Investigation of the reductive cleavage of BINAP and application to the rapid synthesis of phospholes

Article abstract of DOI:10.1021/jo4006393

A rapid and easy entry into λ³-phospholes and λ⁴-phosphole oxides derived from BINAP is reported herein featuring a variety of C and Si substituents and functional groups, as well the investigative work on the mechanistic pathway. DFT calculations using B3LYP functionals have been carried out to rationalize the mechanism. The observed experimental ³¹P resonance shifts were compared with the calculated shifts of the proposed intermediates after calibration of the shielding tensors. The calculations included the use of polarizable continuum models to take into account solvent effects and were found to be in excellent agreement, providing further evidence for the proposed mechanism.

Full text of DOI:10.1021/jo4006393

Article
pubs.acs.org/joc
Investigation of the Reductive Cleavage of BINAP and Application to
the Rapid Synthesis of Phospholes
Chris W. D. Gallop, Mariusz Bobin, Petra Hourani, Jessica Dwyer, S. Mark Roe, and Eddy M. E. Viseux*
School of Life Sciences, Department of Chemistry, University of Sussex, Brighton BN1 9QJ, U.K.
*
S Supporting Information
3
4
ABSTRACT: A rapid and easy entry into λ -phospholes and λ -
phosphole oxides derived from BINAP is reported herein featuring a
variety of C and Si substituents and functional groups, as well the
investigative work on the mechanistic pathway. DFT calculations
using B3LYP functionals have been carried out to rationalize the
3
1
mechanism. The observed experimental P resonance shifts were
compared with the calculated shifts of the proposed intermediates
after calibration of the shielding tensors. The calculations included
the use of polarizable continuum models to take into account
solvent effects and were found to be in excellent agreement,
providing further evidence for the proposed mechanism.
INTRODUCTION
Scheme 1. Predicted Fragmentation of 1 upon Reductive
Cleavage
■
a
Binaphthyl frameworks and phospholes have widespread
applicability which ranges from ligands for transition metals,
to use as catalysts or as drugs,
1
,2
3
−7
to novel building blocks for
materials with unique electronic features that can also be used in
8
−10
self-assembly frameworks,
photonics,
to molecular electronics and
12
2
,11
to π-conjugated polymers. In the context of
developing libraries of polydentate ligands based on a binaphthyl
framework, we investigated the reductive cleavage of BINAP (1)
to phospholes. The cleavage of triarylphosphines with lithium
metal in THF is a well-known method to generate lithium
a
Optimization and frequency calculation at the HF/6-31G+(d) level
of theory.
diarylphosphides (LiPAr ), which are synthetically useful and can
2
1
3,14
be used for further functionalization.
ligands have also been lithiated such as dppm and dppe,
examples of functionalization of the 2′-position of BINAP to 2-
Other diphosphine
phospholide 5. Literature precedent established that the
1
5,16
and
reduction of BINAP and other arylphosphines was dependent
18
on the choice of solvent, whereby the formation of an electride,
as is the case with ammonia, could lead to mixtures of Birch
8,17
diphenylphosphino-1,1′-binaphthyls
requires a multistep
13
process as well as the use of BuLi to chemoselectively cleave
the P−C bonds of a phosphine oxide in the presence of a
phosphine. We report herein on the clean and quantitative
reductive cleavage of BINAP to its corresponding lithium
phospholide and the one-pot functionalization of the resulting
lithium phospholide to silylated and alkylated phospholes and
phosphole oxides.
reduced products. The complexation of aromatic phosphine as
16
phosphine−boranes also leads to Birch reduced product.
Unlike the reductive cleavage of triphenylphosphine, the
reaction of phosphine 1 with lithium proved particularly sensitive
to traces of moisture and oxygen, and all reactions had to be
performed in a glovebox. The lithiation reactions are typically
complete within 48 h. All of the reactions were followed by
31
1
P{ H} NMR spectroscopy of the reaction mixtures using
RESULTS AND DISCUSSION
Young’s NMR tubes equipped with a sealed capillary tube
containing OPPh in d -benzene as an internal standard (δ 25
ppm).
