Development of a series of P(CH2N=CHR)3 and trisubstituted 1,3,5-triaza-7-phosphaadamantane ligands

Article abstract of DOI:10.1021/ic701864g

The synthesis and structure of a series of novel phosphine ligands derived from the condensation of P(CH₂NH₂) with aldehydes are described. Depending on the reaction conditions, either substituted tris(iminornethyl)phosphine, P(CH₂N=CHR)₃, or 1,3,5-triaza-7-phosphaadamantane structures substituted at the lower rim , PTAR₃, are obtained.

Full text of DOI:10.1021/ic701864g

Inorg. Chem. 2007, 46, 10962−10964
Development of a Series of P(CH2NdCHR)3 and Trisubstituted
1,3,5-Triaza-7-phosphaadamantane Ligands
Rongcai Huang and Brian J. Frost*
Department of Chemistry, MS 216, UniVersity of NeVada, Reno, NeVada 89557
Received September 20, 2007
The synthesis and structure of a series of novel phosphine ligands
derived from the condensation of P(CH2NH2) with aldehydes are
described. Depending on the reaction conditions, either substituted
tris(iminomethyl)phosphine, P(CH2NdCHR)3, or 1,3,5-triaza-7-
phosphaadamantane structures substituted at the “lower rim”,
PTAR3, are obtained.
ring.11 A few “ring-opened” derivatives involving cleavage
of either P-C or N-C bonds have also appeared (Figure
1).9,12 We have recently reported a general methodology for
the modification of the “upper rim” of PTA through lithiation
of an R-carbon.5
Herein we report a general method for the modification
of the “lower rim” of PTA, yielding phosphine derivatives
in which the triazacyclohexane ring is trisubstituted. In
addition to the synthesis of these ligands, the coordination
chemistry and properties of the ligands are described.
Frank and Daigle reported in 1981 that the addition of
concentrated HBr to PTA results in the formation of the tri-
ammonium salt P(CH2NH3Br)3.13 Careful addition of aqueous
sodium hydroxide yields the free triammine P(CH2NH2)3.14
P(CH2NHAr)3 ligands have recently been utilized as trian-
ionic triamidophosphine donors to early transition metals.15
We have utilized P(CH2NH2)3 as a precursor to a series
of trisubstituted triazaphosphaadamantane ligands. The cy-
clocondensation of various aldehydes with tris(aminomethyl)-
phosphine leads to the synthesis of PTA derivatives in which
the lower rim of the ligand is trisubstituted. Depending on
the reaction conditions and electronics of the aldehyde, either
a tris(iminomethyl)phosphine or a triazaphosphaadamantane
Our group,1-5 and others,6 have been interested in the
coordination chemistry of the air-stable and water-soluble
heterocyclic phosphine 1,3,5-triaza-7-phosphaadamantane
(PTA).7 Recent reports that ruthenium complexes of PTA
have shown anticancer activity have created a resurgence of
interest in this ligand.8 A handful of PTA derivatives have
appeared in the literature including alkylation of the phos-
phorus9 or nitrogen10 or modification of the triazacyclohexane
* To whom correspondence should be addressed. E-mail: frost@unr.edu.
(1) Frost, B. J.; Bautista, C. M.; Huang, R.; Shearer, J. Inorg. Chem. 2006,
45, 3481-3483.
(2) 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.
(3) Frost, B. J.; Mebi, C. A.; Gingrich, P. W. Eur. J. Inorg. Chem. 2006,
1182-1189.
(4) Mebi, C. A.; Frost, B. J. Inorg. Chem. 2007, 46, 7115-7120.
(5) (a) Wong, G. W.; Harkreader, J. L.; Mebi, C. A.; Frost, B. J. Inorg.
Chem. 2006, 45, 6748-6755. (b) Wong, G. W.; Lee, W.-C.; Frost,
B. J. Inorg. Chem., in press.
(9) Fluck, E.; Weissgraeber, H. J. Chem.-Ztg. 1977, 101, 304.
(10) Daigle, D. J.; Pepperman, A. B. J. J. Heterocycl. Chem. 1975, 12, 579.
