Water Soluble Cationic Phosphine Ligands Containing m-Guanidinium Phenyl Moieties. Syntheses and Applications in Aqueous Heck Type Reactions

Article abstract of DOI:10.1021/jo961140n

Cationic phosphine ligands containing m-guanidinium phenyl substituents {Ph_3-nP[C₆H_4-m-NHC(NH₂)(NMe ₂)]_n}ⁿ⁺ nCl^- (n = 1-3) (17a-c) have been obtained by addition of dimethylcyanamide to the amino groups of tertiary (m-aminophenyl)phosphines in acidic medium. The tertiary (m-aminophenyl)phosphines Ph_3-nP(C₆H₄-m-NH₂)_n (4a-c) were prepared by reaction of (3-[N,N-bis(trimethylsilyl)amino]phenyl)magnesium chloride (1) with chlorophosphines Ph_3-nPCl_n followed by deprotection of the bis(trimethylsilyl)amino groups with methanol. Using a similar protected group synthesis as above, the secondary (m-aminophenyl)phosphine Ph(H)PC₆H₄-m-NH₂ (7) could be prepared as well. It may be employed as a building block for the syntheses of chiral bidentate phosphine ligands (11, 14, and 15) bearing m-aminophenyl substituents. The guanidinium phosphines 17b and 17c are readily soluble in water. A comparative study of 17b and 17c, the aryl alkyl guanidinium phosphines 18 and 19, and TPPTS (P(C₆H₄-m-SO₃Na)₃) in the aqueous phase palladium-catalyzed C-C coupling reaction between p-iodobenzoate and (trifluoroacetyl)propar-gylamine shows 17b to be of surmounting activity.

Full text of DOI:10.1021/jo961140n

2362
J . Org. Chem. 1997, 62, 2362-2369
Wa ter Solu ble Ca tion ic P h osp h in e Liga n d s Con ta in in g
m -Gu a n id in iu m P h en yl Moieties. Syn th eses a n d Ap p lica tion s in
Aqu eou s Heck Typ e Rea ction s
Antonella Hessler and Othmar Stelzer*
Fachbereich 9, Anorganische Chemie, Bergische Universita¨t-GH Wuppertal, Gaussstrasse 20,
D-42097 Wuppertal, Germany
Harald Dibowski, Karin Worm, and Franz P. Schmidtchen*
Institut fu¨r Organische Chemie und Biochemie, Technische Universita¨t Mu¨nchen,
Lichtenbergstrasse 4, D-85747 Garching, Germany
Received J une 17, 1996X
Cationic phosphine ligands containing m-guanidinium phenyl substituents {Ph3-nP[C6H4-m-
NHC(NH2)(NMe2)]n}n+ nCl- (n ) 1-3) (17a -c) have been obtained by addition of dimethylcyanamide
to the amino groups of tertiary (m-aminophenyl)phosphines in acidic medium. The tertiary (m-
aminophenyl)phosphines Ph3-nP(C6H4-m-NH2)n (4a -c) were prepared by reaction of (3-[N,N-
bis(trimethylsilyl)amino]phenyl)magnesium chloride (1) with chlorophosphines Ph3-nPCln followed
by deprotection of the bis(trimethylsilyl)amino groups with methanol. Using a similar protected
group synthesis as above, the secondary (m-aminophenyl)phosphine Ph(H)PC6H4-m-NH2 (7) could
be prepared as well. It may be employed as a building block for the syntheses of chiral bidentate
phosphine ligands (11, 14, and 15) bearing m-aminophenyl substituents. The guanidinium
phosphines 17b and 17c are readily soluble in water. A comparative study of 17b and 17c, the
aryl alkyl guanidinium phosphines 18 and 19, and TPPTS (P(C6H4-m-SO3Na)3) in the aqueous phase
palladium-catalyzed C-C coupling reaction between p-iodobenzoate and (trifluoroacetyl)propar-
gylamine shows 17b to be of surmounting activity.
In tr od u ction
phines are most frequently used as catalysts.7 Only very
few examples of cationic phosphine ligands have been
applied.8
The application of ionic phosphine ligands for the
development of catalytically active transition metal
reagents in aqueous solvent systems during the last
decade is mainly due to the simplification of the catalyst
product separation1,2 and the economy of using water as
a solvent in large-scale industrial syntheses. Compared
with the widely studied anionic phosphine ligands (e.g.,
A (TPPTS)3,4 or B ([Ph2PCH2COO]-Na+)),5 the applica-
tion of cationic phosphines bearing quaternary am-
monium (C (AMPHOS)6a or D6b), phosphonium (E
(PHOPHOS)6c), or sulfobetaine groups (F 6d) has been
investigated but not to a great extent. They were mainly
employed as catalysts for the hydrogenation and hydro-
formylation of olefins. For C-C coupling reactions in
aqueous medium, palladium complexes of anionic phos-
X Abstract published in Advance ACS Abstracts, March 1, 1997.
(1) Kuntz, E. G. Chem. Tech. 1987, 17, 570; FR-B 2314190, J une
20, 1975, Rhoˆne-Poulenc.
(2) Herrmann, W. A.; Kulpe, J .; Kellner, J .; Riepl, H. DE 3840600
A1, Dec 2, 1988, Hoechst AG. Wiebus, E.; Cornils, B. Chem. Ing. Techn.
1994, 66, 916.
(3) Herrmann, W. A.; Kulpe, J . A.; Konkol, W.; Bahrmann, H. J .
Organomet. Chem. 1990, 389, 85. Herrmann, W. A.; Kohlpaintner, C.
W. Angew. Chem. 1993, 105, 1588.
(4)Larpent, C.; Patin, H.; Thilmont, N.; Valdor, J . F. Synth.
Commun. 1991, 21, 495.
(5)Peuckert, M.; Keim, W. Organometallics 1983, 2, 594.
(6) (a) Smith, R. T.; Ungar, R. K.; Sanderson, L. J .; Baird, M. C.
Organometallics 1983, 2, 1138. Markiewicz, M. K.; Baird, M. C. Inorg.
Chim. Acta 1986, 113, 95. (b) Nagel, U.; Kinzel, E. Chem. Ber. 1986,
119, 1731. (c) Renaud, E.; Russell, R. B.; Fortier, S.; Brown, S. J .; Baird,
M. C. J . Organomet. Chem. 1991, 419, 403. (d) Fell, B.; Papadogianakis,
G. J . Mol. Catal. 1991, 66, 143.
In a recent publication,9 we reported on the syntheses
and application in aqueous phase Heck type reactions of
a novel type of cationic phosphine ligand (e.g., G) bearing
peripheral guanidinium functions. The introduction of
one of the most basic and hydrophilic groups adds
pronounced water solubility and anion binding capacity10
to these ligands. Both features are of significance for
their application in transition metal catalyzed transfor-
mations of biologically relevant oxo anion substrates such
(8) Pfeiffer, G.; Chhan, S.; Bendayan, A.; Waegell, B.; Zahra, J . P.
J . Mol. Catal. 1990, 59, 1.
(7) Bumagin, N. A.; Bykov, V. V.; Sukhomlinova, L. I.; Tolstaya, T.
P.; Beletskaya, I. P. J . Organomet. Chem. 1995, 486, 259. Bumagin,
N. A.; More, P. G.; Beletskaya, I. P. J . Organomet. Chem. 1989, 371,
397. Blart, E.; Genet, J . P.; Safi, M.; Savingnac, M.; Sinou, D.
Tetrahedron 1994, 50, 505.
(9) Dibowski, H.; Schmidtchen, F. P. Tetrahedron 1995, 51, 2325.
(10) Yamamoto, Y.; Kojima, S. The Chemistry of Amidines and
Imidates; Patai, S., Rappoport, Z., Eds.; J ohn Wiley & Sons: New York,
1991; Vol. 2, p 485. Schmidtchen, F. P.; Gleich, A.; Schummer, A. Pure
Appl. Chem. 1989, 61, 1535.
S0022-3263(96)01140-1 CCC: $14.00 © 1997 American Chemical Society

Water Soluble Cationic Phosphine Ligands
J . Org. Chem., Vol. 62, No. 8, 1997 2363
Sch em e 1. Syn th eses of Ter tia r y
as nucleotides by Heck type or analogous reactions. The
guanidinium moiety should exert some directing influ-
ence on the reactants by preorientation of the substrates
at the periphery of the active catalyst complex.
