New chiral phosphine-phosphonites derived from (2R,3R)-dimethyl tartrate, (S)-binaphthol and (1R,2S)-ephedrine

Article abstract of DOI:10.1016/S0957-4166(98)00493-5

The reaction of 2-lithiophenyldiphenylphosphine with phosphorus trichloride afforded the new unsymmetric phosphine, dichloro(2- diphenylphosphinophenyl)phosphine (4). Condensation of 4 with (a) (2R,3R)- dimethyl tartrate or (b) (S)-binaphthol in the prese

Full text of DOI:10.1016/S0957-4166(98)00493-5

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 10 (1999) 207–211
New chiral phosphine-phosphonites derived from
2R,3R)-dimethyl tartrate, (S)-binaphthol and (1R,2S)-ephedrine
(
∗
Terence L. Schull and D. Andrew Knight
Department of Chemistry, The George Washington University, 725 21st Street, N.W. Washington, District of Columbia 20052,
USA
Received 26 October 1998; accepted 1 December 1998
Abstract
The reaction of 2-lithiophenyldiphenylphosphine with phosphorus trichloride afforded the new unsymmetric
phosphine, dichloro(2-diphenylphosphinophenyl)phosphine (4). Condensation of 4 with (a) (2R,3R)-dimethyl
tartrate or (b) (S)-binaphthol in the presence of triethylamine gave new chiral phosphine-phosphonite ligands,
0
(
[
2R,3R)-[2-(2 -(diphenylphosphino)phenyl)-4,5-bis(carbomethoxy)-1,3,2-dioxaphospholane] ((2R,3R)-5) and (S)-
0
0
2-(diphenylphosphino)benzene][1,1 -binaphthalen-2,2 -diyl]phosphonite] ((S)-6). The analogous reaction of 4
0
with (1R,2S)-ephedrine using N-methylmorpholine as the base, gave [2-(2 -(diphenylphosphino)phenyl)-3,4-
dimethyl-5-phenyl-1,3,2-oxazaphospholidine] (7) as a 95:5 mixture of diastereoisomers. © 1999 Elsevier Science
Ltd. All rights reserved.
Non-C symmetric bidentate organophosphorus ligands have been the focus of attention of late, in
2
1
transition metal catalyzed asymmetric synthesis. Notable examples are the use of phosphine-phosphite
ligands such as (S,R)-BINAPHOS and (S,R)-BIPHEMPHOS, and phosphine-phosphinite ligands such
as (R,S)-EPHOS, in the rhodium catalyzed hydroformylation of olefins, and bisphosphinites in the
nickel catalyzed hydrocyanation of olefins. Their success has been attributed to the highly asymmetric
2
3
4
5
environment around the metal center that such ligands provide. It is surprising therefore, that alternative
bidentate chelating ligands based on phosphine-phosphonites 1 (Fig. 1) have not been the subject of inves-
tigation, particularly as monodentate TADDOL-type phosphonite ligands have been used with success
6
in the asymmetric rhodium catalyzed hydrosilylation of ketones. The rhodium catalyzed asymmetric
hydrogenation of olefins has also been studied using a chiral bisphosphonite ligand based on a ferrocene
7
backbone. Various chiral bidentate, chelating ligands based on ortho-substituted triphenylphosphine
such as 2 and 3 have recently been applied to enantioselective catalytic reactions including the ruthenium
8
9,10
mediated hydrosilylation of ketones and imines and palladium catalyzed Heck reactions.
To the best
of our knowledge there are no reported examples of phosphonite functionalized phosphine ligands. In
addition to exploring the coordination chemistry of a new ligand class, several additional features of chiral
∗
Corresponding author. E-mail: daknight@gwu.edu
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00493-5

