A synthetic approach to macrocyclic, chiral phosphane derivatives with crown-ether-like structures

Article abstract of DOI:10.1002/ejoc.200500455

(S,S)-Bis(2-hydroxypropyl)(phenyl)phosphane oxide has been prepared, either by ring-opening of (S)-propylene oxide with dilithio(phenyl)phosphane or by catalytic hydrogenation of bis(2-oxopropyl)(phenyl)phosphane oxide, promoted by ruthenium/MeO-BIPHEP. C

Full text of DOI:10.1002/ejoc.200500455

FULL PAPER
DOI: 10.1002/ejoc.200500455
A Synthetic Approach to Macrocyclic, Chiral Phosphane Derivatives with
Crown-Ether-Like Structures
Agnès Theil,[a] Julien Hitce,[a] Pascal Retailleau,[a] and Angela Marinetti*[a]
Keywords: Phosphorus / Crown compounds / Macrocyclic ligands
(S,S)-Bis(2-hydroxypropyl)(phenyl)phosphane oxide has
been prepared, either by ring-opening of (S)-propylene oxide
1-phospha-10-aza-18-crown-6 derivatives, the first examples
of optically pure, crown-ether-like, phosphorus-containing
with dilithio(phenyl)phosphane or by catalytic hydrogena- macrocycles. One of them has been characterised by X-ray
tion of bis(2-oxopropyl)(phenyl)phosphane oxide, promoted
diffraction study. Complexation of Na+ by the crown ether
by ruthenium/MeO-BIPHEP. Catalytic hydrogenation also al- moiety of the macrocyclic ring has been observed by 1H
lowed the enantioselective synthesis of (R,R)-bis(2-phenyl-2-
NMR analysis.
hydroxyethyl)(phenyl)phosphane oxide from the correspond-
ing diketone. These bis(β-hydroxyalkyl)phosphane deriva- (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
tives are suitable chiral starting materials for the synthesis of
Germany, 2006)
by Landis. They were evaluated in rhodium-promoted hy-
droformylation and hydrogenation reactions, with the aim
of exploiting hydrogen-bonding interactions with ammo-
nium cations.
Additional examples are bis(phosphinites) bearing
carbohydrate-based crown ether moieties, which have been
used in asymmetric hydrogenation reactions.[10]
In all the diphosphanes above, the phosphorus centre,
usually a diphenylphosphanyl group, is connected to the
crown ether moiety through carbon linkers. A conceivable
alternate approach to crown-ether-like phosphanes would
be to design macrocycles incorporating a phosphorus centre
in a polyoxygenated chain.
Introduction
The point of the use of functionalised phosphorus li-
gands in enantioselective catalysis is to create secondary in-
teractions between ligands, metal ions and/or substrates
during the catalytic cycles. According to Hayashi[1] and
Ito,[2] who first proposed and developed the concept, such
interactions should affect rates and selectivities, and should
also improve enantiocontrol by differentiating one dia-
stereomeric transition state over another. Consequently, a
variety of chiral phosphanes have been designed so as to
take advantage of hemilabile complexation processes,[3]
electrostatic interactions or hydrogen bonding[4,5] and Lewis
acid–base interactions.[6]
In this context, there have been reports of chiral phos-
phorus ligands in which the structural design is based on
selectivity-directing secondary interactions between a crown
ether function and ammonium or metal cations. Chiral
phosphane–crown ether hybrid ligands were first intro-
duced in Ito’s work.[7] These are ferrocenyl-based diphos-
phanes with planar and central chirality, bearing 1-aza-15-
crown-5, 1-aza-18-crown-6, 1,10-diaza-18-crown-6, or 1-
aza-21-crown-7 units at the ends of their pendant arms.
Electrostatic interactions between an encapsulated metal
cation and a negatively charged substrate should be ex-
pected when such ligands are used in, for instance, enantio-
selective palladium-catalysed allylic substitution reactions.
More recently, 1-aza-15-crown-5-functionalised bis(phos-
phites)[8] and ferrocenyldiphosphanes[9] have been prepared
This unprecedented strategy has been considered here,
and this manuscript outlines an enantioselective synthetic
approach to macrocyclic chiral phosphanes with crown-
ether-like structures.
Results and Discussion
Our synthetic strategy to macrocyclic phosphanes is
based on the use of a single, enantiomerically pure phos-
phorus synthon, easily integrable into a variety of macro-
cyclic structures (Scheme 1). The pseudo-C2-symmetric,
bis(2-hydroxyethyl)phosphane oxides 1 were therefore cho-
sen as the key starting materials.
The hydroxy groups of 1 should be easily alkylated to
introduce oxygen-containing chains of various lengths. The
terminal leaving groups X (X = halide) should react with
bifunctional nucleophiles in the final cyclisation step to af-
ford the desired macrocyclic phosphane oxides.
[a] Institut de Chimie des Substances Naturelles
CNRS UPR 2301
1, avenue de la Terrasse, 91198 Gif-sur-Yvette, France
Fax: + 33-1-69077247
Bis(2-hydroxyethyl)phosphanes of the general formula 1
have been prepared previously, in their racemic forms, by
E-mail: angela.marinetti@icsn.cnrs-gif.fr
154
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Macrocyclic, Chiral Phosphane Derivatives with Crown-Ether-Like Structures
FULL PAPER
As a general rule, ketones bearing functional groups that
would be able to coordinate the metal centre are likely to
allow high enantioselectivities in the ruthenium-promoted
hydrogenation reactions. β-Oxo phosphane oxides fulfil
such structural requirement, as the P=O groups usually dis-
play good coordinating properties toward transition metal
ions, and should thus be suitable substrates for asymmetric
hydrogenation reactions. This hypothesis proved to be cor-
rect, as shown in Scheme 3.
Scheme 1. Synthetic approach to macrocyclic phosphane oxides.
treatment of monosubstituted oxiranes with lithium salts of
primary phosphanes.[11] On the other hand, ring-opening
reactions of optically pure epoxides with phosphorus nu-
cleophiles have been applied to the synthesis of several en-
antiomerically pure β-hydroxyphosphane derivatives.[12]
The same method has been applied here to the stereoselec-
tive synthesis of the phosphane oxide 1a from (S)-propylene
oxide and phenylphosphane, as shown in Scheme 2. The re-
action proceeds with high regioselectivity, as the lithiated Scheme 3. Ruthenium-promoted enantioselective hydrogenation of
β-oxo phosphane oxides.
phosphane attacks essentially at the less substituted carbon
atom of the epoxide to afford (S,S)-bis(2-hydroxypro-
The catalytic hydrogenation of β-oxo phosphane oxides
pyl)(phenyl)phosphane. For this study, the trivalent phos-
was first tested on a model substrate, (2-oxopropyl)di-
phane was not isolated but was rather oxidised directly to
phenylphosphane oxide (2),[17] and was then applied to the
the corresponding phosphane oxide 1a.
phosphane oxides 4a[18] and 4b. Compound 4b[19] has been
prepared by treatment of dichloro(phenyl)phosphane with
the lithium enolate of acetophenone, as described in the
Exp. Sect.