(m -Am in op h en yl)p h osp h in es
Low-coordinated Pd(0) complexes of the type PdL2 (L
) phosphine ligands) are generally assumed to be the
catalytically active species in C-C cross coupling reac-
tions.11 Their formation should be favored by the repul-
sive interaction of the strongly solvated cationic groups
if the guanidininium phosphines are considered as
ligands. The shielding of the Pd atom will be determined
by the rigidity of the spacer unit between the P atoms
and the guanidinium moieties, the phenylene bridge (H)
being more favorable than the flexible trimethylene chain
in G. Placement of the bulky guanidinium substituent
including the reduction of the corresponding (nitro-
phenyl)phosphines15b with molecular hydrogen using
Raney nickel as the catalyst. The overall yields were low,
and the compounds were only poorly characterized.
The structure of 4c was established by X-ray structural
analysis,16 showing the molecular dimensions of the
skeleton of 4c to be very close to those reported for
triphenylphosphine17 and p-TPPTS.18
in the ortho-position should give, however, less stable
intermediate Pd(0) complexes and dissociation with
precipitation of palladium metal should become a serious
side reaction.12 We concentrated therefore on the m-
phenylene-bridged guanidinium phosphines (type H)
bearing the polar group in the same position of the
aromatic ring system as in TPPTS. Here, we report on
their syntheses based on m-aminophenyl-substituted
tertiary phosphines and the application of their Pd
complexes in aqueous phase Heck type reactions.
The technique developed by us for the syntheses of
4a -c can also be used to prepare the secondary (ami-
nophenyl)phosphines (e.g., 7). Protecting groups for the
NH2 and the PH groups have to be introduced in this
case, however. This was achieved by treating dimethyl-
or (diethylamino)phenylchlorophosphine19 with 1 yielding
the aminophosphines 5a and 5b, respectively. They
were, however, not amenable to reduction with LiAlH4
to give the secondary phosphines 8 or 7. The amino-
phosphines 5a or 5b were therefore transformed by
methanolysis into the methoxy derivative 5c. Its reduc-
tion with lithium aluminum hydride gave a mixture of
two compounds in a 30:70 ratio. The 31P{1H} NMR
spectrum of the reaction mixture showed in addition to
the signal at δP ) -38.8 ppm of the desired secondary
phosphine 8 a resonance at δP ) -17.1 ppm which may
be assigned to the diphosphine 9 (cf., δP value for
Ph2PPPh2 of -14.1 ppm).20 Reductive cleavage of the
P-P bond of 9 with excess sodium and subsequent
treatment with ethanol gave 8 in a total yield of ca. 50%
(Scheme 2).
Resu lts a n d Discu ssion
Syn th eses of (m -Am in op h en yl)p h osp h in es a n d
m -Gu a n id in iu m P h en ylp h osp h in es. For the prepa-
ration of the m-guanidinium phenylphosphines, a tri-
methylsilyl-protecting group synthesis13 was developed
in which the guanidinium system was introduced in the
last step. Thus, reaction of (3-[N,N-bis(trimethylsilyl)-
amino]phenyl)magnesium chloride (1)13 with Ph2PCl,
PhPCl2, or PCl3, respectively, gave the silyl derivatives
(2a -c) of the (m-aminophenyl)phosphines (Scheme 1).
The trimethylsilyl moieties blocked the amino groups to
the effects of the P-Cl bonds, since the Si-N bonds were
inert to the chlorophosphines under the reaction condi-
tions. The protecting Me3Si groups in 2a -c could be
removed by methanolysis, the (m-aminophenyl)phos-
phines 4a -c being obtained in fair yields. 4a and 4b
were obtained alternatively in a single-stage synthesis
by Pd-catalyzed P-C coupling of diphenyl- or phenyl-
phosphine with m-iodoaniline.14 Compounds 4a -c have
been reported in the literature previously.15a They were
prepared in small quantities by a multistage synthesis
If PhPCl2 is treated with an equimolar amount of 1,
the reaction mixture contains the chlorophosphine 6a (δP
) 80.5 ppm) and the tertiary phosphine 2b (δP ) -6.5
ppm) in a 1:1 ratio in addition to unreacted PhPCl2 (δP
) 160.2 ppm).21 The assignment of the signal at δP )
80.5 ppm to 6a is based upon the comparison of its δP
(16) Hessler, A.; Stelzer, O.; Sheldrick, W. S. Unpublished results.
The author has deposited atomic coordinates for this structure with
the Cambridge Crystallographic Data Centre. The coordinates can be
obtained, on request, from the Director, Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge, CB2 1EZ, U.K.
(17) Daly, J . J . J . Chem. Soc. 1964, 3799. Dunne, B. J .; Morris, R.
B.; Orpen, A. G. J . Chem. Soc., Dalton Trans. 1991, 653.
(18) Herd, O.; Hessler, A.; Langhans, K. P.; Stelzer, O.; Sheldrick,
W. S.; Weferling, N. J . Organomet. Chem. 1994, 475, 99.
(19) Frank, A. W. Organic Phosphorus Compounds Kosoloapoff, G.
M., Maier, L., Eds.; Wiley Interscience: New York, Sydney, Toronto,
1972, Vol. 4, p 402.
(20) Berger, S.; Braun, S.; Kalinowski, H. O. NMR Spektroskopie
von Nichtmetallen, 31P-NMR Spektroskopie; Georg Thieme Verlag:
Stuttgart, New York, 1993; Vol. 3.
(21) Fild, M.; Schmutzler, R. Organic Phosphorus Compounds;
Kosoloapoff, G. M., Maier, L., Eds.; Wiley Interscience: New York,
Sydney, Toronto, 1972; Vol. 4, p 75.
(11) Heck, R. F. Organic Reactions; Dauben, W. G., Ed.; J ohn Wiley
& Sons: New York, 1991; Vol. 27, p 345. Van Asselt, R.; Elsevier, C.
J . Tetrahedron 1994, 50, 323. Calhorda, M. J .; Brown, J . M.; Cooley,
N. A. Organometallics 1991, 10, 1431.
(12) Ziegler, C. B.; Heck, R. F. J . Org. Chem. 1978, 43, 2941.
(13) Pratt, J . R.; Massey, W. D.; Pinkerton, F. H.; Thames, S. F. J .
Org. Chem. 1975, 40, 1090.
(14) Herd, O.; Hessler, A.; Hingst, M.; Tepper, M.; Stelzer, O. J .
Organomet. Chem. 1996, 522, 69.
(15) (a) Schiemenz, G. P.; Ro¨hlk, K. Phosphorus 1971, 1, 187. (b)
Schiemenz, G. P.; Ro¨hlk, K. Chem. Ber. 1971, 104, 1219.

2364 J . Org. Chem., Vol. 62, No. 8, 1997
Hessler et al.
Sch em e 2. Syn th eses of Secon d a r y
Sch em e 3. Bid en ta te (m -Am in op h en yl)p h osp h in es
(m -Am in op h en yl)p h osp h in es
value with those of Ph2PCl (δP ) 81.5 ppm),21 (2,4,6-
iPr3C6H2)PhPCl (δP ) 77.2 ppm)22 and (3-F-C6H4)2PCl
(δP ) 74.7 ppm).21 Reduction of the chlorophosphine 6a
in the mixture obtained as above with LiAlH4 yielded 8
Sch em e 4. Tr a n sfor m a tion of
(m -Am in op h en yl)p h osp h in es to th e Gu a n id in iu m
P h osp h in es
1
(δP ) -38.8 ppm, J PH ) 220 Hz), which could be
separated from 2b and PhPH2 (formed by reduction of
excess PhPCl2) by fractionated vacuum distillation. Un-
der these conditions, however, the protecting SiMe3
groups were partially removed as indicated by the 1H
NMR spectrum. For a complete deprotection, 8 was
treated with methanol at ambient temperature, 7 (δP )
1
-39.6 ppm, J PH ) 220 Hz) being formed in moderate
yield.
