Triphenylethanediol-derived 2-chloro-1,3,2- dioxaphospholane: Synthesis, structure, and reaction with chiral alcohols

Article abstract of DOI:10.1080/10426500802509624

The reaction of (S)-1,1,2-triphenylethanediol (3) with phosphorus trichloride leads to the diastereoselective formation of (S_C,RP)-2- chloro-1,3,2-dioxaphospholane (2). Its configuration has been determined by single crystal X-ray diffraction.

Full text of DOI:10.1080/10426500802509624

Phosphorus, Sulfur, and Silicon, 184:2536–2544, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802509624
Triphenylethanediol-Derived 2-Chloro-1,3,2-
dioxaphospholane: Synthesis, Structure, and Reaction
with Chiral Alcohols
T. Meier, M. Braun, and W. Frank
Department of Chemistry, Institute of Organic and Macromolecular
Chemistry, University of Du¨sseldorf, Du¨sseldorf, Germany
The reaction of (S)-1,1,2-triphenylethanediol (3) with phosphorus trichloride leads
to the diastereoselective formation of (SC,RP)-2-chloro-1,3,2-dioxaphospholane (2).
Its configuration has been determined by single crystal X-ray diffraction. When
reacted with racemic secondary alcohols, diastereomeric phosphites are obtained,
which display substantial shift differences in the 31P NMR spectra. Thus, chlorodi-
oxaphospholane 2 can serve as derivatizing reagent for chiral secondary alcohols
permitting to determine their enantiomeric excess.
Keywords Chirality; crystal structure; 31P NMR; phosphites; stereoselectivity
INTRODUCTION
Cyclic monochlorophosphites 1 are usually obtained from diols and
phosphorus trichloride.1–6 They frequently serve as intermediates in
syntheses of chiral phophoramidites and phosphites, both versatile lig-
ands in asymmetric catalysis.7,8 Moreover, monochlorides of cyclic phos-
phites derived from chiral diols have been found to be suitable deriva-
tizing agents for alcohols and amines.9–11 In most cases, C2 symmetric
diols were chosen for this purpose so that the pyramidal phosphorus
atom does not give rise to the formation of diastereomeric mixtures
upon ring closure.12 In this article, we report on the diastereoselec-
tive formation of the chlorodioxaphospholane 2, the assignment of the
configuration, and its reaction with secondary alcohols (Scheme 1).
Received 10 January 2008; accepted 20 September 2008.
This work was supported by the Deutsche Forschungsgemeinschaft.
Address correspondence to Prof. Dr. Manfred Braun, Institute of Organic and Macro-
molecular Chemistry, University of Du¨sseldorf, D-40225 Du¨sseldorf, Germany. E-mail:
braunm@uni-duesseldorf.de
2536

Triphenylethanediol-Derived 2-Chloro-1,3,2-dioxaphospholane
2537
SCHEME 1
RESULTS AND DISCUSSION
Chlorodioxaphospholane 2 was obtained from (S)-triphenylglycol 3,
which is readily available from the corresponding enantiomer of man-
delic acid.13 Treatment of the diol 3 with phosphorus trichloride in
toluene in the presence of triethylamine yielded crystalline chlorodi-
oxaphospholane 2, which was obtained upon concentrating the reaction
mixture under reduced pressure (Scheme 2). The 31P NMR spectra of
SCHEME 2
both the solid material and the solution revealed a single signal at δ =
168 ppm, indicating the stereoselective formation of the product. Crys-
talline 2 and its solutions must be kept under nitrogen or argon, due to
its sensitivity against moisture. As shown previously,14 ring opening of
2 occurs when it is treated with water and phosphonic acid monoester
4 forms. A crystal structure analysis unambiguously revealed the rel-
ative configuration of the heterocyclic compound 2 to be trans. As the
synthesis started from (S)-diol 3, the (SC,RP)-configuration is assigned
to the chlorodioxaphospholane 2 (Figure 1). The enantiomeric (RC,SP)-2
was obtained from (R)-diol 3 in an analogous way.
Chlorodioxaphospholane 2 reacts readily with secondary alcohols
as demonstrated by treatment of a solution of (RC, SP)-2 with (R)-1-
phenylethanol (5a) to give phosphite 6a. In the 31P NMR spectra, a
minor amount of a diastereomer, which is epimeric at the phosphorus
atom, was detected. When the (S)-enantiomer of 1-phenylethanol was
treated with chlorodioxaphospholane (RC,SP)-2, the phosphite 7a was

