Synthesis and evaluation of P-chirogenic monodentate binaphthyl phosphines

Article abstract of DOI:10.1016/j.tetlet.2012.07.136

P-Chirogenic monodentate binaphthyl phosphines were prepared in five steps from enantiomerically pure BINOL. This approach supposes the utilization of two methods previously developed in our group, the formation of secondary phosphine oxide, and the reduction of tertiary phosphine oxide using the association of tetramethyldisiloxane and Ti(OⁱPr)₄. During the last reduction step, only the formation of the more stable diastereoisomer was observed. This product was employed as a ligand for the palladium catalyzed hydrosilylation of styrene to afford the corresponding alcohol with high yield and enantiomeric excess.

Full text of DOI:10.1016/j.tetlet.2012.07.136

Tetrahedron Letters 53 (2012) 5984–5986
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis and evaluation of P-chirogenic monodentate binaphthyl phosphines
Marie-Christine Duclos a, Yuttapong Singjunla a, Christelle Petit a, Alain Favre-Réguillon a,
Erwann Jeanneau b, Florence Popowycz a, Estelle Métay a, Marc Lemaire a,
⇑
a Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, UMR-CNRS 5246, Equipe Catalyse Synthèse Environnement, Université de Lyon, Université Claude Bernard-Lyon 1,
Bâtiment Curien, 43 Bd du 11 novembre 1918, F-69622 Villeurbanne Cedex, France
b Centre de Diffractométrie Henri Longchambon, Université Claude Bernard Lyon1, 43 Bd du 11 novembre 1918, 69622 Villeurbanne cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
P-Chirogenic monodentate binaphthyl phosphines were prepared in five steps from enantiomerically
pure BINOL. This approach supposes the utilization of two methods previously developed in our group,
the formation of secondary phosphine oxide, and the reduction of tertiary phosphine oxide using the
association of tetramethyldisiloxane and Ti(OiPr)4. During the last reduction step, only the formation
of the more stable diastereoisomer was observed. This product was employed as a ligand for the palla-
dium catalyzed hydrosilylation of styrene to afford the corresponding alcohol with high yield and enan-
tiomeric excess.
Received 18 May 2012
Revised 26 July 2012
Accepted 31 July 2012
Available online 28 August 2012
Keywords:
Phosphine
TMDS
Ó 2012 Published by Elsevier Ltd.
Catalysis
P-chirogenic
Hydrosilylation
Asymmetric catalysis represents an extremely powerful tool to
induce high enantiomeric purity expected in molecules of high-va-
lue added from industry. To induce asymmetry with excellent enan-
tio-/diastereoselectivities, chiral diphosphines such as (S,S)-DIOP,1
(R,R)-DIPAMP2, and well-known atropoisomeric (R)-BINAP3 have
been largely employed by academic research groups. The first indus-
trial process using BINAP was performed by Takasago International
Corporation for the production of menthol in 1984.4 Inspired by the
success of this ligand, a wide range of atropoisomeric ligands have
been thus described for these last twenty years.5
In particular Hayashi has devised the methoxyphosphine ligand
family (MOP), organized through a heterobinaphthyl scaffold with
biaryl axial chirality.6 In parallel, ligands bearing the chirality on
phosphorus atom were developed.7
Classical methods for the synthesis of optically pure P-chirogen-
ic phosphines referred to the separation of a pair of so-formed dia-
stereoisomers (phosphines or boron-phosphinites)8 or to the use of
a chiral inducer such as ephedrine also called the Jugé method.9
Evans described the asymmetric deprotonation of prochiral aryl di-
methyl phosphine boranes.10 Preliminary research performed in
the laboratory reported the synthetic access to chiral phosphorus
ligand derived from Binap.10
First part on the synthesis aimed to obtain a diversity of non-
symmetric secondary phosphine oxides. A new one-pot methodol-
ogy was recently reported in our group, by the reaction of dichlo-
rophenylphosphine with methylimidazole as a base, generating
the ionic liquid 1-methylimidazolium chloride separated by simple
extraction.11 This methodology inspired from the BASIL process
(Biphasic Acid Scavenger using Ionic Liquids)12 was applied to
the synthesis of isopropyl(phenyl)phosphine oxide 1 in 73% yield.