The secondary (aminophenyl)phosphine 7 or its N-silyl
derivative 8 can profitably be used as building blocks for
the syntheses of m-aminophenyl-substituted chiral bi-
dentate phosphines which are hardly accessible by other
routes. Thus, free radical initiated addition of diphen-
ylvinylphosphine23 to 8 gave the ditertiary phosphine 10
containing a protected amino group (Scheme 3). When
10 was deprotected with an ethereal solution of HCl, the
free amino derivative 11 was formed. If 7 was treated
with 1 equiv of n-BuLi, the amino group is deprotonated
primarily as indicated by the δP value of the intermediate
1
(δP ) -39.8 ppm, J PH ) 213 Hz) obtained, which is
almost identical to that of the starting material 7 (δP )
-39.6 ppm, 1J PH ) 220 Hz). Reaction of this intermediate
with trimethylchlorosilane yields 12 (δP ) -40.2 ppm,
1J PH ) 214.2 Hz) which can be metallated with n-BuLi,
the lithium phosphide 13 (δP ) -26.6 ppm) being formed.
Alkylation of 13 with di-tert-butylphosphetanium bro-
mide24a or coupling with 1,3-dibromopropane yields the
ditertiary phosphines 14 or 15, respectively, after depro-
tection of the amino group with methanol.
For the syntheses of the guanidinium phosphines 17a -
c, the corresponding m-aminophenyl derivatives 4a -c
were treated with equivalent amounts of ethereal or
aqueous HCl solution. The HCl adducts 16a -c formed
thereby were isolated and identified by NMR spectro-
scopy. Their phosphorus chemical shifts (δP) were
almost identical to those of the neutral compounds,
indicating that protonation occurred preferably on the
amino groups (Scheme 4) and that the formation of
phosphonium salts may be less important.25 The differ-
ences in the δP values between arylphosphines and their
HCl or HBr adducts are, however, only within a few ppm
(e.g., Ph3P δP ) -6.0; Ph3PH+Br- δP ) -3.1 ppm).25a
The analysis of the 13C{1H} NMR spectra of 16a -c
indicates that all of the amino groups are protonated. The
δC values of C2, C4, and C6 are shifted lowfield by ca.
10 ppm while the resonances of the ipso-carbon atoms
C3 (N) appear about 15 ppm highfield compared with the
corresponding values in neutral 4a -c.
(22) Bitterer, F.; Stelzer, O. Unpublished results.
(23) Berlin, K. D.; Butler, G. B. J . Org. Chem. 1961, 26, 2537.
Rabinowitz, R.; Pellon, J . J . Org. Chem. 1961, 26, 4623.
(24) (a) Brauer, D. J .; Ciccu, A. J .; Hessler, G.; Stelzer, O. Chem.
Ber. 1992, 125, 1987. (b) Tepper, M.; Machnitzki, P.; Stelzer, O.
Unpublished results.
(25) (a) Grim, S. O.; Yankowsky, A. W. J . Org. Chem. 1977, 42, 1236.
(b) Davis, M. A. J . Org. Chem. 1967, 32, 1161. Olah, G. A.; McFarland,
C. W. J . Org. Chem. 1969, 34, 1832.

Water Soluble Cationic Phosphine Ligands
J . Org. Chem., Vol. 62, No. 8, 1997 2365
The introduction of the guanidinium group was achieved
by making use of the well-established addition of anilin-
ium salts to cyanamides.10,26 Thus, reaction of 16a -c
with excess dimethylcyanamide at elevated temperatures
gave the guanidinium phosphines 17a -c in high yields.
As expected, their δP values do not differ significantly
from those of 4a -c and 16a -c. Further evidence for the
successful conversion of 16a -c into guanidines is pro-
vided by the appearance of resonances at δC ) 155.4
(17a ), 156.4 (17b), and 157.5 ppm (17c) or δC ) 38.4
(17a ), 38.2 (17b), and 39.5 ppm (17c) in the 13C{1H} NMR
spectra which may be assigned to the guanidinium
carbon atoms27 or the NMe2 groups, respectively.
While the guanidinium phosphines 17a -c are in-
soluble in most organic solvents, they readily dissolve in
water, methanol, and ethanol, their solubilities in water
being dependent on the counterion. Thus, while 17a
dissolves readily in water, its hexafluorophosphate (17d ),
obtained by a metathesis reaction with ammonium
hexafluorophosphate, is quite insoluble in this solvent.
The same applies for the iodide of 17b, obtained from
PhPH2 by a P-C coupling reaction,24b which is much less
soluble in water than the chloride.
Under aerobic conditions, the solutions of the guani-
dinium phosphines 17b and 17c, with chloride or acetate
as counterions are much more stable toward oxidation
to the phosphine oxide stage when compared to those of
the anionic TPPTS ligand. This is a particularly advan-
tageous feature for the preparation and durability of
water soluble transition metal complexes employed as in
situ formed catalysts for palladium complex promoted
C-C cross-coupling reactions.28
In fact, a stock catalyst solution obtained by mixing
palladium acetate (100 µmol) with 500 µmol of the
phosphine ligands 17b and 17c in water gave no evidence
of palladium precipitation and remained catalytically
active in model C-C couplings over several months when
stored at 4 °C (see below). The prototypical example of
a Castro-Stephens coupling29 between iodobenzoate and
N-(trifluoroacetyl)propargylamine in homogeneous aque-
ous solution (H2O/acetonitrile 50:50 to 70:30) after ad-
dition of a premixed catalyst solution of one of the Pd
ligands 17b or 17c (5-10 mol % Pd), respectively, showed
clean and quantitative conversion to the cross-coupled
product within a few hours at slightly elevated temper-
atures (35-50 °C) (Figure 1). Similar reactions were
F igu r e 1. HPLC analysis (detection UV254) of the Castro-
Stephens coupling (a) in H2O/CH3CN 70:30 catalyzed by 5 mol
% [palladium-guanidinophosphine 17b] complex and 10 mol
% CuI at 35 °C with 200 mol % triethylamine. Peak identifica-
tion: A ) iodobenzoate; B ) Pd complexes/ligand; C ) cross-
coupled product.
(26) Rasmussen, C. R.; Villani, F. J .; Reynolds, B. E.; Plampin, J .
N.; Hood, A. R.; Hecker, L. R.; Nortey, S. O.; Hanslin, A.; Costanzo,
M. J .; Howse, R. M.; Molinari, A. J . Synthesis 1988, 460. Ka¨mpf, A.
Chem. Ber. 1904, 37, 1681.
(27) (a) Kalinowski, H. O.; Berger, S.; Braun, S. 13C-NMR Spectros-
copy; Georg Thieme Verlag: Stuttgart, New York, 1984; p 220. (b)
Cameron, D. G.; Hudson, H. R.; Pianka, M. Phosphorus, Sulfur Silicon
Relat. Elem. 1993, 83, 21.
F igu r e 2. Kinetics of a Castro-Stephens coupling (reaction
a, Figure 1) catalyzed by the various palladium-phosphine
ligand complexes (5 mol % Pd, 10 mol % CuI) in H2O/CH3CN
1:1, T ) 35 °C, 200 mol % triethylamine.
(28) For recent examples for Pd-catalyzed C-C connections in water,
see: (a) Casalnuovo, A. L.; Calabrese, J . C. J . Am. Chem. Soc. 1990,
112, 4324. (b) Li, C. J . Chem. Rev. 1993, 93, 2023. (c) Bumagin, N. A.;
Sukhomlinova, L. I.; Luzikova, E. V.; Tolstaya, T. P.; Beletskaya, I. P.
Tetrahedron Lett. 1996, 37, 897. (d) Roshchin, A. I.; Bumagin, N. A.;
Beletskaya, I. P. Tetrahedron Lett. 1995, 36, 125. (e) Diminnie, J .;
Metts, S.; Parsons, E. J . Organometallics 1995, 14, 4023. (f) Geneˆt, J .
P.; Linquist, A.; Blart, E.; Mouries, V.; Savignac, M.; Vaultier, M.
Tetrahedron Lett. 1995, 36, 1443. (g) Rai, R.; Aubrecht, K. B.; Collum,
D. B. Tetrahedron Lett. 1995, 36, 3111. (h) Kiji, J .; Okano, T.;
Hasegawa, T. J . Mol. Catal. A: Chem. 1995, 97, 73. (i) Sengupta, S.;
Bhattacharyya, S. Tetrahedron Lett. 1995, 36, 4475. (j) Amatore, Ch.;
Blart, E.; Geneˆt, J . P.; J utand, A.; Lemaire-Audoire, S.; Savignac, M.
