 2.8 mmol) in
THF (5 mL) was added dropwise over 15 min. The
reaction mixture was stirred at −80◦C for 15 min
and then allowed to warm up to room temperature
overnight. After removal of the volatiles under
reduced pressure, the remaining oily residue was
extracted with hexane (30 mL). After filtering of
the hexane extract and removal of the volatiles in
vacuo, 8c was obtained as oil. Yield: 0.53 g (41%).
1H NMR (C6D6): δ 0.85 (m, 6H, CH(CH3)2, 0.98 (m,
6H, CH(CH3)2) 1.26 (m, 3H, THP), 1.84 (m, 2H,
THP), 1.91 (s, 3H, CH3), 1.97 (m, 2H, CH(CH3)2),
2.09 (m, 1H, THP), 3.28 (m, 1H, THP), 4.23 (m,
1H, THP), 5.78 (m, 1H, THP), 6.99–7.41 (m, 12H,
arom). 31P NMR (C6D6): δ 31P NMR (C6D6): δ −4.7
(s), −13.3 (s). HRMS (FAB): 493.2426 (MH+) (Calcd
for C30H39O2P2: 493.2425).
ing oil was dissolved in CH2Cl2 (10 mL). Addition
of Et2O (30 mL) precipitated a white solid phospho-
nium salt (31P NMR: δ 37.4, –21.8). Solvents were
removed, the phosphonium salt was suspended in
benzene (20 mL), and NEt3 (2.2 mL, 18.0 mmol) was
added. The resulting mixture was stirred overnight;
filtration and evaporation of all volatiles produced
a solid residue. The crude product was crystal-
lized two times from hexane (30 mL). Yield: 0.65 g
1
(49%). H NMR (CDCl3): δ 0.95 (m, 6H, CH(CH3)2),
1.05 (m, 6H, CH(CH3)2), 2.0 (s, 3H, CH3), 2.05 (m,
2H, CH(CH3)2), 6.40 (s, 1H, OH) 7.00–7.34 (m, 12H,
arom). 31P NMR (CDCl3): δ −16.6 (s), −21.71 (s).
HRMS (FAB): 409.1852 (MH+) (Calcd for C25H31OP2:
409.1850).
2-(Diisopropylphosphino)-6-(diphenylphosphino)-
4-tert-butylphenol (4b). The solution of 11b (1.0 g,
1.87 mmol) in deoxygenated methanol (15 mL) was
treated with O2-free 4 M HCl solution in dioxane
(1.8 mL, 7.4 mmol) at room temperature. The
reaction mixture was stirred overnight, methanol
was removed, and the resulting oil dissolved in
CH2Cl2 (10 mL). The addition of Et2O (30 mL)
precipitated a white solid phosphonium salt (31P
NMR: δ 38.4, −20.7). Solvents were removed under
reduced pressure, and the phosphonium salt was
suspended in benzene/NEt3 (20/1.2 mL) mixture.
The resulting mixture was stirred overnight, filtered
and all volatiles were removed under reduced
2-(4-Tert-butyl-2-(diisopropylphosphino)-6-(diph-
enylphosphino)phenoxy)-tetrahydro-2H-pyran (11b).
To a stirred solution of 10 (1.5 g 3.60 mmol) in THF
(40 mL) at −80◦C was added a solution of 1.3 M
sec-butyl lithium in hexane (3.0 mL, 3.90 mmol).
The resulting yellow solution was stirred for 10 min
at −80◦C; the cooling bath was removed, and the
reaction mixture was stirred while warming up to
room temperature for 1 h. The reaction mixture
was recooled to −80◦C, and the solution of diiso-
propylchlorophosphine (0.58 mL, 3.60 mmol) in
THF (10 mL) was added dropwise over 20 min. The
reaction mixture was stirred at −80◦C for 15 min
and then allowed to warm up to room temperature
overnight. After removal of the volatiles under
vacuo, hexane (50 mL) was added and the extract
was filtered. After removal of all the volatiles under
vacuo, 11b was obtained as oil. Yield: 1.0 g (52%).
1H NMR (CDCl3): δ 0.80 (m, 6H, CH(CH3)2), 0.91
1
pressure, yielding oil. Yield: 0.43 g (51%). H NMR
(C6D6): δ 0.90 (m, 6H, CH(CH3)2), 1.05 (m, 6H,
CH(CH3)2), 1.8 (s, 9H, tBu), 2.02 (m, 2H, CH(CH3)2),
7.10–7.54 (m, 12H, arom). 31P NMR (C6D6): δ −13.7
(s), −20.3 (s). HRMS (FAB): 451.2319 (MH+) (Calcd
for C28H37OP2: 451.2320).
