Practical synthesis of P-stereogenic diphosphacrowns

Article abstract of DOI:10.1021/ol900504e

P-Stereogenic 18-diphosphacrown-6 derivatives containing a chiral bisphosphine unit were synthesized. This is the first practical method for the synthesis of optically pure diphosphacrowns. The diphosphacrowns have the structure of a chiral figure "8" wit

Full text of DOI:10.1021/ol900504e

ORGANIC
LETTERS
2009
Vol. 11, No. 11
2241-2244
Practical Synthesis of P-Stereogenic
Diphosphacrowns
Yasuhiro Morisaki,* Hiroaki Imoto, Kazuhiko Tsurui, and Yoshiki Chujo*
Department of Polymer Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
ymo@chujo.synchem.kyoto-u.ac.jp; chujo@chujo.synchem.kyoto-u.ac.jp
Received March 11, 2009
ABSTRACT
P-Stereogenic 18-diphosphacrown-6 derivatives containing a chiral bisphosphine unit were synthesized. This is the first practical method for
the synthesis of optically pure diphosphacrowns. The diphosphacrowns have the structure of a chiral figure “8” with chiral heteroatoms that
interact directly with guest ions and molecules. Pd(II) and Pt(II) complexes with the P-stereogenic diphosphacrowns were also synthesized
and characterized.
Crown ethers are cyclic oligomers consisting of ethylene
oxide (-CH2CH2-O-) units.1,2 Since the landmark discov-
ery of dibenzo-18-crown-6 by Pedersen in 1967, great
progress has been made in the field of host-guest chemistry
by using crown ethers because of their selective complexation
of alkali metals and organic cations.1 Various crown ether
derivatives such as azacrowns containing nitrogen atoms,2c
thiacrowns containing sulfur atoms,2d,e and phosphacrowns
containing phosphorus atoms2f-h have been prepared. More-
over, optically active crown ethers have been of interest for
chiral recognition. However, to the best of our knowledge,
there have been no reports on the synthesis of optically pure
crown ethers containing chiral heteroatoms that interact
directly with guest ions and molecules.
The trivalent phosphorus atom can act as a chiral center,
similar to a carbon atom, due to its high inversion energy,3
and a wide variety of P-stereogenic phosphines have been
synthesized.4 In particular, P-stereogenic bisphosphines have
played important roles as efficient chiral ligands for transi-
tion-metal-catalyzed asymmetric reactions.4a-c Recently, we
employed P-stereogenic bisphosphines (S,S)-1-BH3 (R ) tert-
Bu or Ph) as chiral building blocks for the synthesis of
(1) Pedersen, C. J. J. Am. Chem. Soc. 1967, 89, 7017–7036
.
(2) (a) Crown Ethers and Analogous Compounds, Studies in Organic
Chemistry 45, M; Hiraoka, M., Ed.; Elsevier: Amsterdam, 1992. (b)
Bradshaw, J. S.; Izatt, R. M.; Bordunov, A. V.; Zhu, C. Y.; Hathaway,
J. K. Crown Ethers; Lehn, J. M., Atwood, J. L., Davies, J. E. D., Macnicol,
D. D., Vogtle, F., Eds.; Comprehensive Supramolecular Chemistry, Vol.
1; Pergamon Press: Oxford, England, 1996; Chapter 2, pp 35-95. (c) Aza-
Crown Macrocycles; Bradshaw, J. S., Krakowiak, K. E., Izatt, R. M., Eds.;
John Wiley & Sons: New York, 1993. (d) Crown Compounds: Toward
Future Applications; Cooper, R. S., Ed.; VCH Publishers: New York, 1992;
Chapters 14 and 15. (e) Adam, R. D. Acc. Chem. Res. 2000, 33, 171–178.
(f) Caminade, A. M.; Majoral, J. P. Chem. ReV. 1994, 94, 1183–1213. (g)
Bader, A.; Lindner, E. Coord. Chem. ReV. 1991, 108, 27–110. (h)
Ciampolini, M.; Dapporto, P.; Dei, A.; Nardi, N.; Zanobini, F. Inorg. Chem.
(3) Weston, R. E. J. Am. Chem. Soc. 1954, 76, 2645–2648.
(4) (a) Yamanoi, Y.; Imamoto, T. ReV. Heteroatom. Chem. 1999, 20,
227–248. (b) Crepy, K. V. L.; Imamoto, T. Top. Curr. Chem. 2003, 229,
1–40. (c) Crepy, K. V. L.; Imamoto, T. AdV. Synth. Catal. 2003, 345, 79–
101. (d) Johansson, M. J.; Kann, N. C. Mini-ReV. Org. Chem. 2004, 1,
233–247. (e) Grabulosa, A.; Granell, J.; Muller, G. Coord. Chem. ReV. 2007,
251, 25–90.
1982, 21, 489–495
.
10.1021/ol900504e CCC: $40.75
Published on Web 05/07/2009
 2009 American Chemical Society