J . Org. Chem. 1995, 60, 6829.
observed with free propargylamine or propiolic acid as
alkyne substrates. Copper(I) iodide (10 mol %) promoted
the rate but was not vital to the success of these C-C
bond formations. Reaction pace, however, was very
sensitive to the phosphine ligand used. Figure 2 il-
lustrates that the conversion was very sluggish with the
anionic TPPTS ligand (A), which barely exceeded the
efficiency of the simple Pd acetate salt promoted back-
ground reaction.
(29) (a) Castro, C. E.; Stephens, R. D. J . Org. Chem. 1963, 28, 2163.
(b) Castro, C. E.; Stephens, R. D. J . Org. Chem. 1963, 28, 3313. (c)
Castro, C. E.; Gaughan, E. J .; Owsley, D. C. J . Org. Chem. 1966, 31,
4071.

2366 J . Org. Chem., Vol. 62, No. 8, 1997
Hessler et al.
Anal. Calcd for C24H32NPSi2: C, 68.36; H, 7.65. Found: C,
68.29; H, 7.79.
On the contrary, all of the cationic guanidinophos-
phines formed quite active catalysts with the biscationic
ligand 17b exhibiting the highest activity. With this
complex system the quantitative coupling of p-iodoben-
zoic acid and propiolic acid was achieved in 30 min at 35
°C using 5 mol % Pd complex and 10 mol % CuI cocatalyst
in 30 vol % acetonitrile in water. The triaryl ligands 17b
and 17c were at least equal or even outperformed cationic
aryl alkyl guanidino phosphine ligands (e.g. 18/19) in any
of these reactions.9
The molar ratio of the substrates had no effect on the
rate or on the product distribution even when the triple-
bonded reaction partner was used in 500 mol % excess.
Thus, homocoupling of the alkynic components which
severely weakened cross-coupling yields for phenylacety-
lene derivatives9 was totally absent when aliphatic
alkynes were employed as substrates.
The reactions required stoichiometric amounts of base
but neither the chemical nature (triethylamine or K2CO3
were equally effective) nor an excess appeared to be
crucial or helpful. Furthermore, the organic solvent
additive (CH3CN or DMF) was only of minor influence,
although it was observed that the reaction rate was more
sensitive to the alteration of the concentration of DMF.
In summary, the cationic guanidino phosphines 17a -c
are suitable ligands for forming water soluble palladium
complex catalysts which are durable and active in very
mild, clean, and quantitative intermolecular C-C con-
nections in homogeneous aqueous solution. A bright
perspective of these catalytic systems in bioconjugation
reactions can be readily predicted.
Syn th esis of 2b. In a manner analogous to that given
above, to 160 mL (0.16 mol) of 1 (1.0 M THF solution) was
added 14.3 g (0.08 mol) phenyldichlorophosphine in 100 mL
of THF at ambient temperature. After a similar workup
procedure, 2b was obtained by short path distillation (160 °C,
0.01 mbar).
P h e n ylb is([N ,N -b is(t r im e t h ylsilyl)a m in o]p h e n yl)-
p h osp h in e (2b): 72% yield; 1H NMR (CD2Cl2) δ 0.1 (s, 36
H), 6.5-7.3 (m, 13 H); 31P{1H} NMR (CDCl3) δ -6.5; 13C{1H}
NMR (CD2Cl2) δ 135.7 (J CP ) 12.1 Hz), 127.2 (J CP ) 23.3 Hz),
146.5 (J CP ) 6.1 Hz),30 133.2 (J CP ) 15.2 Hz), 136.1 (J CP ) 11.7
Hz), 131.7 (J CP ) 19.3 Hz), 128.5, 0.0 (SiMe3); MS (EI) m/ z
580 (M+, 6), 472 (M+ - C6H5, -2 CH3, -H, 7), 221 (C6H4N-
(SiMe3)2 - CH3, 10), 73 (SiMe3, 100). Anal. Calcd for C30H49
N2PSi4: C, 62.01; H, 8.50. Found: C, 62.11; H, 8.43.
-
Syn th esis of 2c. Phosphorus trichloride (10.3 g, 0.075 mol)
in 100 mL of THF was reacted with 250 mL (0.25 mol) of a
1.0 M THF solution of 1 at room temperature. The residue
remaining after evaporation of the reaction mixture was
extracted with petroleum ether (200 mL) and water (50 mL).
The organic phase was separated by decantation and dried
over magnesium sulfate. Compound 2c was obtained as a
viscous oily liquid after removing the solvent in vacuo (20 °C,
0.1 mbar).
T r is ([N ,N -b is (t r im e t h y ls ily l)a m in o ]p h e n y l)p h o s -
p h in e (2c): 93 % yield; 1H NMR (CDCl3) δ 0.1 (s, 54 H), 6.6-
7.2 (m, 12 H); 31P{1H} NMR (CDCl3) δ -6.2; 13C{1H} NMR
(CDCl3) δ 137.4 (J CP ) 11.7 Hz), 128.4 (J CP ) 8.8 Hz), 148.2
(J CP ) 6.6 Hz), 130.2, 129.6, 134.9 (J CP ) 15.4 Hz), 2.1 (SiMe3);
MS (EI) m/ z 740 (M+, 38), 739 (M+ - H, 54), 503 (M+ - H,
-C6H4N(SiMe3)2, 6), 73 (SiMe3, 100). Anal. Calcd for
C36H66N3PSi6: C, 58.40; H, 8.98; N, 5.68. Found: C, 58.04;
H, 8.95; N, 6.10.
Syn th eses of 4a -c. Gen er a l P r oced u r e. The phosphine
ligands 2a (20.0 g, 0.047 mol), 2b (12.5 g, 0.022 mol), or 2c
(7.4 g, 0.01 mol), respectively, were dissolved in 100 mL of pure
methanol (4a or 4b) or a mixture of methanol (15 mL) and
THF (10 mL) (4c) and heated at reflux for 8-15 h. Compounds
4a and 4b precipitated from the reaction mixtures. They were
collected on a sintered glass funnel and dried in vacuo (20 °C,
0.1 mbar). For the isolation of 4c, all volatiles were removed
in vacuo and the remaining residue was washed with petro-
leum ether 40:60 (20 mL). After drying at 20 °C, 0.1 mbar, it
was obtained as a colorless solid.
Exp er im en ta l Section
Gen er a l. 1H, 13C{1H}, and 31P{1H} NMR spectra were
recorded at 400.1, 100.6, and 161.9 or 36.2 MHz. Product
analysis and kinetics were obtained by HPLC. The kinetic
results refer to peak height ratios measured at λ ) 254 nm in
standard HPLC runs, defining conversion as the ratio [product/
product + starting material] × 100. The eluents contained
30 mM H3PO4 and 30 mM NaClO4 in addition to the organic
modifier. All coupling products were isolated and character-
ized by standard 1H/13C NMR techniques. For higher order
Dip h en yl(3-a m in op h en yl)p h osp h in e (4a ): 76% yield; 1H
NMR (CD2Cl2) δ 3.6 (s, br, 2 H), 6.6-7.4 (m, 14 H); 31P{1H}
1
n
NMR (CD2Cl2) δ -3.1; 13C{1H} NMR (CD2Cl2) δ 137.5 (J CP
)
spectra NCP is defined as | J CP + J CP|.
Ch em ica ls. The chlorophosphines Cl(Ph)PNR2 (R ) Me,
Et) were prepared according to the literature methods21 by the
reaction of PhPCl2 with the corresponding silylamines
(Me3SiNR2). Diphenylvinylphosphine23 was obtained from
Ph2PCl and vinylmagnesium chloride. P,P-Di-tert-butylphos-
phetanium bromide24a was prepared by treatment of t-Bu2-
PSiMe3 with 1,3-dibromopropane. (3-[N,N-Bis(trimethylsilyl)-
amino]phenyl)magnesium chloride (1) was purchased from
Aldrich. Other solvents and reagents were of guaranteed
grade and distilled before use.
