Synthesis of P-stereogenic BINAP bissulfide analogues

Article abstract of DOI:10.1016/j.tetasy.2011.09.007

A synthetic route to BINAP disulfide analogues with chirality on one of the phosphorus atoms was developed. The synthesis of these ligands was achieved by step-wise palladium and nickel-catalysed coupling reactions of the precursor binaphthyl triflate wit

Full text of DOI:10.1016/j.tetasy.2011.09.007

Tetrahedron: Asymmetry 22 (2011) 1680–1686
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Tetrahedron: Asymmetry
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Synthesis of P-stereogenic BINAP bissulfide analogues
Eoin Rafter a, Jimmy Muldoon b, Helge Müller Bunz c, Declan G. Gilheany a,
⇑
a Centre for Synthesis and Chemical Biology, Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
b NMR Facility, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland
c X-ray Crystallography Laboratory, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland
a r t i c l e i n f o
a b s t r a c t
Article history:
A synthetic route to BINAP disulfide analogues with chirality on one of the phosphorus atoms was devel-
oped. The synthesis of these ligands was achieved by step-wise palladium and nickel-catalysed coupling
reactions of the precursor binaphthyl triflate with secondary phosphines and phosphine oxides, respec-
tively. C2-Unsymmeric BINAP bissulfide analogues with the same aryl substituents were also synthesized
for the sake of comparison. Preliminary studies of the reduction of these sulfides to the free phosphines
are also described.
Received 12 August 2011
Accepted 13 September 2011
Available online 1 November 2011
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
only recently receiving attention are phosphine sulfides.6,7 These
compounds are not strong
r-donating ligands such as phosphines
The presence of an axially chiral backbone on ligands for catal-
ysis is one of the best known ways to induce enantioselectivity.1–3
Its effectiveness has been proven by the high selectivities achieved
by such ligands as BINAP1,2 and MOP3,4 for hydrogenations and
hydrosilylations, respectively. As a result of the success of these
and other axially chiral ligands, at present, the development of
novel axially chiral ligands is one of the most significant areas of
research in homogeneous catalysis.2,3,8
or carbenes and for this reason their use has only been rarely
studied. Until recently these ligands were only used in situations
where their hemi-labile behaviour was desired. Thus, Aizawa
et al. have proven that bis-phosphine sulfide ligands can be active
for the Suzuki–Miyaura coupling8,9 and research by Saigo et al. and
Hashimoto et al. have shown that phosphine sulfides can be more
active than phosphines for bishydroxycarbonylation.10 Previously,
Faller et al. had also disclosed mixed phosphine/phosphine sulfide
ligands and shown them to be useful for asymmetric allylic
aminations.11–13 For these reasons the synthesis of novel phos-
phine sulfide ligands presents an interesting task for catalysis
research.
The use of P-stereogenicity to induce enantioselectivity has
been used in chiral catalysis with great success for decades with
such ligands as DIPAMP achieving exceptional results.14–17 Despite
the known success of these and axially chiral ligands, there are still
a few cases where both axial and central chirality have been com-
bined.18–21 This is due to the difficulty that the synthesis of such
ligands and the separation of their diastereomers can present.
PPh2
PPh2
PPh2
OMe
(R)-BINAP
(R)-MOP
Despite the huge success of such axially chiral phosphine
ligands in catalysis, a limiting factor in their usefulness has been
their relative air sensitivity, since many of the well known ligands
are prone to oxidation under ambient conditions. Thus, another
motif in catalysis research has been the search for air-stable
ligands for catalysis.5 A class of possible air stable ligands that is
S
PPh2
PR1R2
PPh2
PR1R2
S
⇑
Corresponding author. Fax: +353 1 716 21277.
E-mail address: declan.gilheany@ucd.ie (D.G. Gilheany).
BINAP analogues
BINAP sulfide analogues
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.09.007

E. Rafter et al. / Tetrahedron: Asymmetry 22 (2011) 1680–1686
1681
As part of our work towards P-stereogenic analogues of axially
chiral ligands,22,23 we herein report the synthesis of a series of
disulfide analogues of the BINAP ligand with differing substituents
on the two phosphorus atoms and with chirality at one phospho-
rus. It was our hope that through the procedures that we have
developed we could provide not only new phosphine sulfide li-
gands for catalysis but also a more facile method for the synthesis
and separation of ligands combining two forms of chirality.
Therefore we also describe preliminary studies of the desulfuri-
sation to the respective phosphines, some of which would carry
both axial and central chirality thereby representing a hybrid of
the BINAP ligand and the DIPAMP ligand.17,14–16
catalysed method is that, for steric reasons, only one phosphorus
moiety is introduced. For the same steric reasons, oxide 2 has then
to be reduced to phosphine triflate 3 to allow space for the second
(nickel catalysed) coupling to occur. However, this reduction
proved to be a difficult task because of degradation of the remain-
ing triflate group in various ways, often occurring as a side reac-
tion. After extensive testing of a number of methods, selective
reduction of phosphine was achieved using PhSiH3 under strictly
anhydrous conditions.27
The nickel catalysed coupling to triflate 3 was then performed
with a series of secondary phosphines (Chart 1). The majority of
these are known compounds and were made without incident by
the addition of the appropriate Grignard reagents to either trichlo-
rophosphine or dichlorophenylphosphine to give the doubly
substituted chlorophosphine R1R2PCl, which was then reduced
with LiAlH4 and the crude material distilled to purity under high
vacuum.
2. Results and discussion
2.1. Synthesis of phosphine sulfides
Methylphenylphosphine 10 requires a different route because
double addition of the methyl Grignard reagent to dichlorophenyl-
phosphine occurs readily even at low temperatures (ꢀ78 °C). In-
stead, again according to the literature, dichlorophenylphosphine
was converted to dimethyl phenylphosphonite, rearranged by the
Arbuzov reaction with MeI to methyl methylphenylphosphinate,28
which was reduced with LiAlH4 to give the secondary phosphine.
