Insertion of CO2, ketones, and aldehydes into the C-Li bond of 1,3,5-triaza-7-phosphaadamantan-6-yllithium

Article abstract of DOI:10.1021/ic701936x

The synthesis and structures of a series of new water-soluble phosphine ligands based on 1,3,5-triaza-7-phosphaadamantane (PTA) are described. Insertion of aldehydes or ketones into the C-Li bond of 1,3,5-triaza-7-phosphaadamantan- 6-yllithium (PTA-Li) resulted in the formation of a series of slightly water-soluble β-phosphino alcohols (PTA-CRR′OH, R = C ₆H₅, C₆H₄OCH₃, ferrocenyl; R′ = H, C₆H₅, C₆H ₄OCH₃) derived from the heterocyclic phosphine PTA. Insertion of CO₂ yielded the highly water-soluble carboxylate PTA-CO₂Li, S₂₅° ≈ 800 g/L. The compounds have been fully characterized in the solid state by X-ray crystallography and in solution by multinuclear NMR spectroscopy. The addition of PTA-Li to symmetric ketones results in a racemic mixture of PTA-CR₂OH ligands with a single resonance in the ³¹P{¹H} NMR spectrum between -95 and -97 ppm. The addition of PTA-Li to aldehydes results in a mixture of diasteromeric compounds, PTA-CHROH, with two ³¹P{¹H} NMR resonances between -100 and -106 ppm. Three (η⁶-arene)RuCl ₂(PTA-CRR′OH) complexes of these ligands were synthesized and characterized, with the ligands binding in a κ¹ coordination mode. All the ligands and ruthenium complexes are slightly soluble in water with S₂₅° = 3.9-11.1 g/L for the PTA-CRR′OH ligands and S ₂₅° = 3.3-14.1 g/L for the (η⁶-arene)RuCl ₂(PTA-CRR′OH) complexes.

Full text of DOI:10.1021/ic701936x

Inorg. Chem. 2008, 47, 612−620
Insertion of CO2, Ketones, and Aldehydes into the C
1,3,5-Triaza-7-phosphaadamantan-6-yllithium
−Li Bond of
Gene W. Wong, Wei-Chih Lee, and Brian J. Frost*
Department of Chemistry, MS 216, UniVersity of NeVada, Reno, NeVada 89557
Received September 29, 2007
The synthesis and structures of a series of new water-soluble phosphine ligands based on 1,3,5-triaza-7-
phosphaadamantane (PTA) are described. Insertion of aldehydes or ketones into the C Li bond of 1,3,5-triaza-
7-phosphaadamantan-6-yllithium (PTA Li) resulted in the formation of a series of slightly water-soluble -phosphino
alcohols (PTA CRR OH, R C6H5, C6H4OCH3, ferrocenyl; R′ ) H, C6H5, C6H4OCH3) derived from the heterocyclic
phosphine PTA. Insertion of CO2 yielded the highly water-soluble carboxylate PTA
−
−
â
−
′
)
−
CO2Li, S25° ≈ 800 g/L. The
compounds have been fully characterized in the solid state by X-ray crystallography and in solution by multinuclear
NMR spectroscopy. The addition of PTA
ligands with a single resonance in the 31P
to aldehydes results in a mixture of diasteromeric compounds, PTA
between 100 and 106 ppm. Three ( CRR OH) complexes of these ligands were synthesized
6-arene)RuCl2(PTA
and characterized, with the ligands binding in a κ1 coordination mode. All the ligands and ruthenium complexes are
slightly soluble in water with S25° ) 3.9 11.1 g/L for the PTA CRR OH ligands and S25° ) 3.3 14.1 g/L for the
6-arene)RuCl2(PTA
CRR OH) complexes.
−
{
Li to symmetric ketones results in a racemic mixture of PTA
1H
NMR spectrum between 95 and 97 ppm. The addition of PTA
CHROH, with two 31P 1H
NMR resonances
−
CR2OH
}
−
−
−Li
−
{ }
−
−
η
−
′
−
−
′
−
(
η
−
′
Introduction
have displayed anticancer properties.3-13 Our group has been
interested in the coordination chemistry of PTA14-18 and its
utility as a ligand in catalysis.19,20 A handful of PTA
The air-stable, water-soluble, heterocyclic phosphine 1,3,5-
triaza-7-phosphaadamantane (PTA) has received a great deal
of attention in recent years.1,2 This newfound attention has
been in part due to reports that ruthenium complexes of PTA
(3) Allardyce, C. S.; Dyson, P. J.; Ellis, D. J.; Heath, S. L. Chem. Commun.
2001, 1396-1397.
(4) Dorcier, A.; Dyson, P. J.; Gossens, C.; Rothlisberger, U.; Scopelliti,
R.; Tavernelli, I. Organometallics 2005, 24, 2114-2123.
(5) Scolaro, C.; Bergamo, A.; Brescacin, L.; Delfino, R.; Cocchietto, M.;
Laurenczy, G.; Geldbach, T. J.; Sava, G.; Dyson, P. J. J. Med. Chem.
2005, 48, 4161-4171.
* To whom correspondence should be addressed. E-mail: Frost@
unr.edu.
(1) Phillips, A. D.; Gonsalvi, L.; Romerosa, A.; Vizza, F.; Peruzzini, M.
Coord. Chem. ReV. 2004, 248, 955-993 and references within.
(2) For example see: (a) Vergara, E.; Miranda, S.; Mohr, F.; Cerrada,
E.; Tiekink, E. R. T.; Romero, P.; Mend´ıa, A.; Laguna, M. Eur. J.
Inorg. Chem. 2007, 2926-2933. (b) Gossens, C.; Dorcier, A.; Dyson,
P. J.; Rothlisberger, U. Organometallics 2007, 3969-3975. (c)
Kirillov, A. M.; Smolen˜ski, P; Guedes da Silva, M. F. C.; Pombeiro,
A. J. L. Eur. J. Inorg. Chem. 2007, 2686-2692. (d) Xu, X.; Wang,
C.; Zhou, Z.; Tang, X.; He, Z.; Tang, C. Eur. J. Org. Chem. 2007,
4487-4491. (e) Mohr, F.; Falvello, L. R.; Laguna, M. Eur. J. Inorg.
Chem. 2006, 3152-3154. (f) He, Z.; Tang, X.; Chen, Y.; He, Z. AdV.
Synth. Catal. 2006, 348, 413-417. (g) Krogstad, D. A.; Cho, J.;
DeBoer, A. J.; Klitzke, J. A.; Sanow, W. R.; Williams, H. A.; Halfen,
J. A. Inorg. Chim. Acta 2006, 359, 136-148. (h) Frost, B. J.; Mebi,
C. A. Organometallics 2004, 23, 5317-5323. (i) Bolan˜o, S.; Gonsalvi,
L.; Zanobini, F.; Vizza, F.; Bertolasi, V.; Romerosa, A.; Peruzzini,
M. J. Mol. Catal. A 2004, 224, 61-70. (j) Dyson, P. J.; Ellis, D. J.;
Henderson, W.; Laurenczy, G. AdV. Synth. Catal. 2003, 345, 216-
221. (k) Smolenski, P.; Pruchnik, F. P.; Ciunik, Z.; Lis, T. Inorg. Chem.
2003, 42, 3318-3322. (l) Akbayeva, D. N.; Gonsalvi, L.; Oberhauser,
W.; Peruzzini, M.; Vizza, F.; Bruggeller, P.; Romerosa, A.; Sava, G.;
Bergamo, A. Chem. Commun. 2003, 264-265. (m) Kova´cs, J.; Todd,
T. D.; Reibenspies, J. H.; Joo´, F.; Darensbourg, D. J. Organometallics
2000, 19, 3963-3969.
(6) Dyson, P. J.; Sava, G. Dalton Trans. 2006, 1929-1933.