The catalytic hydrogenation of 2 and 4 in the presence of
(S)-MeO-BIPHEP–ruthenium catalysts allowed quantita-
Scheme 2. Synthesis of the bis(2-hydroxypropyl)phosphane oxide
1a from propylene oxide.
tive and – for 4a and 4b – totally diastereoselective conver-
1
sions into 3, 1a and 1b, respectively, as confirmed by H
NMR analysis of the crude reaction mixture. Enantiomeric
The epoxide ring-opening reaction shown here represents excesses were established to be higher than 98% by chiral
a convenient approach to optically pure bis(β-hydroxyalkyl)- HPLC (see Exp. Sect.). The absolute configurations of the
phosphane derivatives, provided that two conditions are ful- stereogenic centres of 3 and 1a were assigned as (S) by com-
filled: the starting oxirane must be easily available, and the parison of the retention times and [α]D values with those of
ring-opening must be highly regioselective. This is not the known samples.[20] They are consistent with the predicted
case for styrene oxides, ring-openings of which with phos- stereochemical outcome of the hydrogenation reaction, ac-
phorus nucleophiles display poor regioselectivity.[12b] An al- cording to Noyori’s model.[16] By analogy, the absolute con-
ternative and unprecedented strategy has thus been worked figuration of 1b was tentatively assigned as (S,S).
out for the synthesis of the phenyl-substituted phosphane
The few examples given in Scheme 3 indicate that the
oxide 1b.
catalytic hydrogenation of β-oxo phosphane oxides pro-
The synthetic approach to 1b is based on the catalytic moted by atropoisomeric phosphane–ruthenium complexes
enantioselective hydrogenation of the corresponding dike- could represent a general and convenient approach for the
tone 4b, promoted by ruthenium–MeO-BIPHEP complexes enantioselective synthesis of phosphorus derivatives. It
(Scheme 3). The catalytic hydrogenation of functionalised complements other known methods based on catalytic
ketones, first introduced by Noyori and Takaya with BI- enantioselective transformations of prochiral phosphorus-
NAP as the chiral ligand,[13] has become a very powerful containing substrates.[21] For the purposes of this study, it
and widely used tool for the asymmetric synthesis of chiral represents a highly convenient procedure for the synthesis
alcohols.[14] High enantioselectivities are attained, notably of 1a and 1b.
in the hydrogenations of β-functionalised ketones such as
The second step of the sequence shown in Scheme 1 is
β-oxo esters,[13] β-amino ketones[13b] and β-oxo phosphona- the O-alkylation of both hydroxy functions of the phos-
tes[15] and others. According to the stereochemical model phane oxides
1
with polyoxygenated electrophiles
proposed by Noyori,[16] the efficient stereochemical control (Scheme 4), and so 2-(2-chloroethoxy)ethanol and its deriv-
is the result of the ability of these substrates to chelate the atives were selected as alkylating agents. Only triflate was
ruthenium centre in the enantiodetermining step of the found to be an acceptable leaving group for this displace-
catalytic cycle.
ment reaction by the sodium salts of 1. Diethyl ether is the
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155

A. Theil, J. Hitce, P. Retailleau, A. Marinetti
FULL PAPER
solvent of choice, while THF undergoes partial ring-open-
ing oligomerisation to afford contaminating side products.
In diethyl ether the desired phosphane oxides 5 are ob-
tained at room temperature in moderate to good yields.
Figure 1. ORTEP drawing of the crystal structure for compound
7b, showing 30% probability thermal ellipsoids. Hydrogen atoms
are omitted for clarity.
Table 1. Selected bond lengths [Å] and bond angles [°] for com-
pound 7b.
P–C(1)
1.805(6)
1.529(8)
1.429(7)
1.492(8)
1.508(9)
1.494(5)
1.606(5)
P–C(12)
1.808(6)
1.514(9)
1.426(7)
1.468(8)
1.510(8)
1.795(6)
1.772(6)
C(1)–C(2)
C(2)–O(2)
C(6)–N
C(2)–C(1A)
P–O(1)
C(12)–C(11)
C(11)–O(11)
C(7)–N
C(11)–C(1B)
P–C(1Ј)
Scheme 4. O-Alkylation reactions of the phosphane oxides 1 and
cyclisation reactions. Reagents and conditions: a) NaH, diethyl
ether, room temp. b) Cl(CH2)2O(CH2)2OTf, room temp. c) K2CO3,
BuOH, 110 °C. d) K2CO3, DMF, 150 °C.
N–S
S–C(1ЈЈ)
C(1)–P–C(12)
P–C(1)–C(2)
C(1)–C(2)–O(2)
C(1)–C(2)–C(1A) 109.9(5)
C(2)–O(2)–C(3) 115.3(5)
110.5(3)
114.4(4)
106.7(5)
C(6)–N–C(7)
O(1)–P–C(1Ј)
C(12)–C(11)–O(11) 107.1(5)
C(12)–C(11)–C(1B) 112.7(5)
C(11)–O(11)–C(10) 112.2(4)
117.8(6)
112.2(3)
Macrocyclic phosphane derivatives should be obtainable
from compounds 5 through taking advantage of the pres-
ence of chloride leaving groups in their reactions with suit-
able nucleophiles. Catechol was used first in the cyclisation
reaction, with the expected macrocyclic phosphane oxide 6
being obtained, albeit in low yields regardless of the reac-
tion conditions applied.
The most marked shifts of the NMR signals were ob-
Better results were obtained by treatment of 5 with tosyl- served when NaBPh4 was added to CDCl3/MeOD solutions
amine in DMF at reflux in the presence of K2CO3 as the of the macrocyclic hosts 7a or 7b, which is indicative of
base. The 1-phospha-10-aza-18-crown-6 derivatives 7a and efficient bonding of sodium cations (see Figure 2).
1
7b were isolated in acceptable yields after purification by
All signals in the δ = 2–5 ppm region of the H NMR
column chromatography.
spectrum (i.e., signals for the CH2 and CH protons of the
Structural characterisation of 7b was performed by X-ray macrocyclic ring) are shifted by up to 0.4 ppm when
diffraction studies. An ORTEP drawing and selected bond 1 equiv. of NaBPh4 is added. The methyl substituent in the
angles and distances are given in Figure 1; and Table 1, N-tosyl moiety also experiences a slight downfield shift,
respectively.
from δ = 2.40 to 2.45 ppm. The 31P NMR chemical shift of
Compounds 7 represent a new class of chiral, pseudo-C2- 7b is not significantly affected by addition of the sodium
symmetric, macrocyclic phosphane oxides that are potential salt, with a Δδ of only 0.3 ppm. As a Δδ of about 8 ppm
receptors for metal ions, ammonium salts and other sub- was observed previously upon coordination of a P(O) func-
strates. Enantiomeric recognition could be expected in such tion to a sodium salt,[23e] it may be assumed that the P(O)
complexation processes.[22]
As far as we are aware, no enantiomerically pure phos- cess here.
function of 7b does not contribute to the coordination pro-
phane oxides with crown-ether-like structures have been de-
Addition of (R)- and (S)-[1-(1-naphthyl)ethyl]ammonium
scribed before, although several examples of achiral deriva- chloride induces only very small changes in the NMR spec-
tives have been reported.[23]
trum of 7b, while the spectroscopic data of 7a remain al-
In order to examine the complexing ability of 7 we com- most unchanged in the presence of these ammonium salts.