STRUCTURAL CHARACTERIZATIONS
t
(m, 6H, CH(CH3)2), 1.01 (s, 9H, Bu), 1.22 (m, 3H,
X-Ray structure determinations of 6a and 3a-ox. 6a:
crystal (THF/hexane): colorless prism, 0.40 mm ×
0.20 mm × 0.15 mm; orthorhombic Pbnm (no.
THP), 1.45 (m, 2H, THP), 1.80 (m, 1H, THP), 1.97
(m, 2H, CH(CH3)2), 3.40 (m, 1H, THP), 4.20 (m,
1H, THP), 5.50 (s, 1H, THP), 6.65 (m, 1H arom),
6.75 (m, 1H arom), 7.10–7.36 (m, 10H, arom). 31P
NMR (CDCl3): δ −4.2 (s), −12.6 (s). HRMS (FAB):
535.2897 (MH+) (Calcd for C33H45O2P2: 535.2895).
˚
˚
˚
62), a = 8.407(2) A, b= 12.488(3) A, c= 25.742(6) A,
3
˚
˚
V = 2702.6(11) A , Z = 4, ꢀ = 0.71073 A, ρcalcd = 1.205
g/cm3, F(000) = 1032, θ range 1.58–22.46. Final
indices [I > 2σ(I)] R = 0.036, wR2 = 0.0863; R in-
1
dices (all data) R = 0.056, wR2 = 0.095. 3a-ox:
1
O-Deprotection. 2-(Diisopropylphosphino)-6-(dip-
henylphosphino)-4-methylphenol (3c). A solution of
8c (1.60 g, 3.25 mmol) in deoxygenated methanol
(30 mL) was treated with O2-free anhydrous 2 N
HCl solution in ether (6.5 mL, 13.0 mmol) at room
temperature. The reaction mixture was stirred
overnight, methanol was removed, and the result-
crystal (THF/hexane): white prism, 0.15 mm × 0.10
mm × 0.10 mm; orthorhombic Pbca (no. 61), a =
˚
˚
˚
15.702(3) A, b= 15.782(4) A, c= 21.059(8) A,
3
˚
V = 5219(3) A , Z = 8, ꢀ = 0.71073, ꢁcalcd = 1.239
g/cm3, F(000) = 2040, θ range 1.93–22.47. Final in-
dices [I > 2ꢂ(I)] R = 0.067, wR2 = 0.102; R indices
1
(all data) R = 0.282, wR2 = 0.154. Suitable crystals
1
Heteroatom Chemistry DOI 10.1002/hc

Syntheses of Symmetric and Unsymmetric 2,6-Bis(phosphino)phenols 663
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were identified, rolled in epoxy resin and mounted
on glass fibers.
Data for 6a and 3a-ox were collected at 293 K
on an Enraf-Nonius Turbo CAD-4 X-ray diffractome-
ter. Various crystallographic programs were used to
refine the structure. The data collection and reduc-
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was used as an interface for the solution and refine-
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[30] and then solved using the program SIR97 [31].
6a was arranged on a mirror plane with disorder
in the arrangement of the H-atoms in the para-
methyl group. Complex 3a-ox did not contain any
disorder, but the occupancy of the O atom (O2,
which had an abnormally large thermal parame-
ter when defined at full occupancy) bonded to the
P2 atom was freely refined and this converged to
a value of 63(1)%. This occupancy is reasonable
in light of the intensities in the 31P NMR spectrum
of the crystals indicative of a 2:1 mixture of 3a-
ox (around 66%) and pure diphosphine compound
3a (around 33%). The models were refined with
SHELXL97 [32]. All non-H atoms were refined with
anisotropic thermal parameters, and H-atoms were
constrained to the carbon atoms to which they were
attached.
CCDC 283562 for 6a and CCDC 283563 for
3a-ox contain the supplementary crystallographic
data. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from
the Cambridge Crystallographic Data Centre, 12,
Union Road, Cambridge CB2 1EZ, UK; fax: +44
1223 336033; or deposit@ccdc.cam.ac.uk).
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ACKNOWLEDGMENT
AB thanks the Council for International Exchange
of Scholars for providing the Fulbright visiting
scholarship.
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[32] Sheldrick, G. M. Program for Crystal Structure Re-
finement; University of Go¨ttingen, Germany, 1997.
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Heteroatom Chemistry DOI 10.1002/hc