Selective syntheses of mono- and diphosphanyltriazines as novel ligands for transition metal catalysts

Article abstract of DOI:10.1002/ejoc.200900429

1,3,5-Triazines bearing one, two or three diphenylphosphanyl group(s) were selectively synthesized from cyanuric chloride by the one-pot step-by-step addition of silylphosphane and other nucleophiles. Mono- and diphosphanyltriazines with a variety of substituents on the triazine ring could be easily prepared in good yields. The Pd complexes of mono- and diphosphanyltriazine were isolated, and the crys-tal structures were determined. Polymer-supported and water-soluble ligands were prepared. The Mizorogi-Heckreaction and the Suzuki-Miyaura coupling reaction using the phosphanyltriazine-Pd catalysts are described.

Full text of DOI:10.1002/ejoc.200900429

FULL PAPER
DOI: 10.1002/ejoc.200900429
Selective Syntheses of Mono- and Diphosphanyltriazines as Novel Ligands for
Transition Metal Catalysts
Minoru Hayashi,*[a] Toshikazu Yamasaki,[a] Yusuke Kobayashi,[a] Yoshito Imai,[a] and
Yutaka Watanabe[a]
Keywords: Synthetic methods / Phosphorus / Nucleophilic substitution / P ligands / Cross-coupling
1,3,5-Triazines bearing one, two or three diphenylphos-
phanyl group(s) were selectively synthesized from cyanuric
chloride by the one-pot step-by-step addition of silylphos-
phane and other nucleophiles. Mono- and diphosphanyltri-
azines with a variety of substituents on the triazine ring could
be easily prepared in good yields. The Pd complexes of
mono- and diphosphanyltriazine were isolated, and the crys-
tal structures were determined. Polymer-supported and
water-soluble ligands were prepared. The Mizorogi–Heck re-
action and the Suzuki–Miyaura coupling reaction using the
phosphanyltriazine-Pd catalysts are described.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
active linker for functional phosphane synthesis, by de-
veloping a procedure for stepwise substitutions by silyl-
phosphanes and other nucleophiles, as shown in Scheme 1.
Introduction
The synthesis of organophosphorus compounds have re-
ceived much attention due to their essential roles in various
fields of chemistry, especially as ligands in transition-metal
catalysis.[1] However, the synthesis of organophosphanes
with various functional groups still has many difficulties
due to limitations in P–C bond formation.[1] One of the
promising ways to prepare such functional phosphanes is
to use a suitable multifunctional, reactive linker, which con-
nects functional side-chains with the phosphane parts.
1,3,5-Triazine should be advantageous as such a linker be-
cause there are plenty of synthetic examples of triazine de-
rivatives prepared by the step-by-step addition of nucleo- Scheme 1. Step-by-step syntheses of functional phosphanes with a
philes to cyanuric chloride[2] as potential building blocks
triazine core.
in materials chemistry.[3] In addition, Hoge et al. recently
Herein, we wish to report a novel synthesis of phosphan-
reported the synthesis and properties of tris-triazinophos-
yltriazines by the one-pot, stepwise addition of silylphos-
phane derivatives prepared from chlorotriazine derivatives
phane and other nucleophiles. The formation of their Pd
and tris(trimethylsilyl)phosphane [P(SiMe3)3].[4] This result
complexes and the application in the catalytic reaction are
also described.