For the coupling of the secondary phosphines to phosphine tri-
flate 3, we followed the nickel catalysed procedure originally re-
ported by Cai et al. for the synthesis of BINAP.29 This has been
widely used since it was first reported and has proven a versatile
method for the synthesis of novel phosphines.24,30 We expected
many of the resultant bisphosphines to be easily oxidised in air
to the bis-phosphine oxides. Although it would be possible to sep-
arate the diastereomers as their respective oxides, this was not de-
sired as the subsequent reduction could result in racemisation
about the phosphorus centre, as previously observed in our
group.23,22 Since we were targeting phosphine sulfides anyway,
we therefore treated the crude products of the coupling reaction
directly with sulfur.
This was achieved by step-wise palladium and nickel-catalysed
coupling reactions of phosphine oxides and secondary phosphines,
respectively (Scheme 1). Methods such as this using sequential
metal catalysed phosphine oxide and phosphine coupling reactions
have been used to synthesise other BINAP analogues, such as BINA-
PAS and BINAPP0.24,25
PPh2
PAr2
PPh2
AsPh2
(R)-BINAPP'
(R)-BINAPAS
The synthesis, as shown in Scheme 1, begins with the triflation
of enantiomerically pure (R)-BINOL using triflic anhydride in the
presence of a base to give bis-triflate 1 and its coupling to diphen-
ylphosphine oxide using the method reported by Morgans et al.26
to give phosphine oxide triflate 2. An advantage of this palladium
The results of the coupling reaction (as measured by the sulfide
yields) are given in Table 1 and the resultant isolated products are
listed in Chart 2. It can be seen that the efficiency of the coupling,
already not very high, is significantly reduced as the bulk of the
OTf
OH
(i)
OH
OTf
OTf
(ii)
P(O)Ph2
1
2
(R)-BINOL
(iii)
S
(iv)
PR1R2
PPh2
S
OTf
PPh2
3
Scheme 1. Reagents: (i) TfO2, pyridine, (ii) Ph2P(O)H, Pd(OAc)2, DPPB, EtNiPr2, (iii) PhSiH3, (iv) (1) R1R2PH, [NiCl2(dppe)], DABCO, (2) S8.

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E. Rafter et al. / Tetrahedron: Asymmetry 22 (2011) 1680–1686
hydrogenolysed starting material. We can rule out an electronic ef-
fect31–33 in these latter cases because the methylphenyl case 10
gives the best yield and would have similar electronic properties.
The bis-phosphine sulfides were then purified by column chro-
matography to afford the pure compounds. In the case of 11 and
12, but not 13, it was possible to separate the individual diastereo-
mers. For the methylphenyl derivative 11 crystals could be ob-
tained which were suitable for X-ray analysis and assignment of
configuration (Fig. 1). However, we were unable to form suitable
crystals for any of the other analogues. In the cases of the more
hindered analogues 14 and 15, this was partly because their solu-
bility in most solvents was very poor. This poor solubility was pos-
sibly caused by decreased internal freedom of movement. Also
heavily arylated compounds in general can be quite insoluble.
The 1H NMR of the di-o-tolyl phosphine bissulfide 15 unexpect-
edly showed a significant difference in the shifts of the methyl
peaks along with discernable differences in linewidth. Similar dif-
ferences in linewidth were observed at lower temperatures in the
31P NMR spectra. Such differences may be attributable to the
restricted rotation of substituents about their bonds to phospho-
rus—the environment around the phosphorus in these compounds
is crowded due to the presence of sulfur and large ortho-substituted
aryl rings (see Fig. 2). Further work is currently being planned to
investigate these phenomena.
P
H
P
H
P
H
OMe
OMe
OMe
4
5
6
P
H
P
H
P
H
7
8
9
P
H
10
Chart 1. Secondary phosphines synthesised.
Table 1
Yields from nickel coupling reactions to triflate 3 according to Scheme 1(iv) using the
secondary phosphines from Chart 1a
2.2. Tests of the reduction of phosphine sulfides
Phosphines
Yield from coupling reactionb
Cyclohexylphenylphosphine 4
tert-Butylphenylphosphine 5
Di-o-tolylphosphine 6
Nil
Nil
8%
The important issue in the reduction of these compounds is that
there should be conversion with stereoretention at the P-stereo-
genic centre; hence we sought reductants that did not require
heating. We chose Raney nickel and triethylphosphine (Et3P) and
tested both in the reduction of triphenylphosphine sulfide at room
temperature. With Raney nickel this proceeded well with a 60%
conversion in 16 h (as judged by 31P NMR), while Et3P gave effec-
tively no reduction after 86 h.
Di-anisylphosphine 7
4%
o-Tolylphenylphosphine 8
Anisylphenylphosphine 9
Methylphenylphosphine 10
29%
32%
36%
a
Reactions carried out under nitrogen in flame dried glassware.
Yields judged by yield of converted phosphine sulfide retrieved.
b
We then tested Raney nickel further on BINAP-S2.34 We sought
this further test as it has been observed that the reduction of
BINAPO2 (bisoxidised BINAP) is far more difficult than a regular tri-
aryl phosphine oxide.35 Indeed, BINAPS2 desulfurisation was much
slower than that of triphenylphosphine sulfide. However, it did still
give the half-reduced product (80%) after four days at room
temperature.
coupling phosphine increases. Thus, although the introduction of
one ortho-substituted aryl group in cases 8 and 9 does not have a
very detrimental effect, the second ortho-substituted group in 6
and 7 causes a large loss of yield. In the cases of cyclohexylphenyl
and tert-butylphenyl, 4 and 5, the only observed product was the
S
S
S
PPh2
PPh2
PPh2
S
P
S
P
S
P
MeO
12
11
13
S
S
PPh2
PPh2
OMe
S
P
S
P
14
15
MeO
Chart 2. Bis-phosphine sulfides synthesised, P-stereogenic centres marked in red.

E. Rafter et al. / Tetrahedron: Asymmetry 22 (2011) 1680–1686
1683
hexylphenyl case (one of the problem cases earlier) and we were
also able to achieve chromatographic separation of the diastereo-
mers of phosphine oxide triflate 16 and crystallise for X-ray assign-
ment of the configuration at the phosphorus (Fig. 3). These
compounds had previously been reported but their specific stereo-
chemistry has not been fully assigned before.36
Figure 1. X-ray crystal structure of (R,R)-diastereomer of 2-(methylphenyl
phosphinothioyl)-20-(diphenylphosphinothioyl)-1,10-binaphthyl 11. The hydrogen
atoms are omitted for clarity.