(7) Dorcier, A.; Ang, W. H.; Bolan˜o, S.; Gonsalvi, L.; Juillerat-Jeannerat,
L.; Laurenczy, G.; Peruzzini, M.; Phillips, A. D.; Zanobini, F.; Dyson,
P. J. Organometallics 2006, 25, 4090-4096.
(8) Scolaro, C.; Geldbach, T. J.; Rochat, S.; Dorcier, A.; Gossens, C.;
Bergamo, A.; Cocchietto, M.; Tavernelli, I.; Sava, G.; Rothlisberger,
U.; Dyson, P.J. Organometallics 2006, 25, 756-765.
(9) Ang, W. H.; Dyson, P. J. Eur. J. Inorg. Chem. 2006, 4003-4018.
(10) Allardyce, C. S.; Dyson, P. J.; Ellis, D. J.; Salter, P. A.; Scopelliti, R.
J. Organomet. Chem. 2003, 668, 35-42.
(11) Grguric-Sipka, S.; Kowol, C. R.; Valiahdi, S.-M.; Eichinger, R.;
Jakupec, M. A.; Roller, A.; Shova, S.; Arion, V. B.; Keppler, B. K.
Eur. J. Inorg. Chem. 2007, 2870-2878.
(12) Leyva, L.; Sirlin, C.; Rubio, L.; Franco, C.; Le Lagadec, R.; Spencer,
J.; Bischoff, P.; Gaiddon, C.; Loeffler, J.-P.; Pfeffer, M. Eur. J. Inorg.
Chem. 2007, 3055-3066.
(13) Casini, A.; Mastrobuoni, G.; Ang, W. H.; Gabbiani, C.; Pieraccini,
G.; Moneti, G.; Dyson, P. J.; Messori, L. ChemMedChem 2007, 2,
631-635.
(14) Mebi, C. A.; Frost, B. J. Inorg. Chem. 2007, 46, 7115-7120.
(15) Mebi, C. A.; Frost, B. J. Z. Anorg. Allg. Chem. 2007, 633, 368-371.
(16) Frost, B. J.; Bautista, C. M.; Huang, R.; Shearer, J. Inorg. Chem. 2006,
45, 3481-3483.
612 Inorganic Chemistry, Vol. 47, No. 2, 2008
10.1021/ic701936x CCC: $40.75
© 2008 American Chemical Society
Published on Web 12/22/2007

Chiral Water-Soluble Phosphine Ligands
R′OH, and carboxylates, PTA-CO2Li, based on the insertion
of electrophiles into the C-Li bond of PTA-Li.
Experimental Section
Figure 1. PTAR3 and PTA-PPh2.
Materials and Methods. Unless otherwise noted, all manipula-
tions were performed on a double-manifold Schlenk vacuum line
under nitrogen or in a nitrogen-filled glovebox. Tetrahydrofuran
(THF) was freshly distilled under nitrogen from sodium/benzophe-
none. Dichloromethane and chloroform were degassed and dried
with activated molecular sieves. Water was distilled and deoxy-
genated before use. Benzophenone, anisaldehyde, ferrocene car-
Scheme 1
derivatives have been published with most of the modifica-
tions focused on the “lower rim” PTA; i.e., the triazacyclo-
hexane ring.21-26 Cleavage of C-N or C-P bonds has led
to a few different “ring-opened” PTA derivatives, which have
appeared in the literature over the years.27-31 Most recently,
we have focused on developing derivatives that maintain the
core structure of PTA.32,33 We have recently shown that the
“lower-rim” of PTA may be trisubstituted, leading to
sterically bulky derivatives of PTA (Figure 1).33 The “lower-
rim” PTA derivatives are interesting; however, modification
of the triazacyclohexane ring of PTA leads to changes distant
from phosphorus and, therefore, any coordinated metal
center. Of particular interest are chiral “upper-rim” PTA
derivatives where a stereogenic center can be installed at
the carbon adjacent to phosphorus.
boxaldehyde, and instrument-grade CO2 were purchased from
13
commercial sources and used as received. NMR solvents and
-
CO2 were purchased from Cambridge Isotopes and used as received.
Tetrakis(hydroxymethyl)phosphonium chloride was obtained from
Cytec and used without further purification. 1,3,5-Triaza-7-phos-
phaadamantane (PTA),34 PTA-Li,32 [(η6-C6H6)RuCl2]2,35 and[(η6-
35
C6H5CH3)RuCl2]2 were synthesized as reported in the literature.
NMR spectra were recorded with Varian Unity Plus 500 FT-NMR
or Varian NMR System 400 spectrometers. 1H and 13C NMR spectra
were referenced to residual solvent relative to tetramethylsilane
(TMS). Phosphorus chemical shifts are relative to an external
reference of 85% H3PO4 in D2O with positive values downfield of
the reference. IR spectra were recorded on a Perkin-Elmer 2000
FT-IR spectrometer as KBr pellets. X-ray crystallographic data were
collected at 100((1) K on a Bruker APEX CCD diffractometer
with Mo KR radiation (λ ) 0.71073 Å) and a detector-to-crystal
distance of 4.94 cm. Data collection was optimized utilizing the
APEX 2 software36 with 0.5° rotation between frames. Data
integration, correction for Lorentz and polarization effects, and final
cell refinement were performed using SAINTPLUS and corrected
for absorption using SADABS. The structures were solved by direct
methods and refined using SHELXTL, version 6.10.36 Crystal-
lographic data and data collection parameters are listed in Table 1.
A complete list of bond lengths and angles may be found in the
Supporting Information.
We have previously reported a method for the synthesis
of upper-rim PTA derivatives, in which the first step is
lithiation at the R-carbon of PTA (Scheme 1).32 Using PTA-
Li we synthesized and characterized PTA-PPh2 (Figure 1);
unfortunately, it was isolated in low yield and insoluble in
water.32
Herein, we report the synthesis and characterization of a
series of water-soluble â-phosphino alcohols, PTA-CR-
(17) Frost, B. J.; Mebi, C. A.; Gingrich, P. W. Eur. J. Inorg. Chem. 2006,
1182-1189.
Caution! PTA-Li is a highly pyrophoric solid, igniting Violently
upon exposure to air.
(18) Frost, B. J.; Miller, S. B.; Rove, K. O.; Pearson, D. M.; Korinek, J.
D.; Harkreader, J. L.; Mebi, C. A.; Shearer, J. Inorg. Chem. Acta 2006,
359, 283-288.
Synthesis of Lithium 1,3,5-Triaza-7-phosphaadamantane-6-
carboxylate (PTA-CO2Li). PTA-Li (1.23 g, 7.56 mmol) was
suspended in 35 mL of dry THF and cooled to -78 °C. Dry CO2-
(g) was bubbled into the solution for 2 h at -78 °C. The solution
was then warmed to room temperature, and CO2 bubbled through
the solution for an additional 2 h. The solvent was removed under
vacuum, and the solid washed with CHCl3 to remove residual PTA,
resulting in 1.38 g of an off-white solid (88% yield). 1H NMR (400
MHz, D2O): 4.75-4.28 (m, 6H, NCH2N); 3.95 (m, 1H, PCHN);
3.85-3.6 (m, 4H, PCH2N). 31P{1H} NMR (162 MHz, D2O): -88.0
(s). IR νCO2 (KBr, cm-1): PTA-CO2Li, 1614 (s, asymmetric strech)
and 1399 (m, symmetric stretch); PTA-13CO2Li, 1592 (s) and 1371
(m).
(19) Mebi, C. A.; Nair, R. P.; Frost, B. J. Organometallics 2007, 26, 429-
438.
(20) Mebi, C. A.; Frost, B. J. Organometallics 2005, 24, 2339-2346.
(21) Navech, J.; Kraemer, R.; Majoral, J. P. Tetrahedron Lett. 1980, 21,
1449-1452.
(22) Benhammou, M.; Kraemer, R.; Germa, H.; Majoral, J. P.; Navech, J.
Phosphorus Sulfur Relat. Elem. 1982, 14, 105-119.
(23) Daigle, D. J.; Boudreaux, G. J.; Vail, S. L. J. Chem. Eng. Data 1976,
21, 240-241.