clearly indicated that phosphanyltriazines could be accessed
by P–C bond formation using a silylphosphane. However,
there is no practical synthesis of 1,3,5-triazines bearing
phosphane groups by the selective and stepwise addition of
Results and Discussion
phosphane functionalities to cyanuric chloride.[5]
We have developed some synthetic reactions of organ-
ophosphanes by using a silylphosphane as a P source.[6]
Therefore, we have tried to apply cyanuric chloride as a re-
We attempted the selective substitution of three chlorines
on cyanuric chloride by a silylphosphane in the initial stage
of the research. We treated cyanuric chloride 1 with 1.0, 2.2
or 4.5 equiv. of (trimethylsilyl)diphenylphosphane (2) and
monitored each reaction by 31P NMR spectroscopy. Due to
the distinct difference in the reactivities between the substi-
tution steps, we accomplished the selective substitution with
one, two or three phosphane group(s) simply by changing
the amount of the nucleophile, as shown in Figure 1. Since
[a] Department of Materials Science and Biotechnology, Graduate
School of Science and Engineering, Ehime University,
3 Bunkyo-cho, Matsuyama 790-8577, Japan
Fax: +81-89-927-9944
E-mail: hayashi@eng.ehime-u.ac.jp
4956
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 4956–4962

Phosphanyltriazines as Ligands for Catalysts
the intermediate phosphanyltriazines were too unstable to
isolate, we identified these intermediates by their FABMS
spectra and NMR spectra. Silylphosphane 2 was the best
suited for the present selective substitution; other phospho-
rus nucleophiles, such as lithium diphenylphosphide
(LiPPh2) and diphenylphosphane (Ph2PH), could not ac-
complish the controlled mono- and disubstitution.[7]
Scheme 2.
two amines (Table 1, Entry 7). We also incorporated alkoxy
substituents by the reaction of 3a with an alcohol as a sol-
vent (Table 1, Entry 8) or with an equimolar amount of
alcohol in the presence of CsF in DMF (Table 1, Entry 9).
Since only one alkoxy group was incorporated into 3a in
the absence of CsF, we could prepare triazine 4i with P, O
and N substituents in one pot in good selectivity (Table 1,
Entry 10).
We obtained bis(phosphane)-substituted 1,3,5-triazines
in good yield by the reaction of 1 with 2.2 equiv. of silyl-
phosphane 2 in THF, followed by substitution with an
amine or an alcohol. The results are shown in Table 2 and
Scheme 3.
Figure 1. 31P NMR spectra of the reaction mixture of cyanuric
chloride and (a) silylphosphane (1.0 equiv.); (b) silylphosphane
(2.2 equiv.) or (c) silylphosphane (4.5 equiv.) in THF.
To convert the unstable intermediates to more stable de-
rivatives, we performed further substitutions by other nu-
cleophiles before isolation. We conducted the syntheses of
mono-phosphane-substituted 1,3,5-triazines by the reaction
of cyanuric chloride with 1.1 equiv. of silylphosphane 2 in
THF at 0 °C. We then reacted the intermediate dichloride
3a with amines and/or alcohols in the presence of an ade-
quate base to give amino- and/or alkoxy-substituted phos-
phanyltriazines 4a–i. The results are shown in Table 1 and
Scheme 2.
When we treated an excess of amine with 3a, the symmet-
rically substituted diaminophosphanyltriazines formed in
good yields (Table 1, Entries 1 and 3–5). In addition to the
primary and secondary amines, we also applied an aqueous
solution of a small amine ( Table 1, Entries 3 and 4). Diiso-
propylethylamine (DIPEA) was the best-suited base for this
substitution when we used an equimolar amount of the
amine.[8] In this case, each step of the substitution by two
Table 2. Selective synthesis of diphosphanyltriazines.
Entry NuH
Base
Conditions Product Yield [%][a]
[b]
1
2
3
4
5
6
7
morpholine
morpholine
–
r.t., 3 h
r.t., 3 h
r.t., 1 h
r.t., 1.5 h
r.t., 1.5 h
r.t., 5 h
5a
5a
5b
5c
5d
5e
5f
87
87
55
87
63
68
63
DIPEA
[b]
nBuNH2
–
[c]
[b]
NH3
–
PhCHMeNH2 DIPEA
CH3OH DIPEA
Ph(CH2)3OH CsF, DIPEA r.t., 15 h
[a] Isolated yield. [b] An excess amount of amine was used. [c]
Aqueous solution was used.
Phosphanyltriazines have multiple sites for interaction
moles of amine were also highly selective. Thus, we could with transition metals through both the organophosphane
also prepare asymmetrically substituted diaminophosphan- part(s) and the Ns on the triazine ring. Thus, the intricate
yltriazines by the stepwise addition of a silylphosphane and behavior of their complex formation has been forecasted.[9]
Table 1. Selective synthesis of mono-phosphanyltriazines.