208
T. L. Schull, D. A. Knight / Tetrahedron: Asymmetry 10 (1999) 207–211
Figure 1.
phosphine-phosphonites were attractive to us: (1) the chelating ligands have non-C symmetry which
2
has recently been shown to be an important consideration for certain classes of transition metal catalyzed
asymmetric carbon–carbon bond formation; and (2) a wide variety of inexpensive, readily available chiral
diols, amino alcohols and diamines of both antipodes would allow us to investigate a large number of
optically active ligands in enantioselective catalytic reactions. This communication describes the first
synthesis of optically active phosphine-phosphonite ligands derived from the chiral vicinal diols, (2R,3R)-
dimethyl tartrate and (S)-binaphthol, and the chiral amino alcohol (1R,2S)-ephedrine. Representative
transition metal complexes are also described.
Cyclic phosphonites and 1,3,2-oxazaphospholidines may be prepared readily via the nucleophilic
attack of mono and bi-functional diols or 1,2-amino alcohols on phosphorus dichlorides,11 and one of
the initial problems associated with this strategy was the lack of synthetic accessibility of unsymmetric
dichlorophosphino-phosphines. While symmetric dichlorophosphines have been known for some time,12
there are no reports on the synthesis of phosphines of the type o-Cl PC H PR . The synthetic methods
2
6
4
2
available for the synthesis of arylphosphonous dichlorides include chlorination of primary phosphines
1
2
13
using phosgene or thionyl chloride; decomposition of pentavalent dichlorides; the reaction of
1
1
13
PCl with diarylmercury compounds; and the Friedel–Crafts reaction. The use of either Grignard
3
reagents or organolithium precursors is often deliberately avoided due to facile formation of mixtures
of monoaryl-, diaryl- and triarylphosphines, even at low temperatures.14 The reaction of phosphorus
trichloride with o-lithiophenyldiphenyl phosphine generated from o-bromophenyldiphenylphosphine15
and two equivalents of t-butyllithium in THF at −78°C resulted in the clean conversion to the desired
31
dichlorophosphine 4 as evidenced by P NMR and mass spectral data (Scheme 1). It seemed reasonable
to suggest that the steric bulk of the diphenylphosphino-substituted aryllithium suppresses additional
substitution reactions and subsequent formation of the diaryl and triaryl derivatives. The 3 P NMR
spectrum of 4 in THF contained two sets of doublets at −20.7 and 156.7 ppm typical of a triarylphosphine
and an arylphosphonous dichloride, respectively, with a coupling constant of 347 Hz. Compound 4 was
isolated as a viscous, air sensitive, yellow oil which could not be distilled or crystallized without extensive
decomposition, and further condensation reactions were performed using 4 in situ.
1
Scheme 1. Synthesis of dichlorophosphine 4
Compound 4 was then reacted with either (2R,3R)-dimethyl tartrate, (S)-binaphthol, or (1R,2S)-
ephedrine in the presence of base or in CH Cl to give the new mixed phosphine-phosphonites (2R,3R)-5
2
2
and (S)-6, respectively (Scheme 2).
After removal of hydrochloride salts by filtration, solvent removal and column chromatography of the
resulting residues, the diastereomerically pure binaphthol and dimethyl tartrate derivatives (2R,3R)-5 and

T. L. Schull, D. A. Knight / Tetrahedron: Asymmetry 10 (1999) 207–211
209
Scheme 2. Synthesis of chiral phosphine-phosphonites (2R,3R)-5 and (S)-6
(S)-6 were isolated as white solids in good yield. The phosphonites are particularly sensitive to hydrolysis
and oxidation, and all attempts to obtain analytically pure samples of (2R,3R)-5 and (S)-6 using repeated
16
column chromatography or crystallization were unsuccessful. The sensitivity of phosphonite ligands to
7
31
hydrolysis has been previously documented. The P NMR spectra of (2R,3R)-5 and (S)-6 show typical
1
4
17
chemical shift values for triarylphosphines and arylphosphonites.
Using the same methodology but with N-methylmorpholine as the base, the 1,3,2-oxazaphospholidine
7
was formed as a mixture of diastereomers (Scheme 3).18 Attempts to separate the diastereomers using
chromatography or fractional crystallization led to varying degrees of oxidation. However, the formation
31
of 7 was followed in situ using P NMR and the initial spectrum contained two doublets at 142.6
2
2
and −17.0 ppm ( J =119 Hz), and 154.2 and −18.6 ppm ( J =115 Hz), in a 95:5 ratio which have
PP
PP
been assigned to the major and minor diastereomers (2R,4S,5R)-7 and (2S,4S,5R)-7 respectively (90%
1
31
de). The stereochemical assignment of individual diastereomers was made on the basis of H and
P
17
NMR chemical shifts. In addition, the formation of the major isomer (2R,4S,5R)-7, which contains the
diphenylphosphino and phenyl groups in the trans disposition, would be favored on steric grounds.
The new phosphine-phosphonites form metal complexes in which the ligands are coordinated via a
bidentate chelate ring as expected. The thermal displacement of carbon monoxide from W(CO) with
6
0
(
2R,3R)-5 in refluxing toluene for 36 hours yielded a new yellow complex cis-[W(CO) (L–L )] 8 for
4
31
which the IR and P NMR spectra are consistent with a structure in which the phosphine-phosphonite
ligand is binding in bidentate, chelating mode as shown in Scheme 4.19
Other phosphine-phosphonite complexes have been prepared in situ and show similar binding proper-
ties. For example, the, slow, controlled addition of a pre-cooled THF solution of (S)-6 to [RhCl(cod)]
2
in THF at −78°C resulted in a color change from yellow to orange and a 3 P NMR spectrum of the
1
solution contained two sets of doublets of doublets at 182.9 ppm (JRhP=346 Hz, J =47 Hz) and 78.0 ppm
PP
(
JRhP=197 Hz, J =47 Hz) which we have tentatively assigned to the phosphine-phosphonite complex
PP
0
20
[RhCl(L–L )(cod)].
In conclusion, we have prepared the first examples of chiral phosphine-phosphonite ligands and
representative organometallic derivatives. The application of these new ligands in enantioselective
catalytic reactions will be presented in future publications.