1
pared, in qualitative experiments, the H NMR spectra of In the case of 7b, in which signals on the “left-side”, aro-
the macrocyclic phosphane oxides alone and in the presence matic portion of the spectrum are the most affected, it may
of potential guests {sodium tetraphenylborate and [1-(1- be tentatively assumed that π-stacking between aromatic
naphthyl)ethyl]ammonium chloride}.
rings is the main host–guest interaction taking place here,
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Macrocyclic, Chiral Phosphane Derivatives with Crown-Ether-Like Structures
FULL PAPER
expected complex 9 as an air-stable, yellow-orange com-
pound.
Conclusions
This report describes a convenient approach to the enan-
tiomerically pure, phosphorus-containing diols 1, by cata-
lytic asymmetric hydrogenation of the corresponding dike-
tones. Diols 1 have been shown to be suitable starting mate-
rials for the synthesis of chiral phosphorus-containing
macrocycles with crown-ether-like structures. The phos-
phane oxides 6 and 7, and the corresponding trivalent phos-
phanes, are representative examples of this new class of chi-
ral phosphorus derivatives.
To the best of our knowledge, a single family of chiral
macrocyclic phosphanes had been prepared previously with
the purpose of studying their catalytic properties in transi-
tion-metal-promoted reactions,[26] so very little information
on the effects of the macrocyclic structure of phosphorus
ligands on catalysis is so far available. Consequently, in the
next step of this work we intend to examine the catalytic
applications of selected transition metal complexes of phos-
phanes 8, with the aim of identifying how their macrocyclic
crown ether structures affect rates and selectivities through
secondary interactions.
1
Figure 2. H NMR spectra of the aza-phospha-crown ether 7b: at
4×10–3 mmolmL–1 in CDCl3/MeOH (95:5) (a), after addition of
0.5 equiv. of NaBPh4 (b), and after addition of 1 equiv. of NaBPh4
(c).
while hydrogen-bonding interactions are comparatively
weak. If it is assumed that the P(O) group does not inter-
vene in the complexation process, inducing a break in the
crown ether structure, compounds 7 may be compared to Experimental Section
18-crown-5 derivatives, which usually display moderate af-
General: The phosphane oxide 4a was prepared by ozonolysis of
finities to ammonium salts through hydrogen bonding.[24]
Phosphane oxides 7a and 7b have been converted into
the corresponding trivalent phosphanes 8a and 8b by re-
duction with AlH3 under mild conditions (0 °C to 50 °C),
according to the reported method (Scheme 5).[25]
3,4-dimethyl-1-phenyl-3-phospholene oxide[27] as described in
ref.[18] Aluminium hydride solutions were prepared from LiAlH4
and sulfuric acid, or from LiAlH4 and AlCl3, according to reported
methods.[28] All reactions were performed under argon.
(S,S)-Bis(2-hydroxypropyl)(phenyl)phosphane Oxide (1a). Method A
(from Propylene Oxide): nBuLi (7.5 mL, 2.5 m solution in hexane)
was added at –78 °C to a solution of phenylphosphane (1.0 g,
9 mmol) in THF (30 mL). The mixture was allowed to warm to
room temperature and stirring was maintained for 1 h. After the
system had been cooled to 0 °C, (S)-propylene oxide (1,32 mL,
18.9 mmol) was added. The reaction mixture was stirred at about
25–30 °C for 2 h, during which time the yellow-orange solid
(PhPLi2) dissolved to afford a yellow solution. Water (1 mL) was
added and THF was removed. The residue was taken up in a di-
ethyl ether/water mixture. The aqueous layer was extracted success-
ively with diethyl ether and dichloromethane. After drying
(MgSO4) and evaporation of the solvents, the residue containing
the trivalent phosphane [δ(31P) = –38 ppm] and its oxide 1a was
dissolved in acetone (10 mL) and then cooled to 0 °C. The phos-
phane was oxidised by addition of H2O2 (30% solution, 1.5 mL)
and stirring at room temperature for about 30 min. An aqueous
solution of sodium thiosulfate was added and the reaction mixture
was then extracted with dichloromethane. The organic extracts
were dried with MgSO4 and solvents were removed to afford the
crude oxide 1, which was purified by column chromatography on
silica gel (diethyl ether/methanol, 90:10). Compound 1 was ob-
tained in 55% yield (1.2 g), as a colourless oil. Method B (by Cata-
lytic Hydrogenation): The ruthenium catalyst was prepared by ad-
dition of a methanolic HBr solution (0.19 m, 0.11 mL) to a mixture
Scheme 5. Synthesis of trivalent macrocyclic phosphanes and coor-
dination to ruthenium.