Entry
Nu1H
Nu2H
Base
Conditions
Product
Yield [%][a]
[b]
[b]
1
2
3
4
5
6
7
morpholine
morpholine
Me2NH[c]
NH3
nBuNH2
PhMeCHNH2
morpholine
CH3OH
Ph(CH2)3OH
Ph(CH2)2OH
–
–
r.t., 1 h
r.t., 1 h
r.t., 2.5 h
r.t., 4 d
r.t., 1.5 h
r.t., 1.5 h
r.t., 2 h
r.t., 5 h
r.t., 14 h
r.t., 10 h
4a
4a
4b
4c
4d
4e
4f
4g
4h
4i
57
85
64
49
74
50
76
55
66
68
–
DIPEA
[b]
[b]
–
–
[c]
[b]
[b]
–
–
–
[b]
[b]
–
[b]
–
DIPEA
DIPEA
DIPEA
CsF, DIPEA
DIPEA
Et2NH
–
–
8
9[d]
10
morpholine
[a] Isolated yield. [b] An excess amount of nucleophile and/or amine was used. [c] Aqueous solution was used. [d] DMF was used instead
of THF in the latter step.
Eur. J. Org. Chem. 2009, 4956–4962
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4957

M. Hayashi, T. Yamasaki, Y. Kobayashi, Y. Imai, Y. Watanabe
FULL PAPER
Scheme 3.
Figure 3. ORTEP drawing of complex Pd-5c (30% probability for
thermal ellipsoids; hydrogen atoms and solvent molecules are omit-
ted for clarity.).
Indeed, various complexes were formed depending on both
the ligand structure and the metal/ligand (M/L) ratio, espe-
cially the metal/P ratio. We note that we observed simple
complex formation when we reacted PdII and phosphanyl-
triazine 4a or 5c in an adequate Pd/P ratio (1:2 for 4a and
1:1 for 5c). In both cases, 31P NMR showed a single signal
around 30 ppm, which indicated the formation of a P-Pd
complex. Complexes Pd/4a and Pd/5c gave single crystals
suitable for X-ray crystallographic analyses.[10] The ORTEP
drawings are shown in Figures 2 and 3, respectively. The P
atoms are coordinated to Pd in both complexes in accord-
ance with the NMR results. Two triazine rings are parallel
to each other at a distance of about 3.6 Å. We note that the
Pd in both complexes had a cis orientation in a square
planar configuration; two ligand molecules behave formally
as bidentate ligands probably due to the π-interaction of
the two triazine rings. Thus, bis-phosphane ligand 5c gave
the bridging dinuclear complex due to the orientation of
the two phosphanyl groups, whereas mono-phosphane li-
gand 4a exclusively gave the cis complex.
We applied phosphanyltriazine 4a to the Mizorogi–Heck
reaction as a model ligand. The coupling reactions under
several conditions are summarized in Table 3. The coupling
reaction of 6 with butyl acrylate proceeded quite smoothly
(Scheme 4).
Table 3. Phosphanyltriazine-Pd-catalyzed Mizorogi–Heck reac-
tion.[a]
Entry
Pd/P
Ligand
Time [min] Conversion [%][b]
1
2
3
4
5
1:4
1:2
1:1
1:4
1:4
4a
4a
4a
4d
5a
30
5
5
60
60
100
97
96
82
100
[a] Reactions were conducted by using 2 mol-% Pd(OAc)2 in DMA
at 140 °C. NaOAc was used as a base. [b] Determined by 1H NMR
spectroscopy.
Scheme 4.
The activity of the catalyst strongly depended on the Pd/
ligand. In the case of Pd/P = 1:2, the initial rate of the
catalytic reaction was quite high; the reaction completed
within 5 min. However, the turn over number (TON) was
as high as 7000.[11] In contrast, when we used Pd/P = 1:4,
the initial rate was slower than in the former case. However,
the TON reached up to 18000.[11] These results were much
better than those of the reaction using the triarylphos-
phane-Pd catalysts [PPh3: 4 h, 86%; P(o-Tol)3: 1.5 h, 92%].