O
P
S
P
S
S
P
S
P
O
Figure 3. X-ray crystal structure of (R,R)-(+)-2-cyclohexylphenylphosphinyl-20
((trifluoromethanesulfonyl)oxy)-1,10-binaphthyl 16.
However, we subsequently found that these compounds could
not be successfully reduced to their phosphines in the same man-
ner as diphenylphosphine oxide/triflate 2. We were not so worried
about epimerisation in the reduction because we could have car-
ried a mixture through to the sulfides, which we were confident
we could separate. Much more disappointing was that, in the case
of cyclohexylphenylphosphine oxide/triflate 16, the reduction of
the adjacent triflate group always occurred to some degree
(Scheme 2). Also in the case of anisylphenyl phosphine oxides,
the P-stereogenic centre was racemised in the reduction step.
These two hindrances in the route meant that any possible advan-
tage achieved by the early addition of the unsymmetrically substi-
tuted phosphorus moiety was lost.
Another alternative that we attempted involved purification of
the bis-phosphine products from the nickel catalysed coupling as
their respective boranes. This was simply achieved by switching
to a work up with borane–THF. However two interlinked issues
soon became apparent. Firstly and most importantly, the diaste-
reomers of bisphosphine boranes were inseparable by column
chromatography. Secondly they were unstable in air, slowly con-
verting to the bisphosphine oxides over time. This was due to
the establishment of an equilibrium between phosphine borane
and the free phosphine, which was then oxidised to the oxide over
Figure 2. Hindered environment around the phosphine sulfide.
Finally we tested one of the diastereomers of 2-(anis-
ylphenylphosphinothioyl)-20-(diphenylphosphinothioyl)-1,10-
binaphthyl 12. As expected, this reacted similarly to BINAPS2 with
a slow desulfurisation over several days. After 96 h, the 31P NMR of
the reaction showed both half-reduction products. We are cur-
rently investigating this reduction further in our laboratory.
2.3. Investigation of alternative routes
Due to the limitations in the nickel-catalysed coupling of the
bulky secondary phosphines, we investigated two other ap-
proaches for the synthesis of our target compounds. The first of
these involved the palladium-catalysed addition of the unsymmet-
rically substituted secondary phosphine (as the oxide) as the first
coupling in the synthesis (Scheme 2). We hoped then to reduce
to phosphine and add the diphenyl-substituted moiety by nickel
catalysis. Secondary phosphine oxides were synthesised using
the method of Busacca et al. or by direct air oxidation of a second-
ary phosphine and tested in the palladium coupling step.39 Indeed
the initial palladium-catalysed coupling worked well for the cyclo-
(i)
(ii)
OTf
OTf
OTf
P
OTf
P
Cy
H
P
Ph
Ph
Ph
Cy
Cy
O
16
Scheme 2. Alternative route via P-stereogenic oxide/triflate. Reagents: (i) CyPhP(O)H, Pd(OAc)2, DPPB, EtNiPr2, (ii) PhSiH3.
1

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E. Rafter et al. / Tetrahedron: Asymmetry 22 (2011) 1680–1686
time; through this dissociation and oxidation, what started out as a
clean phosphine borane would become a mixture of phosphine
borane, phosphine, and phosphine oxide.
binaphthyl (1.3 g, 2.2 mmol, 1.0 equiv) was added to a 100 mL
round bottomed flask equipped with an N2 inlet and stirring bar.
The solid reagent was dissolved in neat phenylsilane (11.7 g,
13.30 mL, 0.108 mol, 50.00 equiv). The solution was heated on a
110 °C oil bath and stirred overnight. The solution was allowed
to return to room temperature, and was charged with dry degassed
ethyl acetate (30 mL). The solvent was removed in vacuo. The yel-
low oily residue was redissolved in a 4:1 cyclohexane/ethyl acetate
solution (5 mL) and passed through a short pad of silica under a N2
flow. The pad was washed with 4:1 cyclohexane/ethyl acetate
solution (5 mL). The solvent was removed in vacuo to give the
crude product (1.26 g, 97% crude yield) as an off-white solid. The
product is prone to oxidation, and was therefore carried through
to the next step without further purification. 1H NMR (300 MHz,
CDCl3) d 7.82 (d, J = 9.1, 1H, ArH), 7.73 (d, J = 8.5, 1H, ArH), 7.68
(d, J = 8.3, 2H, ArH), 7.47–6.85 (m, 17H, ArH), 6.81 (d, J = 8.3, 1H,
ArH) ppm; 19F NMR (282 MHz, CDCl3) d ꢀ74.7 ppm; 31P NMR
(121 MHz, CDCl3) d ꢀ13.0 ppm.
This lability of our phosphine boranes compared to the other
known stable phosphine boranes must be due to the reduced Lewis
basicity of our phosphines. In the majority of cases where boranes
are used to protect a phosphine, there is one or more alkyl (elec-
tron donating) substituent on phosphine.32,37,33 Our tri-arylphos-
phines would not have as much electron density present on
phosphine, reducing their basicity and weakening the P–B bond
in the borane.
3. Conclusion
In conclusion, we have shown that the synthesis of certain P-
stereogenic BINAP sulfide analogues can be achieved through a
short synthesis without arduous separation required. This synthe-
sis also presents a possible approach to novel phosphine ligands
and potential hybrid DiPAMP/BINAP ligands. However, of particu-
lar note are the steric limitations in the use of nickel catalysed
phosphine coupling reactions. Several ways to overcome this lim-
itation were investigated with only limited success. Initial tests
of the reduction of phosphines sulfides to their respective phos-
phines have also been carried out, with promising results.