Finally, the coordinating ability of 8b toward transition
metals has been observed through its reaction with the [(p-
cymene)RuCl2]2 complex, which quantitatively affords the of (cod)Ru(2-methylallyl)2 (3.2 mg, 0.01 mmol) and (S)-MeO-BI-
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A. Theil, J. Hitce, P. Retailleau, A. Marinetti
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PHEP (6.4 mg, 0.011 mmol, Aldrich) in anhydrous acetone.[29] Af-
ter the mixture had been stirred at room temperature for 40 min,
the solvent was removed under vacuum and the residue was taken
up in methanol (1 mL). Bis(2-oxopropyl)(phenyl)phosphane oxide
(4a, 0.12 g, 0.5 mmol) was added to the reaction vessel, which was
then placed in a stainless steel autoclave. The argon was replaced
by hydrogen, at a pressure of 20 bar, and the reaction was allowed
to proceed at 50 °C for 24 h. Complete conversion into the diol
1a was confirmed by NMR spectroscopy. After evaporation of the
solvent, the phosphane oxide 1a was purified by column
chromatography as above. The enantiomeric excess was Ͼ98%. 1a:
PCH2), 128.6, 128.7, 128.7, 128.9, 130.7, 130.9, 132.0, 132.4, 133.8,
2
136.9 (CPh)193.6 (d, JC,P = 5.8 Hz, CPh) ppm. 31P NMR (CDCl3):
δ = 32 ppm. C22H19O3P (362.11): calcd. C 72.92, H 5.29; found C
71.73, H 5.21. (b): The hydrogenation reaction was performed as
described above for the synthesis of 1a. The reaction was performed
on a 12 mmol scale (4.5 g), under 20 bar H2, at 50 °C for 4 d. After
chromatography on silica gel with diethyl ether/methanol (97:3) as
the eluent, the final product was obtained in 78% yield (1.4 g) as
a colourless solid, m.p. 171 °C. [α]D = +49 (c = 1, CHCl3). 1H
2
2
NMR (400 MHz, CDCl3): δ = 2.26 (ddd, JAB = 15.0, JH,P = 9.1,
3J = 2.0 Hz, 1 H, PCH2), 2.40 (ddd, JAB = 15.1, JH,P = 10.6, J
= 2.7 Hz, 1 H, PCH2), 2.57 (dt, JAB = 15.1, J = 10.6 Hz, 1 H,
2
2
3
1
2
[α]D = +42 (c = 1, CHCl3). H NMR (200 MHz, CDCl3): δ = 1.23
(dd, 3J = 6.1, 4J = 1.7 Hz, 3 H, Me), 1.29 (dd, 3J = 6.2, 4J = 1.7 Hz,
3 H, Me), 1.96 (ddd, 2JAB = 14.8, J = 8.3, J = 1.8 Hz, 1 H, PCH2),
PCH2), 2.68 (ddd, JAB = 15.0, 3J = 10.7, JH,P = 8.7 Hz, 1 H,
PCH2), 4.18 (1 H, OH), 4.50 (1 H, OH), 5.15 (t, J = 10.0 Hz, 1 H,
CHOH), 5.26 (t, J = 9.8 Hz, 1 H, CHOH), 7.2–7.3 (10 H, Ph), 7.5
(3 H, Ph), 7.7 (2 H, Ph) ppm. 13C NMR (75 MHz, CDCl3): δ =
2
2
2
2.18 (m, 2 H, PCH2), 2.37 (dt, JAB = 14.8, J = 10.2 Hz, 1 H,
PCH2), 3.9 (br., 1 H, OH), 4.1 (br., 1 H, CHOH), 4.4 (br., 2 H),
7.5 (3 H, Ph), 7.6–7.8 (2 H, Ph) ppm. 13C NMR (75 MHz, CDCl3):
40.1 (d, JC,P = 64.9 Hz, PCH2), 40.8 (d, JC,P = 64.3 Hz, PCH2),
1
1
1
2
2
δ = 25.06 (Me), 25.22 (Me), 38.6 (d, JC,P = 67.8 Hz, PCH2), 39.8
68.6 (d, JC,P = 4.5 Hz, CH), 69.0 (d, JC,P = 3.6 Hz, CH), 125.5,
1
2
1
(d, JC,P = 67.0 Hz, PCH2), 62.8 (d, JC,P = 5.2 Hz, CH), 63.3 (d, 127.6, 128.5, 128.7, 128.9, 130.0, 130.1, 132.0, 132.4 (d, JC,P
=
=
2JC,P = 5.3 Hz, CH), 128.8, 129.0, 129.9, 130.1, 132.2 (CHPh), 132.1
94.8 Hz, Cipso), 144.1 (d, JC,P = 15.2 Hz, CPh), 144.3 (d, JCP
3
3
1
(d, JC,P = 94.9 Hz, Cipso) ppm. 31P NMR (CDCl3): δ = 43 ppm.
13.1 Hz, CPh) ppm. 31P NMR (CDCl3): δ = 43 ppm. EI-MS: m/z
(%) = 366 (17) [M]+, 348 (13) [M – 18]+, 216 (93), 140 (100).
EI MS: m/z (%) = 242 (2) [M]+, 227 (18) [M – Me]+, 209 (20) [M –
2×Me]+, 184 (46), 140 (100). C12H19O3P (242.11): calcd. C 59.99, C22H23O3P (366.14): calcd. C 72.12, H 6.33; found C 71.95, H 6.48.
H 7.13; found C 59.13, H 7.77. HPLC assay: Chiralcel AS-H, 9:1
hexane/iPrOH, flow 1 mLmin–1, detection by UV at 544 nm, reten-
tion times 16.4 min (R,R) and 24.0 min (S,S).
HPLC assay: Chiralcel OD-H, 9:1 hexane/iPrOH, flow 1 mLmin–1,
detection by UV at 544 nm, retention times 13.7 min (S,S) and
19.0 min (R,R).
(S,S)-Bis{2-[2-(2-chloroethoxy)ethoxy]propyl}(phenyl)phosphane
Oxide (5a). (a): 2-(2-Chloroethoxy)ethyl trifluoromethanesulfonate
was prepared from 2-(2-chloroethoxy)ethanol: a mixture contain-
ing 2-(2-chloroethoxy)ethanol (8.5 mL, 80 mmol) and triethylamine
(11.5 mL, 82 mmol) in dichloromethane (50 mL) was added slowly
at 0 °C to a CH2Cl2 solution (120 mL) of triflic anhydride (25 g,
88 mmol). The mixture was stirred at room temperature for 6 h and
was then hydrolysed with cold water. The organic layer was washed
with cold water and dried with MgSO4. Evaporation of the solvent
afforded 18.8 g (92 % yield) of crude triflate,[31] which was used
without further purification. 1H NMR (300 MHz, CDCl3): δ = 3.64
(m, 2 H, CH2Cl), 3.79 (m, 2 H, CH2O), 3.85 (m, 2 H, CH2O), 4.64
(m, 2 H, CH2OTf) ppm. (b): NaH (0.84 g, 21 mmol, 60% in min-
eral oil) was added portionwise to a solution of 1a (2.4 g, 10 mmol)
in diethyl ether (130 mL). The mixture was heated at 30 °C for
about 1 h and was then cooled to 0 °C. A solution of 2-(2-chloroe-
thoxy)ethyl trifluoromethanesulfonate (5.6 g, 22 mmol) in diethyl
ether (5 mL) was added. After 24 h of stirring at room temperature,
the mixture was hydrolysed with water (10 mL). After extraction of
the aqueous layer with dichloromethane, the organic layers were
dried with MgSO4 and the solvents were evaporated. The crude
product was purified by column chromatography on silica gel, with
a diethyl ether/MeOH gradient (from 95:5 to 90:10) as the eluent,
to yield 5a (2.9 g, 65%) as a colourless oil. 5a: [α]D = +12 (c = 1,
Catalytic Hydrogenation of (2-Oxopropyl)diphenylphosphane Oxide
(2): The hydrogenation reaction was performed on a 1 mmol scale,
with 1% ruthenium catalyst, at 50 °C, under 10 bar of H2, as de-
scribed above. Both (R)- and (S)-MeO-BIPHEP were used in suc-
cessive experiments. Total conversion was observed by 1H NMR
spectroscopy. The enantiomeric excesses were determined by HPLC
assay. The absolute configurations were assigned by comparison of
the retention times with that of a known sample prepared from
(S)-propylene oxide.[30]
(2-Hydroxypropyl)diphenylphosphane Oxide (3): 1H NMR
3
4
(400 MHz, CDCl3): δ = 1.28 (dd, J = 6.2, J = 1.8 Hz, 3 H, Me),
2
2
3
2.36 (ddd, JAB = 14.8, JH,P = 7.4, J = 2.1 Hz, 1 H, PCH2), 2.48
2
2
3
(ddd, JAB = 14.8, JH,P = 11.7, J = 9.9 Hz, 1 H, PCH2), 4.2–4.3
(m, 1 H, CHOH), 4.5 (br., OH), 7.5 (m, 3 H, Ph), 7.7 (m, 2 H, Ph)
ppm. 31P NMR (CDCl3): δ = 35 ppm. HPLC assay: Chiralcel OD-
H, 9:1 hexane/iPrOH, flow 1 mLmin–1, retention times 15.8 min
(R) and 24.2 min (S).