■
3
6
P
Lithiation Studies. Experimental Studies. Preliminary
investigation of the stability of a tetraanion of BINAP in the
singlet state (HF/6-31G/Opt+Freq) suggested the fragmenta-
tion pattern described in Scheme 1 to organolithiums 2−4 with
no reduction of the aromatic systems to the corresponding
cycloalkenes. This postulated lack of any Birch reduction
products from BINAP was confirmed by our experiments,
though the obtained compound was found to be the binaphthyl
Reaction of 1 with lithium metal in THF furnished a dark red
solution that exhibited two signals in the 31P{ H} NMR
spectrum at +50 and −22 ppm. The resonance peak at −22
1
Received: April 8, 2013
Published: June 4, 2013
©
2013 American Chemical Society
6522
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3
1
a
ppm was identified as LiPPh (4) by performing the lithiation of
Table 2. Calculated P Isotropic Shielding Tensors
2
PPh and recording the NMR of the mixture of the resulting
3
σcalcd
(CPCM)
σcalcd
(IEFPCM)
σcalcd
(gas phase)
δexptl
(ppm)
solutions. Lithium phosphides (such as 4) typically have negative
entry compd
chemical shifts. This was found to be inconsistent with one of the
1
2
3
4
5
LiPPh2
341.83
367.55
299.39
327.20
334.31
334.23
367.39
301.07
327.25
334.34
302.01
365.42
302.64
310.75
334.21
−21.6
−40.5
24.7
31
two P signals recorded at 50 ppm. DFT calculations described
herein provided a calculated chemical shift of 49 ppm for
HPPh2
OPPh3
PPh3
3
1
1
phospholide 5. Mathey also reported 3 P{ H} NMR data for
−5.0
−14.9
1
1
phenyl-substituted phospholides with P{ H} chemical shifts
19
BINAP
between +58 and +100 ppm. This strongly suggested that our
signal at 50 ppm was a cyclic phospholide (Fgure 1). The
a
GIAO-MPW1K/6-311G++(2d,2p)//B3LYP/6-31G(d).
model (IEFPCM), performed both with and without explicit
solvent molecules in the geometry optimization gave good
results. The solvent was modeled by using polarizable continuum
models (IEF and CPCM) to keep the calculations computa-
tionally cheap with a level of accuracy sufficient for the rapid
31
1
determination of P{ H} shifts of unknown intermediates.
The direct results from GIAO NMR calculations are isotropic
shielding tensors (σ); these values must be converted to chemical
shift values (δ) using eq 1.
Figure 1. Dinaphthylphospholide anion.
structure was subsequently confirmed by negative ESI mass
spectroscopy with an accurate mass corresponding to that of 5
and by trapping experiments described herein and X-ray
crystallography of the resulting compounds.
The influence of the number of equivalents of lithium on the
reaction was also investigated (Table 1). A substoichiometric
δcalcd = σref − σcalcd
(1)
In order to determine σ , we extended the multistandard
ref
1
13
approach used for H and C by Tantillo, Rablen, and Bally to
31
23,24
31
the P nucleus.
The linear regression for calculated
P
31
isotropic shielding tensors against experimental P shifts was
performed using five known compounds (PPh , PPh O, BINAP,
3
3
3
1
Table 1. P NMR Data for the Lithiation of
LiPPh , and HPPh ). As expected, the plot of the gas-phase
a
2
2
Triarylphosphines in THF
calculated shielding tensors against experimental chemical shifts
2
3
1
1
b
gave a poor correlation with a low R value (0.55) (Figure 2). The
entry
compd
BINAP
amt of lithium (equiv)
P{ H} δ (ppm)
1
2
3
4
0
−14.89 (s)
50.25 (s), −21.67 (s)
−21.61 (s)
BINAP
4
PPh3
2
BINAP + PPh3
4 (BINAP), 2 (PPh3)
50.33 (s), −21.76 (s)
a
The lithiations were carried out using the general procedure
described in the Experimental Section. Reactions were typically
complete in 48 h. Multiplicities indicated in parentheses.
b
amount (2 equiv) led to the partial lithiation of BINAP, and an
excess (6 equiv) did not seem to impact negatively on the
reaction; products resulting from Birch reduction were never
observed in the course of this study, as corroborated by
20
Meijboom in his investigation on other triarylphosphines.
The lithiated solution was reasonably stable over an extended
period of time (two months at room temperature under argon),
with the appearance of trace signals at −14.9 and −15.9 ppm.
The signal at −15.9 ppm was attributed to a small amount of
Figure 2. Linear regression of the calculated shielding tensors vs
1
5,21
dimerization of 4 to Ph P−PPh .
2
2
2
experimental chemical shifts. Regression and R values: (i) gas phase, y =
2
DFT Calculations. Shielding tensors were calculated using
−0.8069x + 313.81, R = 0.51743; (ii) IEFPCM, y = −0.9519x + 322.01,
3
1
1
2
2
DFT calculations and then were converted to P{ H} chemical
shifts, in order to support our assignments of the experimentally
observed shifts (Table 2). Gas-phase geometry optimizations
were performed using Gaussian 09 using the B3LYP/6-31G(d)
level of theory; all geometries were confirmed as minima by the
absence of imaginary frequencies. The NMR single-point
calculations were performed using GIAO-MPW1K/6-311G+
R = 0.94281; (iii) CPCM, y = −1.0136x + 322.5, R = 0.98416.
solvent is known to have an impact on both the calculated and
the experimental shifts. This was further demonstrated by the
31
linear regression of P isotropic shielding tensors against
experimental 31P shifts obtained using IEFPCM solvation (R
2
+
(2d,2p) both in the gas phase and using a CPCM (conductor
31
2
like polarizable continuum) solvent model to obtain the
P
= 0.94) and a CPCM (R = 0.98). CPCM solvation was chosen
shielding tensors. The MPW1K functional has been shown to be
an adequate functional for the calculation of P chemical shifts.