(11) (a) Darensbourg, D. J.; Yarbrough, J. C.; Lewis, S. J. Organometallics
2003, 22, 2050-2056. (b) Benhammou, M.; Kraemer, R.; Germa, H.;
Majoral, J. P.; Navech, J. Phosphorus Sulfur 1982, 14, 105-119. (c)
Navech, J.; Kraemer, R.; Majoral, J. P. Tetrahedron Lett. 1980, 21,
1449-1452. (d) Daigle, D. J.; Boudreaux, G. J.; Vail, S. L. J. Chem.
Eng. Data 1976, 21, 240-241. (e) Delerno, J. R.; Majeste, R. J.;
Trefonas, L. M. J. Heterocycl. Chem. 1976, 13, 757-760. (f) Daigle,
D. J.; Pepperman, A. B., Jr.; Boudreaux, G. J. Heterocycl. Chem. 1974,
11, 1085-1086.
(6) (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) Kirillov, A. M.; Smolen´ski, P.; Guedes da Silva, F.
C.; Pompeiro, A. J. L. Eur. J. Inorg. Chem. 2007, 2686-2692. (c)
Mohr, F.; Falvello, L. R.; Laguna, M. Eur. J. Inorg. Chem. 2006,
3152-3154. (d) Lidrissi, C.; Romerosa, A.; Saoud, M.; Serrano-Ruiz,
M.; Gonsalvi, L.; Peruzzini, M. Angew. Chem., Int. Ed. 2005, 44,
2568-2572.
(7) For an excellent review of PTA chemistry, see: Phillips, A. D.;
Gonsalvi, L.; Romerosa, A.; Vizza, F.; Peruzzini, M. Coord. Chem.
ReV. 2004, 248, 955-993.
(12) (a) Krogstad, D. A.; Ellis, G. S.; Gunderson, A. K.; Hammrich, A. J.;
Rudolf, J. W.; Halfen, J. A. Polyhedron 2007, 26, 4093-4100. (b)
Mena-Cruz, A.; Lorenzo-Luis, P.; Romerosa, A.; Saoud, M.; Serrano-
Ruiz, M. Inorg. Chem. 2007, 46, 6120-6128. (c) Darensbourg, D. J.;
Ortiz, C. G.; Kamplain, J. W. Organometallics 2004, 23, 1747-1754.
(d) Assmann, B.; Angermaier, K.; Paul, M.; Riede, J.; Schmidbaur,
H. Chem. Ber. 1995, 128, 891-900. (e) Assmann, B.; Angermaier,
K.; Schmidbaur, H. J. Chem. Soc., Chem. Commun. 1994, 941-942.
(f) Siele, V. I. J. Heterocycl. Chem. 1977, 14, 337-339.
(8) For example, see: (a) 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. (b) Grguric-Sipka,
S.; Kowol, C. R.; Valiahdi, S.-M.; Eichinger, R.; Jakupec, M. A.;
Roller, A.; Shova, S.; Arion, V. B.; Keppler, B. Eur. J. Inorg. Chem.
2007, 2870-2878. (c) Ang, W. H.; Dyson, P. J. Eur. J. Inorg. Chem.
2006, 4003-4018. (d) 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.
(e) 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. (f) Dorcier, A.; Dyson, P. J.; Gossens,
C.; Rothlisberger, U.; Scopelliti, R.; Tavernelli, I. Organometallics
2005, 24, 2114-2123. (g) Allardyce, C. S.; Dyson, P. J.; Ellis, D. J.;
Heath, S. L. Chem. Commun. 2001, 1396-1397.
(13) Frank, A. W.; Daigle, D. J. Phosphorus Sulfur 1981, 10, 255-259.
(14) See the Supporting Information for details.
(15) (a) Han, H.; Elsmaili, M.; Johnson, S. A. Inorg. Chem. 2006, 45,
7435-7445. (b) Keen, A. L.; Doster, M.; Han, H.; Johnson, S. A.
Chem. Commun. 2006, 1221-1223. (c) Hatnean, J. A.; Raturi, R.;
Lefebvre, J.; Leznoff, D. B.; Lawes, G.; Johnson, S. A. J. Am. Chem.
Soc. 2006, 128, 14992-14999.
10962 Inorganic Chemistry, Vol. 46, No. 26, 2007
10.1021/ic701864g CCC: $37.00
© 2007 American Chemical Society
Published on Web 11/29/2007

COMMUNICATION
Table 1. 31P NMR Data for PTAR3 and P(CH2NdCHR)3
R group
31P{1H} NMR
% yield
PTAR3
C6H5 (1)
C6H4OMe (2)
C6H4CN (3)
-111.6a
-112.1a
-110.9a
69
67
41
Figure 1. Examples of ring-opened PTA derivatives.