(S,S)-Bis(2-hydroxy-2-phenylethyl)(phenyl)phosphane Oxide (1b):
Compound 1b was obtained by catalytic hydrogenation of 4b. (a):
Acetophenone (60 mmol) was added to a cooled solution (–78 °C)
of LiHMDS (66 mmol) in THF (80 mL). After the mixture had
been allowed to stand at –78 °C for 1 h, a THF solution of dichlo-
ro(phenyl)phosphane (4.1 mL, 30 mmol) was added dropwise. The
mixture was allowed to warm to room temperature and stirred for
14 h. Hydrolysis was performed at 0 °C, by pouring the reaction
mixture into HCl solution (5%, 120 mL). After evaporation of the
THF, the residue was taken up in CH2Cl2. The organic layer was
dried and then stirred in air for about 12 h, which allows oxidation
of the bis(2-oxo-2-phenylethyl)(phenyl)phosphane under mild con-
ditions. The final product was purified by chromatography on silica
gel with cyclohexane/ethyl acetate (3:7) as the eluent. Compound
4b[19] was obtained in 42% yield (1.5 g): colourless solid, m.p.
132 °C. 1H NMR (400 MHz, CDCl3): δ = 4.08 (ABX, 2JAB = 15.0,
1
3
CHCl3). H NMR (400 MHz, CDCl3): δ = 1.17 (d, J = 5.3 Hz, 3
3
H, Me), 1.23 (d, J = 6.1 Hz, 3 H, Me), 2.00 (ddd, J = 15.0, J =
13.1, J = 4.8 Hz, 1 H, PCH2), 2.3–2.4 (m, 3 H, PCH2), 3.20 (m, 2
H), 3.35 (m, 1 H), 3.4–3.8 (m, 14 H), 4.0 (m, 1 H), 7.4 (3 H, Ph),
7.7 (2 H, Ph) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.2 (Me),
21.3 (Me), 38.3 (d, 1JC,P = 51.0 Hz, PCH2), 39.3 (d, 1JC,P = 51.5 Hz,
PCH2), 42.6 (CH2Cl), 67.5 (CHO), 67.6 (CHO), 70.3, 70.6, 70.9,
71.2, 71.3 (OCH2), 128.3, 128.5, 130.2, 130.4, 131.2 (CHPh), 133.8
1
(d, JC,P = 94.4 Hz, Cipso) ppm. 31P NMR (CDCl3): δ = 35 ppm.
CI-MS (NH3) {35Cl}: m/z (%) = 455 [M + 1]+. HRMS {35Cl}:
calcd. for C20H33Cl2O5P·Na 477.1340; found 477.1321.
2
2
2JH,P = 15.0 Hz, 2 H, PCH2), 4.13 (ABX, JAB = 15.0, JH,P
=
15.0 Hz, 2 H, PCH2), 7.4–7.6 (9 H, Ph), 7.86 (2 H, Ph), 7.94 (4 H,
(S,S)-Bis{2-[2-(2-chloroethoxy)ethoxy]-2-phenylethyl}(phenyl)phos-
phane Oxide (5b): The synthesis of 5b from 1b (1.5 g, 4 mmol) fol-
Ph) ppm. 13C NMR (75 MHz, CDCl3): δ = 42.0 (d, 1JC,P = 62.8 Hz,
158
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Eur. J. Org. Chem. 2006, 154–161

Macrocyclic, Chiral Phosphane Derivatives with Crown-Ether-Like Structures
FULL PAPER
lowed the same procedure as for 5a. After 36 h of stirring at room
temperature, the reaction mixture was hydrolysed and 5b was puri-
fied by column chromatography on silica gel with CH2Cl2/MeOH
(97:3) as the eluent. Yield 2.1 g (90%) of a colourless oil. 5b: [α]D
δ = 37 ppm. EI/MS: m/z (%) = 398 [M – Ts]+ (46). CI/MS (NH3):
m/z = 554 [M + 1]+. HRMS (E.S.I.): calcd. for C27H40NO7PS·Na
576.2161; found 576.2151.
(S,S)-1,3,17-Triphenyl-10-tosyl-4,7,13,16-tetraoxa-10-aza-1-phos-
phacyclooctadecane 1-Oxide (7b): Compound 7b was prepared ac-
cording to the same procedure as for 7a, from 5b (2.3 g, 4 mmol).
Compound 7b was obtained in 44% yield (1.2 g) as a colourless
solid, m.p. 68 °C. [α]D = +38 (c = 1, CHCl3). 1H NMR (500 MHz,
CDCl3): δ = 2.40–2.45 (m, 2 H), 2.43 (s, Me), 2.94 (m, 1 H), 3.07
(m, 1 H), 3.15 (m, 1 H), 3.28 (m, 1 H), 3.38 (m, 1 H), 3.4–3.8 (13
1
= +45 (c = 1, CHCl3). H NMR (400 MHz, CDCl3): δ = 2.18 (td,
2
2
J = 14.8, J = 2.9 Hz, 1 H, PCH2), 2.64 (td, JH,P = JH,H = 16.0,
3J = 2.7 Hz, 1 H, PCH2), 2.7–2.9 (m, 2 H, PCH2), 3.15 (m, 2 H),
3.25 (m, 1 H), 3.3–3.6 (m, 14 H), 3.75 (m, 1 H), 4.53 (ddd, J =
10.9, J = 8.6, J = 2.6 Hz,1 H, CHOH), 4.93 (ddd, J = 10.6, J =
8.0, J = 3.0 Hz, 1 H, CHOH), 7.3 (10 H, Ph), 7.4 (3 H, Ph), 7.8 (2
1
H, Ph) ppm. 13C NMR (75 MHz, CDCl3): δ = 40.2 (d, JC,P
=
H), 4.36 (m, 1 H), 4.87 (m, 1 H), 7.2–7.8 (Ar), 8.03 (1 H) ppm. 13
C
1
48.8 Hz, PCH2), 41.5 (d, JC,P = 49.3 Hz, PCH2), 42.5 (CH2Cl),
NMR (75 MHz, CDCl3, selected data): δ = 21.4 (Me), 40.2 (d, 1JC,P
= 67.9 Hz, PCH2), 49.0 (NCH2), 67.6, 68.0, 70.1, 70.2, 70.3, 70.5
(CH2), 76.9, 77.0 (CH) ppm. 31P NMR (CDCl3): δ = 35 ppm.