The route to innovative MOP ligands begins with the pallado-cat-
alyzed coupling of isopropylphenyl phosphine oxide 1 with (R)-2,20-
bis(trifluoromethanesulfonyloxy)-1,10-binaphthyl (obtained from
(R)-Binol reacting with triflic anhydride (1.05 equiv) in pyridine/
dichloromethane).13 The optimized coupling conditions require
the use of Pd(OAc)2 (10 mol %) as a catalyst, diphenylphosphinobu-
tane (10 mol %) as a ligand, diisopropylethylamine (4 equiv) as a
base in pre-heated anhydrous DMSO at 100 °C for 16 h affording
compound 2 in 65% yield with around 1:1 ratio of both diastereoiso-
mers (Scheme 1). At this stage of the synthesis, the diastereoisomers
(20 and 200) were successfully separated by flash chromatography in
respectively 30% and 35% yields.
Both compounds 20 and 200 were independently submitted to
hydrolysis of the triflate group. Subsequent methylation conditions
on crude phenol intermediates provided 30 and 300, respectively in
63% and 50% yields. Final step implied the reduction of phosphine
oxides into non-symmetrical mono-phosphine ligands. The reduc-
tion of phosphine oxide into the corresponding phosphine has
been largely described in the literature with the use of LiAlH4,14 DI-
BAL-H,15 BH3ꢀMe2S,16 Ph2SiH2,17 and HSiCl3.18 Specifically, Gilhe-
In this Letter we report the last results obtained on the synthe-
sis and evaluation of monophosphine with double chirality (axial
along with chiral phosphorus).
⇑
Corresponding author. Tel.: +33 4 72 43 14 07; fax: +33 4 72 43 14 08.
E-mail address: marc.lemaire@univ-lyon1.fr (M. Lemaire).
0040-4039/$ - see front matter Ó 2012 Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tetlet.2012.07.136

M.-C. Duclos et al. / Tetrahedron Letters 53 (2012) 5984–5986
5985
Pd(OAc)2 (10 mol%)
1. 3N NaOH (4 eq),
dppb (10 mol%),
O
O
H
DIPEA (5 eq.)
DMSO, 100°C, 16 h
1,4-dioxane / MeOH (1/2),
18 hours, rt
OTf
OTf
P
iPr
P
iPr
P
O
(R)
Ph
OTf
Ph
OMe
iPr
2. K2CO3 (4 eq.), MeI (4 eq.)
acetone, reflux, 16 h
(2 eq)
1
(1 eq.)
2' (dia 1): 30%
2''(dia 2): 35%
3' (dia 1): 63%
3'' (dia 2): 50%
Scheme 1. Synthetic scheme of phosphine oxides.
any already studied the reduction of P-chirogenic MOP-oxides to P-
chirogenic MPOs with different reducing agents, and only the use
of Si2Cl6 prevent the epimerisation.19 In our continuing efforts to
find new alternate reducing agents in a sustainable approach,
regarding the criteria of toxicity and security, the already in-use
methods cited above are no more compatible with future industrial
development. Indeed boron and aluminum salts as well as silanes
are reported to be toxic. Metal hydrides react with strong evolution
of heat when exposed to either water or air. Silanes have the po-
tential of redistributing themselves in pyrophoric SiH4 gas. In this
context, hydrosiloxanes represent an alternative hydride source in
comparison with other classical methods, with a significant advan-
tage on the security and ease of handling parameters. Hydrosilox-
anes are low viscous liquids, soluble in most of the organic
solvents, sluggish to water and air. Taking advantage of these
attractive properties, 1,1,3,3,-tetramethyldisiloxane (TMDS) was
investigated in the laboratory on miscellaneous functional groups
to evaluate its potential as a reducing agent.20 The reduction of
phosphine oxide was already optimized in our laboratory and best
conditions were defined as following: 10 mol % of Ti(OiPr)4
1.25 equiv of TMDS at 60 °C with 10 wt % of Na2SO4 as a desiccant.
Experiments realized on the MOP ligand oxide pushed us to define
new conditions. Phosphine oxide 30 was treated by one equivalent
of titanium tetraisopropoxide in the presence of a large excess of
1,1,3,3,-tetramethyldisiloxane in toluene at room temperature
during 72 h providing compound 40 in 30% recrystallisation yield.