(24) Delerno, J. R.; Majeste, R. J.; Trefonas, L. M. J. Heterocycl. Chem.
1976, 13, 757-760.
(25) Daigle, D. J.; Pepperman, A. B., Jr.; Boudreaux, G. J. Heterocycl.
Chem. 1974, 11, 1085-1086.
(26) Darensbourg, D. J.; Yarbrough, J. C.; Lewis, S. J. Organometallics
2003, 22, 2050-2056.
(27) (a) Siele, V. I. J. Heterocycl. Chem. 1977, 14, 337-339. (b) Fluck,
E.; Weissgraeber, H. J. Chem.-Ztg. 1977, 101, 304.
(28) (a) Assmann, B.; Angermaier, K.; Paul, M.; Riede, J.; Schmidbaur,
H. Chem. Ber. 1995, 128, 891-900. (b) Assmann, B.; Angermaier,
K.; Schmidbaur, H. J. Chem. Soc., Chem. Commun. 1994, 941-942.
(29) Darensbourg, D. J.; Ortiz, C. G.; Kamplain, J. W. Organometallics
2004, 23, 1747-1754.
Synthesis of Methyl-1,3,5-triaza-7-phosphatricyclo[3.3.1.13,7]-
decane-6-carboxylate (PTA-CO2CH3). In a 50 mL Schlenk flask,
1.03 g (4.98 mmol) PTA-CO2Li was dissolved in 50 mL of
(30) Mena-Cruz, A.; Lorenzo-Luis, P.; Romerosa, A.; Saoud, M.; Serrano-
Ruiz, M. Inorg. Chem. 2007, 46, 6120-6128.
(34) (a) Daigle, D. J.; Pepperman, A. B., Jr.; Vail, S. L. J. Heterocycl.
Chem. 1974, 11, 407-408. (b) Daigle, D. J. Inorg. Synth. 1998, 32,
40-45.
(31) Krogstad, D. A.; Ellis, G. S.; Gunderson, A. K.; Hammrich, A. J.;
Rudolf, J. W.; Halfen, J. A. Polyhedron 2007, 26, 4093-4100.
(32) Wong, G. W.; Harkreader, J. L.; Mebi, C. A.; Frost, B. J. Inorg. Chem.
2006, 45, 6748-6755.
(35) Bennett, M. A.; Smith, A. K. J. Chem. Soc., Dalton. Trans. 1974,
233-241.
(36) Sheldrick, G. M. SHELXTL: Structure Determination Software Suite,
version 6.10; Bruker AXS: Madison, WI, 2001.
(33) Huang, R.; Frost, B. J. Inorg. Chem. 2007, 46, 10962-10964.
Inorganic Chemistry, Vol. 47, No. 2, 2008 613

Wong et al.
Table 1. Crystallographic Data for OdPTAsCO2Me, PTA-C(C6H5)2OH, OdPTAsC(C6H4OCH3)2OH, OdPTAsCH(C6H4OCH3)OH,
PTA-CH(ferrocenyl)OH, (η6-C6H5CH3)Ru(PTA-C(C6H5)2OH)Cl2, (η6-C6H6)Ru(PTA-C(C6H4OCH3)2OH)Cl2, and
(η6-C6H6)Ru(PTA-CH(C6H4OCH3)OH)Cl2
OdPTA-C-
(C6H4OCH3)2OH
OdPTAsCH-
(C6H4OCH3)OH
OdPTAsCO2Me
PTA-C(C6H5)2OH
empirical formula
fw
T (K)
C8H14N3O3P
231.19
100(2) K
0.71073
monoclinic
P21/c
5.9476(4)
25.4104(18)
7.1910(5)
90
112.581(3)
90
1003.47(12)
4
1.530
0.266
C40H44N6O3P2
718.75
100(2)
0.71073
triclinic
C29H42N3O6P
559.63
100(2)
0.71073
triclinic
C14H20N3O3P
309.30
100(2) K
0.71073
monoclinic
P2(1)/c
11.3234(5)
11.3340(4)
11.0327(4)
90
92.691(2)
90
1414.37(9)
4
1.453
λ, Å
cryst syst
space group
a (Å)
P1h
P1h
10.1057(4)
10.4672(4)
17.5115(6)
102.716(2)
98.658(2)
99.068(2)
1751.02(11)
2
11.7005(2)
11.7013(2)
12.9305(2)
63.3210(10)
82.1920(10)
62.5270(10)
1397.78(4)
2
b (Å)
c (Å)
R (deg)
â (deg)
γ (deg)
V (Å3)
Z
D
calc (Mg/m3)
1.363
0.174
1.330
0.146
abs coeff (mm-1
cryst size (mm3)
)
0.209
0.18 × 0.07 × 0.03
1.60 to 25.25
-7 e h e 7
-18 e k e 30
-8 e l e 8
8889
0.17 × 0.07 × 0.03
1.21 to 23.50
-11 e h e 11
-11 e k e 11
-19 e l e 19
15 978
0.19 × 0.19 × 0.06
1.77 to 25.50
-12 e h e 14
-13 e k e 14
-15 e l e 15
22 924
0.28 × 0.08 × 0.03
1.80 to 25.50
-13 e h e 13
-13 e k e 13
-13 e l e 13
21 738
θ for data collect (deg)
index ranges
reflns collected
indep reflns
1814
5172
5079
2638
[R(int) ) 0.0810]
[R(int) ) 0.0833]
[R(int) ) 0.0313]
[R(int) ) 0.1403]
abs correction
data/rest/params
GOF F2
SADABS
SADABS
SADABS
SADABS
1814/0/136
1.053
5172/0/470
1.043
5079/0/354
1.051
2638/0/190
1.050
final R indices
[I > 2σ(I)]
R indices
(all data)
CCDC no.
R1 ) 0.0593
wR2 ) 0.1472
R1 ) 0.1064
wR2 ) 0.1640
662202
R1 ) 0.0654
wR2 ) 0.1482
R1 ) 0.1138
wR2 ) 0.1679
662207
R1 ) 0.0432
wR2 ) 0.1089
R1 ) 0.0578
wR2 ) 0.1154
662205
R1 ) 0.0694
wR2 ) 0.1192
R1 ) 0.1168
WR2 ) 0.1331
662203
(η6-C6H5CH3)Ru(PTA-C-
(η6-C6H6)Ru(PTA-C-
(C6H4OCH3)2OH)Cl2
(η6-C6H6)Ru(PTA-CH-
(C6H4OCH3)OH)Cl2
PTA-CH(ferrocenyl)OH
(C6H5)2OH)Cl2
empirical formula
C17H22FeN3OP
C26H30Cl2N3OPRu
C27.50H32.50Cl3.50N3-
O3PRu
C21.50H26Cl6.50N3-
O2PRu
fw
T (K)
371.20
100(2)
603.47
100(2)
709.18
100(2)
720.92
100(2)
λ, Å
0.71073
orthorhombic
Pca2(1)
14.4830(8)
5.9165(4)
18.3195(9)
90
0.71073
monoclinic
p21/c
9.7656(3)
20.5066(7)
12.6430(4)
90
95.3640(10)
90
0.71073
monoclinic
P2(1)/c
13.5213(3)
26.9050(5)
16.3829(3)
90
101.3200(10)
90
0.71073
triclinic
P1h
cryst syst
space group
a (Å)
3.1047(4)
14.6644(4)
15.7220(5)
66.1460(10)
87.2920(10)
82.3810(10)
2738.79(14)
4
b (Å)
c (Å)
R (deg)
â (deg)
γ (deg)
V (Å3)
Z
90
90
1569.77(16)
4
1.571
2520.79(14)
4
1.590
5844.0(2)
8
1.612
D
calc (Mg/m3)
1.748
1.292
abs coeff (mm-1
)
1.070
0.923
0.947
cryst size (mm3)
0.06 × 0.05 × 0.05
2.22 to 25.49
-17 e h e 14
-7 e k e 7
-22 e l e 22
18 952
0.17 × 0.08 × 0.04
1.90 to 23.55
-10 e h e 10
-22 e k e 23
-14 e l e 14
18 722
0.14 × 0.11 × 0.03
1.48 to 26.00
-16 e h e 16
-33 e k e 33
-20 e l e 20
99 182
0.15 × 0.13 × 0.08
1.42 to 26.00
-16 e h e 15
-18 e k e 18
-19 e l e 19
40 011
θ for data collect (deg)
index ranges
reflns collected
indep reflns
2923
3737
11 496
10 766
[R(int) ) 0.1787]
SADABS
2923/1/212
1.028
R1 ) 0.0616
wR2 ) 0.0831
R1 ) 0.1014
wR2 ) 0.0933
662201
[R(int) ) 0.0764]
[R(int) ) 0.0767]
[R(int) ) 0.0683]
abs correction
data/rest/params
GOF F2
final R indices
[I > 2σ(I)]
R indices
SADABS
SADABS
SADABS
3737/0/311
1.014
R1 ) 0.0360
wR2 ) 0.0689
R1 ) 0.0603
wR2 ) 0.0784
662206
11496/0/711
1.067
R1 ) 0.0467
wR2 ) 0.0961
R1 ) 0.0689
wR2 ) 0.1028
662208
10766/0/676
1.093
R1 ) 0.0552
wR2 ) 0.1341
R1 ) 0.0909
wR2 ) 0.1491
662204
(all data)
CCDC no.