optically active oligomers,5 polymers,6 and dendrimers.7
Further, we reported the stereospecific synthesis of trans-
1,4-diphosphacyclohexanes8 by the intramolecular cyclization
of (S,S)-1-BH3 and the construction of a 12-phosphacrown-4
skeleton5a by the intramolecular cyclization of (S,R,R,S)-2-
BH3, as shown in Scheme 1. This 12-phosphacrown-4 is the
chiral phosphorus atoms and four oxygen atoms. The
synthesis was carried out by using P-stereogenic bisphos-
phines (S,S)-3-BH3 and (R,R)-3-BH3 as the key building
blocks. This is the first practical method for the synthesis of
optically pure diphosphacrowns. The synthetic procedure,
characterization, and complexation with Pd(II) and Pt(II) are
described.
The synthesis of (S,S)-18-diphosphacrown-6 is illustrated
in Scheme 2. P-Stereogenic bisphosphine (S,S)-1-BH3 was
Scheme 1. Stereospecific Construction of
trans-1,4-Diphosphacyclohexane and 12-Phosphacrown-4
Skeletons
Scheme 2. Synthesis of (S,S)-4-BH3
first example of
a phosphacrown comprising only
-CH2CH2-PR- units;5a,9 however, chiralities of optically
active precursors (S,S)-1-BH3 and (S,R,R,S)-2-BH3 disappear
from the ring structure. On the other hand, Lippard and co-
workers reported the synthesis of 21-diphosphacrown-7
derivatives,10 which consist of two phosphorus atoms and
five oxygen atoms, and the separation of meso and racemic
21-diphosphacrown-7 derivatives from their Pd(II) com-
plexes. Optical resolution of this racemic 21-diphosphac-
rown-7-Pd(II) complex was also achieved using Pasteur’s
method.10
prepared with >99% ee8 from dimethylphenylphosphine by
following the procedure given in the literature.11 The
dilithiation of two methyl groups of (S,S)-1-BH3 by sec-BuLi/
N,N,N′,N′-tetramethylenediamine (TMEDA) and subsequent
CO2 bubbling afforded dicarboxy acid, which was used
without purification for the subsequent reaction. The reduc-
tion of two carboxylic groups with BH3·THF yielded the
optically pure dialcohol (S,S)-3-BH3 in 42% isolated yield.
The reaction of (S,S)-3-BH3 with NaH and triethyleneglycol
bis(p-toluenesulfonate) was carried out to obtain the corre-
sponding optically pure 18-diphosphacrown-6 (S,S)-4-BH3
in 17% isolated yield.
Next, the preparation of enantiomer (R,R)-4-BH3 was
attempted, as shown in Scheme 3. The enantioselective
lithiation of dimethylphenylphosphine-borane by sec-BuLi/
(-)-sparteine and the reaction with CO2 bubbling provided
the corresponding carboxylic acid, which was used without
purification for the subsequent reaction. The reduction of the
carboxylic acid by BH3·THF afforded alcohol (S)-5-BH3 in
71% yield with 87% ee.12 The remaining methyl group in
(S)-5-BH3 was lithiated with sec-BuLi/TMEDA, and then it
In this communication, we report the synthesis of optically
active 18-diphosphacrown-6 derivatives consisting of two
(5) (a) Morisaki, Y.; Ouchi, Y.; Fukui, T.; Naka, K.; Chujo, Y.
Tetrahedron Lett. 2005, 46, 7011–7014. (b) Morisaki, Y.; Ouchi, Y.; Naka,
K.; Chujo, Y. Tetrahedron Lett. 2007, 48, 1451–1455. (c) Morisaki, Y.;
Ouchi, Y.; Naka, K.; Chujo, Y. Chem. Asian J. 2007, 2, 1166–1173.
(6) (a) Ouchi, Y.; Morisaki, Y.; Ogoshi, T.; Chujo, Y. Chem. Asian J.
2007, 2, 397–402. (b) Morisaki, Y.; Ouchi, Y.; Tsurui, K.; Chujo, Y. J.
Polym. Sci., Part A: Polym. Chem. 2007, 45, 866–872. (c) Morisaki, Y.;
Ouchi, Y.; Tsurui, K.; Chujo, Y. Polym. Bull. 2007, 58, 665–671.
(7) Ouchi, Y.; Morisaki, Y.; Chujo, Y. Polym. Bull. 2007, 59, 339–
349.
(8) Morisaki, Y.; Imoto, H.; Ouchi, Y.; Nagata, Y.; Chujo, Y. Org. Lett.
2008, 10, 1489–1492.
(9) Cyclic diphosphines with a small ring size are reviewed, see: (a)
Alder, R. W.; Canter, C.; Gil, M.; Gleiter, R.; Harris, C. J.; Harris, S. E.;
Lange, H.; Orpen, A. G.; Taylor, P. N. J. Chem. Soc., Perkin Trans. 1
1998, 1643–1655. See also as a recent example: (b) Bates, J. I.; Gates, D.
P J. Am. Chem. Soc. 2006, 128, 15998–15999
.
(10) (a) Wei, L. W.; Bell, A.; Warner, S.; Williams, I. D.; Lippard, S. J.
J. Am. Chem. Soc. 1986, 108, 8302–8303. (b) Wei, L. W.; Bell, A.; Ahn,
K. H.; Holl, M. M.; Warner, S.; Williams, I. D.; Lippard, S. J. Inorg. Chem.
1990, 29, 825–837.
(11) Muci, A. R.; Campos, K. R.; Evans, D. A. J. Am. Chem. Soc. 1995,
117, 9075–9076.
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Org. Lett., Vol. 11, No. 11, 2009