2538
T. Meier et al.
FIGURE 1 ORTEP view of the molecular structure of (2R,5S)-2 in the crys-
tal. Displacement ellipsoids are drawn at the 50% probability level, radii of
hydrogen atoms are chosen arbitrarily, and the hydrogen atom labels are omit-
ted for clarity. Selected geometric parameters [Å] and [◦]: P1–Cl1 2.1094(7),
P1–O1 1.6054(12), P1–O2 1.6060(13), O1–C1 1.480(2), O2–C2 1.4525(19),
C1–C2 1.570(2), C1–C3 1.519(2), C1–C9 1.532(2), C2–C15 1.499(2), C3–C4
1.385(2), C3–C8 1.390(2), C4–C5 1.389(3), C5–C6 1.374(3), C6–C7 1.379(3),
C7–C8 1.379(3), C9–C10 1.387(2), C9–C14 1.377(3), C10–C11 1.387(3),
C11–C12 1.372(3), C12–C13 1.367(3), C13–C14 1.388(2), C15–C16 1.378(3),
C15–C20 1.378(3), C16–C17 1.380(3), C17–C18 1.369(4), C18–C19 1.366(4),
C19–C20 1.381(3), Cl1–P1–O1 100.82(5), Cl1–P1–O2 99.65(5), O1–P1–O2
95.09(6), P1–O1–C1 114.39(10), P1–O2–C2 110.51(10), O1–C1–C3 107.53(13),
O1–C1–C9 105.37(12), C3–C1–C9 112.96(13), O1–C1–C2 103.48(12),
C3–C1–C2 111.46(13), C9–C1–C2 115.09(14), O2–C2–C15 109.20(13),
O2–C2–C1 104.88(13), C1–C2–C15 117.38(14).
obtained. Its 31P NMR data clearly differ from those of 6a. Again, a
minor product, epimeric at the phosphorus atom, also formed (Scheme
3).
The substantial shift differences in the 31P NMR spectra, which are
easily obtained from the reaction mixture, suggest the idea to use enan-
tiomerically pure chlorodioxaphospholanes 2 as a tool for derivatizing
chiral alcohols in order to determine their enantiomeric excess. For this
purpose, the commercially available secondary alcohols 5a–c in their

Triphenylethanediol-Derived 2-Chloro-1,3,2-dioxaphospholane
2539
SCHEME 3
racemic as well as enantiomerically pure form were treated with a so-
lution of 2 in the presence of triethylamine, and the 31P NMR spectra
of the products 6 and/or 7 were measured directly from the reaction
mixture. The chemical shifts of the 31P resonances are given in Table I
for the major and the minor epimer at the phosphorus atom. Except for
the phosphites 6b/7b derived from 2-butanol (5b), not only the major
epimers but also the minor ones showed sufficiently large shift differ-
ences. Their formation is not necessarily a drawback inasmuch as its
31P MNR signals serve as an additional probe to determine the enan-
tiomeric excess of the alcohol. The derivatization of racemic carbinols 5
clearly indicates that no kinetic resolution has occurred upon reaction
with chlorodioxaphospholane 2.
In summary, the triphenylglycol motif, frequently applied as an aux-
iliary group in asymmetric synthesis,15 is now used to generate chloro-
dioxaphospholane 2, which forms in a diastereoselective manner. The
chlorophosphite 2 readily reacts with chiral secondary alcohols and
permits determination of their optical purity by simply taking the 31P
NMR spectra of the reaction mixture.
EXPERIMENTAL
Specific rotations were determined with a Perkin-Elmer 341 polarime-
ter. NMR spectra were determined using a Bruker DRX 200 and
DRX 500. Toluene was distilled from sodium wire under nitrogen and
was taken from the receiving flask with syringes. Triethylamine was