11.7 Hz), 119.7 (J CP ) 20.5 Hz), 146.9 (J CP ) 8.1 Hz), 115.3,
129.4 (J CP ) 8.1 Hz), 123.5 (J CP ) 19.8 Hz), 138.1 (J CP ) 10.3
Hz), 133.7 (J CP ) 19.8 Hz), 128.5 (J CP ) 6.6 Hz), 128.6; IR ν
(cm-1) 3439, 3356; MS (EI) m/ z 277 (M+, 100), 198 (M+ - C6H5,
-2H, 48), 183 (Ph2P - 2H, 31), 92 (C6H4NH2, 5). Anal. Calcd
for C18H16NP: C, 77.97; H, 5.82; N, 5.05. Found: C, 78.07; H,
5.88; N, 5.25.
P h en ylbis(3-a m in op h en yl)p h osp h in e (4b): 84% yield;
31P{1H} NMR (DMSO-d6) δ 0.2; 13C{1H} NMR (DMSO-d6) δ
137.1 (J CP ) 9.5 Hz), 118.5 (J CP ) 22.0 Hz), 148.6 (J CP ) 8.8
Hz), 114.4, 128.9 (J CP ) 8.1 Hz), 120.7 (J CP ) 19.1 Hz), 137.7
(J CP ) 12.5 Hz), 133.2 (J CP ) 19.1 Hz), 128.3 (J CP ) 6.6 Hz),
128.4; IR ν (cm-1) 3445, 3367; MS (EI) m/ z 292 (M+, 100), 291
(M+ - H, 14), 213 (M+ - 2H, -C6H5, 28), 198 (M+ - C6H4NH2,
- 2H, 57). Anal. Calcd for C18H17N2P: C, 73.96; H, 5.86; N,
9.58. Found: C, 73.89; H, 5.87; N, 9.21.
Syn th esis of 2a . To a 1.0 M THF solution of (3-[N,N-
bis(trimethylsilyl)amino]phenyl)magnesium chloride (1) (100
mL; 0.10 mol) was added 22.1 g (0.10 mol) of diphenylchloro-
phosphine dissolved in 100 mL THF at ambient temperature.
After 2 h of stirring, all volatiles were removed in vacuo (20
°C, 0.1 mbar). The residue was extracted with diethyl ether
(150 mL). From the oily residue remaining after removal of
the solvents, pure 2a was obtained by short path distillation
in vacuo (140 °C; 0.01 mbar).
D ip h e n y l([N ,N -b is (t r im e t h y ls ily l)a m in o ]p h e n y l)-
p h osp h in e (2a ): 66% yield; 1H NMR (CDCl3) δ 0.1 (s, 18 H),
6.5-7.2 (m, 14 H); 31P{1H} NMR (CDCl3) δ -6.1; 13C{1H} NMR
(CDCl3) δ 137.1 (J CP ) 11.0 Hz), 128.5 (J CP ) 8.8 Hz), 148.2
(J CP ) 7.3 Hz), 130.3, 129.5, 135.1 (J CP ) 16.1 Hz), 137.4 (J CP
) 11.0 Hz), 133.6 (J CP ) 19.8 Hz), 128.5, 128.2, 2.1 (SiMe3);
MS (EI) m/ z 421 (M+, 26), 406 (M+ - CH3, 27), 221
(C6H4N(SiMe3)2 - CH3, 6), 185 (Ph2P, 15), 73 (SiMe3, 100).
Tr is(3-a m in op h en yl)p h osp h in e (4c): 91% yield; 1H NMR
(DMSO-d6) δ 4.0 (s, br, 6 H), 6.3-7.2 (m, 12 H); 31P{1H} NMR
(DMSO-d6) δ 1.1; 13C{1H} NMR (DMSO-d6) δ 138.6 (J CP ) 9.7
Hz), 119.6 (J CP ) 22.5 Hz), 149.3 (J CP ) 8.7 Hz), 115.1, 129.6
(J CP ) 7.5 Hz), 121.7 (J CP ) 18.2 Hz); IR ν (cm-1) 3470, 3367;
MS (EI) m/ z 307 (M+, 100); 306 (M+ - H, 14); 214 (M+
-
C6H4NH2, - H, 16). Anal. Calcd for C18H18N3P: C, 70.33; H,
5.91; N, 13.68. Found: C, 70.90; H, 6.21; N, 14.00.
(30) Overlap of three resonances in the range for δC of 126.8-126.4
ppm.

Water Soluble Cationic Phosphine Ligands
J . Org. Chem., Vol. 62, No. 8, 1997 2367
Syn th eses of 5a -c. (Dimethylamino)phenylchlorophos-
phine (26.3 g, 0.14 mol) or (diethylamino)phenylchlorophos-
phine (17.3 g, 0.08 mol), respectively, dissolved in THF (100
mL) were added to a solution of 140 mL (0.14 mol) or 80 mL
(0.08 mol) of (3-[N,N-bis(trimethylsilyl)amino]phenyl)magnesium
chloride (1.0 M) in THF and stirred for 16 h at ambient
temperature. The residue obtained after evaporation of the
reaction mixture in vacuo was extracted with petroleum ether
40:60 (150 mL). After the filtrate was evaporated to dryness
and the remaining oily residue was fractionated in vacuo at
150 or 160 °C, respectively, using a short path distillation
apparatus, 5a and 5b were obtained as colorless liquids. For
the preparation of 5c, methanol (30 mL) was added to the
solutions of 50 g (0.13 mol) of 5a or 22.5 g (0.054 mol) of 5b,
respectively, in 50 or 30 mL of toluene and the reaction
mixtures were heated at reflux for 10 min or 12 h, respectively.
The oily residue obtained after removal of all volatiles was
fractionated in vacuo at 120 °C, 0.1 mbar.
100). Anal. Calcd for C18H28NPSi2: C, 62.56; H, 8.17.
Found: C, 62.50; H, 8.25.
P r ep a r a tion of 7 fr om P h P Cl2. To a solution of 38.7 g
(0.22 mol) of phenyldichlorophosphine in THF (300 mL) was
added 195 mL (0.195 mol) of (3-[N,N-bis(trimethylsilyl)ami-
no]phenyl)magnesium chloride dropwise at -50 °C within 1
h. After the addition was complete, the reaction mixture was
allowed to warm to 20 °C and stirred for 2 h at this
temperature. The residue obtained after the solvent was
removed contained, in addition to unreacted phenyldichloro-
phosphine, the tertiary phosphine 2b (δP ) 80.5 ppm) and the
chlorophosphine 6a in a 1:1 ratio as indicated by the 31P{1H}
NMR spectrum of a sample. For the reduction of 6a (δP )
-6.5 ppm), the reaction mixture was dissolved in diethyl ether
(300 mL). This solution was added at 0 °C within 2 h to a
suspension of 7.6 g (0.20 mol) of LiAlH4 and stirred for 2 h.
After hydrolytic workup of the reaction mixture (by addition
of 20 mL of water), the organic phase was separated and dried
over magnesium sulfate. The solvent was removed under
reduced pressure. Evaporation of the crude product gave
phenylphosphine (70 °C, 0.1 mbar), and subsequent short-path
distillation at 140 °C yielded a fraction which, according to
the 1H NMR spectrum, contained 8 in addition to the depro-
tected secondary phosphine 7. In order to get an uniform
product, the mixture was stirred for 1 h in methanol. After
removing all volatiles at 50 °C, 0.1 mbar, the unprotected
phosphine 7 was obtained.
(3-[N,N-Bis(t r im et h ylsilyl)a m in o]p h en yl)(d im et h yl-
a m in o)p h en ylp h osp h in e (5a ): 94% yield; 31P{1H} NMR
(CDCl3) δ 64.1; 13C{1H} NMR (CDCl3) δ 138.5 (J CP ) 16.1 Hz),
128.2 (J CP ) 14.0 Hz), 147.8 (J CP ) 6.6 Hz), 130.3, 127.2, 133.5
(J CP ) 17.6 Hz), 138.9 (J CP ) 13.9 Hz), 131.8 (J CP ) 19.1 Hz),
128.1 (J CP ) 5.1 Hz), 127.8, 2.1 (SiMe3), 41.8 (NMe2) (J CP
)
14.7 Hz); MS (EI) m/ z 388 (M+, 36), 330 (M+ - SiMe2, 14),
311 (M+ - C6H5, 9), 152 (PhPNMe2, 14), 73 (SiMe3, 100). Anal.
Calcd for C20H33N2PSi2: C, 61.81; H, 8.56. Found: C, 61.88;
H, 8.58.