methanol, resulting in a homogeneous yellow solution. Trimeth-
ylsilyl chloride (1.70 g, 15.65 mmol) was added dropwise over the
course of 15 min, resulting in a white precipitate. The reaction was
stirred overnight at room temperature, and 4 mL of triethylamine
was added, resulting in a clear yellow solution. The solvent was
removed under reduced pressure, and the residue dissolved in 80
614 Inorganic Chemistry, Vol. 47, No. 2, 2008

Chiral Water-Soluble Phosphine Ligands
mL of CH2Cl2. The solution was filtered through Celite, and the
solvent removed under reduced pressure. The resulting solid was
extracted with 6 × 50 mL diethyl ether. Removal of the Et2O
yielded 506 mg of PTA-CO2CH3 as a white solid (47% isolated
yield). Anal. Calcd For C8H14O2N3P: C, 44.65; H, 6.56; N, 19.53.
Found: C, 44.31; H, 6.51; N, 19.34. 1H NMR (400 MHz, CDCl3):
4.88, 4.70 (AB quartet, J ) 14 Hz, 1H, PCHN); 4.62 (s, 2H,
NCH2N); 4.38-4.53 (m, 4H, NCH2N); 3.78-4.10 (m, 4H, PCH2N);
3.76 (s, 3H, OCH3). 13C{1H} NMR (100 MHz, CDCl3): 170.3 (d,
X-ray-quality crystals of O)PTA-C(C6H4OCH3)2OH were
obtained by layering a THF solution of PTA-C(C6H4OCH3)2OH
with hexanes, resulting in colorless blocks over the course of 3
days.
Synthesis of 4-Methoxyphenyl-(1,3,5-triaza-7-phosphatricyclo-
[3.3.1.13,7]dec-6-yl)methanol (PTA-CH(C6H4OCH3)OH). p-
Anisaldehyde (0.84 g, 6.1 mmol) was slowly added via cannula to
a cold (-78 °C) suspension of 15 mL THF and 1.0 g (6.1 mmol)
PTA-Li. The yellow-white suspension was stirred at -78 °C for
15 min and warmed to room temperature after which time the
suspension was stirred under nitrogen for 12 h. Water was slowly
added until the suspension temporarily cleared. After a few minutes,
a white precipitate was observed and the solvent was removed under
reduced pressure. The resultant white solid was washed with 50
mL of acetone yielding 1.13 g (63% isolated yield) of the
diasteromeric product in a ratio of ∼2.5:1 RS/SR:RR/SS. 1H
NMR of RS/SR diastereomer (400 MHz, CDCl3): 7.39 (d, J )
8.8 Hz, Ar); 6.90 (dd, J ) 6.4 and 2.0 Hz, Ar); 5.33 (dd, J ) 8.4
and 5.2 Hz, 1H, PCHCH(C6H4OCH3)OH); 3.5-5.0 (m, 11H,
PCH2N and NCH2N). 13C{1H} NMR of RS/SR diastereo-
mer (100 MHz, DMSO-d6): 158.9 (s, Ar); 137.7 (s, Ar); 128.3
(s, Ar); 113.8 (s, Ar); 76.5 (s, NCH2N); 76.1 (s, NCH2N); 74.1
3
2JPC ) 8.9 Hz, CdO); 74.6 (s, NCH2N); 72.5 (d, JPC ) 2.2 Hz,
3
1
NCH2N); 67.9 (d, JPC ) 3.0 Hz, NCH2N); 60.1 (d, JPC ) 25.4
1
Hz, PCHC); 51.5 (s, OCH3); 50.2 (d, JPC ) 21.6 Hz, PCH2N);
47.2 (d, JPC ) 24.6 Hz, PCH2N). 31P{1H} NMR (162 MHz,
1
CDCl3): -93.7 (s). IR νCdO (KBr): 1729 cm-1. X-ray-quality
crystals of OdPTAsCO2CH3 were obtained over the course of a
week by layering a THF solution of PTA-CO2CH3 with hexanes.
Synthesis
of
Diphenyl(1,3,5-triaza-7-phosphatricyclo-
[3.3.1.13,7]dec-6-yl)methanol (PTA-C(C6H5)2OH). Benzophenone
(2.20 g, 12.1 mmol) was dissolved in 40 mL THF and placed in a
slush bath at -78 °C (dry ice/acetone). This solution was transferred
cold to a Schlenk flask containing 2.00 g (12.2 mmol) lithiated
PTA, resulting in a tan suspension. The mixture was stirred at -78
°C for 15 min, after which time the reaction was allowed to warm
to room temperature. After stirring for 1 h, a white solid was
observed precipitating from the yellow solution. Following 2 h of
stirring, 0.5 mL water was added to quench the reaction, resulting
in a yellow suspension. The solvent was removed under reduced
pressure, and the yellow solid washed with a 1:1 mixture of water/
acetone resulting in isolation of 3.0 g (73% yield) of an off-white
solid. Further purification may be performed by dissolving PTA-
C(C6H5)2OH in a minimum of warm degassed toluene and storing
at ∼0 °C overnight, resulting in the isolation of a white crystalline
analytically pure solid. Anal. Calcd For C19H22O1N3P: C, 67.24;
3
2
(d, JPC ) 3 Hz, NCH2N); 67.8 (d, JPC ) 4 Hz, *CHOH); 66.2
(d, JPC ) 22 Hz, P*CN); 55.7 (s, -OCH3); 51.2 (d, 20 Hz,
PCN); 48.3 (d, 24 Hz, PCN). 31P{1H} NMR (162 MHz, CDCl3):
-102.6 (s, RS/SR diastereomer), -105.7 (s, RR/SS diastereomer).
Colorless X-ray-quality plates of OdPTAsCH(C6H4OCH3)OH
were obtained over the course of a week by layering a CH2Cl2
solution of PTA-CH(C6H4OCH3)OH with diethyl ether at
10 °C.