Scheme 1
P(CH2NdCHR)3
C6H3(OH)(OMe) (4)
C6H4OH (5)
C6H4CN (6)
-23.7b
-23.1c
-18.1a
70
55
65
a In CDCl3. b In DMSO-d6. c In CD3OD.
structure is obtained. Under acidic conditions, condensation
is followed by ring closure, yielding the heterocyclic ring tri-
azaphosphaadamantane PTAR3 (R ) C6H5, C6H4OMe, C6H4-
CN; Scheme 1a).16 However, under basic conditions, tris-
(iminomethyl)phosphine ligands are obtained from a 3-fold
condensation reaction of the aldehyde with tris(aminometh-
yl)phosphine (Scheme 1b).17 The tris(iminomethyl)phos-
phines cannot be converted into PTAR3 ligands by heating
or the addition of acid, leading us to conclude that the syn-
thesis of PTAR3 ligands occurs in a stepwise manner (con-
densation followed by nucleophilic attack and ring closure).
We have characterized these ligands by 31P and 1H NMR
spectroscopy and X-ray crystallography. The two isomeric
Figure 2. Thermal ellipsoid plots (50% probability) showing the molecular
structures of 2. Hydrogen atoms have been omitted for clarity. Selected
bond lengths (Å) and angles (deg): P-Cave ) 1.863(2), N-Cave ) 1.480-
(3), C4-C7 ) 1.525(3), C5-C14 ) 1.514(3), C6-C21 ) 1.526(3),
C-P1-C ) 95.61(11)°.
products may be quickly identified utilizing 31P NMR
spectroscopy. The PTAR3 complexes exhibit 31P NMR
chemical shifts at approximately -110 ppm, upfield of PTA
(-97 ppm, CDCl3), whereas the P(CH2NdCHR)3 com-
pounds exhibit 31P NMR chemical shifts between -18 and
-25 ppm (Table 1). The tris(iminomethyl)phosphines are
somewhat air-sensitive relative to the cage compounds,
forming phosphine oxide over the course of a day in solution
or a few days in the solid state.
The substitution pattern of the triazacyclohexane ring is
consistently two equatorial and one axial substituent (R),
when R ) aryl. Density functional theory calculations on
the various possible isomers of PTAR3 (e.g., eee, eea, eaa,
and aaa) reveal that the eea isomer observed is indeed the
lowest in energy by ∼3 kJ/mol relative to the next lowest
energy isomer (eee).18 NMR spectroscopy shows only one
isomer present in solution, and based on X-ray crystal-
lography, it is only the eea isomer that is isolated. Figure 2
contains a thermal ellipsoid representation of the anisole
derivative of PTAR3, including selected bond lengths and
angles.19 Crystals of the triiminophosphine derived from
vanillin (4-hydroxy-3-methoxybenzaldehyde) have also been
obtained (Figure 3).19
(16) General procedure for the synthesis of PTAR3 ligands. Tris(amino-
methyl)phosphine trihydrobromide (1.819 g, 5.0 mmol) and sodium
hydroxide (600 mg, 15 mmol) were added to a 100 mL Schlenk flask
in a drybox. Freshly distilled methanol (50 mL) was added via syringe,
resulting in a clear solution. Hydrogen chloride (2.0 M) in Et2O (50
µL, 0.10 mmol) and the appropriate aldehyde (25 mmol) were added
to the flask and the reaction stirred overnight under nitrogen. The
solvent was removed under reduced pressure, resulting in a white solid.
Methylene chloride (100 mL) was added to the residue and the solution
washed with water (2 × 50 mL). The organic layer was dried over
anhydrous potassium carbonate and filtered, and the solvent was
removed under reduced pressure. The residue was recrystallized from
a minimum of CH2Cl2 (5 mL), followed by the addition of 120 mL
of absolute ethanol and storage at -5 °C overnight. The product was
collected as a white crystalline solid in 40-70% yield, following two
washings with 15 mL of ethanol and drying under vacuum.