Scheme 3. Synthesis of (R,R)-4-BH3
was treated with CuCl2 and aqueous NH3 to yield a mixture
of meso-3-BH3 and racemi-3-BH3 due to 87% ee of (S)-5-
BH3. The diastereomer meso-3-BH3, which was formed by
the coupling reaction between (S)- and (R)-5-BH3, and
enantiomer (S,S)-3-BH3 could be removed by the repeated
recrystallization (three or four times) from hot toluene and
hexane and afforded optically pure dialcohol (R,R)-3-BH3
in 36% isolated yield (>99% ee).13 Optically pure diphos-
phacrown (R,R)-4-BH3 was obtained in 22% isolated yield
by following the same synthetic procedure as in the case of
(S,S)-4-BH3.
The structure of the optically pure 18-diphosphacrown-6
was confirmed by 1H, 13C, and 31P NMR spectroscopy, mass
analysis, elemental analysis,14 and X-ray crystallography. The
ORTEP drawings of (S,S)-4-BH3 are shown in Figure 1; they
indicate the presence of two conformations. One conformer
possesses two phenyl groups on the side opposite to the
diphosphacrown ring (side view I in Figure 1), and the other
possesses two phenyl groups above the ring (side view II in
Figure 1). In other words, two phenyl groups occupy
pseudoequatorial positions (side view I) or pseudoaxial
positions (side view I) to the crown ring. In solution, the
ring structure of the diphosphacrown is flexible, and the rapid
interconversion of two conformers occurs.15 The optically
active diphosphacrown has the structure of a chiral figure
eight “8”, which is formed by two chiral phosphorus atoms
(front views I and II in Figure 1), and two phenyl groups at
Figure 1. ORTEP drawings of (S,S)-4-BH3 with 50% thermal
ellipsoids. Selected bond lengths (Å) and angles (deg): P1-C20,
1.827(3); P1-C23, 1.822(4); P4-C13, 1.829(4); P4-C34, 1.827(4);
P1-B4, 1.906(5); P4-B3, 1.909(4); P2-C21, 1.817(4); P2-C24,
1.810(4); P3-C16, 1.810(4); P3-C25, 1.831(4); P2-B2, 1.915(5);
P3-B1, 1.917(4); C23-P1-C20, 110.03(17); C13-P4-C34,
105.26(18); C21-P2-C24, 104.82(18); C16-P3-C25, 109.68(18).
chiral phosphorus atoms are found in two diagonal quadrants.
Because of the long P-C bonds (average length: ap-
proximately 1.83 Å), the ring size of 18-diphosphacrown-6
is slightly larger than that of 18-crown-6.
The coordinated boranes of diphosphacrown (S,S)-4-BH3
could be easily removed by treatment with organic amines
such as 1,4-diazabicyclo[2.2.2]octane (DABCO)16 to afford
the corresponding diphosphacrown (S,S)-4 as an air sensitive
colorless solid in 90% isolated yield. To obtain insight into
the complexation behavior with transition metals as well as
the asymmetric environment created by the optically active
diphosphacrown (S,S)-4, palladium and platinum complexes
(12) This compound was synthesized on the basis of the procedure
reported in the literature by Ohashi, Imamoto, and co-workers: (a) Ohashi,
A.; Kikuchi, S.; Yasutake, M.; Imamoto, T. Eur. J. Org. Chem. 2002, 2535–
2546. The ee value was determined by HPLC with Daicel Chiralcel OD-H
column, as shown in Figure S1.
(13) Its optical purity (>99% ee) was confirmed by HPLC with Daicel
Chiralcel OD-H column, as shown in Figure S2.
(14) See Supporting Information.
(15) 31P NMR spectrum of (S,S)-4-BH3 exhibits a sharp single signal
with a P-B coupling, as shown in Figure S8.
(16) Imamoto, T.; Oshiki, T.; Onozawa, T.; Kusumoto, T.; Sato, K.
J. Am. Chem. Soc. 1990, 112, 5244–5252.
Org. Lett., Vol. 11, No. 11, 2009
2243