The authors showed that for GIAO NMR calculations, with an
integral equation formalism polarizable continuum solvent
for the purpose of this study. The intercept of the regression line
with the y axis provided the shielding tensor value for 0 ppm,
which was used as a reference for calculated chemical shifts as
shown in eq 1.
3
1
22
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The 31P NMR shifts for the postulated species and
intermediates of the lithiation reaction (Figure 3) were calculated
using this methodology, with σref determined as 322.5.
lithium phosphide and phospholide and BuCl as previously
reported.
t
25
Interestingly, the use of a strong acid gave a very different
outcome to the previous proton sources. When methanesulfonic
acid (5 equiv) was used, two new doublets appeared,
corresponding to HPPh (−40.5 ppm) and to protonated 5
2
(
−62 ppm, d, J = 198.5 Hz), which was observed by Gladiali
using a different route and is consistent with the formation of a
20
P−H bond.
Silylation Studies. We initially attempted to trap the
lithiated species as boron adducts, but 11B NMR proved
inconclusive. Different trapping experiments were attempted
Figure 3. Postulated species involved in the lithiation of BINAP.
26
using silanes to form silylated phosphines useful in addition
27
and cross-coupling reactions. We have shown here that the
lithiated phosphides and phospholides can be cleanly trapped as
their silylated analogues. TMSCl and TMSOTf were both
successful in trapping the lithium phosphide species and gave
The unusual shift observed at 50.3 ppm was initially thought to
pertain to structure 2 or 6, but DFT calculations estimated their
chemical shifts at −14.8 and −96.9 ppm, respectively. Of note, a
shift at −15.0 ppm was observed in trace quantities when the
lithiated solution was left over a period of 15 days. Most
importantly, the calculated shift of 49.3 ppm for cyclic
dinaphthylphospholide 5 is in agreement with the observed
shift, validating the involvement of lithium phospholide 5 in the
postulated mechanism (Scheme 3). This equation shows good
agreement with the experimental chemical shift (±10%), as
shown in the Supporting Information.
1
29
31
1
three signals by H/ Si HMBC and two singlets by P{ H}
NMR at −58.53 and −58.69 ppm (Table 4).
3
1
1
Table 4. P{ H} NMR Data for TMS-Derived Reaction
Mixtures
amt of
TMSOTf
(equiv)
31
1
a
entry
compd
P{ H} δ (ppm)
Protonation Studies. The mechanisms reported for the
1
5,21
lithiation of diphosphines often involve complex equilibria.
1
2
3
BINAP + 4 Li
4
2
−58.53 (s), −58.69 (s)
−58.60 (s)
−58.54 (s), −58.69 (s)
Wild found that the presence of a phosphorus-based radical
dianion could affect the outcome of the hydrolysis, which could
follow various pathways. The burgundy color of the reaction
PPh + 2 Li
3
{BINAP + 4 Li} +
4 (BINAP),
b
{
PPh + 2 Li}
2 (PPh3)
3
8
a
b
mixture is characteristic of the formation of radical anions, and
Multiplicity indicated in parentheses. Approximately equal quantities
of entry 1 and entry 2 were mixed in an NMR tube.
the addition of water to the dark red solution changes the color to
yellow. Comparative experiments were carried out between the
hydrolysis of lithiated Ph P and lithiated BINAP (Table 3). The
The lithiated reaction mixtures were also trapped with the
more sterically hindered TBSOTf. The singlets were obtained at
3
31
31
1
a
Table 3. P NMR and P{ H} NMR after Hydrolysis
−61.9 ppm (TBSPPh ) and at −57 ppm (P-silylated
2
dinaphthylphosphole) (Table 5). A small amount of the
hydrolyzed diphenylphosphide was also observed at −40.5
ppm, likely due to a trace amount of trifluoromethanesulfonic
acid.
3
1
1
31P δ (ppm)
entry
1
reactants
P{ H} δ (ppm)
BINAP + 4 Li
−40.59 (s), 48.76 −40.60 (d, J = 216.2 Hz),
(
s, trace)
48.76 (s, trace)
2
3
PPh + 2 Li
−40.52 (s)
−40.48 (s)
−40.51 (d, J = 218.7 Hz)
−40.48 (d, J = 217.7 Hz)
3
{BINAP + 4 Li} +
3
1
1
b
Table 5. P{ H} NMR Data for TBS-Derived Reaction
Mixtures
{
PPh + 2 Li}
3
a
b
Multiplicity and J values indicated in parentheses. Approximately
equal quantities of entry 1 and entry 2 were mixed in an NMR tube.
amt of
TBSOTf
3
1
1
a
entry
1
compd
(equiv)
P{ H} δ (ppm)
−40.45 (s) trace, −57.06 (s),
former experiment showed the disappearance of the singlet at
BINAP + 4 Li
4
2
−
21.6 ppm and the appearance of a doublet at −40.5 ppm (J =
−
61.86 (s)
1
2
18.7 Hz) in the proton-coupled 3 P NMR spectrum which
2
3
PPh + 2 Li
−40.44 (s) trace, −61.87 (s)
−40.53 (s) trace, −57.15 (s),
3
overlapped with that of the hydrolysis of the lithiated BINAP.