(17) General procedure for the synthesis of tris(iminomethyl)phosphine
ligands, P(CH2NdCHR)3. Tris(aminomethyl)phosphine trihydrochlo-
ride (461 mg, 2.0 mmol) and sodium hydroxide (240 mg, 6 mmol)
were dissolved in 40 mL of freshly distilled methanol, resulting in a
clear solution. After stirring for 30 min, the solvent was removed and
the residue dissolved in 7 mL of CH2Cl2 and filtered to remove NaCl.
CH2Cl2 was removed under vacuum and the residue dissolved in 40
mL of methanol. Sodium hydroxide (15 mg, 0.37 mmol) and the
appropriate aldehyde (10 mmol) were added to the solution. The
resulting mixture was stirred overnight and the solvent removed under
vacuum. The residue was recrystallized at -5 °C from either THF or
CHCl3 and diethyl ether. The product was obtained as a yellow solid
in 55-70% yield, following washing with diethyl ether (2 × 10 mL)
and drying under vacuum. This proceeds well with the bromide salt,
P(CH2NH3Br)3; however, for separation reasons, the chloride salt,
P(CH2NH3Cl)3, is preferred.
(18) Calculations were performed on optimized structures using the
LANL2DZ basis set at the B3LYP level of theory as implemented in
Gaussian03.
Inorganic Chemistry, Vol. 46, No. 26, 2007 10963

COMMUNICATION
Figure 3. Thermal ellipsoid plots (50% probability) showing the molecular
structures of 4. Selected bond lengths (Å) and angles (deg): P-Cave
)
1.857(3), N1-C2 ) 1.278(3), N2-C11 ) 1.304(3), N3-C20 ) 1.274(3),
C1-P1-C19 ) 97.88(12), C10-P1-C19 ) 100.41(13)m C1-P1-C10
) 98.02(12).
Figure 4. Thermal ellipsoid plots (50% probability) showing the molecular
structures of 10. Hydrogen atoms have been omitted for clarity. Selected
bond lengths (Å) and angles (deg): Pd1-P1 ) 2.2980(9), Pd1-Cl1 )
2.2983(9), P-Pd-P ) 180.00(3), Cl-Pd1-Cl1 ) 180.00(3), P1-Pd1-
Cl1 ) 87.68(3).
Table 2. Spectroscopic, 31P NMR and ν(CO), Data for trans-ClRh-
(PTAR3)2CO Compounds in CHCl3, Where R ) H and PTAR3 ) PTA
Rh(CO)Cl(PR3)2
31P{1H} NMR
1JP-Rh (Hz)
ν(CO) (cm-1
)
20,22
PR3 ) PPh3
-29.6
129
117
1979
1960
Table 3. Cone Angle and Percentage of Sphere Coverage by the
PTAR3 and P(CH2NdCHR)3 Ligands As Calculates by Solid G21
23
PR3 ) P(CH2OH)3
PR3 ) PTAR3
R ) H23
R ) C6H5 (7)
R ) C6H4OMe (8)
R ) C6H4CN (9)
10.8
b
b
θa
%
θa
%
-60.1
-54.4
-55.3
-54.4
127
117
117
121
1963
1979
1978
1987
PTA
105
111
128
19.6
21.8
28.1
2
4
112
149
21.9
36.5
c
PMe3
c
PPh3
a Solid G cone angle (deg). b Percentage of metal shielded by the ligand.
Modification of the triazacyclohexane ring of PTA is
interesting because it affords the ability to alter the sterics
of the phosphine while making minimal changes to the
electronics. Comparison of ν(CO) for a series of trans-Rh-
(CO)Cl(PTAR3)2 complexes indicates that these ligands are
similar electronically (Table 2). The PTAR3 ligands (1-3)
are less electron-donating than PTA. When R ) C6H5 (1)
or C6H4OMe (2), the electronic parameter is similar to that
of PPh3 [ν(CO) ) 1979 cm-1];20 however, when R ) C6H4-
CN (3), the ligand is significantly less electron-donating
(Table 2). Of interest is that the steric bulk of the PTAR3
ligands is some distance from the phosphorus and, therefore,
any metal center. For example, the trans-PdCl2(PTAR3)2
c See ref 24.
complex synthesized by the reaction of PdCl2(COD) with 2
equiv of PTAR3 yields compound 10, depicted in Figure 4.