2540
T. Meier et al.
TABLE I 31P Chemical Shiftsa of Phosphites 6/7 Obtained from Alco-
hols 5 with Chlorodioxaphospholane 2
Chiral
Alcohol 5
Enantiomer of 2
(RC,SP)-2
Phosponites 6/7 31P Chemical Shifts
(RC,SP)-2
(SC,RP)-2
1
a 31P{ H}NMR-data, measured in toluene.
refluxed over CaH2 for several hours and distilled under nitrogen. The
receiving flask was closed thereafter with a septum and rinsed with
nitrogen. All reactions were carried out under an atmosphere of an-
hydrous argon. Reaction temperatures below 0◦C were monitored by a
thermocouple connected to a resistance thermometer (Ebro).
(2R,5S)-2-Chloro-4,4,5-triphenyl-1,3,2-dioxaphospholane (2)
A 250-mL flask was equipped with a stirring bar, and a connection to
a combined argon/vacuum line and was closed with a septum. The air
in the flask was replaced by argon, PCl3 (1.53 mL, 17.5 mmol) and
triethylamine (4.86 mL, 34.9 mmol) were injected by syringes, and the
mixture was cooled to –78◦C. Triphenylglycol (S)-3 (5.08 g, 17.5 mmol)
was suspended in toluene (100 mL) under argon and added through

Triphenylethanediol-Derived 2-Chloro-1,3,2-dioxaphospholane
2541
a cannula under stirring at such a rate that the temperature did not
exceed −60◦C. The mixture was slowly warmed up to room temperature
and stirred for 60 h. The precipitate that formed during the reaction
was removed by filtration through a frit under argon. The residue was
rinsed twice with toluene (10 mL each time). The combined filtrates
were concentrated under reduced pressure at room temperature. In
the course of this, crystalline (2R,5S)-2 formed gradually and was used
for single crystal X-ray diffraction. [α]D25 = +123.6 (c 3.9 in toluene);1H
NMR (C6D6, 200 MHz): δ = 6.69 (d, J = 1.7 Hz, 1H, 5-H), 6.87–7.08 (m,
9H), 7.12–7.31 (m, 4H), 7.76–7.83 (m, 2H) (arom-H). 31P NMR (C6D6,
1
81 MHz): δ = 168 (broad s). 13C{ H} NMR (C6D6, 125 MHz): δ = 85.5 (d,
J = 7.0 Hz, C-5), 92.5 (d, J = 7.1 Hz, C-4), 126.3–127.6 (Carom), 133.2
(d, J = 5.7 Hz), 138.2 (d, J = 2.5 Hz), 140.5 (s, C-i).
Crystal Structure Determination of (2R,5S)-2
A well-shaped crystal of the compound was selected by means of an
optical microscope, sealed in a thin-walled glass capillary (Hilgenberg
GmbH, Germany). Data collection was performed at –40◦C on an
STOE IPDS diffractometer, using graphite monochromatized Mo Kα
radiation (λ = 0.71073 Å). Unit cell parameters were determined by
least-squares refinement on the positions of 8000 strong reflections,
distributed equally in reciprocal space in the range 2.05◦ < ꢀ < 25.95◦.
An orthorhombic lattice was found, and by inspection of the systematic
extinctions space group, P212121 was uniquely determined. Crystal
data, as well as details of data collection and structure refinement, are
listed in Table II. LP corrections were applied to the collected data, and
the structure was solved by direct methods16 and subsequent Fourier
syntheses. Approximate positions of all hydrogen atoms were found via
difference Fourier syntheses. Refinement by full-matrix least-squares
17
calculations on F2
converged (max. shift/esd: 0.000) to the final
indicators given in Table II. Refined parameters include anisotropic
displacement parameters for all the atoms heavier than hydrogen. The
H atoms were treated as riding on their parent carbon atoms in ideal-
ized positions. Isotropic displacement parameters were kept equal to
120% of the equivalent isotropic displacement parameters of the parent
carbon atom. The refined Flack parameter (–0.01(6)) clearly indicated
the choice of the correct enantiomorph. Scattering factors, dispersion
corrections, and absorption coefficients were taken from International
Tables for Crystallography (1992, Vol. C, Tables 6.114, 4.268, and
4.2.4.2). Crystallographic data (excluding structure factors) for the
structure reported in this article have been deposited with the Cam-
bridge Crystallographic Data Centre as supplementary publication no.