{BINAP + 4 Li} +
4 (BINAP),
2 (PPh
t
b
BuCl is often used to quench organolithium byproducts in
{PPh
3
+ 2 Li}
)
3
−61.95 (s)
a
b
phosphine lithiation reactions, and the protolysis with this
weaker acid gave a different result. The use of 2 equiv was shown
Multiplicity indicated in parentheses. Approximately equal quantities
of entry 1 and entry 2 were mixed in an NMR tube.
to rapidly protonate PhLi. Upon addition of another 1 equiv of
t
BuCl, the protonation of LiPPh was found to be much slower
The difference in reactivity between lithium phosphide 4 and
lithium phospholide 5 was demonstrated by using a less reactive
silane, and reaction with TBSCl with dinaphthylphospholide was
found to be very slow (typically 12 h). Treatment with water
2
(
typically 6 h at room temperature), with little to no change in
31
1
color, the solution retaining a dark burgundy color. P{ H}
NMR spectroscopy showed the disappearance of the signal at
31
1
−
22 ppm and the appearance of a doublet at −40.5 ppm.
resulted in the facile cleavage of the P−Si bond, as P{ H} NMR
Interestingly, the phospholide at 50 ppm did not react with a
of the crude reaction mixture solely showed signals at −40.5 ppm
t
slight excess of BuCl, even when left for over 1 month. With a 12-
fold excess, however, the phospholide signal disappeared and the
peak for HPPh (−40.5 ppm) was the only signal observed. Of
note, no nucleophilic substitution was observed between the
(HPPh ) and −62 ppm (phosphole-H).
2
Alkylation Studies. The synthesis of binaphthylphospho-
lides is a multistep process involving arylphosphole intermedi-
ates obtained by either nucleophilic substitutions on highly toxic
2
6
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20
aryldichlorophosphines or reduction of bis-phosphine mon-
8
,28
oxides with a large excess of n-butyllithium.
The access to
phospholides subsequently requires an extra reductive step to
cleave the C−P bond. The direct lithiation of BINAP allows a
convenient one-pot access to structurally diverse dinaphthyl-
phospholes utilizing the intermediary phospholide 5 with a
variety of electrophiles (Scheme 2). The reactions were
Scheme 2. Preparation of Alkylated Dinaphthylphosphole
a
Oxides
a
Isolated yield after purification and recrystallization. All reactions
31
1
showed 100% conversion by P{ H} NMR spectroscopy except for
the oxidation of entry 5. 90% conversion by NMR.
b
monitored by 31P NMR spectroscopy, and the signals of all
alkylated phospholes were observed between −17 and 8 ppm. Of
note, a color change also proved useful as an indicator, with
changes from dark red for the lithiated species to pale yellow
upon treatment with a slight excess of alkyl halide. The rate of
color change was dependent on the halide used and the nature of
the electrophile. Tertiary halides failed to give any substituted
3
1
phospholes. The corresponding oxides, with P NMR signals
ranging from 30 to 50 ppm, were obtained after workup and
purification in air. Interestingly and in contrast to all the other
analogues, the cyclobutyl phosphole required extended vigorous
stirring in air to convert to its corresponding oxide.
13
1
C{ H} NMR spectra of the alkylated dinaphthyl phosphole
oxides gave indications of the fluxional behavior of the binaphthyl
20
Figure 4. NMR data supporting dynamic exchange of the binaphthyl
backbone, as previously observed by Gladiali. Broad signals in
the aromatic region corresponding to C1 and C13 (Scheme 2)
are consistently observed for all our substrates. The broad signals
backbone for oxide 7b: (A) comparison of 13C and C{ P} spectra in
13
31
1
CDCl showing the aliphatic region; (B) comparison of H NMR
3
1
3
31
spectra in CDCl at variable temperatures, with toluene used as internal
3
are not due to poorly resolved C− P coupling, as no resolution
1
standard (δ 2.34); (C) comparison of H NMR spectra in toluene-d at
1
3
31
H
8
was observed in a C{ P} experiment. This broadening is
attributed to the dynamic exchange between the various
conformers of the binaphthyl backbone. The α and β aliphatic
carbon atoms show a clear coupling with the phosphorus atom,
variable temperatures.
temperature is raised, which rules out diastereotopic protons
and suggests the existence of two distinct atropoisomers. The
signals of the α protons (multiplet between 2.15 and 2.45 ppm)
are also resolved at low temperature but overlap for both
conformers. The effective line width of the signal due to the
1
3
31
which is absent in the C{ P} experiment (Figure 4A).