We have examined the steric demand of the PTAR3 and
triimine ligands utilizing the Solid G program developed by
Guzei and Wendt.21 Not surprisingly, θ for the PTAR3
ligands (112° for 2) is somewhat larger than that for PTA
(θ ) 105°; Table 3).
In conclusion, we have reported here the first example of
substitution of the N-CH2-N methylenes of PTA. The mod-
ifications described have led to an interesting series of phos-
phine ligands in which the cone angle is large yet near the
metal center the ligand is sterically similar to the parent PTA
ligand. We are currently exploring the scope of the ligand
synthesis and further details of the properties of the ligands.
Acknowledgment. The authors thank the National Sci-
ence Foundation (NSF) CAREER program (Grant CHE-
0645365) for support. Financial support from the NSF is
acknowledged for the X-ray and NMR facilities (Grants
CHE-0226402 and CHE-0521191). We also thank Dr. Ilia
Guzei for allowing us access to Solid G and Dr. Donald
Daigle for helpful discussions.
(19) X-ray diffraction data were collected at 100 ((1) K on a Bruker APEX
CCD diffractometer with Mo KR radiation (λ ) 0.710 73 Å) and a
detector-to-crystal distance of 4.94 cm. Data collection was optimized
utilizing the APEX 2 software suite. Data integration, correction for
Lorentz and polarization effects, and final cell refinement were
performed using SAINT+ and corrected for absorption using SADABS
as implemented within the APEX 2 software. Structures were solved
using direct methods, followed by successive least-squares refinement
on F 2. All non-hydrogen atoms were refined anisotropically; hydrogen
atoms were located on the difference map for each structure or refined
in idealized positions using a riding model. Crystallographic details
may be found in Table 1-S of the Supporting Information. A complete
list of bond lengths and angles as well as all calculated atomic
coordinates and anisotropic thermal parameters may be obtained from
the Cambridge Crystallographic Data Centre. Crystal data for com-
pound 2 (CCDC 661303): C27.50H30N3O3P, MW ) 516.96, triclinic,
P1h, Z ) 2, a ) 7.0594(3) Å, b ) 10.9914(5) Å, c ) 17.0315(7) Å,
R ) 76.0650(10)°, â ) 86.2170(10)°, γ ) 74.0730(10)°, V ) 1233.39-
(9) Å3, 15 186 reflections, 4568 independent reflections (Rint ) 0.0410),
R1 ) 0.0450, and wR2 ) 0.1024. Crystal data for compound 4 (CCDC
661305): C28H34N3O7P, MW ) 555.55, triclinic, P1h, Z ) 2, a )
9.7133(6) Å, b ) 11.2111(7) Å, c ) 13.3168(8) Å, R ) 99.750(4)°,
â ) 97.639(4)°, γ ) 100.634(4)°, V ) 1384.34(15) Å3, 21 006
reflections, 5149 independent reflections (Rint ) 0.0620), R1 ) 0.0506,
and wR2 ) 0.01204. Crystal data for compound 10 (CCDC 661304):
C56H64N6O6Cl6P2Pd, MW ) 1298.17, monoclinic, P2(1)/c, Z ) 2, a
) 14.7270(3) Å, b ) 22.0291(4) Å, c ) 8.75330(10) Å, R ) 90°, â
) 98.8130(10)°, γ ) 90°, V ) 2806.24(8) Å3, 28 103 reflections, 6452
independent reflections (Rint ) 0.0727), R1 ) 0.0479, and wR2 )
0.1126.
Supporting Information Available: Detailed experimental
procedures, crystallographic details in CIF format, and NMR spectra
of all compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
IC701864G
(21) (a) Guzei, I. A.; Wendt, M. Program Solid G; Madison, WI, 2004.
(b) Guzei, I. A.; Wendt, M. Dalton Trans. 2006, 3991-3999.
(22) van Vliet, P. I.; Kuyper, J.; Vrieze, K. J. Organomet. Chem. 1976,
122, 99-111.
(23) Pruchnik, F. P.; Smolen´ski, P.; Raksa, I. Polish J. Chem. 1995, 69,
5-8.
(24) Landis, C. R.; Nelson, R. C.; Jin, W.; Bowman, A. C. Organometallics
2006, 25, 1377-1391.
(20) Roodt, A.; Otto, S.; Steyl, G. Coord. Chem. ReV. 2003, 245, 121-137.
10964 Inorganic Chemistry, Vol. 46, No. 26, 2007