P h en yl(3-am in oph en yl)ph osph in e (7): 21% yield; 31P{1H}
NMR (CD2Cl2) δ -39.6 (1J PH ) 220 Hz); 13C{1H} NMR (CD2Cl2)
δ 134.4 (J CP ) 9.5 Hz), 119.9 (J CP ) 16.9 Hz), 146.1 (J CP ) 7.3
Hz), 115.1, 129.1 (J CP ) 7.3 Hz), 123.6 (J CP ) 16.9 Hz), 135.0
(J CP ) 8.8 Hz), 133.5 (J CP ) 16.9 Hz), 128.2 (J CP ) 5.9 Hz),
128.0; MS (EI) m/ z 201 (M+, 58), 198 (M+ - 3H, 12), 124 (M+
- C6H5, 26), 109 (PhPH, 100), 92 (C6H4NH2, 35). Anal. Calcd
for C12H12NP: C, 71.63; H, 6.01. Found: C, 71.58; H, 6.20.
Syn t h esis of Bid en t a t e 3-Am in op h en yl-Su b st it u t ed
P h osp h in es. P r ep a r a tion of 10 a n d 11. A solution of 3.0
g (8.7 mmol) of 8 and 1.84 g (8.7 mmol) of diphenylvinylphos-
phine in toluene (20 mL) was stirred at 70 °C for 4 d. In order
to initiate and continue the free radical addition, aliquots of
AIBN (ca. 20 mg) were added to the reaction mixture every
24 h. After the solvent was removed in vacuo, 10 was obtained
as a colorless viscous liquid. For deprotection, the product
obtained above was dissolved in methanol. After an ethereal
solution of HCl (1 mL, 1.65 M) was added, 11 precipitated as
a colorless solid from the reaction mixture. It was isolated by
filtration on a glass funnel and dried in vacuo.
(3-[N ,N -Bis(t r im e t h ylsilyl)a m in o]p h e n yl)(d ie t h yl-
a m in o)p h en ylp h osp h in e (5b): 97% yield; 1H NMR (CDCl3)
3
3
δ 0.0 (s, 18 H), 0.9 (t, 6 H, J HH ) 7.7 Hz), 3.0 (q, 4 H, J HH
)
7.7 Hz), 6.8-7.4 (m, 9 H); 31P{1H} NMR (CDCl3) δ 60.9;
13C{1H} NMR (CDCl3) δ 140.2 (J CP ) 1.5 Hz), 128.2 (J CP ) 3.7
Hz), 147.7 (J CP ) 5.9 Hz), 130.1, 127.2, 133.5 (J CP ) 18.3 Hz),
140.8, 131.7 (J CP ) 19.1 Hz), 128.0 (J CP ) 2.0 Hz), 127.2, 2.1
(SiMe3), 44.2 (NCH2CH3) (J CP ) 15.4 Hz), 14.5 (NCH2CH3) (J CP
) 2.9 Hz); MS (EI) m/ z 416 (M+, 20), 344 (M+ - NEt2, 10),
180 (PhPNEt2, 6), 73 (SiMe3, 100). Anal. Calcd for C22H37
N2PSi2: C, 63.41; H, 8.95. Found: C, 63.59; H, 8.72.
-
(3-[N ,N -Bis(t r im e t h ylsilyl)a m in o]p h e n yl)m e t h oxy-
p h en ylp h osp h in e (5c): 81% yield; 1H NMR (CDCl3) δ 0.0
(s, 18 H), 3.6 (d, 3 H, 3J PH ) 14.0 Hz), 6.6-7.8 (m, 9 H); 31P{1H}
NMR (CDCl3) δ 116.5; 13C{1H} NMR (CDCl3) δ 141.2 (J CP
)
4.4 Hz), 128.4 (J CP ) 8.1 Hz), 148.0 (J CP ) 7.3 Hz), 126.3, 130.9
(J CP ) 6.6 Hz), 131.7 (J CP ) 19.8 Hz), 142.0 (J CP ) 2.7 Hz),
129.5 (J CP ) 15.4 Hz), 128.2 (J CP ) 6.6 Hz), 125.2, 2.0 (SiMe3),
56.5 (OMe) (J CP ) 17.6 Hz); MS (EI) m/ z 375 (M+, 21), 360
(2-(Dip h en ylp h osp h in o)eth yl)([3-N,N-bis(tr im eth ylsi-
lyl)am in o]ph en yl)ph en ylph osph in e (10): 83% yield; 31P{1H}
NMR (CDCl3) δ -11.0, -11.4 (3J PP ) 33.1 Hz); 13C{1H} NMR
(CDCl3) δ 138.8 (J CP ) 11.2 Hz), 128.3 (J CP ) 16.3 Hz), 148.6
(J CP ) 7.1 Hz), 130.9, 129.0, 135.0 (J CP ) 17.4 Hz), 139.0 (J CP
) 13.1 Hz), 133.6 (J CP ) 19.2 Hz), 129.0 (J CP ) 11.6 Hz), 128.7,
24.6-24.2 (m), 138.7 (J CP ) 12.3 Hz), 133.3 (J CP ) 18.1 Hz),
128.8 (J CP ) 6.3 Hz), 128.8, 2.6 (SiMe3); MS (EI) m/ z 557 (M+,
35), 183 (Ph2P - 2H, 13), 73 (SiMe3, 100). Anal. Calcd for
C32H41NP2Si2: C, 68.90; H, 7.41. Found: C, 68.95; H, 7.45.
(2-(Dip h en ylp h osp h in o)et h yl)(3-a m in op h en yl)p h en -
(M+ - CH3, 13), 73 (SiMe3, 100). Anal. Calcd for C19H30
NOPSi2: C, 60.76; H, 8.05. Found: C, 60.92; H, 8.05.
-
Red u ction of 5c w ith LiAlH4. Syn th esis of 8. To a
suspension of 1.8 g (47.4 mmol) of LiAlH4 in diethyl ether (200
mL) was added a solution of 17.5 g (46.6 mmol) of 5c at
ambient temperature, and the reaction mixture was stirred
for 3 h. After dropwise addition of 20 mL of water within a
period of 1 h, the organic phase was separated and evaporated
to dryness in vacuo (20 °C, 0.01 mbar). According to the
31P{1H} NMR spectrum of a sample, the residue contained the
desired secondary phosphine 8 in addition to the diphosphine
9 in ca. 1:2.3 ratio. In order to reduce 9, the reaction mixture
was dissolved in methyl tert-butyl ether (300 mL) and treated
with 15.0 g (0.65 mol) of sodium at reflux for 28 h. After
cooling the solution to room temperature, excess sodium was
separated by decantation. Ethanol (15 mL) and water (50 mL)
were added to the solution. The organic layer was separated
and evaporated under reduced pressure. Distillation of the
crude product gave the secondary phosphine 8 as a colorless
air-sensitive liquid.
1
ylp h osp h in e (11): 76% yield; H NMR (CDCl3) δ 2.4 (m, 4
H), 2.8 (s, br, 2 H), 6.9-7.5 (m, 19 H); 31P{1H} NMR (CDCl3)
δ -10.6, -11.2 (3J PP ) 33.4 Hz); 13C{1H} NMR (CDCl3) δ 139.6
(J CP ) 12.2 Hz), 120.8 (J CP ) 17.3 Hz), 148.0 (J CP ) 7.1 Hz),
117.4, 130.7 (J CP ) 7.1 Hz), 124.3 (J CP ) 17.3 Hz), 140.1 (J CP
) 11.2 Hz), 134.1 (J CP ) 16.3 Hz), 130.1 (J CP ) 8.1 Hz), 130.1,
25.2 (NCP ) 22.4 Hz), 25.3 (NCP ) 23.4 Hz) (CH2CH2), 139.4
(NCP ) 17.3 Hz), 134.1 (J CP ) 18.3 Hz), 129.8 (J CP ) 8.1 Hz),
129.9; MS (EI) m/ z 413 (M+, 80), 385 (M+ - C2H4, 34), 185
(Ph2P, 34), 183 (Ph2P - 2H, 100). Anal. Calcd for C26H25
-
NP2: C, 75.53; H, 6.09; N, 3.39. Found: C, 75.18; H, 6.40; N,
3.16.