Reduction was also performed on the other 300 diastereoisomer
and the corresponding phosphine was collected in 47% after
recrystallisation (Scheme 2).
OTf
OTf
(1 eq.)
(R)
Pd(OAc)2 (10 mol%)
dppb (10 mol%),
O
H
P
Cy
DIPEA (5 eq.)
P
O
Ph
DMSO, 100°C, 16 h
Cy
OTf
5' (dia 1): 26%;
5'' (dia 2): 40%
1. 3 N NaOH (4 eq),
1,4-dioxane / MeOH (1/2),
18 hours, rt
2. K2CO3 (4 eq.), MeI (4 eq.)
acetone, reflux, 16 h
Ti(OiPr)4 (1 eq)
TMDS (10 eq)
toluene,
O
P
Cy
P
Cy
rt, 72 h
Ph
Ph
OMe
OMe
7' (dia 1): 25%;
7'' (dia 2): 52%
6' (dia1): 48%;
6'' (dia 2): 50%
Scheme 3.
were noticed in the reduction step, the chemical shifts of the phos-
phorus NMR of products 60 and 600 were different while the same
was observed for both 70 and 700. The X-ray analysis confirmed
the formation of a unique diastereoisomer during the reduction
step. (Fig. 1)
The MOP ligands were thus evaluated for their activity on the
hydrosilylation reaction (Scheme 4 and Table 1). First step of
hydrosilylation was performed in the presence of allyl palladium
(II) chloride dimer (0.04 mol %) and a chiral phosphine ligand L⁄
(0.08 mol %).21 The investigation included the commercially avail-
able (R)-MOP ligand (also named as (R)-(+)-2-(diphenylphos-
phino)-20-methoxy-1,10-binaphthyl as an internal reference. In
the conditions settled up in our laboratory, the (R)-MOP ligand in-
duced a moderate enantioselectivity of 36%. This modest result
could be explained by the difference of temperature, Hayashi
If both diastereoisomers 30 and 300 display two different phos-
phorus NMR chemical shifts, the same one was observed for the
corresponding reduced products. This was confirmed by another
analytical technique. Indeed, both molecules 40 and 400 were crys-
tallized and analyzed through X-ray diffraction and the configura-
tion of phosphorus atom was clearly identified for both isopropyl
diastereoisomers. The X-ray study unfortunately reveals that the
reduction of 30 and 300 affords the same product with the same ste-
reochemistry. A complete inversion of the phosphorus configura-
tion took place during the reduction step to afford the formation
of the most stable substrate. In order to control if this phenomenon
was not due to the presence of isopropyl substituent, the cyclo-
hexyl derivative was also prepared following the same synthetic
approach (Scheme 3).
Similar results were obtained with the cyclohexyl pattern for
the conversion and isolated yield of each step. Same observations
Ti(OiPr)4 (1 eq)
TMDS (10 eq)
O
toluene,
rt, 72 h
P
iPr
P
iPr
Ph
OMe
Ph
OMe
3' (dia 1)
3'' (dia 2)
4' (dia 1): 30%
4'' (dia 2): 47%
Scheme 2. Reduction of phosphine oxide by TMDS/Ti(OiPr)4 system.
Figure 1. X-ray study of MOPs (R,S)-40 and (R,R)-70.

5986
M.-C. Duclos et al. / Tetrahedron Letters 53 (2012) 5984–5986
[PdCl(πC3H5)]2 (0.04 mol%)
H2O2 30% (10 eq), KF (6 eq)
OH
SiCl3
L* (0.08 mol%), HSiCl3 (1.2 eq)
KHCO3 (6 eq), THF, MeOH
rt, 18 h
rt, 16 h
Scheme 4. Conditions used for asymmetric hydrosilylation of styrene.
3. (a) Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.; Souchi, T.; Noyori,
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Table 1
Isolated yield and enantiomeric excess of the alcohol obtained after asymmetric
hydrosilylation of styrene with trichlorosilane catalyzed by palladium complexes
Entry
Ligand
Yield (%)
eea (%)
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Ligands in Asymmetric Catalysis: Synthesis and Applications; WILEY-VCH Verlag
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(R)-MOP
4
7
67
92
85
36
91
72
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Stereogenic Ligands in Enantioselective Catalysis; Royal Society of Chemistry,
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a
Determined by GC analysis on a Chiralcell column (70 °C during 3 min, increase
of 3 °C per min until 150 °C, 5 min at 150 °C).