This suggests that the triazine rings in the ligand have posi-
tive effects for both the reactivity and the stability of the
catalyst.
Figure 2. ORTEP drawing of complex Pd-4a (30% probability for
thermal ellipsoids; one of the independent Pd complex molecules
is shown; hydrogen atoms are omitted for clarity; one of the morph-
oline ring has disordered conformations.).
4958
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 4956–4962

Phosphanyltriazines as Ligands for Catalysts
The phosphanyltriazine-Pd catalysts are also effective in
Suzuki–Miyaura coupling reactions (Scheme 5). The cou-
pling of phenylboronic acid with p-bromotoluene proceeded
smoothly under the usual coupling conditions to give the
coupling product in excellent yield.
Scheme 8. PEG–phosphanyltriazine-Pd-catalyzed Suzuki–Miyaura
coupling in water.
Polymer-supported phosphanyltriazine 4k was also a
good ligand for the Suzuki–Miyaura coupling. After the re-
action was complete, we recovered the PSt-supported 4k-
Pd catalyst simply by filtration, washing with solvent, dry-
ing and reusing it in the next reaction. We reused it five
times without loss of reactivity. However, reusing it more
than five times caused a remarkable decrease in reactivity
(Scheme 9, Table 4). The further effects of the substituents
on the phosphanyltriazines and the property tuning of the
supported ligands are still under investigation.
Scheme 5.
We note that the properties and efficiency of the catalyst
are easily tunable since the present synthesis allows for the
preparation of phosphanyltriazines bearing a variety of
substituents with functionality, such as water-soluble chains
or a solid support, as shown below (Scheme 6 and
Scheme 7).
Scheme 9.
Table 4. Repetitive use of polymer-supported, phosphanyltriazine-
Pd catalyst in a Suzuki–Miyaura coupling reaction.[a]
Entry
Run
Reuse[b]
Time [h]
Yield [%][c]
1
2
3
4
5
6
7
1
2
3
4
5
6
7
0
1
2
3
4
5
6
2
2
2
2
2
2
2
Ͼ99
Ͼ99
Ͼ99
Ͼ99
98
76
43
Scheme 6. Phosphanyltriazine ligand with a PEG side chain.
[a] Reactions were conducted by using 5 mol-% Pd-4k in dioxane at
100 °C. Cs2CO3 was used as a base. [b] The polystyrene-supported
catalyst was recovered by filtration. The recovered catalyst was
1
washed and dried before the next use. [c] Determined by H NMR
spectroscopy.
Conclusions
A simple and straightforward synthesis of phosphanyltri-
azines with one or two phosphane group(s) and other sub-
stituent(s) has been developed. Several types of 1,3,5-tri-
azines with P, N and O substituents were synthesized, and
Scheme 7. Phosphanyltriazine ligands on a solid support.
The tunable solubility was well-demonstrated by the the Pd complex of those phosphanyltriazines could be pre-
properties of PEG-phosphanyltriazine 4j; it was soluble in pared by mixing a Pd source and the ligand in an adequate
both water and most organic solvents. We tuned the solubil- ratio. The phosphanyltriazine was successfully applied as
ity by changing the length of the PEG chain and the sub- a ligand to the Pd-catalyzed Mizorogi–Heck reaction and
stituent on the other site. The tuned ligand 4j worked well Suzuki–Miyaura coupling reaction. The properties of the
in the Pd-catalyzed cross coupling in water (Scheme 8).
phosphanyltriazine could be tuned by introducing a func-
Eur. J. Org. Chem. 2009, 4956–4962
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4959

M. Hayashi, T. Yamasaki, Y. Kobayashi, Y. Imai, Y. Watanabe
FULL PAPER
CH3), 127.8 (d, 3JC,P = 7.4 Hz, 4 C, meta-C), 128.5 (s, 2 C, para-C),
tional side chain, which was well-demonstrated by the syn-
thesis and application of the PEG-connected and the PSt-
supported phosphanyltriazines.