(3-[N,N-Bis(tr im eth ylsilyl)a m in o]p h en yl-p h en yl)p h os-
1
p h in e (8): 46% yield; H NMR (CD2Cl2) δ 0.0 (s, 18 H), 5.2
1
(d, 1 H, J PH ) 217.1 Hz), 6.6-7.5 (m, 9 H); 31P{1H} NMR
P r ep a r a tion of 14. To a solution of 4.62 g (23.0 mmol) of
7 in THF (100 mL) was added 15 mL (23.0 mmol) of 1.6 N
n-BuLi at -70 °C. The reaction mixture was allowed to warm
to -40 °C, and 2.50 g (23.0 mmol) of Me3SiCl were added at
this temperature. After cooling the solution to -70 °C, the
protected secondary phosphine was metallated with n-BuLi
(CD2Cl2) δ -38.8 (1J PH ) 217.1 Hz); 13C{1H} NMR (CD2Cl2) δ
135.5 (J CP ) 10.3 Hz), 128.9 (J CP ) 5.1 Hz), 148.5 (J CP ) 6.6
Hz), 130.5, 129.8, 134.9 (J CP ) 10.3 Hz), 135.9 (J CP ) 15.4 Hz),
133.9 (J CP ) 16.9 Hz), 128.5 (J CP ) 1.5 Hz), 128.7, 2.1 (SiMe3);
MS (EI) m/ z 345 (M+, 19), 330 (M+ - CH3, 31), 73 (Me3Si,

2368 J . Org. Chem., Vol. 62, No. 8, 1997
Hessler et al.
(15 mL; 23.0 mmol). To the solution of the lithium phosphide
formed was added 6.13 g (23.0 mmol) of 1,1-di-tert-butylphos-
phetanium bromide. After 18 h of stirring at ambient tem-
perature, all volatiles were removed under reduced pressure.
The residue was extracted with petroleum ether 40:60, and
the extracts were evaporated in vacuo giving a yellow viscous
liquid. For deprotection, the crude product (δP ) 24.3 (PA),
-18.3 ppm (PB)) was dissolved in methanol (20 mL) at 20 °C.
Volatile material was removed under reduced pressure to give
14 as a viscous yellow liquid.
[P h en ylbis(3-a m in op h en yl)p h osp h in e] d ih yd r och lo-
r id e (16b): 98% yield; 31P{1H} NMR (CD3OD) δ -3.6; 13C{1H}
NMR (CD3OD) δ 139.8 (J CP ) 15.3 Hz), 127.7 (J CP ) 18.3 Hz),
131.6 (J CP ) 6.1 Hz), 123.9, 130.4 (J CP ) 7.1 Hz), 133.9 (J CP
)
20.4 Hz), 135.1 (J CP ) 11.2 Hz), 134.0 (J CP ) 22.4 Hz), 129.0
(J CP ) 7.1 Hz), 129.8; IR ν (cm-1) 2820; MS (EI) m/ z 292 (M+
- 2HCl, 47), 276 (M+ - 2HCl, -NH2, 12), 198 (M+ - 2HCl,
-C6H4NH2, - 2H, 100), 123 (PC6H4NH2, 11).
[Tr is(3-a m in op h en yl)p h osp h in e] t r ih yd r och lor id e
(16c): 77% yield; 31P{1H} NMR (D2O) δ -5.3; 13C{1H} NMR
(D2O) δ 137.8 (J CP ) 11.2 Hz), 127.4 (J CP ) 21.4 Hz), 131.3
(J CP ) 9.2 Hz), 124.0, 130.8 (J CP ) 7.1 Hz), 133.7 (J CP ) 18.3
Hz); IR ν (cm-1) 2856; MS (EI) m/ z 307 (M+ - 3HCl, 100),
306 (M+ - 3HCl, -H, 18), 213 (M+ - 3HCl, -C6H4NH2, - 2H,
(3-(Di-ter t-b u t ylp h osp h in o)p r op yl)(3-a m in op h en yl)-
1
p h en ylp h osp h in e (14): 43% yield; H NMR (CD2Cl2) δ 1.1
3
(d, 18 H, J PH ) 11.0 Hz); 1.3-1.7 (m 6 H); 6.6-7.4 (m, 9 H);
31P{1H} NMR (CD2Cl2) δ 25.3 (P(t-Bu)), -16.5 (P(Ph)); 13C{1H}
NMR (CD2Cl2) δ 138.7 (J CP ) 14.2 Hz), 118.0 (J CP ) 19.5 Hz),
80), 38 (H37Cl, 60), 36 (H35Cl, 100). Anal. Calcd for C18H21
-
146.0 (J CP ) 7.5 Hz), 114.3, 128.4 (J CP ) 7.2 Hz), 121.6 (J CP
)
Cl3N3P: C, 51.88; H, 5.08; N, 10.08. Found: C, 51.69; H, 5.73;
N, 9.54.
18.3 Hz), 139.2 (J CP ) 12.7 Hz), 131.9 (J CP ) 18.3 Hz), 127.5
(J CP ) 6.5 Hz), 26.1-25.6 (m), 22.1 (J CP ) 21.4, 12.3 Hz), 30.3
(J CP ) 20.9 Hz), 28.7 (J CP ) 13.8 Hz) (CH2CH2CH2); MS (EI)
m/ z 330 (M+ - C4H9, 100), 274 (M+ - C4H9, -C4H8, 44), 273
(M+ - 2C4H9, 14), 198 (PhPC6H4NH2 - 2H, 17). Anal. Calcd
for C23H35NP2: C, 71.29; H, 9.10; N, 3.62. Found: C, 70.81;
H, 8.97; N, 3.20.
Syn t h eses of t h e Gu a n id in iu m P h osp h in es 17a -c.
Gen er a l P r oced u r e. The anilinium phosphines 16a (2.20
g, 7.9 mmol), 16b (1.24 g, 4.2 mmol), and 16c (1.4 g, 4.6 mmol)
were added to excess dimethylcyanamide (2.90 g, 41.1 mmol;
1.20 g, 17.1 mmol; or 4.37 g, 62.3 mmol, respectively) and
stirred for 12 h at 110 °C. In order to remove excess
dimethylcyanamide, the highly viscous reaction mixtures were
extracted with ether (30 mL). The guanidinium phosphines
were obtained as creme-colored solids which were dried
overnight in vacuo.
P r ep a r a tion of 15. The solution of 2.17 g (10.8 mmol) of
7 in diethyl ether (20 mL) was treated at -60 °C with 6.3 mL
(10.8 mmol) of n-BuLi dissolved in n-hexane. After 30 min,
1.17 g (10.8 mmol) of Me3SiCl was added at -40 °C with
stirring. For the metallation of the intermediate, protected
secondary phosphine 12 6.3 mL (10.8 mmol) of n-BuLi were
added at -60 °C and subsequently 1.09 g (5.4 mmol) of 1,3-
dibromopropane. The reaction mixture was allowed to warm
and was stirred for 72 h at ambient temperature. The residue
remaining after evaporation was treated with a mixture of
dichloromethane (20 mL) and water (5 mL). The organic phase
was separated, dried over magnesium sulfate, and filtered, and
the solvent removed under reduced pressure to give the
protected ditertiary phosphine. The protecting groups were
removed as for 14, leaving 15 as a colorless powder.
[Dip h en yl(3-(N,N-d im et h ylgu a n id in o)p h en yl)p h os-
1
p h in e] h yd r och lor id e (17a ): 92% yield; H NMR (D2O) δ
3.2 (s, 6 H), 5.0 (s, br, 3 H), 7.2-7.7 (m, 14 H); 31P{1H} NMR
(CD3OD) δ -1.2; 13C{1H} NMR (D2O) δ 139.0 (J CP ) 12.2 Hz),
128.1 (J CP ) 18.3 Hz), 136.8 (J CP ) 8.1 Hz), 124.5, 132.0, 131.0
(J CP ) 20.4 Hz), 136.3 (J CP ) 10.2 Hz), 133.7 (J CP ) 20.3 Hz),
128.9 (J CP ) 7.1 Hz), 129.3, 155.4 (CN3), 38.4 (NMe2). Anal.
Calcd for C21H23ClN3P: C, 65.71; H, 6.04; N, 10.95. Found:
C, 65.23; H, 6.34; N, 11.42.