MCl2[(S,S)-4] (M ) PdII and PtII) were synthesized by the
reaction of MCl2(cod) with (S,S)-4 (cod ) 1,5-cyclooctadi-
ene), as shown in Scheme 4. Both the reaction with PdII and
Two phenyl groups are also found at two diagonal quadrants
and occupy quasi-equatorial positions (front view). This is
similar to the case of a series of rhodium-(P-chiral bispho-
sphine) complexes.4a-c,18 In addition, the corresponding
palladium complex PdCl2[(S,S)-4] also shows the same
conformation around the metal center (Supporting Informa-
tion, Figure S19). On the other hand, according to the
ORTEP drawings of the PdCl2[21-diphosphacrown-7] com-
plex reported by Lippard and co-workers, it seems that the
complex adopts the different conformation around palladium;
that is, the two phenyl groups occupy quasi-axial positions
in the crystal.10 In these cases, PdCl2 and PtCl2 are located
outside of the crown ring, and two phenyl groups at
phosphorus are in the anti orientation with respect to the
coordination plane.
Scheme 4. Synthesis of MCl2[(S,S)-4] (M ) Pd and Pt) and
ORTEP Drawings of PtCl2[(S,S)-4] with 50% Thermal
Ellipsoidsa
In summary, we have demonstrated the practical synthesis
of optically pure crown ether derivatives containing two
asymmetric phosphorus atoms in the chains. We have also
synthesized new P-stereogenic bisphosphines as precursors.
The obtained optically pure diphosphacrowns have the
structure of a chiral figure “8”, which contains chiral
heteroatoms (phosphorus atoms) that interact directly with
guest ions and molecules. Pd(II) and Pt(II) complexes with
the diphosphacrowns were synthesized and characterized.
Further studies on the synthesis of a series of optically pure
diphosphacrowns with several ethylene oxide (-CH2-
CH2O-) units and their binding properties with the guest
ions are in progress. Future studies will focus on transition-
metal-catalyzed asymmetric reactions involving the use of
optically pure diphosphacrowns as an asymmetric ligand.
a Selected bond lengths (Å) and angles (deg): Pt1-P6, 2.2259(10);
Pt1-P7, 2.2298(9); Pt1-Cl1, 2.3641(10); Pt1-Cl2, 2.3613(8); P6-C19,
1.835(4); P6-C34, 1.834(4); P7-C28, 1.820(4); P7-C37, 1.833(4);
P6-Pt1-P7, 87.22(3); P6-Pt1-Cl2, 91.30(3); P7-Pt1-Cl1, 91.79(3);
Cl1-Pt1-Cl2, 89.87(3); C19-P6-C34, 108.75(18); C28-P7-C37,
109.02(18).
Acknowledgment. This work was supported by Grant-
in-Aid for Science Research on Priority Areas (No. 20036027,
Synergy of Elements) from Ministry of Education, Culture,
Sports, Science and Technology, Japan.
that with PtII proceeded smoothly to yield the corresponding
MCl2[(S,S)-4] complex in 69% and 58% isolated yield,
respectively. Their structures were confirmed by 1H, 13C, and
31P NMR spectroscopy, mass analysis, elemental analysis,
and X-ray crystallography. In the 31P NMR spectrum of
PtCl2[(S,S)-4], the typical satellite signal obtained from the
phosphorus-platinum coupling (JP-Pt) was observed at δ
+46.6 ppm with JP-Pt ) 3594.0 Hz.17 The ORTEP drawing
of PtCl2[(S,S)-4] is shown in Scheme 4. The X-ray analysis
revealed that (S,S)-4 was coordinated to the platinum center,
which existed outside the diphosphacrown ring (top view).
Supporting Information Available: Experimental pro-
cedures, compound characterization data, NMR spectra,
X-ray crystallographic data, and an X-ray crystallographic
files (CIFs). This material is available free of charge via the
Internet at http://pubs.acs.org.
OL900504E
(18) (a) Vineyard, B. D.; Knowles, W. S.; Sabacky, M. J.; Bachman,
G. L.; Weinkauff, D. J. J. Am. Chem. Soc. 1977, 99, 5946–5952. (b)
Imamoto, T.; Watanabe, J.; Wada, Y.; Masuda, H.; Yamada, H.; Tsuruta,
H.; Matsukawa, S.; Yamaguchi, K. J. Am. Chem. Soc. 1998, 120, 1635–
(17) 31P NMR spectrum of PtCl2[(S,S)-4] is shown in Figure S17.
1636.
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