4.2. General procedure for the synthesis of phosphine sulfides
A dry 100 mL J.YoungÒ’s flask was charged with [NiCl2(dppe)]
(30.0 mg, 0.17 mmol, 0.10 equiv) using a glovebox apparatus. The
flask was charged with dry degassed DMF (10 mL) and the second-
ary phosphine (1.0 mmol, 0.6 equiv). The solution was heated for
60 min in a 100 °C oil bath after which the reaction was charged
with a solution of (R)-(+)-2-diphenylphosphino-20((trifluorometh-
anesulfonyl)oxy)-1,10-binaphthyl(0.97 g, 1.65 mmol, 1.00 equiv)
and DABCO (0.74 g, 6.60 mmol, 4.00 equiv) in dry degassed DMF
(15 mL). The dark red solution was maintained at 100 °C for
4. Experimental
4.1. General
X-ray diffraction experiments on 11 and 16 were carried out at
100 K, for 16 on a Bruker SMART diffractometer using Mo Ka radi-
ation, k = 0.71073 Å and for 11 on a SuperNova. A Diffractometer by
Agilent Technologies (formerly known as Oxford Diffraction) using
60 min and then
a second aliquot of phosphine (1.0 mmol,
0.6 equiv) was added. The solution was stirred at 100 °C for 16 h
and the final aliquot of phosphine (1.0 mmol, 0.6 equiv) was added.
The reaction was maintained in a 100 ° oil bath for 86 h after which
it was allowed to cool to 60 °C and then the solvent was removed
in vacuo. The residue was dissolved in dry degassed toluene after
which sulfur (0.53 g, 16.5 mmol, 10.0 equiv) was added to the mix-
ture. The mixture was stirred for 16 h and the solvent was removed
in vacuo. The crude product was purified by column
chromatography.
Cu Ka radiation, k = 1.54184 Å. Absorption corrections were based
on equivalent reflections and structures refined against all F2 data.
Crystallographic data for the structural analyses have been depos-
ited with the Cambridge Crystallographic Data Centre [ref. CCDC
838736 and 838737].
All reactions were carried out under a N2 atmosphere in dry
glassware using Schlenk-line techniques. Air and moisture sensi-
tive liquids and solutions were transferred via syringe. All ‘dry’ sol-
vents were dried and distilled by standard procedures38 or through
Grubbs dry solvent apparatus. All ‘anhydrous’ solvents or solutions
were purchased dry from chemical suppliers. Solutions were con-
centrated under reduced pressure by rotary evaporator. Chromato-
graphic purification38 of products was accomplished on Merck
Silica Gel 60 (0.040–0.063 mm).
The standard NMR spectra were recorded at 25 °C on Varian
VNMRS 300, 400, and 500 MHz spectrometers. 13C spectra with
31P decoupling were performed at 30 °C on a Varian VNMRS
600 MHz spectrometer equipped with a triple resonance probe.
Tetramethylsilane was used as an internal standard for routine
1H and 13C spectra and 85% H3PO4 for 31P spectra. 31P and 13C NMRs
were performed proton decoupled.
4.2.1. 2-(Methylphenylphosphinothioyl)-20-(diphenylphos-
phinothioyl)-1,10-binaphthyl 11
(R,R)-Diastereomer: 1st elute: 193 mg, 18.2% yield [a]D = +3 (c 1,
CH2Cl2); IR (KBr, cmꢀ1) 898, 1096, 1433, 1634, 2361, 3050, 3461;
1H NMR (600 MHz, CDCl3) d 8.44 (ddd, J = 13.4, 6.6, 3.2 Hz, 2H,
ArH), 8.00 (dd, J = 8.8, 2.0 Hz, 1H, ArH), 7.90 (d, J = 8.2 Hz, 1H,
ArH), 7.74–7.63 (m, 3H, ArH), 7.60 (dd, J = 8.8, 1.6 Hz, 1H, ArH),
7.58–7.51 (m, 5H, ArH), 7.46 (td, J = 7.2, 1.6 Hz, 1H, ArH), 7.40
(td, J = 7.5, 3.0 Hz, 3H, ArH), 7.33–7.19 (m, 5H, ArH), 7.11–7.04
(m, 1H, ArH), 6.84 (td, J = 8.0, 3.2 Hz, 2H, ArH), 6.79–6.68 (m, 2H,
ArH), 1.65 (d, J = 13.8 Hz, 3H, PCH3) ppm;13C NMR (151 MHz,
CDCl3) (P–C decoupled) d 141.4, 136.8, 135.3, 134.4, 134.2, 133.5,
133.2, 133.0, 132.7, 132.19, 132.15, 132.12, 132.07, 132.03,
131.98, 131.3, 131.1, 130.5, 129.9, 129.8, 129.33, 129.29, 129.2,
129.0, 128.7, 128.53, 128.49, 128.4, 128.31, 128.27, 127.7, 127.31,
127.28, 127.2, 127.10, 127.07, 126.0, 110.3, 22.6 (PCH3) ppm; 13C
FT-IR data were collected using a Varian 3100 FT-IR spectrome-
ter. Routine electrospray mass spectra were obtained on a Micro-
mass Quattro Spectrometer and high resolution mass spectra
were carried out on a Micromass LCT system at UCD.
NMR (126 MHz, CDCl3)
d 141.4, 136.8, 135.6, 134.9, 134.6,
134.17, 134.15, 134.0, 133.6, 133.5, 133.3, 133.2, 133.1, 132.8,
132.7, 132.6, 132.24, 132.15, 132.11, 132.06, 132.03, 131.98,
131.30, 131.27, 131.25, 130.5, 130.5, 130.2, 129.9, 129.5, 129.4,
129.3, 129.0, 128.88, 128.7, 128.61, 128.55, 128.5, 128.3, 128.2,
127.72, 127.69, 127.6, 127.3, 127.2, 127.1, 126.9, 126.0, 22.8
(PCH3), 22.3 (PCH3) ppm; 31P NMR (243 MHz, CDCl3) d 43.2,
39.8 ppm; m/z (% intensity) [MH]+ 625.5 (100), [MH+1]+ 626.5.