[P h en ylb is(3-(N,N-d im et h ylgu a n id in o)p h en yl)p h os-
p h in e] d ih yd r och lor id e (17b): 91% yield; 1H NMR (CD3OD)
δ 3.2 (s, 12 H), 5.1 (s, br, 6 H), 6.8-8.3 (m, 13 H); 31P{1H}
1,3-Bis[(3-a m in op h e n yl)p h e n ylp h osp h in o]p r op a n e
NMR (CD3OD) δ -0.9; 13C{1H} NMR (CD3OD) δ 139.7 (J CP
)
1
(15): 39% yield; H NMR (CD2Cl2) δ 1.1-1.3 (m, 2 H), 2.1-
2.2 (m, 4 H), 3.8 (s, br, 4 H), 6.5-7.5 (m 18H); 31P{1H} NMR
(CDCl3) δ -17.2; 13C{1H} NMR (CD2Cl2) δ 139.7 (J CP ) 14.2
Hz), 119.2 (J CP ) 15.3 Hz), 147.2 (J CP ) 7.1 Hz), 115.6, 129.6
(J CP ) 8.1 Hz), 122.9 (J CP ) 19.3 Hz), 140.1 (J CP ) 13.2 Hz),
132.1 (J CP ) 18.3 Hz), 128.8 (J CP ) 7.0 Hz), 128.8, 29.81 (NCP
) 25.4 Hz), 29.78 (NCP ) 24.4 Hz) (diastereoisomers), 23.08
(J CP ) 17.8 Hz), 23.04 (J CP ) 17.3 Hz) (diastereoisomers); IR
13.7 Hz), 129.4 (J CP ) 19.9 Hz), 137.3 (J CP ) 9.0 Hz), 125.2,
130.2 (J CP ) 7.1 Hz), 131.9 (J CP ) 20.3 Hz), 136.2 (J CP ) 10.0
Hz), 134.1 (J CP ) 20.8 Hz), 129.0 (J CP ) 7.2 Hz), 129.6, 156.4
(CN3), 38.2 (NMe2). Anal. Calcd for C24H31Cl2N6P: C, 57.03;
H, 6.18; N, 16.63. Found: C, 56.75; H, 6.33; N, 16.57.
[Tr is(3-(N,N-dim eth ylgu an idin o)ph en yl)ph osph in e] tr i-
h yd r och lor id e (17c): 94% yield; 1H NMR (CD3OD) δ 3.2 (s,
18 H), 4.8 (s, br, 9 H), 7.3-7.6 (m, 12 H); 31P{1H} NMR
(CD3OD) δ -0.5; 13C{1H} NMR (CD3OD) δ 140.1 (J CP ) 13.2
Hz), 130.8 (J CP ) 21.2 Hz), 138.5 (J CP ) 8.1 Hz), 126.7, 131.6
(J CP ) 7.3 Hz), 133.4 (J CP ) 19.8 Hz), 157.5 (CN3), 39.5 (NMe2).
Anal. Calcd for C27H39Cl3N9P: C, 51.72; H, 6.27; N, 20.10.
Found: C, 51.48; H, 6.57; N, 19.83.
ν (cm-1) 3442, 3356; MS (EI) m/ z 442 (M+, 72), 365 (M+
-
C6H5, 100), 350 (M+ - C6H4NH2, 85), 123 (PC6H4NH2, 35).
Anal. Calcd for C27H28N2P2: C, 73.28; H, 6.38. Found: C,
72.78; H, 6.21.
P r ep a r a tion of th e Gu a n id in iu m P h osp h in es 17a -c.
Syn th esis of th e An ilin iu m P h osp h in es 16a -c. To the
solutions of 4a (1.46 g, 5.3 mmol) or 4b (1.24 g, 4.2 mmol) in
dichloromethane (20 mL) or THF (20 mL), respectively, was
added 3.5 or 5.1 mL of etheral HCl (1.65 N) with stirring.
Compound 16b was precipitated as an off white solid, which
was collected on a fritted glass funnel. For the isolation of
16a , the solvent was evaporated. The remaining residue
crystallized upon addition of a small quantity of diethyl ether.
Compounds 16a and 16b were dried in vacuo. The anilinium
salt 16c was obtained on treating an aqueous suspension of
4c (2.75 g, 9.0 mmol) in 100 mL of water with 13.5 mL of
hydrochloric acid (2 N). The clear solution was stirred for 30
min at ambient temperature. After the solvent was removed
under reduced pressure at 60 °C, 16c was obtained as a
colorless solid.
[Dip h en yl(3-a m in op h en yl)p h osp h in e] h yd r och lor id e
(16a ): 98% yield; 31P{1H} NMR (CDCl3) δ -5.1; 13C{1H} NMR
(CDCl3) δ 141.5 (J CP ) 15.7 Hz), 128.6 (J CP ) 21.7 Hz), 130.7
(J CP ) 7.0 Hz), 124.2, 130.4 (J CP ) 7.0 Hz), 136.4 (J CP ) 8.7
Hz), 134.3 (J CP ) 19.1 Hz), 129.2 (J CP ) 6.1 Hz), 129.6; IR ν
(cm-1) 2842; MS (EI) m/ z 277 (M+ - HCl, 100), 183 (Ph2P -
2H, 34), 123 (PC6H4NH2, 26), 36 (H35Cl, 3). Anal. Calcd for
C18H17ClNP: C, 68.90; H, 5.46; N, 4.46. Found: C, 68.48; H,
5.30; N, 4.15.
Syn th esis of 17d by Meta th esis Rea ction . To 0.93 g (2.4
mmol) of 17a dissolved in water (5 mL) was added an aqueous
solution of 0.39 g (2.4 mmol) of NH4PF6 at ambient tempera-
ture. The precipitate formed was separated by filtration and
dried in vacuo (25 °C, 0.1 mbar). After recrystallization from
ethanol, 17d was obtained as colorless crystals.
[Diph en yl((3-N,N-dim eth ylgu an idin o)ph en yl)] h exaflu -
or op h osp h a te (17d ): 81% yield; 31P{1H} NMR (CD3OD) δ
1
-1.4 (s, 1 P); -140.7 (septet, J PF ) 710 Hz); 13C{1H} NMR
(CD3OD) δ 140.2 (J CP ) 14.2 Hz), 129.0 (J PF ) 16.3 Hz), 136.7
(J CP ) 5.1 Hz), 124.8, 131.9 (J CP ) 10.2 Hz), 131.7 (J CP ) 20.3
Hz), 136.5 (J CP ) 11.2 Hz), 133.6 (J CP ) 19.3 Hz), 128.5 (J CP
) 7.1 Hz), 129.0, 156.1 (CN3), 37.8 (NMe2). Anal. Calcd for
C21H23F6N3P2: C, 51.12; H, 4.70; N, 8.52. Found: C, 51.46;
H, 4.73; N, 8.30.
Gen er a l P r oced u r e for P r ep a r in g th e Ca ta lyst Stock
Solu tion s. Palladium acetate (100 µmol) and the phosphine
ligands (500 µmol) were dissolved under nitrogen in 10 mL of
degassed water followed by stirring at rt for 1-3 h. The
resulting homogeneous solutions were stored under nitrogen
at 4 °C in the refrigerator. The catalytic activity remained
constant over months as evidenced by a standard C-C cross
coupling between p-iodobenzoic acid and propiolic acid.

Water Soluble Cationic Phosphine Ligands
J . Org. Chem., Vol. 62, No. 8, 1997 2369
Gen er a l P r oced u r e for C-C Cou p lin g Rea ction s. p-
Iodobenzoic acid (10 µmol) and the alkyne coupling partner
(20 µmol) were dissolved in 1 mL of an aqueous solvent
mixture (30-50% CH3CN/DMF). The reaction vial was ther-
mostated in an oil bath at 35 or 50 °C, respectively. Addition
of base (20-50 µmol) gave a homogeneous solution. The
starting point for kinetic measurements of the coupling
reaction was marked by the addition of catalyst stock solution
(5 mol % Pd) and CuI solution in CH3CN (ratio Cu/Pd 2:1).
Hoechst AG is thanked for financial support and gener-
ous gift of chemicals. Fonds der Chemischen Industrie
is thanked for financial support of this work.
Su p p or tin g In for m a tion Ava ila ble: 13C{1H} NMR spec-
tra of 4c, 11, 14, 15, and 16c (11 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
Ack n ow led gm en t. This work was supported by a
grant from the Bundesministerium fu¨r Bildung, Wis-
senschaft, Forschung und Technologie (BMBF).
J O961140N