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describing an excellent enantioselectivity of 92% by running the
reaction at 0 °C. In our case, our ligands are not sensitive to the
temperature as satisfactory enantioselectivities (respectively 91%
and 72%) were determined for ligands 4’ and 7’. This transforma-
tion is regioselective as only the branched silylated derivatives
were formed. The chirality of the alcohols (S) coming from the oxi-
dation of silyl derivatives was determined by GC analysis and by
co-injection with a reference. It was the same whatever be the chi-
rality of the phosphorus. These results are in agreement with the
literature data explaining the influence of the naphthyl ring of
the ligand which is close to the palladium.22 From previous results,
Hayashi6 assumed that the enantioselectivity during the hydrosily-
lation of styrene is related to the dihedral angle between the two
naphthyl rings in the binaphthyl skeleton which is controlled by
the steric bulkiness of the 20-substituent.23 In this work, the dihe-
dral angle is not controlled by the –OMe group indeed these values
are different (79.99 for compound 4, 84.94 for the R-MOP, and
89.93 for the 7) as a consequence these angles are not related to
the enantioselectivity.24 However, an electronic, a steric, and/or a
match/mismatch effect of the cyclohexyl and isopropyl groups
can explain the higher enantiomeric excess.
The MOP ligands (R,S)-40 and (R,R)-700 produce similar global ef-
fects on the scope of the hydrosilylation reaction, both on the yield
and the enantioselectivity. Also the most important result from
this study is that the configuration of the phosphorus atom is not
decisive for the asymmetric induction. Axial chirality is definitely
the most influential factor or the driving force to obtain efficiently
chiral secondary alcohols. Nevertheless, both electronic and/or ste-
ric effects seem important to increase the yield and selectivity. The
mechanism is currently under investigation.
22. Han, J. W.; Hayashi, T. Tetrahedron: Asymmetry 2010, 21, 2193–2197.
23. (a) Hayashi, T. Catal. Today 2000, 62, 3–15; (b) Kocovsky, P.; Vyskocil, S.;
Smrcina, M. Chem. Rev. 2003, 103, 3213–3246.
Acknowledgments
24. Crystal
data
for
(R,S)-2-(isopropylphenylphosphino)-20-methoxy-1,10-
We thank F. Albrieux, C. Duchamp, and N. Henriques from the
Centre Commun de Spectrométrie de Masse (ICBMS UMR-5246),
for the assistance and access to the Mass Spectrometry facilities.
binaphthyl 40:Molecular formula: C30H27OP, MW = 434.52, Orthorhombic,
space group P212121, a = 9.076 (1) Å, b = 15.049 (2) Å, c = 17.050 (2) Å,
V = 2328.8 (5) Å3, Z = 4, Dx = 1.239 Mg mꢁ3
,
l
= 0.14 mmꢁ1,T = 110 K,
F(000) = 920, Flack parameter: ꢁ0.18 (12), 17567 measured reflections, 5700
independent reflections (Rint = 0.056), CCDC deposition number : 871758.
Crystal data for (R,R)-2-(cyclohexylphenylphosphino)-20-methoxy-1,10-
binaphthyl 70: Molecular formula: C33H31OP, MW = 474.58, Orthorhombic,
P212121, a = 8.2439 (9) Å, b = 15.923 (2) Å, c = 19.648 (2) Å, V = 2579.1 (5) Å3,
References and notes
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2. (a) Knowles, W. S.; Sabacky, M. J. Chem. Commun. 1968, 1445–1446; (b)
Vineyard, B. D.; Knowles, W. S.; Sabacky, M. J.; Bachman, G. L.; Weinkauff, D. J. J.
Am. Chem. Soc. 1977, 99, 5946–5952.
Z = 4, Dx = 1.222 Mg mꢁ3 = 0.13 mmꢁ1, T = 110 K, Flack parameter: 0.07 (12),
, l
19324 measured reflections, 6237 independent reflections(Rint = 0.058), CCDC
deposition number 871759.