(50), [MH+2]+ 627.5 (20); HRMS calcd for [MH]+ = C39H31P2S2
Compounds 1 and 2 were prepared according to the literature
procedures.26,3
4.1.1. Synthesis of (R)-2-diphenylphosphino-20 ((trifluoro-
methanesulfonyl)oxy)-1,10-binaphthyl 3
The procedure of Hiemstra et al. was incorporated.27 (R)-(+)-2-
Diphenylphosphinyl-20-((trifluoromethanesulfonyl)oxy)-1,10-

E. Rafter et al. / Tetrahedron: Asymmetry 22 (2011) 1680–1686
1685
625.1342; found 625.1326. X-ray quality crystals were obtained by
slow diffusion of hexane into a solution in dichloromethane, see
Figure 1.
128.45, 128.0, 127.9, 127.7, 127.6, 127.50, 127.48, 127.42, 127.37,
127.3, 127.2, 127.13, 127.08, 126.9, 126.12, 126.08, 125.0, 123.9,
120.8, 112.3, 55.7 (OCH3) ppm; 13C NMR (151 MHz, CDCl3) d
160.4 (COMe), 139.7, 139.6, 134.7, 134.6, 134.2, 134.1, 133.72,
133.70, 133.6, 133.50, 133.48, 133.32, 133.30, 133.2, 133.0, 132.9,
132.8, 132.3, 132.2, 132.18, 132.15, 131.6, 130.57, 130.55, 130.5,
130.19, 130.17, 130.07, 130.05, 130.0, 129.9, 129.8, 129.3, 128.5,
128.4, 128.1, 127.98, 127.95, 127.9, 127.7, 127.6, 127.5, 127.4,
127.26, 127.23, 127.14, 127.09, 126.9, 126.1, 125.0, 124.1, 123.6,
120.8, 120.7, 112.29, 112.25, 55.7 (OCH3) ppm; 31P NMR
(243 MHz, CDCl3) d 43.8, 40.4 ppm; m/z (% intensity) [MH]+ 717.6
(100), [MH+1]+ 718.5 (50) .
(S,R)-Diastereomer: 2nd elute: 185 mg, 18% yield; [
a]
D = ꢀ86 (c
0.25, CH2Cl2); IR (KBr, cmꢀ1) 711, 897, 1097, 1434, 1635, 3464. 1H
NMR (500 MHz, CDCl3) d 8.20 (dd, J = 14.0, 8.8 Hz, 1H, ArH), 7.86
(dd, J = 8.8, 1.6 Hz, 1H, ArH), 7.81 (d, J = 8.2 Hz, 1H, ArH), 7.75 (dt,
J = 12.9, 7.9 Hz, 3H, ArH), 7.65 (d, J = 8.9 Hz, 1H, ArH), 7.58 (d,
J = 8.2 Hz, 1H, ArH), 7.50–7.35 (m, 5H, ArH), 7.34–7.27 (m, 3H,
ArH), 7.18 (dd, J = 8.2, 6.7 Hz, 1H, ArH), 7.11–7.02 (m, 5H, ArH),
6.95 (t, J = 7.6 Hz, 1H, ArH), 6.91–6.85 (m, 3H, ArH), 6.82 (d,
J = 8.6 Hz, 1H, ArH), 1.81 (d, J = 13.7 Hz, 3H, PCH3) ppm;13C NMR
(151 MHz, CDCl3) (P–C decoupled) d 139.7, 136.0, 134.7, 134.0,
133.8, 133.6, 133.42, 132.41, 132.37, 132.33, 132.28, 132.24,
132.19, 131.9, 131.5, 131.0, 130.54, 130.51, 130.4, 130.0, 129.3,
129.1, 128.63, 128.59, 128.2, 128.04, 128.01, 127.9, 127.8, 127.7,
127.6, 127.5, 127.30, 127.26, 127.12, 127.07, 126.4, 90.6, 21.6
(PCH3) ppm; 13C NMR (126 MHz, CDCl3) d 138.8, 138.72, 138.69,
138.66, 134.99, 134.95, 134.1, 133.4, 132.8, 132.7, 132.6, 132.5,
132.4, 131.5, 131.4, 131.3, 131.2, 130.9, 130.8, 130.2, 130.04,
130.02, 129.7, 129.6, 129.5, 129.44, 129.42, 129.11, 129.07, 129.0,
128.3, 128.2, 128.1, 127.7, 127.6, 127.2, 127.1, 127.0, 126.8,
126.71, 126.69, 126.6, 126.5, 126.28, 126.27, 126.1, 126.0, 125.4,
20.8 (PCH3), 20.4 (PCH3) ppm; 31P NMR (243 MHz, CDCl3) d 44.2,
39.8 ppm; m/z (% intensity) [MH]+ 625.5 (100), [MH+1]+ 626.5.
(50), [MH+2]+ 627.5 (20); HRMS calcd for [MH]+ = C39H31P2S2
625.1342; found 625.1326.
4.2.3. 2-(o-Tolylphenylphosphinothioyl)-20-(diphenylphosphino-
thioyl)-1,10-binaphthyl 13
Crude mixture: 31P NMR (162 MHz, CDCl3) d 43.61, 42.51, 41.80,
41.05 ppm; m/z (% intensity) phosphine oxide/sulfide [MH]+ 685.7
(100), bisphosphine sulfide [MH]+ 701.4 (100), [MH+1]+ 702.7 (50).