Synthesis of PTA-CH(ferrocenyl)OH. Ferrocene carboxalde-
hyde (650 mg, 3.0 mmol) was dissolved in 25 mL of THF and
transferred by cannula to a Schlenk flask charged with 510 mg
(3.1 mmol) of PTA-Li at -78 °C. Upon addition, the appearance
of an orange precipitate was observed. After stirring for 1.5 h at
-78 °C, the reaction was allowed to warm to room temperature
and stirred overnight (∼10 h). Water (∼0.5 mL) was added
dropwise until the solution became clear red. The solvent was
removed under reduced pressure, and the solid was washed with
diethyl ether (3 × 15 mL), resulting in 790 mg of a red-orange
powder (70% yield) isolated as a mixture of diasteromers in a ratio
1
H, 6.53; N, 12.38. Found: C, 66.98; H, 6.48; N, 12.31. H NMR
(400 MHz, CDCl3): 7.65 (d, J ) 7.0 Hz, 2H, Ar); 7.57 (d, J ) 7.5
Hz, 2H, Ar); 7.2-7.4 (m, 6H, Ar); 5.33 (s, 1H, PCHN); 4.78 (d, J
) 13.0 Hz, 1H, NCH2N); 4.4-4.6 (m, 3H, NCH2N); 4.34 (d, J )
13.0 Hz, 1H, NCH2N); 4.17 (d, J ) 13.0 Hz, 1H, PCH2N); 4.08
(at, J ) 14 Hz, 1H, PCH2N); 3.95 (m, 1H, PCH2N); 3.52 (at, J )
14 Hz, 1H, PCH2N); 3.12 (m, 1H, PCH2N); 2.35 (s, 1H, OH). 13C-
{1H} NMR (100 MHz, CD2Cl2): 147.7 (s, Ar); 145.8 (s, Ar); 128.2
1
of ∼1.8:1 RS/SR:RR/SS. H NMR (400 MHz, CDCl3): 5.03 (dt,
(d, JPC ) 4.6 Hz, Ar); 127.3 (s, Ar); 127.0 (s, Ar); 126.9 (d, JPC
)
J ) 13.6 and 2.4 Hz, 1H, PCHN RS/SR); 4.88 (m, 2H, C5H4 RS/
SR); 4.80 (dd, J ) 13.2 and 1.6 Hz, 1H, PCHN RR/SS); 4.71 (m,
2H, C5H4 RS/SR); 4.60-4.48 (m, 4H, C5H4 RR/SS); 4.47-4.36
(m, NCH2N RS/SR and RR/SS); 4.32-4.20 (m, NCH2N RS/SR
and RR/SS); 4.22-3.95 (m, PCH2N RS/SR and RR/SS); 4.26 (s,
5H, Cp SS/RR); 4.23 (s, 5H, Cp SR/RS). 31P{1H} NMR (162 MHz,
CDCl3): -100.6 (s, major RS/SR), -103.1 (s, minor SS/RR). ESI-
MS: 370.2 (M-). Orange X-ray-quality crystals were obtained as
blocks by the slow evaporation of a diethyl ether solution of PTA-
CH(ferrocenyl)OH.
5.5 Hz, Ar); 126.3 (d, JPC ) 5.7 Hz, Ar); 78.5 (s, N-CH2-N);
78.4 (d, JPC ) 7.0 Hz, C-C(C6H5)2OH); 74.3 (d, JPC ) 1.9 Hz,
NCH2N); 66.9 (d, JPC ) 2.8 Hz, NCH2N); 66.0 (d, JPC ) 27.5 Hz,
PCHC(C6H5)2OH); 52.2 (d, JPC ) 20.0 Hz, PCH2N); 47.4 (d, JPC
) 25.1 Hz, PCH2N). 31P{1H} NMR (162 MHz, CDCl3): -95.5
(s). Crystals suitable for X-ray diffraction were obtained by the
slow diffusion of pentane into a THF solution of PTA-C(C6H5)2-
OH under nitrogen, resulting in colorless plates over the course of
a few days.
Synthesis of Bis-4-methoxyphenyl-(1,3,5-triaza-7-phospha-
tricyclo[3.3.1.13,7]dec-6-yl)methanol (PTA-C(C6H4OCH3)2OH).
PTA-C(C6H4OCH3)2OH was synthesized in a manner analogous
to that for PTA-C(C6H5)2OH, resulting in an off-white solid in
General Synthesis of OdPTAsCRR′OH. The phosphine
oxides OdPTAsCRR′OH and OdPTAsCO2Li were obtained
quantitatively by the addition of 30% H2O2 (0.2 mmol) to a 1 mL
D2O solution of PTA-CRR′OH or PTA-CO2Li (0.1 mmol). 31P-
{1H} NMR (162 MHz, D2O): -2.27 (s), OdPTAsCO2Li; -2.88
(s), OdPTAsCO2CH3; 3.97 (s), OdPTAsC(C6H5)2OH; 4.14 (s),
OdPTAsC(C6H4OCH3)2OH; 1.72 (s), 2.74 (s), OdPTAsCH-
(C6H4OCH3)OH; 1.75 (s), 2.82 (s), Od PTAsCH(ferrocenyl)OH.
31P{1H} NMR (162 MHz, CDCl3): -0.91 (s), OdPTAsCO2Li;
-11.0 (s), OdPTAsCO2CH3; -3.46 (s), OdPTAsC(C6H5)2OH;
-3.1 (s), OdPTAsC(C6H4OCH3)2OH; -1.48 (s), -3.19 (s),
1
62% yield. H NMR (400 MHz, CDCl3): 7.52 (d, J ) 9 Hz, 2H,
Ar); 7.45 (d, J ) 8 Hz, 2H, Ar); 6.84 (m, 4H, Ar), 5.15 (s, 1H,
OH); 4.78, 4.35 (AB quartet, J ) 12.8 Hz, 2H, NCH2N); 4.4-4.6
(m, 4H, NCH2N); 4.17 (d, J ) 13.6 Hz, 1H, PCHN); 4.07 (d, J )
12.8 Hz, 1H, PCH2N); 3.88 (m, 1H, PCH2N); 3.77 (s, 6H, OCH3);
3.54 (at, J ) 14.8 and 12.8 Hz 1H, PCH2N); 3.23 (m, 1H, PCH2N).
31P{1H} NMR (162 MHz, CDCl3): -96.4 (s).
Inorganic Chemistry, Vol. 47, No. 2, 2008 615

Wong et al.
Scheme 2
OdPTAsCH(C6H4OCH3)OH; -0.06 (s), -1.35 (s), Od PTAs
CH(ferrocenyl)OH.
Synthesis of [(η6-C6H5CH3)RuCl2(PTA-C(C6H5)2OH)]. A 50
mL Schlenk flask was charged with 68 mg (0.2 mmol) PTA-
C(C6H5)2OH and 53 mg (0.1 mmol) [Ru(η6-C6H5CH3)Cl2]2 and
placed under nitrogen. Dichloromethane (10 mL) was added, and
the solution stirred for 15 min and filtered. The solvent was removed
under vacuum, yielding 102 mg of an orange solid (85% yield).
1H NMR (400 MHz, CDCl3): 7.91 (d, J ) 7.6 Hz, 2H, Ar); 7.56
(d, J ) 7.6 Hz, 2H, Ar); 7.40 (t, J ) 7.5 Hz, 2H, Ar); 7.21 (m, 4H,
Ar); 7.08 (t, J ) 7.4 Hz, 2H, Ar); 5.47 (s, 1H, PCHN); 5.7-5.0
(m, 4H, Ar); 4.1-4.9 (m, 9H, NCH2N and PCH2N and Ar); 3.79
(d, J ) 13.6 Hz, 1H, PCH2N); 3.68 (d, J ) 5.6 Hz, 1H, PCH2N).
31P{1H} NMR (162 MHz, CDCl3): -31.0 (s). Orange-red X-ray-
quality plates were obtained by layering a chloroform solution with
hexanes under nitrogen.
highly water-soluble (S25° ∼ 800 g/L) off-white solid and
exhibits a 31P{1H} NMR resonance at -88.0 ppm (s). In
addition to water, PTA-CO2Li is soluble in methanol,
ethanol, and DMSO. A solid-state IR spectrum obtained for
PTA-CO2Li contains the expected absorbances at 1614 and
1399 cm-1 for the asymmetric and symmetric C-O stretches,
respectively. Isotopically labeled PTA-13CO2Li was syn-
thesized from 13CO2 (vide infra) resulting in shifts in the IR
stretching modes to 1592 and 1371 cm-1 for the asymmetric
and symmetric modes, respectively. The observed IR shifts
of 22-28 cm-1 are slightly less than the 36 cm-1 predicted
from a simple Hooke’s law calculation due to coupling of
the two vibrational modes.