1
The aliphatic region of the H NMR shows two distinct
multiplets for the β protons at 1.48−1.61 and 1.72−1.84 ppm at
−
30 °C (Figure 4B). These signals coalesce when the
6
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Figure 5. Comparative graphs between C−P distances and C−P−O angles around the P center.
exchange process is greater than the coupling constant at 30 °C,
and the broad signals observed for the α and β protons are
indicative of an intermediary state of exchange on the NMR time
scale. In the fast exchange limit, at higher temperature (Figure
diastereomeric equilibration of a P-alkyl bis-naphthyl phosphole.
0
2
The distortion causes a decrease in steric clash between H13
and H8 (Figure 6). This appears to reduce the energy barrier in
comparison to BINAP, as the exchange process between the two
atropoisomers is observed at 30 °C by NMR.
4C), the peaks narrow and the coupling begins to resolve. All
observations are consistent with exchange between the
atropoisomers of the binaphthyl backbone.
Postulated Mechanism. On the basis of the observations
presented herein, we propose the mechanism highlighted in
Scheme 3. The first 2 equiv of lithium reductively cleaves the
Oxides 7a−e yielded crystals that were suitable for X-ray
diffraction studies. In all cases, full structural data are included in
the Supporting Information. The molecular structures of these
complexes all contain a tetracoordinate phosphorus atom linked
to an oxygen atom with unexceptional P−O and P−C bond
distances and C−P−O bond angles. Inspection of the CCSD
showed that, of the 39 structures that contain phospholes, all are
tetrahedral at the phosphorus atom, with conventional distances
except for those where the system is particularly structurally
constrained or complexed to a transition metal (Figure 5). All of
the obtained structures show that the formation of a five-
membered phosphole introduced strain in the naphthyl
backbone and caused the fused naphthyl rings to distort and
pucker in comparison with BINAP (Figure 6). Gladiali also
observed this change in conformation in his studies of
Scheme 3. Proposed Mechanism for the Reductive Cleavage
a
of 1 with 4 equiv of Li Metal
a
The dihedral angles ϕ of intermediates 8 and 6 are −88 and −32°,
respectively.
phosphorus−C
bond to yield the corresponding lithiated
naphtyl
aromatic species 8 and LiPPh (4) as a byproduct. The steric
2
hindrance imparted by the diphenylphosphine groups is relieved
and allows the binaphthyl C−C bond to rotate. During rotation it
can form the reactive and electron-rich P(V) phosphoranide 6, as
8
previously postulated by Hayashi in 2001 and further supported
by a potential energy surface (PES) scan in this study (Figure 7).
The initial dihedral angle used for intermediate 8 was assumed to
2
9
be approximately the same as that of BINAP (87°).
Interestingly, intermediate 6 (dihedral angle of −32°) was
found to have the lowest energy of all possible structures when
scanning dihedral angles from −88 to 272° with increments of 1°.
Intermediate 6 can then undergo a facile, rapid, and
irreversible elimination of phenyllithium to phosphole 9.
Phosphole 9 was never observed by NMR but is known to
react rapidly with lithium to yield the corresponding phospholide
20
Figure 6. Solid-state structure of 7b.
5. This mechanism may also occur via a radical pathway, as
6
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spectrometer. Unless stated otherwise, all reactions were carried out in a
glovebox or on a Schlenk line.
General Procedure for the Lithiation of Phosphines. The
lithiations were carried out on a 0.01 M solution of the desired
29
phosphine in a Young’s ampule equipped with a glass stirrer bar. The
appropriate amount of lithium was weighed and cut into small pieces
and cleaned with fine glass paper.30 Upon addition the reaction mixture
changed from colorless to yellow, typically within 30 s of addition. The
reaction mixtures were stirred vigorously for 2−7 days, until no lithium
3
1
1
metal was visible and the solution was burgundy in color. P{ H} NMR
of the solution routinely showed peaks at 50 and −22 ppm upon
completion.
General Procedure for the Trapping of the Lithiated
Solutions. The required amount of the lithiated solution was syringed
into an ampule or a glass vial and the necessary trapping reagent added.
Most quenching agents were handled and added in the glovebox or,
alternatively, by standard Schlenk techniques.
General Procedure for the Alkylation of Binaphthylphosp-
holes. A solution of lithiated BINAP (0.16 mmol) was syringed into an
ampule or a glass vial, and the requisite alkyl halide (0.64 mmol) was
added in one portion. The solution was left at room temperature until
31
P NMR showed the disappearance of the peaks at 50 and −22 ppm and
the appearance of two new peaks between 0 and −15 ppm. The resultant
solution was then removed from the glovebox, quenched with saturated
ammonium chloride solution, and extracted with dichloromethane. The
combined organic layers were washed with water and brine, dried over
sodium sulfate, filtered, and evaporated under reduced pressure to yield
a yellow oil. The phosphine oxides were separated by flash
chromatography using a gradient solvent system (80 to 100%
EtOAc in hexanes) to give a yellow waxy solid, which was further
purified by recrystallization from toluene and hexanes.
