Diastereospecific synthesis of phosphinidene-capped cyclodextrins leading to "introverted" ligands

Article abstract of DOI:10.1039/b315802k

α-Cyclodextrins (α-CDs) containing "PPh" units which cap the primary face of the CD were obtained in high yield by reaction of Li₂PPh with A,B- or A,C-dimesylated and A,B,D,E-tetramesylated precursors; the resulting phosphines are diaster-eomer

Full text of DOI:10.1039/b315802k

Diastereospecific synthesis of phosphinidene-capped cyclodextrins
leading to “introverted” ligands†
Eric Engeldinger,a Laurent Poorters,a Dominique Armspach,*a Dominique Matt*a and Loïc Toupetb
a Laboratoire de Chimie Inorganique Moléculaire, UMR 7513, Université Louis Pasteur, 1 rue Blaise
Pascal, F-67008 Strasbourg cedex, France. E-mail: darmspach@chimie.u-strasbg.fr.
E-mail: dmatt@chimie.u-strasbg.fr
b Groupe Matière Condensée et Matériaux, UMR 6626, Université de Rennes 1, Campus de Beaulieu, Bât.
11A, F-35042 Rennes cedex, France. E-mail: toupet@univ-rennes1.fr
Received (in Cambridge, UK) 4th December 2003, Accepted 30th January 2004
First published as an Advance Article on the web 20th February 2004
a-Cyclodextrins (a-CDs) containing “PPh” units which cap the
primary face of the CD were obtained in high yield by reaction
of Li2PPh with A,B- or A,C-dimesylated and A,B,D,E-tetra-
mesylated precursors; the resulting phosphines are diaster-
eomerically pure and constitute valuable precursors for the
synthesis of metallo-cavitands.
An endo-orientation of the phosphorus lone pair was also found
in phosphine 2, as revealed by its reaction with [PdCl(o-
C6H4NMe2]2, which quantitatively produces complex 6. A 2D
ROESY experiment unambiguously showed a spatial proximity
between the two diastereotopic NMe groups and three of the
Metal-capped cyclodextrins (CDs) constitute useful tools for the
study of metal-centred reactions occurring inside a confined
environment1 as well as for the synthesis of supramolecular
catalysts suitable for industrial reactions.2 The construction of such
complexes most often relies on the use of CDs bearing several
pendant ligands arranged in a manner allowing chelation about one
of the two edges. A properly configured podand set is expected to
maintain the complexed metal centre near the cavity entrance. In
this respect the length of the binding units as well as their rigidity
are crucial factors for controlling the position of the metal with
respect to the cavity. In the present report we describe the first
syntheses of cyclodextrins containing the (very short) “PhP”
capping unit. The reported cavity-shaped ligands are characterized
by endo-oriented donor atoms.
Reaction of Li2PPh in THF with the A,B-dimesylated precursor
1 afforded the primary face-capped CD 2‡ in ca. 70% yield
(Scheme 1). It is noteworthy that no intermolecular coupling
occurred. The 31P NMR spectrum of the resulting phosphine shows
1
a singlet at 216.2 ppm. In the H NMR spectrum, the 6 distinct
anomeric signals appear in a narrow range (Ddmax ca. 0.1 ppm),
indicating that bridge formation does not cause a significant
distortion of the CD torus. This situation contrasts with that found
in the related A,C-bridged CD 4 formed in 60% yield from the
1
corresponding dimesylate 3. In this case the H NMR spectrum
reveals a considerable dispersion of the H-1 protons (ranging
between 4.66 and 5.69 ppm), in keeping with a marked shape
modification. The latter was confirmed by an X-ray diffraction
study carried out on the corresponding oxide 5 (vide infra).
Cyclisation reactions involving the PhP22 dianion and a dimesy-
lated CD precursor are unprecedented, although the synthesis of
chiral phosphiranes according to this scheme has been reported
recently.3
Scheme 1 Syntheses of the capped CDs 2 and 4.
The solid state structure of 5§ (Fig. 1) reveals discrete
supramolecular dimers resulting from inclusion of a single phenyl
ring in the neighbouring CD cavity. As expected, the two CDs of
dimeric 5 are elliptically distorted, glucose ring B adopting an
almost perfect 5S1 skew boat4 conformation.¶ Interestingly, the
observed head-to-tail assembly is not repeated indefinitely, in stark
contrast with many other monoarylated CDs which form polymeric
chains in the solid state.5 The most striking feature in each CD unit
is the orientation of the P–O bond which points towards the centre
of the cavity, the phenyl ring being exo-orientated with respect to
the CD. Thus, this structural determination also establishes the
diastereospecificity of the reaction leading to 4.
† Electronic supplementary information (ESI) available: synthesis and full
characterization of all compounds. See http://www.rsc.org/suppdata/cc/b3/
b315802k/
Fig. 1 Supramolecular structure of 5 in the solid state. Bond lengths (Å): P–
O 1.488(4), PA–OA 1.482(4).
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C h e m . C o m m u n . , 2 0 0 4 , 6 3 4 – 6 3 5
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