Synthesis of [(η6-C6H6)RuCl2(PTA-C(C6H4OCH3)2OH)]. Dry
degassed CH2Cl2 (40 mL) was added to a 50 mL Schlenk flask
charged with [(η6-C6H6)RuCl2]2 (192 mg, 0.38 mmol) and PTA-
C(C6H4OCH3)2OH (307 mg, 0.77 mmol). The suspension was
stirred under nitrogen for 1 h, resulting in a clear red solution. The
solution was filtered, and the solvent was removed under reduced
pressure yielding 405 mg of a red-orange powder (81% isolated
yield). Anal. Calcd for C27H32O3N3PCl2Ru: C, 49.93; H, 4.97; N,
We have also synthesized PTA-CO2Li without organic
solvent, utilizing a heterogeneous solid/gas reaction of CO2-
(g) with powdered PTA-Li in a cold bath.37 Compared with
the reaction in THF, the neat CO2(g) reaction is not as clean,
resulting in two resonances in the 31P{1H} NMR spectrum
of PTA-CO2Li (-88.4 and -87.4 ppm). The minor product
at -87.4 ppm varies in yield from 5 to 45% of the total
product. In an effort to determine the nature of these two
products, we synthesized PTA-13CO2Li, utilizing 13CO2. The
31P NMR spectrum of PTA-13CO2Li in CD3OD is similar
to that of the unenriched product, containing two reso-
nances: a doublet at -90.8 ppm (2JPC ) 7.6 Hz) and a triplet
at -93.4 ppm (2JPC ) 9.5 Hz). In D2O, the triplet was
observed further downfield than the doublet at -87.4 ppm
1
6.47. Found: C, 48.87; H, 4.85; N, 6.23. H NMR (400 MHz,
CDCl3): 7.76 (d, J ) 8.8 Hz, 2H, Ar); 7.43 (d, J ) 8.8 Hz, 2H,
Ar); 6.93 (d, J ) 8.4 Hz, 2H, Ar); 6.74 (d, J ) 8.8 Hz, 2H, Ar);
5.60 (br s, 1H, OH); 5.32 (s, 1H, PCHN); 5.08 (s, 6H, C6H6); 4.9-
4.2 (m, 10H, PCH2N and NCH2N); 3.76 (s, 3H, OCH3); 3.73 (s,
3H, OCH3). 31P{1H} NMR (162 MHz, CDCl3): -31.3 (s). Orange-
red X-ray-quality plates were obtained by layering a CHCl3 solution
of the complex with pentane under nitrogen.
Synthesis of [(η6-C6H6)RuCl2(PTA-CH(C6H4OCH3)OH)]. In
a 50 mL Schlenk flask containing 101 mg (0.2 mmol) of [(η6-
C6H6)RuCl2]2, 118 mg (0.4 mmol) of PTA-CH(C6H4OCH3)OH
was placed under nitrogen. Upon addition of methylene chloride
(20 mL), all of the phosphine ligand dissolved while some of the
ruthenium complex remained suspended in the brown solution. After
stirring at room temperature for 4 h, most of the brown solid
dissolved. The solution was filtered, and the solvent was removed
under reduced pressure resulting in isolation of 182 mg of brown
2
2
(t, JPC ) 8.8 Hz) and -88.4 ppm (d, JPC ) 7.6 Hz). The
carbonyl region of the 13C{1H} NMR spectrum of PTA-13-
CO2Li in CD3OD contained two doublets at 175.5 ppm (2JPC
) 7.4 Hz) and 174.2 ppm (2JPC ) 9.75 Hz). From the
coupling constants, we determined that the resonance at 175.5
ppm in the 13C NMR spectrum corresponds to the 31P{1H}
NMR resonance at -90.8 ppm (2JPC ) 7.4 Hz). The doublet
at 174.2 ppm in the 13C{1H} NMR spectrum correlates with
the triplet at -93.4 ppm observed in the 31P{1H} NMR
spectrum of PTA-13CO2Li. Together, these data suggest that
the second product observed in the 31P and 13C NMR spectra
is the dicarboxylated product PTA-(CO2Li)2.
1
solid (84% yield). H NMR (400 MHz, CDCl3): 7.35 (d, J ) 8
Hz, 2H, Ar); 6.93 (d, J ) 6 Hz, 2H, Ar); 5.71 (s, 1H, PCHN); 5.65
(s, 6H, C6H6); 5.42 (s, 1H); (4.7-4.1 (m, 10H, PCH2N and
NCH2N); 3.81 (s, 3H, OCH3). 31P{1H} NMR (162 MHz, CD2Cl2):
-33.12 (s, major diasteromer); -32.33 (s, minor diasteromer).
X-ray-quality crystals were obtained as orange blocks by the slow
evaporation of a CHCl3 solution of the complex.
Results and Discussion
Mass spectrometry data was also obtained on both the
PTA-13CO2Li and PTA-CO2Li samples. Notable peaks
include [PTA-13CO2]- (m/z 201.17) and the comparable
[PTA-CO2]- anion at (m/z 200.17). Also seen in the spectra
are the dicarboxylate species: [PTA-(13CO2)2Li]- and
[PTA-(CO2)2Li]- at m/z 252.25 and 250.18, respectively.
The esterification of PTA-CO2Li was accomplished by
the addition of Me3SiCl to a methanol solution of the
carboxylate (Scheme 3).38 The product is soluble in water,
acetone, THF, diethyl ether, chloroform, methylene chloride,
and acetronitrile. A shift in the 31P{1H} NMR spectrum of
We have previously described the synthesis of PTA-Li
and its reaction with ClPPh2 resulting in PTA-PPh2.32 While
this work demonstrated that “upper-rim” PTA derivatives
are accessible, we were discouraged that the yield of PTA-
PPh2 was low and the ligand was not soluble in water. In an
attempt to increase both the yield and the water solubility,
we have explored the reaction of PTA-Li with a variety of
electrophiles: namely, CO2, ketones, and aldehydes.
Insertion of CO2. Insertion of CO2 into the C-Li bond
of PTA-Li proceeds in high yield, >85%, by bubbling CO2
through a THF suspension of PTA-Li at -78 °C (Scheme
2). The resulting PTA-CO2Li can be isolated as an air-stable,
(37) See the Supporting Information for more details.
616 Inorganic Chemistry, Vol. 47, No. 2, 2008

Chiral Water-Soluble Phosphine Ligands
Scheme 3
Table 2. 31P{1H} NMR and Solubility Data for the Series of
PTA-CRR′OH, PTA-CO2Li, and PTA-CO2CH3 Compounds;
Phosphine Oxide Chemical Shift in Parentheses
31P{1H} NMR
-98.3b (-2.49)
S°25 (g/L)
PTA1,34
235
PTA-CRR′OH
R ) C6H5, R′ ) C6H5
R ) C6H4OMe,
R′ ) C6H4OMe
R ) C6H4OMe, R′ ) H
-95.5a (-3.46)
-96.4a (-3.1)
5.9
10.6
Figure 2. Thermal ellipsoid representation (50% probability) of OdPTAs
CO2CH3 with the atomic numbering scheme. Only the R enantiomer is
shown; however, both the R and S enantiomers are present in the structure.
Selected bond lengths (Å) and angles (deg): P1-O3 ) 1.483(3); P1-C1
) 1.834(4); P1-C2 ) 1.815(4); P1-C3 ) 1.818(4); C7-O1 ) 1.219(5);
C1-N1 ) 1.484(5); C1-C7 ) 1.491(5); P1-C1-C7 ) 110.2(3); C7-
C1-N1 ) 116.6(3).
-102.6a (-1.48)
-105.7a (-3.19)
-100.6a (-0.06)
-103.1a (-1.35)
-88.0b (-0.91)
-93.7c (-11.0)
11.1
11.1
3.9
R ) ferrocenyl, R′ ) H
3.9
PTA-CO2Li
PTA-CO2Me
∼800
d
Scheme 4
a In CDCl3. b In D2O. c In CD3OD. d Not determined.