Figure 7. Plot of the PES of intermediate 8 on varying the dihedral angle
(
defined by highlighted atoms in the structure given below the plot)
through 360° with increments of 1°. The relaxed PES scan was carried
out at the B3LYP/6-31G(d) level of theory.The lowest energy structure
31
(
marked with a cross) is depicted in the plotand corresponds to
intermediate 6. Structures were modeled as anions without explicit Li
atoms.
7
-Benzyl-7H-benzo[e]naphtho[2,1-b]phosphindole 7-oxide (7a):
synthesized as a pale yellow solid (22.4 mg, 36%); R (60/40, EtOAc/
f
1
hexanes) 0.32; mp 195.7−196.7 °C; H NMR (CDCl , 500 MHz) δ
3
H
8
.20−7.91 (m, 6H), 7.90−7.66 (m, 1H), 7.61 (t, J = 7.5 Hz, 2H), 7.48 (t,
highlighted in previous studies into the reductive cleavage of
2
5
J = 7.7 Hz, 2H), 6.99 (dt, J = 14.7, 7.7 Hz, 3H), 6.91−6.82 (m, 2H),
arylphosphines.
13
3
(
.76−3.22 (m, 2H); C NMR (CDCl , 125 MHz) δ 137.2 (s), 131.2
3
C
d, J = 7.6 Hz), 129.9 (s, br), 129.6 (d, J = 5.3) 128.6 (s, br), 128.0 (d, J =
CONCLUSIONS
■
3
1
.0 Hz), 127.9 (s, br), 127.45 (s), 126.7 (d, J = 3.4 Hz), 125.61 (s, br),
We have reported herein a thorough investigation of the
reductive cleavage of commercially available BINAP to form
lithiated dinaphthylphospholide, along with a suggested
mechanism. Its reactivity and potential are demonstrated by
examples of one-pot substitution to silylated and alkylated
dinaphthylphospholes, bearing a variety of functional groups
useful for further functionalization. We have also confirmed and
31
1
24.46 (s, br), 38.2 (d, J = 63.9 Hz); P{ H} NMR (CDCl , 162 MHz)
3
−1
δP 41.8 (s); IR (neat, νmax, cm ) 3039, 2939, 1497, 1334, 1232, 1205,
1175, 1145, 881, 818, 748, 700, 657; HRMS C H OPNa mass calcd
27
19
413.1071, mass found 413.1071.
7
-(Pent-4-yn-1-yl)-7H-benzo[e]naphtho[2,1-b]phosphindole 7-
oxide (7b): synthesized as a yellow solid (32.7 mg, 56%); R (75/25,
f
1
EtOAc/hexanes) 0.29; H NMR (CDCl , 500 MHz) δ 8.17 (d, J = 8.6
3
H
Hz, 2H), 8.05 (dd, J = 8.1, 3.4 Hz, 2H), 7.98 (q, J = 8.2 Hz, 4H), 7.64 (t, J
7.5 Hz, 2H), 7.53 (dd, J = 8.4, 7.0 Hz, 2H), 2.38−2.24 (m, 2H), 2.20
extended the usefulness of DFT calculations for predicting 31
P
=
chemical shifts as a tool for identifying unknown compounds and
intermediates in synthesis.
13
(td, J = 6.9, 2.5 Hz, 2H), 1.91 (t, J = 2.7 Hz, 1H), 1.68 (s br, 2H);
C
NMR (CDCl , 125 MHz) δ 137.3 (s), 130.3 (s, br), 128.9 (s), 128.8
3
C
(
s), 128.0 (s), 127.6 (s), 125.8 (s), 123.9 (s, br), 82.6 (s), 69.6 (s), 29.1
3
1
1
EXPERIMENTAL SECTION
(d, J = 69.9 Hz), 21.4 (d, J = 2.1 Hz), 19.5 (d, J = 16.7 Hz); P{ H}
■
−1
General Methods. Starting materials and reagents were purchased
from commercial sources and were used without any prior purification
unless otherwise noted. Both TMS triflate and TBS triflate were purified
by distillation under an inert atmosphere. All solvents were dried and
NMR (CDCl , 162 MHz) δ 43.7 (s); IR (neat, νmax, cm ) 3250, 3043,
3 P
2944, 1445, 1338, 1186, 1147, 966, 883, 821, 757, 729, 657; HRMS
20OP mass calcd 367.1252, mass found 367.1248.