2
1
134.8 (d, JC,P = 19.0 Hz, 4 C, ortho-C), 135.9 (d, JC,P = 7.5 Hz, 2
3
C, ipso-C), 163.8 (d, JC,P = 9.0 Hz, 2 C, triazine-4,6), 182.0 (d,
3JC,P = 19.0 Hz, 1 C, triazine-2) ppm. 31P{1H} NMR (162 MHz,
CDCl3, 25 °C): δ = –1.20 ppm. FABMS: 353 [M + H]+.
4,6-Diamino-2-(diphenylphosphanyl)-1,3,5-triazine (4c): 1H NMR
(400 MHz, [D6]DMSO, 25 °C): δ = 6.63 (br., 4 H, NH2), 7.30–7.36
(m, 6 H, arom.), 7.40–7.48 (m, 4 H, arom.) ppm. 13C{1H} NMR
Experimental Section
General: (Trimethylsilyl)diphenylphosphane (2) was prepared from
Ph3P, Li and TMSCl in THF. The other chemicals were purchased
and purified prior to use. Experimental procedures and characteri-
zation data (1H, 13C, and 31P NMR and MS) are reported below.
3
(100 MHz, [D6]DMSO, 25 °C): δ = 128.8 (d, JC,P = 7.6 Hz, 4 C,
2
meta-C), 129.4 (s, 2 C, para-C), 135.0 (d, JC,P = 19.9 Hz, 4 C,
1
3
ortho-C), 136.1 (d, JC,P = 7.5 Hz, 2 C, ipso-C), 166.0 (d, JC,P
=
1
9.0 Hz, 2 C, triazine-4,6), 183.4 (d, JC,P = 19.4 Hz, 1 C, triazine-
2) ppm. 31P{1H} NMR (162 MHz, [D6]DMSO, 25 °C): δ = –2.40
ppm. FABMS: 296 [M + H]+.
General Procedure for the Synthesis of Monophosphanyltriazine 4:
To a THF solution of cyanuric chloride (1) was added silylphos-
phane 2 (1.0–1.1 equiv.) at 0 °C under Ar. After the mixture was
stirred for 1 h, the solvent and TMSCl formed were removed under
reduced pressure. THF, DIPEA (2.5 equiv. when used) and the nu-
cleophilic reagent (2.0–2.5 equiv. or an excess amount) were added
to the residue, and then the mixture was stirred for 1 h. After THF
was removed, water was added, and the product was extracted
twice with CHCl3. The extraction should be done as soon as pos-
sible to avoid oxidation of the desired phosphane. The extract was
dried and evaporated, and the crude product was then purified with
column chromatography on silica gel to give the pure products 4a
(85% yield, 1.37 g from 3.72 mmol of 1), 4b (64% yield, 796 mg
from 3.55 mmol of 1), 4c (49% yield, 504 mg from 3.52 mmol of
1), 4d (74% yield, 2.22 g from 7.36 mmol of 1), 4e (50% yield,
4,6-Bis(butylamino)-2-(diphenylphosphanyl)-1,3,5-triazine (4d): 1H
NMR (400 MHz, [D6]DMSO, 100 °C): δ = 0.85 (t, J = 7.3 Hz, 6
H, -CH3), 1.26 (sextet, J = 7.3 Hz, 4 H, -CH2-CH3), 1.44 (quintet,
J = 7.2 Hz, 4 H, -CH2-CH2-CH2-), 3.18 (q, J = 6.0 Hz, 4 H, NH-
CH2-), 6.45–6.55 (br., 2 H, NH), 7.28–7.34 (m, 6 H, arom.), 7.47–
7.55 (m, 4 H, arom.) ppm. 13C{1H} NMR (100 MHz, [D6]DMSO,
100 °C): δ = 13.8 (2 C, -CH3), 19.9 (2 C, -CH2-CH3), 31.8 (2 C,
3
-CH2-CH2-CH2-), 41.0 (2 C, N-CH2-), 128.3 (d, JC,P = 7.5 Hz, 4
2
C, meta-C), 129.0 (s, 2 C, para-C), 134.7 (d, JC,P = 19.7 Hz, 4 C,
1
3
ortho-C), 136.6 (d, JC,P = 9.3 Hz, 2 C, ipso-C), 165.0 (d, JC,P
=
1
9.1 Hz, 2 C, triazine-4,6), 182.5 (d, JC,P = 17.0 Hz, 1 C, triazine-
2) ppm. 31P{1H} NMR (162 MHz, [D6]DMSO, 100 °C): δ = –0.50
884 mg from 3.51 mmol of 1), 4f (76% yield, 298 mg from ppm. FABMS: 409 [M + H]+.