4.2.4. (R)-2-(Bisanisylphosphinothioyl)-20-(diphenylphosphino-
thioyl)-1,10-binaphthyl 14
[a
]
D = ꢀ61 (c 1, CH2Cl2); IR (KBr, cmꢀ1) 470, 500, 6923, 7477,
1020, 1959, 2278, 2929, 3051, 5446; (very broad peaks were ob-
served in all NMRs, notably some peaks were not visible in 13C as
a result) 1H NMR (600 MHz, CDCl3) d 7.90 (d, J = 8.6 Hz, 1H, ArH),
7.84–6.10 (m, 29H, ArH), 3.95 (s, 3H, OCH3), 3.40 (s, 3H, OCH3)
ppm; 13C NMR (151 MHz, CDCl3) (P–C decoupled) d 159.8 (COMe),
136.7, 133.9, 133.6, 133.2, 133.1, 133.0, 132.6, 132.0, 131.3, 130.5,
130.2 129.83, 127.82, 127.6, 127.4, 127.3, 127.1, 127.0, 126.7,
125.0, 124.9, 123.2, 121.1, 120.4, 110.2, 109.8, 54.5 , 29.7 ppm;
13C NMR (151 MHz, CDCl3) d 159.8, 140.9, 136.7, 134.8, 133.91,
133.89, 133.7, 133.6, 133.1, 133.01, 132.94, 132.7, 132.1, 132.0,
131.4, 131.3, 130.6, 130.5, 130.2, 129.9, 129.8, 128.1, 127.9,
127.74, 127.66, 127.5, 127.4, 127.14, 127.05, 126.7, 125.5, 125.4,
124.9, 123.6, 123.0, 121.1, 120.4, 119.7, 119.6, 113.0, 109.82,
109.78, 54.5 (OCH3), 29.7 (OCH3) ppm; 31P NMR (243 MHz, CDCl3)
d 42.0, 39.0 ppm; m/z (% intensity) [MH]+ 747.6 (100) [MH +1]+
748.6 (50); HRMS calcd for [MH]+ = C46H37O2P2S2 747.1710; found
747.1689.
4.2.2. 2-(o-Anisylphenylphosphinothioyl)-20-(diphenylphos-
phinothioyl)-1,10-binaphthyl 12
Diastereomer A 1st elute: 98 mg, 8.3% yield; [a]D = +56.6 (c 0.5,
CH2Cl2); IR (KBr, cmꢀ1) 707, 1095, 1269, 1432, 1470, 1632, 2361,
3950, 3445.; 1H NMR (400 MHz, CDCl3) d 8.02–7.90 (m, 3H, ArH),
7.74–7.54 (m, 8H, ArH), 7.45–7.27 (m, 10H, ArH), 7.13 (m, 4H,
ArH), 7.01 (d, J = 8.5 Hz, 1H, ArH), 6.85 (t, J = 7.5 Hz, 1H, ArH),
6.72 (dd, J = 7.8, 5.6 Hz, 1H, ArH), 6.59 (t, J = 7.2 Hz, 1H, ArH),
6.35 (d, J = 8.5 Hz, 1H, ArH), 6.26 (t, J = 7.6 Hz, 1H, ArH), 3.43 (s,
3H, OCH3) ppm; 13C NMR (151 MHz, CDCl3) (P–C decoupled) d
159.8 (COMe), 141.3, 139.5, 136.9, 136.2, 134.5, 134.0, 133.9,
133.7, 133.3, 133.2, 133.11, 133.07, 132.8, 132.50, 132.46, 132.1,
131.6, 131.2, 130.7, 130.5, 130.1, 123.0, 129.6, 128.4, 128.1,
127.9, 127.8, 127.55, 127.45, 127.4, 127.2, 126.9, 126.4, 125.94,
125.90, 125.7, 125.03, 124.99, 121.2, 118.0, 110.3, 110.0, 54.5
(OCH3) ppm; 13C NMR (151 MHz, CDCl3) d 159.8 (COMe), 141.3,
139.5, 136.9, 136.8, 136.5, 135.9, 134.8, 134.2, 134.00, 133.99,
133.92, 133.90, 133.73, 133.72, 133.5, 133.3, 133.3, 133.2, 133.1,
133.0, 132.9, 132.8, 132.54, 132.47, 131.7, 131.6, 131.3, 131.2,
130.8, 130.7, 130.47, 130.45, 130.3, 130.2, 130.1, 130.04, 129.97,
129.64, 129.56, 128.4, 128.24, 128.17, 128.1, 127.9, 127.83,
127.75, 127.5, 127.4, 127.3, 127.2, 126.88, 126.87, 126.4, 126.0,
125.9, 125.7, 125.0, 121.3, 121.2, 118.3, 117.7, 110.01, 109.97,
105.0, 54.5 (OCH3) ppm; 31P NMR (243 MHz, CDCl3) d 43.5,
41.9 ppm. m/z (% intensity) [MH]+ 717.6 (100), [MH+1]+ 718.5
(50); HRMS calcd for [MH]+ = C45H35OP2S2 717.1605; found
717.1605.
4.2.5. (R)-2-(Bis-o-tolylphosphinothioyl)-20-(diphenylphosphino-
thioyl)-1,10-binaphthyl 15
Analysis of the crude material: [a]D = +26.5 (c 1, CH2Cl2); IR
(KBr, cmꢀ1) 713, 1096, 1434, 1630, 2342, 3050, 3435.; 1H NMR
(600 MHz, CDCl3) d 7.88 (d, J = 2.2 Hz, 2H, ArH), 7.85–7.65 (m,
5H), 7.58 (d, J = 10.2 Hz, 1H, ArH), 7.53–7.42 (m, 3H, ArH), 7.41–
7.26 (m, 6H, ArH), 7.22 (d, J = 5.9 Hz, 3H, ArH), 7.15 (d,
J = 24.8 Hz, 2H, ArH), 6.96 (dd, J = 25.1, 19.2 Hz, 3H, ArH), 6.74 (s,
1H, ArH), 6.60 (s, 1H, ArH), 6.53–6.29 (m, 3H, ArH), 3.02 (s, 3H,
CH3), 1.98 (s, 3H, CH3) ppm; 13C NMR (151 MHz, CDCl3) (P–C
decoupled) d 144.0, 143.0, 140.9, 140.5, 137.1, 135.8, 134.7,
134.0, 133.77, 133.2, 133.1, 132.8, 132.71, 132.65, 132.2,
131.9,131.4, 131.3, 131.1, 130.6, 130.4, 129.8, 129.5, 129.4, 128.5,
128.3, 128.21, 128.16, 127.83, 127.79, 127.75, 127.4, 127.3,
127.12, 127.10, 126.8, 126.4, 126.1, 125.6, 125.36, 125.31, 110.3,
107.4, 24.7 (CH3), 24.0 (CH3) ppm; 13C NMR (151 MHz, CDCl3) d
164.2, 153.1, 144.0, 143.0, 140.9, 140.8, 140.5, 137.3, 136.7,
135.7, 134.72, 134.66, 134.2, 134.0, 133.7, 133.2, 132.8, 132.7,
132.66, 132.2, 132.2, 131.3, 131.1, 131.0, 130.6, 130.5, 130.4,
129.8, 129.7, 128.8, 128.23, 128.15, 127.8, 127.7, 127.39, 127.37,
127.34, 127.28, 127.1, 126.8, 126.4, 126.0, 125.6, 125.5, 125.4,
125.3, 105.0, 24.7 (CH3), 24.0 (CH3) ppm; 31P NMR (121 MHz,
CDCl3) d 43.6, 41.1 ppm; m/z (% intensity) [MH]+ 715.6 (100),
[MH+1]+ 716.6 (50,), [MH+2]+ 717.6 (20); HRMS calcd for
[MH]+ = C46H37P2S2 715.1812; found 715.1834.