7-Isopropyl-7H-benzo[e]naphtho[2,1-b]phosphindole 7-oxide
7c): synthesized as a pale yellow solid (22.0 mg, 40%); R (80/20,
C H
25
1
13
(
distilled using standard methods. H NMR and C NMR spectra were
f
1
EtOAc/hexanes) 0.30; H NMR (CDCl , 500 MHz) δ 8.15 (d, J = 8.6
collected at 30 °C in CDCl using a 500 MHz spectrometer (500 and
3
H
3
Hz, 2H), 8.07−7.91 (m, 6H), 7.63 (t, J = 8.2, 2H), 7.52 (t, J = 8.4 Hz,
2
MHz) δ 137.12 (s), 129.9 (s, br), 128.8 (s), 128.7 (s), 128.0 (s), 127.4
1
25 MHz, respectively), and referenced using the residual solvent signal
H), 2.43 (sept, J = 7.3 Hz, 1H), 1.12 (s, 6H); 13C NMR (CDCl , 125
13
31
(
δ 7.27, δ 77). C{ P} NMR spectra were recorded on a 600 MHz
3
H
C
31
spectrometer at 150.81 MHz. The majority of P NMR spectra were
carried out in THF with a sealed capillary tube containing OPPh in d -
C
(
s), 125.7 (s), 124.4 (s, br), 110.0 (s), 29.0 (d, J = 70.5 Hz), 15.69 (s);
3
6
31
31
1
−1
benzene as an internal standard (δ 25). P NMR of the phosphole
P{ H} NMR (CDCl
3 P
, 162 MHz) δ 51.3 (s); IR (neat, νmax, cm )
P
oxides was carried out in CDCl and referenced to an 85% aqueous
3050, 2965, 2926, 2869, 1662, 1443, 1338, 1257, 1198, 1178, 1133,
3
31
solution of H PO (δ 0). P NMR spectra were collected at 30 °C
1026, 886, 814, 749, 692, 654; HRMS C23H20OP mass calcd 343.1252,
3
4
P
using a 400 MHz spectrometer (161.72 MHz). The IR spectra were
recorded using a FT-IR spectrometer equipped with an ATR accessory
with a diamond top plate. High-resolution mass spectra were obtained
using ESI in either positive or negative mode with a Brucker Daltonics
Epics III 4.7 T Fourier transform ion cyclotron resonance mass
mass found 343.1236.
7-Allyl-7H-benzo[e]naphtho[2,1-b]phosphindole 7-oxide (7d):
synthesized as a yellow solid (23.0 mg, 42%); R (80/20, EtOAc/
f
1
hexanes) 0.26; mp 213.9−214.5 °C; H NMR (CDCl , 500 MHz) δ
8.16 (d, J = 8.6 Hz, 2H), 8.07−7.92 (m, 6H), 7.63 (t, J = 7.1 Hz, 2H),
3
H
6
527
dx.doi.org/10.1021/jo4006393 | J. Org. Chem. 2013, 78, 6522−6528

The Journal of Organic Chemistry
Article
7
2
.53 (ddd, J = 8.3, 6.8, 1.3 Hz, 2H), 5.64 (ddtd, J = 17.5, 10.1, 7.5, 5.4 Hz,
Dr. Hazel Cox and Mr. Gavin Roffe for support in the theoretical
side of our research. We thank Dr. Iain Day for the NMR service
and Dr. Ali Abdul Sadaa for mass spectroscopy and useful
discussions.
13
H), 5.12−4.93 (m, 2H), 3.01 (s br, 2H); C NMR (CDCl , 125 MHz)
3
δ 137.2 (s), 130.1 (s, br), 128.8 (s), 128.7 (s), 128.7 (s), 128.0 (s),
C
1
Hz), 35.8 (d, J = 66.3 Hz); P{ H} NMR (CDCl , 162 MHz) δ 40.8
27.5 (s), 126.7 (d, J = 8.9 Hz), 125.7 (s), 124.2 (s, br), 120.6 (d, J = 12
31
1
3
P
−1
(
s); IR (neat, νmax, cm ) 3043, 2936, 1444, 1420, 1334, 1221, 1183,
REFERENCES
1
146, 1027, 985, 915, 882, 818, 774, 749, 663; HRMS C H OP mass
■
23
18
(
1
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-Cyclobutyl-7H-benzo[e]naphtho[2,1-b]phosphindole 7-oxide
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4
1
H), 2.96 (td, J = 8.9, 4.2 Hz, 1H), 2.76−2.02 (m, 4H), 1.96 (dt, J = 9.9,
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3
C
28.8 (s), 128.7 (s), 128.0 (s), 127.4 (s), 125.6 (s), 124.3 (s, br), 33.64
31
1
(
d, J = 71.2 Hz), 22.1 (d, J = 5.2 Hz), 20.4 (d, J = 15.7 Hz); P{ H}
−1
NMR (CDCl , 162 MHz) δ 43.9 (s); IR (neat, ν , cm ) 3045, 2979,
3
P
max
2
933, 2858, 1572, 1443, 1339, 1182, 1148, 1003, 907 812, 749; HRMS
C H OP mass calcd 355.1246, mass found 355.1252.
24
20
(
E)-7-(3,7-Dimethylocta-2,6-dien-1-yl)-7H-benzo[e]naphtho[2,1-
b]phosphindole 7-oxide (7f): synthesized as a pale yellow solid (26.4
1
mg, 37%); R (80/20, EtOAc/hexanes) 0.33; H NMR (CDCl , 500
f
3
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206.