HRMS (E.S.I.): calcd. for C37H44NO7PS·Na 700.2474; found
700.2447. Crystals of 7b suitable for X-ray diffraction studies were
grown from a dichloromethane/ethanol mixture.
2
42.7 (CH2Cl), 68.0, 70.2, 70.4, 71.0, 71.1 (OCH2), 76.8 (d, JC,P
=
2
3.1 Hz, CHO), 77.0 (d, JC,P = 3.0 Hz, CHO), 126.4, 126.5, 127.9,
128.0, 128.3, 128.4, 128.6, 128.7, 130.3, 130.7, 131.2, 134.2 (d, 1JC,P
= 72.2 Hz, Cipso), 141.9 (d, J = 6.0 Hz, CPh), 142.0 (d, J = 4.8 Hz,
C
Ph) ppm. 31P NMR (CDCl3): δ = 37 ppm. HRMS {35Cl}: calcd.
for C30H37O5PCl2·Na 601.1653; found 601.1683.
X-ray Crystallography: Details of data collection and solution re-
finement are given in Table 2. X-ray data were collected with a
Nonius Kappa CCD diffractometer with use of graphite-mono-
chromated Mo-Kα radiation (λ = 0.71073 Å). A combination of
1.7° (exposure of 60 s/°) φ and ω (with κ offsets) scans was used to
collect sufficient data to 2θ = 19.8°. The data frames were inte-
grated and scaled by use of the Denzo-SMN package.[32] The struc-
ture was solved by direct methods (SHELX-S) and all non-hydro-
gen atoms were refined with anisotropic displacement parameters
by use of SHELX-L by full-matrix least squares on F2 values. Some
hydrogen atoms were located in difference Fourier syntheses (the
rest of them were placed in calculated positions) but all were in-
cluded in the final cycles of refinement in a riding model, with
3,20-Dimethyl-1-phenyl-11,12-benzo-4,7,10,13,13,19-hexaoxa-1-
phosphacyclohenicosane 1-Oxide (6): A mixture of catechol
(145 mg, 1.3 mmol) and K2CO3 (182 mg, 1.3 mmol) in butanol
(8 mL) was heated to reflux for 20 min. A solution of the phos-
phane oxide 5a (200 mg, 0.43 mmol) in butanol (4 mL) was then
added dropwise while heating. After the mixture had been heated
at reflux in butanol for 14 h, the solvent was removed and the resi-
due was taken up in a CH2Cl2/water mixture. After the usual
workup, the final product was purified by chromatography with
CH2Cl2/MeOH (98:2). Yield 15% (32 mg). 6: 1H NMR (400 MHz,
3
3
CDCl3): δ = 1.21 (d, J = 5.1 Hz, 3 H, Me), 1.23 (d, J = 4.6 Hz,
3 H, Me), 2.06 (td, J = 14.9, J = 4.9 Hz, 1 H, PCH2), 2.3 (m, 1 H,
PCH2), 2.5 (m, 2 H, PCH2), 3.3 (m, 1 H), 3.4 (m, 1 H), 3.5 (m, 1
H), 3.6–3.8 (m, 8 H), 3.8–3.9 (m, 3 H), 4.0–4.2 (m, 5 H), 6.90 (br.s,
4 H), 7.4 (3 H, Ph), 7.8 (m, 2 H, Ph) ppm. 13C NMR (75 MHz,
Table 2. Crystallographic data for compound 7b.
1
1
C37H44NO7PS·0.5(C2O)[a]
697.77
colourless, thin plate
0.45×0.15×0.025
monoclinic
P21
10.7493(6)
11.2768(11)
16.6953(15)
92.379(5)
CDCl3): δ = 21.0 (d, JC,P = 8.1 Hz, Me), 21.2 (d, JC,P = 9.3 Hz,
Empirical formula
Formula mass
Crystal colour, shape
Crystal size [mm]
Crystal system
Space group
a [Å]
1
1
Me), 38.2 (d, JC,P = 65.9 Hz, PCH2), 38.9 (d, JC,P = 68.2 Hz,
PCH2), 67.1, 67.8, 69.4, 69.9, 70.0, 70.7, 70.9, 71.0, 115.2
(CHo-catechol), 115.6 (CHo-catechol), 121.7 (CHm-catechol), 121.8
1
(CHm-catechol), 128.4, 128.5, 130.4, 130.5, 131.4, 133.4 (d, JC,P
=
93.5 Hz, Cipso), 149.3 (Cipso-catechol) ppm. 31P NMR (CDCl3): δ =
36 ppm. CI/MS (NH3): m/z = 493 [M + H]+. HRMS (E.S.I.): calcd.
for C26H37O7P·Na 515.2175; found 515.2139.
b [Å]
c [Å]
β [°]
(S,S)-3,17-Dimethyl-1-phenyl-10-tosyl-4,7,13,16-tetraoxa-10-aza-1-
phosphacyclooctadecane 1-Oxide (7a): Tosylamine (170 mg,
1 mmol), K2CO3 (550 mg, 4 mmol) and the phosphane oxide 5a
(450 mg, 1 mmol) were heated at reflux in anhydrous DMF
(20 mL) for 10 h. After evaporation of the solvent under vacuum,
a saturated aqueous solution of NaHCO3 was added. Extraction
with CH2Cl2 and drying with MgSO4 afforded a crude mixture,
which was separated by chromatography with an Et2O/MeOH gra-
dient (from 95:5 to 90:10). Yield 66% (360 mg of a colourless oil).