2542
T. Meier et al.
TABLE II Crystal Data, X-Ray Measurement, and Structure Determi-
nation Summary for Compound (2R,5S)-2
Empirical formula
C20H16ClO2P
354.75
colorless, prism
0.38 × 0.22 × 0.18
orthorhombic
P212121
Formula weight
Crystal color; habit
Crystal size (mm3)
Crystal system
Space group
Unit cell dimensions
a = 9.4185(5) Å
b = 9.7205(6) Å
c = 18.7925(10) Å
1720.50(17)
4
1.370
233(2)
STOE IPDS
Mo-Kα, λ = 0.71073
0.324
Volume (Å3)
Z
Density (calcd.; g·cm−3
Temperature (K)
Diffractometer
Wavelength (Å)
)
Absorption coefficient (mm−1
F(000)
)
736
Data collection mode
φ-scans
θ Range (◦)
2.17 ≤ θ ≤ 25.96
−11 ≤ h ≤ 11;
−11 ≤ k ≤ 11;
−23 ≤ l ≤ 23
24638/3359;
(Rint = 0.044)
3064
Index ranges
Reflections collected/unique
Observed reflections [I > 2σ(I)]
Data/parameters
3359/217
0.998
Goodness of fit on F2
Final R indices [I > 2σ(I)]
R1 = 0.026;
wR2 = 0.059
R1 = 0.029;
wR2 = 0.060
0.214/−0.153
R indices (all data)
Largest diff. peak/hole (e·Å−3
)
CCDC 666785. Copies of the data can be obtained free of charge upon
application to The Director, CCDC, 12 Union Road, Cambridge CB2
1EZ (fax: int. +1223/336–033; E-mail: teched@chemcrys.cam.ac.uk) or
via the Internet at http://www.ccdc.cam.ac.uk.
Preparation of a Stock Solution of 2 and Derivatization
of Chiral Alcohols
As described above, to a solution of PCl3 (1.6 mL, 18.34 mmol) and tri-
ethylamine (5.0 mL, 35.87 mmol), a suspension of (S)-3 (4.99 g, 17.19

Triphenylethanediol-Derived 2-Chloro-1,3,2-dioxaphospholane
2543
mmol) in toluene was added through a thick cannula at –78◦C within
45 min. The flask containing the diol (S)-3 was thereafter rinsed twice
with toluene (15 mL each time), and both portions were added. The
mixture stirred under argon was allowed to reach room temperature
overnight and was stirred for 48 h. The precipitate was removed by
suction filtration under argon and washed with toluene (20 mL). The
combined filtrates were concentrated under reduced pressure at room
temperature. To the residue, 100 mL of toluene were added. By means
of a cannula, 40 mL of this solution was transferred into a second
flask under argon. A slight white solid material on the bottom of the
first flask must not be transferred. The clear solution was again con-
centrated at room temperature under reduced pressure and the residue
thus obtained was dissolved in 50 mL of toluene so that a clear colorless
solution formed that contained 2 (6.87 mmol); 0.137 M solution. In or-
der to determine the enantiomeric excess, the corresponding secondary
alcohol (1.0 mmol) was dissolved in toluene (2 mL) and added to a mix-
ture of the stock solution of 2 (5 mL, 0.69 mmol) and triethylamine
(0.5 mL, 3.59 mmol) at room temperature. The sample was filtrated
under argon through a syringe filter and subjected to 31P NMR spec-
troscopy. When the derivatization is performed at lower temperatures,
the products, which are diastereomeric at the phosphorus center, form
in a different ratio.
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