Diastereomer B 2nd elute: 131 mg, 11% yield; [
a
]
D = ꢀ43 (c 0.5,
CH2Cl2); IR (KBr, cmꢀ1) 707, 1096, 1272, 1470, 1636, 2360, 3052,
3462; 1H NMR (600 MHz, CDCl3) d 7.87 (dd, J = 12.8, 7.8 Hz, 2H,
ArH), 7.73 (m, 3H, ArH), 7.67–7.60 (m, 4H, ArH), 7.55–7.40 (m,
3H, ArH), 7.37 (dd, J = 13.5, 7.6 Hz, 2H, ArH), 7.33–7.28 (m, 2H,
ArH), 7.23–7.16 (m, 4H, ArH), 7.14 (t, J = 7.0 Hz, 1H, ArH), 7.09
(dd, J = 7.4, 5.1 Hz, 2H, ArH), 6.99–6.86 (m, 6H, ArH), 6.51 (s, 2H,
ArH), 3.65 (s, 3H, OCH3) ppm; 13C NMR (151 MHz, CDCl3)(P-C
decoupled) d 160.4 (COMe), 139.7, 139.6, 134.7, 134.6, 134.1,
133.7, 133.5, 133.3, 133.2, 132.9, 132.82, 132.77, 132.3, 132.22,
132.18, 132.1, 131.9, 130.6, 130.2, 130.10, 130.06, 123.0, 129.53,

1686
E. Rafter et al. / Tetrahedron: Asymmetry 22 (2011) 1680–1686
4.2.6. Synthesis of (+)-2-cyclohexylphenylphosphinyl-20
References
((trifluoromethanesulfonyl)oxy)-1,10-binaphthyl 16
1. Noyori, R.; Takaya, H. Acc. Chem. Res. 1990, 23, 345–350.
2. Noyori, R. Acta Chem. Scand. 1996, 50, 380–390.
3. Uozumi, Y.; Tanahashi, A.; Lee, S. Y.; Hayashi, T. J. Org. Chem. 1993, 58, 1945–
1948.
4. Uozumi, Y.; Kawatsura, M.; Hayashi, T. Org. Synth. 2002, 78, 1–7.
5. Imamoto, T.; Sugita, K.; Yoshida, K. J. Am. Chem. Soc. 2005, 127, 11934–11935.
6. Pellissier, H. Tetrahedron 2007, 63, 1297–1330.
7. Lam, F. L.; Kwong, F. Y.; Chan, A. S. C. Chem. Commun. 2010, 46, 4649–4667.
8. Sen-ichi, A.; Mitsuyoshi, T.; Sakuma, M.; Kubo, A. Chem. Lett. 2007, 36, 130.
9. Aizawa, S.-i.; Majumder, A.; Yokoyama, Y.; Tamai, M.; Maeda, D.; Kitamura, A.
Organometallics 2009, 28, 6067–6072.
10. Hayashi, M.; Takezaki, H.; Hashimoto, Y.; Takaoki, K.; Saigo, K. Tetrahedron Lett.
1998, 39, 7529–7532.
11. Faller, J. W.; Wilt, J. C.; Parr, J. Org. Lett. 2004, 6, 1301–1304.
12. Faller, J. W.; Wilt, J. C. Org. Lett. 2005, 7, 633–636.
13. Faller, J. W.; Wilt, J. C. Organometallics 2005, 24, 5076–5083.
14. Knowles, W. S.; Sabacky, M. J.; Vineyard, B. D.; Weinkauff, D. J. J. Am. Chem. Soc.
1975, 97, 2567–2568.
15. Vineyard, B. D.; Knowles, W. S.; Sabacky, M. J.; Bachman, G. L.; Weinkauff, D. J. J.
Am. Chem. Soc. 1977, 99, 5946–5952.
16. Knowles, W. S.; Sabacky, M. J.; Vinyard, B. D. J. Chem. Soc., Chem. Commun. 1972,
10–11.
17. Knowles, W. S. Angew. Chem., Int. Ed. 2002, 41, 1998–2007.
18. Taylor, A. M.; Altman, R. A.; Buchwald, S. L. J. Am. Chem. Soc. 2009, 131, 9900–
9901.
19. Hamada, T.; Buchwald, S. L. Org. Lett. 2002, 4, 999–1001.
20. Rubio, M.; Vargas, S.; Suárez, A.; Álvarez, E.; Pizzano, A. Chem. Eur. J. 2007, 13,
1821–1833.
21. Rubio, M.; Suarez, A.; Alvarez, E.; Bianchini, C.; Oberhauser, W.; Peruzzini, M.;
Pizzano, A. Organometallics 2007, 26, 6428–6436.
22. Higham, L. J.; Clarke, E. F.; Muller-Bunz, H.; Gilheany, D. G. J. Organomet. Chem.
2005, 690, 211–219.
23. Kerrigan, N. J.; Dunne, E. C.; Cunningham, D.; McArdle, P.; Gilligan, K.;
Gilheany, D. G. Tetrahedron Lett. 2003, 44, 8461–8465.
24. Gladiali, S.; Dore, A.; Fabbri, D.; Medici, S.; Pirri, G.; Pulacchini, S. Eur. J. Org.
Chem. 2000, 2861–2865.