210
T. L. Schull, D. A. Knight / Tetrahedron: Asymmetry 10 (1999) 207–211
Scheme 3. Synthesis of (1R,2S)-ephedrine-derived phosphine-phosphonite 7
Scheme 4. Synthesis of tungsten complex 8
Acknowledgements
The donors of the Petroleum Research Fund administered by the American Chemical Society are
thanked for generous support of this work.
References
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11. Seebach, D.; Hayakawa, M.; Sakaki, J.; Schweizer, W. B. Tetrahedron 1993, 49, 1711.
12. Kyba, E. P.; Kerby, M. C.; Rines, S. P. Organometallics 1986, 5, 1189.
13. Corbridge, D. E. C. Phosphorus: An Outline of its Chemistry, Biochemistry and Use; Elsevier: Amsterdam, 1995 and
references therein.

T. L. Schull, D. A. Knight / Tetrahedron: Asymmetry 10 (1999) 207–211
211
14. Berlin, K. D.; Austin, T. H.; Peterson, M.; Nagabhushanam, M. In Topics in Phosphorus Chemistry; Grayson, M.; Griffith,
E. J., Eds; Wiley Interscience: New York, 1964.
15. Schull, T. L.; Fettinger, J. C.; Knight, D. A. Inorg. Chem. 1996, 35, 6717.
16. The following synthetic procedure is representative: A Schlenk flask was charged with 2-bromophenyldiphenylphosphine
(
0.413 g, 1.14 mmol), ether (15 mL), and a stirrer bar and cooled to −78°C (2-propanol/CO
mmol, 1.5 M in pentane) was added dropwise with stirring. The resulting suspension was stirred for 10 mins and transferred
slowly via catheter to a stirred solution of PCl (1.0 mL, 11 mmol) in ether (20 mL) cooled to −78°C (2-propanol/CO ).
2
). Then t-BuLi (1.5 mL, 2.3
3
2
The cold-bath was removed and the reaction mixture allowed to warm to room temperature. The resulting pale-yellow
suspension was filtered and the solvent was removed under oil-pump vacuum to give a yellow oil (4) which was taken
up in CH
solution stirred overnight. The solvent was removed under oil-pump vacuum and the residue was taken up in benzene
15 mL). The solution was chromatographed on a 12 mm diameter silica gel column (10 g, benzene). The solvent was
2 2 3
Cl (10 mL). Then NEt (0.42 mL, 3.0 mmol) and (S)-binaphthol (0.143 g, 0.499 mmol) were added and the
(
1
removed from the eluate under oil-pump vacuum to give (S)-6 as a white foam (0.257 g, 90%). H NMR (CDCl
3
): δ 7.94
3
1
1
(
d, J=8.8 Hz, 1H), 7.87 (d, J=8.1 Hz, 1H), 7.74 (d, J=8.1 Hz, 1H), 7.56–6.95 (m, 22H), 6.14 (d, J=8.8 Hz, 1H). P{ H}
2
2
NMR (CDCl
(
Hz, JPH=13.6 Hz, CH), 3.72 (s, 3H of 2CH
PAr
3
): δ −19.1 (d, J=207 Hz, PAr
2
), 175.3 (d, J=207 Hz, PO
): δ 7.86–6.64 (m, 2C , C ), 5.51 (d, 1H, JHH=6.6 Hz, CH), 5.32 (dd, 1H, JHH=6.7
O), 3.41 (s, 3H of 2CH
2
). MS: m/e 577 (M+1). Spectroscopic data for
1
3
3
2R,3R)-5: H NMR (CDCl
3
6
H
5
6 4
H
3
31
1
2
3
3 3
O). P{ H} NMR (CDCl ): δ −19.8 (d, J=140 Hz,
2
2 2
), 180.1 (d, J=140 Hz, PO ).
1
1
7. Juge, S.; Genet, G. P. Tetrahedron Lett. 1989, 30, 2783.
1
8. Spectroscopic data for (2R,4S,5R)-7: H NMR (CDCl
.17 (m, C(CH )H), 2.66 (d, J=14.2 Hz, NCH ), 0.40 (d, J=6.7 Hz, CCH
Hz, PAr ), 142.6 (d, J=119 Hz, PO ). Spectroscopic data for (2S,4S,5R)-7: H NMR (CDCl
NCH ), 0.65 (d, J=6.1 Hz, CCH ) (aromatic, and methine protons not observed). P{ H} NMR (CDCl
), 154.2 (d, J=115 Hz, PO ).
9. Spectroscopic data for 8: IR (CH Cl , 0.051 M): ν(CO) 2031 (s), 1991 (sh), 1944 (sh), 1919 (s) cm . P{ H} NMR
, JWP=242 Hz), 220.5 ( J=20 Hz, JWP=345 Hz, PO
0. The 3 P NMR spectrum also contained minor, unidentified rhodium–phosphine species.
3
): δ 7.95–6.78 (m, 3C
6
H
5,
1
C
6
H
4
), 5.20 (d, J=6.7 Hz, C(C
6
2
H
5
)H),
): δ −17.0 (d, J=119
): δ 2.91 (d, J=15.3 Hz,
): δ −18.6 (d,
3
1
3
3
3
3 3
). P{ H} NMR (CDCl
2
1
2
2
3
3
1
1
3
3
3
2
2
J=115 Hz, PAr
2
2
−1
31
1
1
2
2
2
2
2
(
CDCl
3
): δ 43.9 ( J=20 Hz, PAr
2
2
).
1