V [Å3]
2022.0(3)
Z
2
Dcalcd. [gcm–3
]
1.146
F(000)
740
0.165
μ [mm–1
]
λ (Mo-Kα) [Å]
T [K]
0.71073
293(2)
hkl range
–10 Յ h Յ 10
–10 Յ k Յ 10
–15 Յ l Յ 15
2.21 Ͻ 2θ Ͻ 19.77 (99.7)
7833
3484 (Friedel pairs not
merged)/0.03
3474/3081
1
7a: [α]D = +11 (c = 1, CHCl3). H NMR (500 MHz, CDCl3): δ =
1.20 (d, 3J = 6.0 Hz, 3 H, Me), 1.23 (d, 3J = 6.0 Hz, 3 H, Me), 2.06
2θ range [°] (completness [%])
Number of reflections collected
Number of independent reflns/Rint
2
2
2
(td, J = JH,P = 15.0, J = 6.0 Hz, 1 H, PCH2), 2.25 (ddd, JH,P
=
2
3
17.5, J = 15.5, J = 6.5 Hz, 1 H, PCH2), 2.39 (s, 3 H, Me), 2.47
2
3
(ddd, J = 15.5, JH,P = 10.5, J = 7.0 Hz, 1 H, PCH2), 2.59 (m, 1
H, PCH2), 3.2–3.7 (17 H), 4.05 (m, 1 H, MeCHO), 7.29 (d, J =
8.0 Hz, 2 H, Ar), 7.4–7.5 (3 H, Ph), 7.69 (d, J = 8.0 Hz, 2 H, Ar),
7.80 (2 H, Ph) ppm. 13C NMR (75 MHz, CDCl3): δ = 20.6 (d, 1JC,P
Refined data/observed data [I Ͼ 2σ(I)]
Restraints/parameters
79/464
Final R1, wR2 [I Ͼ 2σ(I)]
Final R1, wR2 (all data)
Goodness-of-fit on F2
0.0500, 0.1419
0.0594, 0.1512
1.081
1
= 8.2 Hz, Me), 21.0 (d, JC,P = 8.3 Hz, Me), 21.4 (Me), 37.8 (d,
Δρmin,Δρmax [e·Å–3
]
–0.180, 0.309
1JC,P = 65.7 Hz, PCH2), 38.7 (d, JC,P = 67.9 Hz, PCH2), 48.6
1
(NCH2), 48.7 (NCH2), 67.1, 67.5, 70.3, 70.4, 70.6 (CH), 70.8 (CH),
[a] These are EtOH molecules (0.25%) which are included in the
crystal. The C and O atoms have been taken into account for struc-
1
127.0, 128.3, 128.5, 129.6, 130.4, 130.5, 131.4, 133.0 (d, JC,P
=
93.3 Hz, Cipso), 136.6 (CAr), 143.2 (CAr) ppm. 31P NMR (CDCl3): ture refinement.
Eur. J. Org. Chem. 2006, 154–161
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
159

A. Theil, J. Hitce, P. Retailleau, A. Marinetti
FULL PAPER
Uiso(H) set to Ն 1.2 times that of the attached C atom. The asym-
metric unit consists of one molecule of the compound 7b and disor-
dered solvent molecules in the cavity running through the crystal
along the screwed twofold crystallographic b-axis, and treated as
ethanol with two independent orientations and respective partial
occupancy factor (1/4), allowing hydrogen bonding between the hy-
droxy group and the oxygen atom carried by the phosphorus atom.
Disorder was also found at the level of the C5–O5 bond from the
“central 18-atom cycle” and subsequently treated with alternate po-
sitions for these two atoms with a refined occupancy rate of 60–
40 %. The absolute stereochemistry as determined by Flack’s
method [Flack x parameter = 0.12(13)] was confirmed by weak
intensity differences (owing to anomalous contributions from S and
P atoms) detected for Bijvoet pairs, still showing a significant agree-
ment between ΔFobs and ΔFcalcd. (11 matching pairs over 14
|ΔFcalcd.| Ͼ 0.4). CCDC-264452 contains the supplementary crys-
tallographic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
6.0 Hz, 1 H, CHp-cymene), 7.16–7.22 (4 H, Ar), 7.3 (Ar), 7.4–7.5 (4
H, Ar), 7.5 (3 H, Ar), 7.72 (d, J = 8.5 Hz, 2 H, Ar), 8.02–8.06 (2
H, Ar) ppm. 13C NMR (75 MHz, CDCl3, selected data): δ = 16.7
1
(Me), 20.5 (Me), 21.0 (Me), 21.6 (Me), 28.9 (d, JC,P = 22.6 Hz,
1
PCH2), 29.24 (CHMe2), 37.5 (d, JC,P = 23.3 Hz, PCH2), 49.4
(NCH2), 50.1 (NCH2),65.3, 68.0, 68.8, 69.2, 69.5, 70.7 (OCH2),
76.3 (d, 2JC,P = 9.8 Hz, OCH), 78.2 (d, 2JC,P = 9.8 Hz, OCH), 84.0,
84.8, 85.6, 86.1 (CHp-cymene), 133.8 (d, 1JC,P = 40.0 Hz, PCAr), 134.8
3
3
(CAr), 141.1 (d, JC,P = 9.8 Hz, CAr), 142.2 (CAr), 142.8 (d, JC,P
=
13.6 Hz, CAr) ppm. 31P NMR (CDCl3): δ = 13 ppm. MS (E.S.I.)
{35Cl, 102Ru}: m/z (%) = 932 (4) [M – Cl]+, 762 (32) [(phosphane)
Ru – H]+, 684 [phosphane + Na]+ (100).
[1] T. Hayashi, M. Kumada, Acc. Chem. Res. 1982, 15, 395.
[2] M. Sawamura, Y. Ito, Chem. Rev. 1992, 92, 857.
[3] Cyclodextrin-based molecular recognition sites: a) M. Sawa-
mura, K. Kitayama, Y. Ito, Tetrahedron: Asymmetry 1993, 4,
1829; b) Y. T. Wong, C. Yang, K.-C. Ying, G. Jia, Organometal-
lics 2002, 21, 1782. Remote nitrogen functions: T. Hayashi, K.
Kanehira, H. Tsuchiya, M. Kumada, J. Chem. Soc., Chem.
Commun. 1982, 1162. Phosphane oxide functions: B. Faure, O.
Pardigon, G. Buono, Tetrahedron 1997, 53, 11577.
[4] Carboxylic acid functions: a) Y. Ito, M. Sawamura, E. Shirak-
awa, K. Hayashizaki, T. Hayashi, Tetrahedron Lett. 1988, 29,
235; b) Y. Okada, T. Minami, Y. Umezu, S. Nishikawa, R.
Mori, Y. Nakayama, Tetrahedron: Asymmetry 1991, 2, 667; c)
A. Yamazaki, K. Achiwa, Tetrahedron: Asymmetry 1995, 6, 51.
Amino functions: d) I. Yamada, M. Yamaguchi, T. Yamagishi,
Tetrahedron: Asymmetry 1996, 7, 3339; e) Y. Ito, M. Sawamura,
T. Hayashi, J. Am. Chem. Soc. 1986, 108, 6405.
Reduction Procedure: The phosphane oxides 7a or 7b (0.2 mmol in
1 mL THF) were treated with 3 equiv. of AlH3 in THF[28] at 0 °C.
After the mixture had warmed up to 50 °C, the progress of the
reaction was checked by 31P NMR spectroscopy. After about 20 h,
a few drops of MeOH were added to consume the excess AlH3.
Evaporation of the solvent afforded a white powder, which was
washed twice with pentane. The pentane solution was recovered,
and the solvents were evaporated under vacuum to afford phos-
phanes 8 as air-sensitive, colourless oils.
[5] Hydroxy groups: a) T. Hayashi, K. Kanehira, T. Hagihara, M.
Kumada, J. Org. Chem. 1988, 53, 113; b) T. Hayashi, A. Yama-
moto, Y. Ito, E. Nishioka, H. Miura, K. Yanagi, J. Am. Chem.
Soc. 1989, 111, 6301; c) J. Ward, A. Börner, H. B. Kagan, Tet-
rahedron: Asymmetry 1992, 3, 849; d) A. Börner, Eur. J. Inorg.