PTA-CO2Me (-93.7 ppm in D2O) relative to PTA (-98.3
in D2O) and PTA-CO2Li (-88.0 ppm in D2O) was observed
1
(Table 2). The H NMR spectrum of PTA-CO2Me is very
similar to that of PTA-CO2Li with the exception of the
singlet at 3.76 ppm representing the methyl ester. Likewise,
in the 13C NMR spectrum the methoxy group appears as a
singlet at 51.5 ppm. The 13C NMR resonances for the carbons
in the cage are shifted significantly from those of the parent
PTA ligand. The methylene carbons on the “upper rim” of
PTA can be found at 50.3 ppm (d, JPC ) 21 Hz); PTA-
CO2Me possesses three resonances for the upper rim carbons
Scheme 5
of PTA-CO2Me, 60.1 (d, JPC ) 25.4 Hz) 50.2 (d, JPC
21.6 Hz) and 47.2 (d, JPC ) 24.6 Hz). The “lower rim”
)
bond(s) adjacent to the carbonyl functionality.39 Nucleophilic
addition of PTA-Li to an aldehyde or ketone formally results
in an alkoxide, which has not been isolated due to issues
associated with separation from residual PTAsan omnipres-
ent side product in reactions with PTA-Li. Quenching the
product with H2O allows for the isolation and purification
of the â-phosphino alcohols. The reaction of PTA-Li with
symmetric ketones results in a racemic mixture of products;
the single chiral center in the PTA-Li starting material
renders it chiral and racemic (Scheme 4). Both benzophenone
and p-methoxybenzophenone react cleanly and easily with
PTA-Li, and single resonances are observed in the 31P NMR
carbons, which are now chemically inequivalent, appear as
3
a singlet and two doublets at 74.6 (s), 72.5 (d, JPC ) 2.2
3
Hz), and 67.9 (d, JPC ) 3.0 Hz). The carbonyl carbon is
2
observed as a doublet at 170.3 ppm (d, JPC ) 8.9 Hz).37
Structure of OdPTAsCO2Me. PTA-CO2Me is stable
in the solid state, but somewhat air-sensitive in solution.
Crystals of PTA-CO2Me grown over the course of a few
days afford crystals of the oxide OdPTAsCO2CH3. The
solid-state structure of OdPTAsCO2CH3 was determined
by X-ray crystallography (Figure 2). Similar to the PTA-
PPh2 and other upper rim PTA derivatives described herein,
the P1-C1 bond length is slightly elongated at 1.834(4) Å
relative to that of the adjacent methylenes (P1-C2 ) 1.815-
(4), P1-C3 ) 1.818(4) Å).
Addition to Aldehydes and Ketones. The synthesis of
â-phosphino alcohols has been accomplished through the
insertion of ketones or aldehydes into the C-Li bond of
PTA-Li. The reaction proceeds cleanly in moderate to good
yield (>60% isolated yield) for aryl aldehydes and ketones.
Addition to aliphatic ketones and aldehydes is slightly more
complex, presumably due to the acidic nature of the C-H
1
spectra of the resulting products (Table 2). The H NMR
spectra of the products are not first order and thus very
complicated due to unusual coupling patterns and the close
proximity of many of the chemical shifts.
Unlike ketones, which result in enantiomeric products, the
addition to aldehydes leads to PTA-CHR(OH) ligands with
two contiguous chiral centers and, therefore, diasteromeric
1
mixtures of products (Scheme 5). The H NMR spectra of
the PTA-CHROH compounds are even more complicated
than the analogous PTA-CR2OH ligands, as each spectrum
provides data on diasteromeric compounds. The 31P{1H}
NMR spectrum of PTA-CH(C6H4OCH3)OH contains two
(38) (a) Nakao, R.; Oka, K.; Fukumoto, T. Bull. Chem. Soc. Jpn. 1981,
54, 1267-1268. (b) Brook, M. A.; Chan, T. H. Synthesis 1983, 3,
201-203.
(39) Wong, G. W.; Frost, B. J., unpublished results.
Inorganic Chemistry, Vol. 47, No. 2, 2008 617

Wong et al.
Figure 3. Thermal ellipsoid representation (50% probability) of PTA-
C(C6H5)2OH with the atomic numbering scheme. Only the R enantiomer
is shown; however, both the R and S enantiomers are present in the structure.
Hydrogen atoms have been omitted for clarity. Selected bond lengths (Å)
and angles (deg): P1-C1 ) 1.880(4); P1-C2 ) 1.871(5); P1-C3 ) 1.864-
(4); C7-O1 ) 1.435(5); C1-N1 ) 1.494(5); C1-C7 ) 1.523(6); P1-
C1-C7 ) 112.8(3); C7-C1-N1 ) 114.9(3); C8-C7-C14 ) 109.5(3).
Figure 4. Thermal ellipsoid representation (50% probability) of OdPTAs
C(C6H4OCH3)2OH with the atomic numbering scheme. Only the S
enantiomer is shown; however, both the R and S enantiomers are present
in the structure. Hydrogen atoms have been omitted for clarity. Selected
bond lengths (Å) and angles (deg): P1-O1 ) 1.4926(14); P1-C1 ) 1.838-
(2); P1-C2 ) 1.822(2); P1-C3 ) 1.817(2); C7-O2 ) 1.425(2); C1-N1
) 1.490(2); C1-C7 ) 1.562(3); P1-C1-C7 ) 117.61(13); C7-C1-N1
) 112.75(15).
singlets at -102.6 and -105.7 ppm, one for each diaster-
omer. The ferrocenyl derivative, PTA-CH(ferrocenyl)OH,
exhibits two 31P NMR resonances at -100.6 and -103.1
ppm. Some diasteroselectivity is observed in the synthesis
of the products as we isolate PTA-CH(C6H4OCH3)OH as
a 2.5:1 mixture of diasteromers and PTA-CH(ferrocenyl)-
OH as a 1.8:1 mixture of diasteromers.
The parent PTA ligand is highly water-soluble with S25°
) 235 g/L;1,34 PTA-CO2Li is 3-4 times more soluble in
water and S25° ≈ 800 g/L (vide supra). The PTA-CRR′OH
ligands are soluble in water (S25° ) 3.9-11.1 g/L); however,
they are much less soluble than PTA (Table 2).
The solid-state structures of PTA-C(C6H5)2OH, Od
PTAsC(C6H4OCH3)2OH, OdPTAsCH(C6H4OCH3)OH, and
PTA-CH(ferrocenyl)OH were determined by X-ray crystal-
lography. Figures 3-6 contain thermal ellipsoid representa-
tions of each compound along with selected bond lengths
and angles. As seen with other upper rim PTA derivatives
Figure 5. Thermal ellipsoid representation (50% probability) of OdPTAs
CH(C6H4OCH3)OH with the atomic numbering scheme. Only the R(C1)/
S(C7) enantiomer is shown; however, both R(C1)/S(C7) and S(C1)/R(C7)
are present in the structure. Hydrogen atoms have been omitted for clarity.
Selected bond lengths (Å) and angles (deg): P1-O3 ) 1.478(3); P1-C1
) 1.832(4); P1-C2 ) 1.815(4); P1-C3 ) 1.815(3); C7-O1 ) 1.419(4);
C1-N1 ) 1.492(4); C1-C7 ) 1.536(5); P1-C1-C7 ) 117.5(3); C7-
C1-N1 ) 111.4(3).
32
(PTA-PPh2 and OdPTAsCO2CH3), P1-C1 is slightly
elongated with respect to the other P-CH2 bonds due to the
addition of the substituent. Derivatives of PTA substituted
at the upper rim are air-stable in the solid state; in solution
they oxidize over the course of days (vide supra).32 Crystals
of PTA-C(C6H4CH3)2OH and PTA-CH(C6H4CH3)OH grown
over the course of a week resulted in X-ray-quality crystals
of the phosphine oxides (Figures 4 and 5). X-ray-quality
crystals of PTA-C(C6H5)2OH and PTA-CH(ferrocenyl)-
OH were grown with careful exclusion of oxygen (Figures
3 and 6). All four structures contain both enantiomers: R/S
for OdPTAsC(C6H4OCH3)2OH and PTA-C(C6H5)2OH and
R-S/S-R for OdPTAsCH(C6H4OCH3)OH and PTA-CH-
(ferrocenyl)OH.