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H
Hz, 2H), 7.50 (t, J = 7.7 Hz, 2H), 5.01−4.76 (m, 2H), 3.00 (d, J = 15.5
Hz, 2H), 1.78−1.59 (m, 4H), 1.57 (s, 3H), 1.40 (s, 3H), 1.27 (d, J = 3.9
(
8) Shimada, T.; Kurushima, H.; Cho, Y.; Hayashi, T. J. Org. Chem.
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Nyulaszi, L.; Hissler, M.; Reau, R. J. Am. Chem. Soc. 2012, 134, 6524−
2
13
Hz, 3H); C NMR (CDCl , 125 MHz) δ 141.2 (d, J = 12.5 Hz), 137.1
3
C
(
s), 131.5 (s), 130.0 (s, br), 128.7 (s), 127.9 (s), 127.4 (s), 125.6 (s),
(
1
24.1 (s, br), 123.7 (s), 111.7 (d, J = 8.7 Hz), 39.4 (d, J = 2.9 Hz), 34.1
31
1
(
(
2
s), 30.5 (d, J = 67.2 Hz), 17.5 (s), 16.4 (d, J = 2.8 Hz); P{ H} NMR
(
̋
−1
CDCl , 162 MHz) δ 42.6 (s); IR (neat, ν , cm ) 3192. 3050, 2967,
3
P
max
́
́
918, 2850, 1443, 1336, 1178, 1140, 1026, 970, 864, 815, 748, 730;
6
527.
HRMS C H OP mass calcd 437.2029, mass found 437.2040.
30
30
(12) Morisaki, Y.; Aiki, Y.; Chujo, Y. Macromolecules 2003, 36, 2594−
7
-(4-(tert-Butyl)benzyl)-7H-benzo[e]naphtho[2,1-b]phosphindole
2
597.
7
2
-oxide (7g): synthesized as a pale yellow solid (13.5 mg, 19%); R (80/
f
(
13) Bulbrook, M.; Chu, M.; Deane, K.; Doyle, R. J.; Hinc, J.; Peterson,
C.; Salem, G.; Thorman, N.; Willis, A. C. Dalton Trans. 2010, 39, 8878−
881.
1
0, EtOAc/hexanes) 0.24; mp 179.2−183.3 °C; H NMR (CDCl , 500
3
MHz) δ 8.08−7.91 (m, 6H), 7.89−7.71 (m, 1H), 7.60 (dd, J = 8.1, 6.9
H
8
Hz, 2H), 7.53−7.39 (m, 2H), 6.95 (d, J = 8.0 Hz, 2H), 6.77 (dd, J = 8.2,
(
14) Garner, A. Y.; Tedeschi, A. A. J. Am. Chem. Soc. 1962, 84, 4734−&.
2
1
1
(
1
.4 Hz, 2H), 3.49 (d, J = 67.8 Hz, 2H), 1.12 (s, 9H); 13C NMR (CDCl ,
3
(15) Dogan, J.; Schulte, J.; Swiegers, G.; Wild, S. B. J. Org. Chem. 2000,
25 MHz) δ 149.6 (s), 137.1 (s), 129.2 (d, J = 5.2 Hz), 128.6 (s, br),
27.8 (d, J = 7.4 Hz), 127.4 (s), 125.6 (s, br), 124.8 (d, J = 3.0 Hz), 124.4
s, br), 37.6 (d, J = 64.3 Hz), 34.3 (s), 31.2 (s); P{ H} NMR (CDCl ,
62 MHz) δ 42.5 (s); IR (neat, ν , cm ) 3051, 2960, 2906, 2898,
P max
C
6
(
7
(
5, 951−957.
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31
1
3
−1
1
507, 1455, 1336, 1206, 1142, 1024, 882, 812, 746, 723; HRMS
C H NaOP mass calcd 469.1692, mass found 469.1712.
31
27
(
Crystallography. All crystallographic details for compounds 7a−e
respectively CCDC 916549−916553) are provided in the Supporting
Information.
(
(
1
(
ASSOCIATED CONTENT
Supporting Information
■
Chem. 1994, 59, 6363−6371.
*
S
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4782−4782.
1
13
31
Figures, tables, and CIF files giving H, C and P NMR spectra
for all alkylated phosphole oxides, X-ray crystallographic data of
phosphole oxides, and DFT calculation details, including
geometries and energies for calculated structures, shielding
tensors, and full scan data for the PES calculations. This material
is available free of charge via the Internet at http://pubs.acs.org.
(
(
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AUTHOR INFORMATION
Corresponding Author
E.M.E.V.: tel, +44 (0) 1273 678621; e-mail, e.m.e.viseux@
sussex.ac.uk.
(27) Holz, J.; Monsees, A.; Kadyrov, R.; Bo
̈
rner, A. Synlett 2007, 599−
■
*
6
02.
(
(
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported in part by a Bader award. We also thank
Dr. John Turner and Dr. Ian Crossley for useful discussions and
6
528
dx.doi.org/10.1021/jo4006393 | J. Org. Chem. 2013, 78, 6522−6528