25. Cho, S. Y.; Shibasaki, M. Tetrahedron Lett. 1998, 39, 1773–1776.
26. Kurz, L.; Lee, G.; Morgans, D.; Waldyke, M. J.; Ward, T. Tetrahedron Lett. 1990,
31, 6321–6324.
27. Botman, P. N. M.; Fraanje, J.; Goubitz, K.; Peschar, R.; Verhoeven, J. W.; van
Maarseveen, J. H.; Hiemstra, H. Adv. Synth. Catal. 2004, 346, 743–754.
28. Michaelis, A.; Kaehne, R. Ber. Deut. Chem. Gesell. 1898, 31, 1048–1055.
29. Cai, D.; Payack, J. F.; Bender, D. R.; Hughes, D. L.; Verhoeven, T. R.; Reider, P. J. J.
Org. Chem. 1994, 59, 7180–7181.
30. Shimizu, H.; Nagasaki, I.; Saito, T. Tetrahedron 2005, 61, 5405–5432.
31. Mitterhofer, F.; Schindlbauer, H. Monatsh. Chem. 1967, 98, 206–213.
32. Tolman, C. A. Chem. Rev. 1977, 77, 313.
33. Strohmeier, W.; Müller, F.-J. Chem. Ber. 1967, 100, 2812–2821.
34. Chapman, C. J.; Frost, C. G.; Gill-Carey, M. P.; Kociok-Köhn, G.; Mahon, M. F.;
Weller, A. S.; Willis, M. C. Tetrahedron: Asymmetry 2003, 14, 705–710.
35. Wu, H.-C.; Yu, J.-Q.; Spencer, J. B. Org. Lett. 2004, 6, 4675–4678.
36. Lei, Z.-Y.; Ma, G.-N.; Shi, M. Eur. J. Org. Chem. 2008, 2008, 3817–3820.
37. Mitterhofer, F.; Schindlbauer, H. Monatsh. Chem. 1967, 98, 206–213.
38. Harwood, L. M.; Moody, C. J.; Percy, J. M. Experimental Organic Chemistry, 2nd
ed.; Blackwell Science Ltd: England, 1999.
A modified version of the procedure reported by Hayashi et al.
was employed.3 The solid reagents (R)-2,20-bis((trifluoromethane-
sulfonyl)oxy)-1,10-binaphthyl (1.0 g, 1.8 mmol, 1.0 equiv), cyclo-
hexylphenylphosphine oxide (0.75 g, 3.63 mmol, 2.00 equiv),
palladium diacetate (31 mg, 0.2 mmol, 0.1 equiv), and bis(diphen-
ylphosphino)butane (78.0 mg g, 0.73 mmol, 0.10 equiv) were
charged to a flame dried 250 mL round bottomed flask under a
N2 atmosphere. The flask was charged with dry degassed dimethyl
sulfoxide (30 mL). Next, N2 was bubbled through the solution for
30 min after which diisopropylethylamine (1.25 mL, 0.93 g,
7.23 mmol, 4.00 equiv) was added. This was stirred for 16 h on a
100 °C oil bath. The solution turned a dark red colour. The progress
of the reaction was monitored by 19F NMR. When the reaction was
deemed complete, it was allowed to cool to 60 °C and the solvent
was removed in vacuo. The dark red residue was dissolved in
diethyl ether (30 mL) and was washed with H2O (3 ꢁ 10 mL). The
aqueous layers were combined and extracted with diethyl ether
(20 mL). The organic layers were combined and dried over Mg2SO4.
The solvent was removed in vacuo to give the crude product as a
yellow solid. This was purified by column chromatography (2:1
ethyl acetate: cyclohexane) to give the product diastereomers as
an off-white solid. Crystals were obtained of the (R,R)-diastereo-
mer by slow evaporation of DCM from
diastereomer.
a solution of the
(R,R)-Diastereomer: 0.32 g 33% yield. 1H NMR (300 MHz, CDCl3)
d 8.21–8.07 (m, 2H, ArH), 8.01 (d, J = 9.1 Hz, 1H, ArH), 7.98–7.89
(m, 2H, ArH), 7.51 (dd, J = 11.1, 3.9 Hz, 1H, ArH), 7.48–7.40 (m,
1H, ArH), 7.36 (d, J = 9.1 Hz, 1H, ArH), 7.32–7.21 (m, 2H, ArH),
7.17–6.97 (m, 6H, ArH), 6.74 (d, J = 8.5 Hz, 1H, ArH), 1.42 (s, 10H,
CH2) ppm; 31P NMR (121 MHz, CDCl) d 33.4 ppm (lit.13 34.6); 19F
NMR (282 MHz, CDCl3) d ꢀ75.2 ppm.
(R,S)-Diastereomer: 0.25 g 23% yield. 1H NMR (300 MHz, CDCl3)
d 8.13 (t, J = 9.2 Hz, 1H, ArH), 7.99 (d, J = 7.6 Hz, 1H, ArH), 7.87 (d,
J = 9.1 Hz, 1H, ArH), 7.79 (d, J = 8.0 Hz, 1H, ArH), 7.69 (d,
J = 8.2 Hz, 1H, ArH), 7.36 (d, J = 9.1 Hz, 2H, ArH), 7.22
(ddd, J = 12.8, 11.7, 7.6 Hz, 3H, ArH), 7.14–7.05 (m, 1H, ArH),
7.05–6.83 (m, 5H, ArH), 6.76 (d, J = 8.5 Hz, 1H, ArH), 1.90 (s, 10H,
ArH) ppm; 31P NMR (121 MHz, CDCl3) d 34.5 ppm (lit.13 35.7);
19F NMR (282 MHz, CDCl3) d ꢀ74.8 ppm.
Acknowledgement
39. Busacca, C. A.; Lorenz, J. C.; Grinberg, N.; Haddad, N.; Hrapchak, M.; Latli, B.;
Lee, H.; Sabila, P.; Saha, A.; Sarvestani, M.; Shen, S.; Varsolona, R.; Wei, X.;
Senanayake, C. H. Org. Lett. 2005, 7, 4277–4280.
This research was partly supported by the Science Foundation
Ireland under grant 06/RFP/CHO013.