Ruthenium Complexes. Dyson and others have reported
that ruthenium arene complexes of PTA and PTA derivatives,
(η6-arene)RuX2PTA, show anticancer activity.3-13 A library
of compounds has been explored through substitutions to
the arene and X fragments.5,9 Due to the small number of
PTA derivatives available, only a limited number of substitu-
tions have been made thus far to the PTA fragment. The
synthesis of various PTA derivatives described herein, via
the electrophile insertion into PTA-Li, offers the opportunity
to develop a large library of PTA derivatives in a minimal
time frame. We have synthesized three such ruthenium arene
derivatives with our new chiral phosphines.
The synthesis of (η6-arene)RuCl2(PTA-CRR′OH) com-
plexes was accomplished in moderate to good yield by
addition of PTA-CRR′OH to a solution of [Ru(η6-arene)-
Cl2]2 in CH2Cl2 (Scheme 6). These complexes have exhibited
modest water solubility, 5.4 g/L for (η6-C6H5CH3)RuCl2-
(PTA-C(C6H5)2OH) and a slightly more soluble 14.1 g/mL
for (η6-C6H6)RuCl2(PTA-C(C6H5OCH3)2OH). The com-
pounds were characterized by NMR spectroscopy and X-ray
crystallography. The 31P{1H} NMR spectra of (η6-C6H6)-
RuCl2(PTA-C(C6H5OCH3)2OH) and (η6-C6H5CH3)RuCl2-
(PTA-C(C6H5)2OH) contain a single resonance at -31.3 and
618 Inorganic Chemistry, Vol. 47, No. 2, 2008

Chiral Water-Soluble Phosphine Ligands
Figure 6. Thermal ellipsoid representation (50% probability) of PTA-
CH(ferrocenyl)OH with the atomic numbering scheme. Only the S(C1)/
R(C7) enantiomer is shown; however, both R(C1)/S(C7) and S(C1)/R(C7)
are present in the structure. Hydrogen atoms have been omitted for clarity.
Selected bond lengths (Å) and angles (deg): P1-C1 ) 1.867(7); P1-C2
) 1.867(7); P1-C3 ) 1.868(7); C7-O1 ) 1.443(7); C1-N1 ) 1.469(8);
C1-C7 ) 1.555(8); P1-C1-C7 ) 115.4(5); C7-C1-N1 ) 109.3(5).
Figure 8. Thermal ellipsoid representation (50% probability) of [(η6-C6H6)-
Ru(PTA-C(C6H4OCH3)2OH)Cl2] with the atomic numbering scheme. Only
the R enantiomer is shown; however, both enantiomers are present in the
structure. Hydrogen atoms have been omitted for clarity. Selected bond
lengths (Å) and angles (deg): Ru1-P1 ) 2.3255(11); Ru1-Cl1 ) 2.4343-
(10); Ru1-Cl2 ) 2.4184(11); Ru1-arenecent ) 1.692; C7-O1 ) 1.428-
(5); P1-Ru1-Cl1 ) 85.76(4); P1-Ru1-Cl2 ) 85.89(4); Cl1-Ru1-Cl2
) 87.66(4).
Figure 7. Thermal ellipsoid representation (50% probability) of [(η6-C6H5-
CH3)Ru(PTA-C(C6H5)2OH)Cl2] with the atomic numbering scheme. The
R enantiomer is shown here, but both R and S are present in the structure.
Hydrogen atoms have been omitted for clarity. Selected bond lengths (Å)
and angles (deg): Ru1-P1 ) 2.3294(11); Ru1-Cl1 ) 2.4119(12); Ru1-
Cl2 ) 2.4077(12); Ru1-arenecent ) 1.694; C7-O1 ) 1.416(5); P1-Ru1-
Cl1 ) 83.76(4); P1-Ru1-Cl2 ) 84.63(4); Cl1-Ru1-Cl2 ) 88.79(4).
Figure 9. Thermal ellipsoid representation (50% probability) of [(η6-C6H6)-
Ru(PTA-CH(C6H4OCH3)OH)Cl2] with the atomic numbering scheme. Only
the S(C1)/R(C7) enantiomer is shown; however, both R(C1)/S(C7) and
S(C1)/R(C7) are present in the structure. Selected bond lengths (Å) and
angles (deg): Ru1-P1 ) 2.3108(15); Ru1-Cl1 ) 2.4122(14); Ru1-Cl2
) 2.4229(16); Ru1-arenecent ) 1.704; C7-O1 ) 1.446(7); P1-Ru1-Cl1
) 82.70(5); P1-Ru1-Cl2 ) 84.41(5); Cl1-Ru1-Cl2 ) 89.00(6).
Scheme 6
31P{1H} resonance of ∼8-10 ppm was observed. For
example, the 31P{1H} resonance for (η6-C6H6)RuCl2(PTA-
C(C6H5OCH3)2OH) shifted from -31 to -23 ppm upon the
addition of base. Similar shifts were observed for (η6-C6H6)-
RuCl2(PTA-CH(C6H5OCH3)OH), where a resonance at
-24.55 has been observed and attributed to a chelating P,O
bound ligand. Attempts to isolate and characterize the metal
complexes with chelating ligands have, thus far, been
unsuccessful.
-31.0 ppm, respectively. The diasteromeric compound (η6-
C6H6)RuCl2(PTA-CH(C6H5OCH3)OH) contains two 31P-
{1H} chemical shifts for the two possible stereoisomers at
-33.1 and -32.3 ppm for the major and minor diasteromer,
respectively.
The structures of three ruthenium arene complexes were
determined, with each containing a PTA-CRR′OH ligand
bound in a κ1 binding mode wherein the phosphorus is bound
to the metal center. Figures 7-9 contain thermal ellipsoid
representations of three (η6-arene)RuCl2(PTA-CRR′OH)
complexes along with selected bond lengths and angles.
Conclusion
We have reported the addition of PTA-Li to CO2, ketones,
and aldehydes. These chiral upper-rim derivatives of PTA
provide some of the benefits of the parent ligand, namely,
that they are air-stable and somewhat water soluble. In
The ligands we have described should be capable of
chelating to metal centers upon deprotonation of the alcohol
functionality. Attempts to deprotonate the ligand and enforce
a chelating κ2 P,O or N,O binding mode were promising.40
Upon the addition of either CsCO3 or NaOH, a shift in the
(40) We have obtained a preliminary crystal structure of a complex in which
PTA-CH(ferrocenyl)O- is bound to one ruthenium center in a κ2 N,O
binding mode and the phosphorus atom is bound to a second ruthenium
arene center. See the Supporting Information for further details.
Inorganic Chemistry, Vol. 47, No. 2, 2008 619

Wong et al.
solution, the ligands oxidize slowly over the course of days
to weeks. All the ligands synthesized herein have the
potential to bind metals in a κ2 (P,O or N,O) binding mode,
although only the κ1-P mode was observed in this report.
We are currently working on separating the ligand enanti-
omers for use in asymmetric catalysis and for the synthesis
of enantio-enriched Ru complexes.
G.W.W. acknowledges the McNair’s Scholars program,
NSF-EPSCoR (0447416), and the UNR Office of Under-
graduate Research for funding. Support from the NSF is also
acknowledged for the X-ray and NMR facilities (CHE-
0226402 and CHE-0521191). The authors would also like
to thank Drs. S. Cummings and R. Huang for their assistance.
Supporting Information Available: Detailed experimental
procedures, crystallographic details, and NMR spectra of all
compounds. This material is available free of charge via the Internet
at http://pubs.acs.org.
Acknowledgment. Acknowledgment is made to the
National Science Foundation CAREER program (CHE-
0645365) and the donors of the American Chemical Society
Petroleum Research Fund (PRF 43574-G3) for support.
IC701936X
620 Inorganic Chemistry, Vol. 47, No. 2, 2008