Chem. 2001, 327.
[6] Boron functions: a) A. Börner, J. Ward, K. Kortus, H. B. Ka-
gan, Tetrahedron: Asymmetry 1993, 4, 2219; b) L. B. Field,
E. N. Jacobsen, Tetrahedron: Asymmetry 1993, 4, 2229; c)
B. F. M. Kimmich, C. L. Landis, D. R. Powell, Organometallics
1996, 15, 4141.
[7] a) M. Sawamura, H. Nagata, H. Sakamoto, Y. Ito, J. Am.
Chem. Soc. 1992, 114, 2586; b) M. Sawamura, Y. Nakayama,
W.-M. Tang, Y. Ito, J. Org. Chem. 1996, 61, 9090.
[8] D. K. MacFarland, C. R. Landis, Organometallics 1996, 15,
483.
(S,S)-3,17-Dimethyl-1-phenyl-10-tosyl-4,7,13,16-tetraoxa-10-aza-1-
phosphacyclooctadecane (8a): H NMR (500 MHz, CDCl3): δ =
1
1.14 (d, 3J = 6.5 Hz, 3 H, Me), 1.21 (d, 3J = 6.0 Hz, 3 H, Me), 1.76
(dd, J = 13.5, J = 6.0 Hz, 1 H, PCH2), 2.04 (dd, JAB = 14.0, J =
5.5 Hz, 1 H, PCH2), 2.14 (dd, JAB = 14.0, J = 6.0 Hz, 1 H, PCH2),
2.33 (ddd, J = 13.5, J = 7.5, J = 2.0 Hz, 1 H, PCH2), 2.44 (s, 3 H,
Me), 3.4–3.7 (18 H), 7.31 (d, J = 8.8 Hz, 2 H, Ar), 7.4 (3 H, Ph),
7.56 (2 H, Ph), 7.73 (d, J = 8.5 Hz, 2 H, Ar) ppm. 31P NMR
(CDCl3): δ = –34 ppm. HRMS (E.S.I.): calcd. for C27H40NO6PS·H
538.2392; found 538.2410.
(S,S)-1,3,17-Triphenyl-10-tosyl-4,7,13,16-tetraoxa-10-aza-1-phos-
phacyclooctadecane (8b): 1H NMR (300 MHz, CDCl3): δ = 1.89
(dd, J = 13.5, J = 3.9 Hz, 1 H, PCH2), 2.3 (m, 2 H, PCH2), 2.33
(s, 3 H, Me), 2.48 (dd, J = 13.8, J = 9.6 Hz, 1 H, PCH2), 3.2–3.8
(m, 16 H), 4.3 (m, 2 H), 7.0–7.8 (Ph) ppm. 31P NMR (CDCl3): δ
= –32 ppm. HRMS (E.S.I.): calcd. for C37H44NO6PS·Na 684.2525;
found 684.2524.
[9] C. R. Landis, R. A. Sawyer, E. Somsook, Organometallics
2000, 19, 994.
[10] F. Faltin, V. Fehring, R. Kadyrov, A. Arrieta, T. Schareina, R.
Selke, R. Miethchen, Synthesis 2001, 638.
[11] K. Issleib, H.-R. Roloff, Chem. Ber. 1965, 98, 2091.
[12] a) H. Brunner, A. Sicheneder, Angew. Chem. Int. Ed. Engl.
1988, 27, 718; b) G. Muller, D. Sainz, J. Organomet. Chem.
1995, 495, 103; c) J. Scherer, G. Huttner, M. Büchner, J. Bakos,
J. Organomet. Chem. 1996, 520, 45; d) D. J. Brauer, P. Machn-
itzki, T. Nickel, O. Stelzer, Eur. J. Inorg. Chem. 2000, 65; e)
J. Duran, D. Oliver, A. Polo, J. Real, J. Benet-Buchholz, X.
Fontrodona, Tetrahedron: Asymmetry 2003, 14, 2529.
[13] a) R. Noyori, T. Ohkuma, M. Kitamura, H. Takaya, N. Sayo,
H. Kumobayashi, S. Akutagawa, J. Am. Chem. Soc. 1987, 109,
5856; b) M. Kitamura, T. Ohkuma, S. Inoue, N. Sayo, H. Ku-
mobayashi, S. Akutagawa, T. Ohta, H. Takaya, R. Noyori, J.
Am. Chem. Soc. 1988, 110, 629.
Synthesis of the Ruthenium Complex 9: The ruthenium dimer [(p-
cymene)RuCl2]2 (34 mg, 0.055 mmol) was added to a solution of
the crude phosphane 8b in CH2Cl2 (2 mL), obtained by reduction
of the phosphane oxide 7b (100 mg, 0.14 mmol). After the mixture
had been stirred at room temperature for 15 min, 31P NMR analy-
sis showed total conversion of 8b into the ruthenium complex 9.
The final product was purified by flash chromatography on silica
gel with hexane/ethyl acetate (30:70) as the eluent. 9: Orange-red
solid, m.p. 124 °C. [α]D = +8 (c = 0.2, CHCl3). 1H NMR
3
3
(500 MHz, CDCl3): δ = 1.10 (d, J = 6.5 Hz, 3 H, Me), 1.20 (d, J
= 7.0 Hz, 3 H, Me), 1.68 (s, Me), 2.3 (m, 2 H, CHMe2 + CH2),
2.43 (s, Me), 2.54 (dd, J = 14.0, J = 5.5 Hz, 1 H, CH2), 2.92 (ddd,
J = 16.0, J = 9.0, J = 3.5 Hz, 1 H, CH2), 3.08–3.17 (m, 3 H), 3.3–
3.65 (m, 9 H), 3.7 (m, 1 H), 3.77 (m, 1 H), 3.85–3.96 (m, 3 H), 4.3
[14] R. Noyori, Angew. Chem. Int. Ed. 2002, 41, 2008.
[15] a) M. Kitamura, M. Tokunaga, R. Noyori, J. Am. Chem. Soc.
1995, 117, 2931; b) I. Gautier, V. Ratovelomanana-Vidal, P.
Savignac, J.-P. Genêt, Tetrahedron Lett. 1996, 37, 7721.
[16] R. Noyori, Acta Chem. Scand. 1996, 50, 380.
3
(q, J = 7.5 Hz, 1 H, CHO), 5.03 (d, J = 6.0 Hz, 1 H, CHp-cymene),
5.19 (t, 3J = 10.0 Hz, 1 H, CHO), 5.23 (d, 3J = 6.0 Hz, 1 H,
CHp-cymene), 5.28 (d, 3J = 6.0 Hz, 1 H, CHp-cymene), 5.35 (d, 3J =
[17] F. Mathey, P. Savignac, Tetrahedron 1978, 34, 649.
160
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Macrocyclic, Chiral Phosphane Derivatives with Crown-Ether-Like Structures
FULL PAPER
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Received: June 22, 2005
Published Online: October 31, 2005
Eur. J. Org. Chem. 2006, 154–161
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