primary methoxy groups. No through-space correlations were
detected between CD protons and aromatic ones. These findings
clearly indicate that the palladacycle lies above the cavity and its
plane roughly parallels that of the CD axis. Furthermore, the
significant downfield shift experienced by proton H-5A (ca. 0.6
ppm) on going from free 2 to 6 is fully consistent with
encapsulation of the chloride atom within the CD. The “chlor-
ophilic” behaviour of CDs has been documented recently.6
Finally, the aforementioned capping reaction could be extended
to the high-yield preparation of a doubly-bridged cyclodextrin, only
the second example of this type.7 Thus, reaction of the A,B,D,E-
tetramesylate 7 with Li2PPh in excess afforded the C2-symmetrical
diphosphine 8 (31P: 216.8 ppm) in 90% yield (Scheme 2). Each
bridging reaction involves selective substitution of adjacent mesyl
groups. As for 2, there is no indication for an anomalous distortion
of the CD core. Ligand 8 is a rare example of a chelating ligand
behaving selectively as a trans-chelator when bound to d8-metal
ions. For example, its reaction with the complexes [PtCl2(PhCN)2],
[PdCl2(PhCN)2] and [PdClMe(1,5-cyclooctadiene)] afforded quan-
titatively the complexes 9–11, respectively (Scheme 3). Again, in
each of these complexes one metal–chlorine bond points towards
the centre of the cavity, as shown by the presence of downfield-
shifted H-5 signals in the corresponding 1H NMR spectra.
In summary, A,B- or A,C-dimesylated and A,B,D,E-tetra-
mesylated cyclodextrins are valuable synthons for the high yield
synthesis of phosphinidene-capped CDs. The coupling reactions
with Li2PPh are not only diastereospecific but also lead to
introverted ligands suitable for partial encapsulation of metal–
organic fragments.
Scheme 3 trans-Chelating behaviour of diphosphine 8.
Notes and references
‡ All compounds were fully characterized on the basis of their spectral data
and C–H–N analysis (see ESI). Selected spectroscopic data: 2: 31P{1H}
NMR (121.5 MHz, CDCl3): d = 216.2 (s). 4: 31P{1H} NMR (121.5 MHz,
CDCl3): d = 221.1 (s). 5: 31P{1H} NMR (121.5 MHz, CDCl3) d 35.3 (s).
6: 31P{1H} NMR (121.5 MHz, CDCl3): d = 17.4 (s). 8: 31P {1H} NMR
(121.5 MHz, CDCl3, 25 °C): d = 216.8 (s). 9: 31P {1H} NMR (121.5 MHz,
CDCl3, 25 °C): d = 26.5 (s with Pt satellites, 1JPt,P = 2463 Hz). 10: 31
P
{1H} NMR (121.5 MHz, CDCl3, 25 °C): d = 20.4 (s). 11: 31P {1H} NMR
(121.5 MHz, CDCl3, 25 °C): d = 3.8 (s). As unambiguously shown by a
ROESY experiment, the H atoms of the PdMe group correlate with aromatic
protons as well as some H-6 protons.
§ Crystal data for 2C58H95O29P2·CHCl3·1.5C4H8O·H2O 5: M = 2800.11,
monoclinic, space group P21, a = 14.8015(1), b = 29.1555(3), c =
17.1807(2) Å, b = 99.330(1)°, U = 7316.2(1) Å3, Z = 2, T = 110 (1) K,
1706 variables and 18612 reflections with [I > 2s(I)], R = 0.078, Rw
=
0.189, Sw = 1.012, Dr < 1.26 e Å23. The dimer co-crystallized with
molecules of chloroform, diethyl ether, and water (ratio: 1:1.5:1). The two
molecules of the asymmetric unit have the same absolute configuration.
CCDC 219493. See http://www.rsc.org/suppdata/cc/b3/b315802k for crys-
tallographic data in .cif or other electronic format.
¶ All other glucose units are in a typical chair conformation.
1 See for example: Modified Cyclodextrins, eds. C. J. Easton and S. F.
Lincoln, Imperial College Press, London, 1999; D. Armspach, D. Matt, F.
Peruch and P. Lutz, Eur. J. Inorg. Chem., 2003, 805; E. Engeldinger, D.
Armspach, D. Matt and P. G. Jones, Chem. Eur. J., 2003, 9, 3091; E.
Engeldinger, D. Armspach and D. Matt, Chem. Rev., 2003, 103, 4147.
2 See for example: M. T. Reetz and S. R. Waldvogel, Angew. Chem., Int.
Ed., 1997, 36, 865; E. Engeldinger, D. Armspach, D. Matt, L. Toupet and
M. Wesolek, C. R. Chim., 2002, 5, 359.
3 A. Marinetti, V. Kruger and F.-X. Buzin, Tetrahedron Lett., 1997, 38,
2947.
4 S. Immel, J. Brickmann and F. W. Lichtenthaler, Liebigs Ann., 1995,
929.
5 K. Harata, Chem. Rev., 1998, 98, 1803.
6 E. Engeldinger, D. Armspach, D. Matt, P. G. Jones and R. Welter, Angew.
Chem., Int. Ed., 2002, 41, 2593.
7 I. Tabushi, L. C. Yuan, K. Shimokawa, K-i Yokota, T. Mizutani and Y.
Kuroda, Tetrahedron Lett., 1981, 24, 2273.
Scheme 2 Synthesis of diphosphine 8.
C h e m . C o m m u n . , 2 0 0 4 , 6 3 4 – 6 3 5
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