0.93 mmol of 1), 4g (55% yield, 665 mg from 3.72 mmol of 1), 4h
2-(Diphenylphosphanyl)-4,6-bis[(R)-1-phenylethylamino]-1,3,5-tri-
(66% yield, 312 mg from 0.89 mmol of 1) and 4i (68% yield,
297 mg from 0.93 mmol of 1).
1
azine (4e): H NMR (400 MHz, CDCl3, 25 °C): δ = 1.25–1.55 (m,
6 H, -CH3), 4.85–5.55 (m, 2 H, -CHPh), 7.00–8.00 (m, 10 H, arom.)
ppm. 13C{1H} NMR (100 MHz, CDCl3, 25 °C, mixture of rota-
mers): δ = 22.5 (2 C, -CH3), 49.7–51.0 (m, 2 C, -CH-Ph), 126.1,
127.0, 128.0–128.8 (m), 128.5, 129.0, 131.7–132.5 (m), 134.5–135.1
Typical Procedure for the Synthesis of Diphosphanyltriazine 5: To a
THF solution of cyanuric chloride (1) was added silylphosphane 2
(2.1–2.5 equiv.) at room temp. under Ar. After the mixture was
stirred for 1 h, the solvent and TMSCl formed were removed under
reduced pressure. THF and an amine (2.5–5.3 equiv.) were added
to the residue, and the mixture was then stirred for 1–3 h. After
THF was removed, water was added, and the product was extracted
twice with CHCl3. The extraction should be done as soon as pos-
sible to avoid oxidation of the desired phosphane. The extract was
dried and evaporated, and the crude product was then purified with
column chromatography on silica gel to give the pure products 5a
(87% yield, 413 mg from 0.89 mmol of 1), 5b (66% yield, 1.35 g
from 3.65 mmol of 1), 5c (87% yield, 706 mg from 1.74 mmol of
1), 5d (63% yield, 555 mg from 1.55 mmol of 1), 5e (68% yield,
289 mg from 0.89 mmol of 1) and 5f (63% yield, 268 mg from
0.89 mmol of 1).
3
(m), 143.8–144.3 (m), 163.7 (d, JC,P = 8.2 Hz, 2 C, triazine-4,6),
1
183.1 (d, JC,P = 13.4 Hz, 1 C, triazine-2) ppm. 31P{1H} NMR: δ
= –0.51 ppm. FABMS: 504 [M + H]+.
6-(Diethylamino)-2-(diphenylphosphanyl)-4-morpholino-1,3,5-tri-
azine (4f): 1H NMR (400 MHz, CDCl3, 25 °C): δ = 0.92 (t, J =
6.8 Hz, 3 H), 1.17 (t, J = 6.8 Hz, 3 H, -CH3), 3.35 (q, J = 6.8 Hz,
2 H, -CH2-CH3), 3.47 (q, J = 6.8 Hz, 2 H, -CH2-CH3), 3.65 (br., 4
H, CH2-N), 3.67 (br., 4 H, CH2-O), 7.27–7.34 (m, 6 H, arom.),
7.52–7.59 (m, 4 H, arom.) ppm. 13C{1H} NMR (100 MHz, CDCl3,
25 °C): δ = 12.9 (1 C, -CH3), 13.3 (1 C, -CH3), 41.2 (1 C, -CH2-
CH3), 41.6 (1 C, -CH2-CH3), 43.4 (2 C, -CH2-N), 66.8 (2 C, -CH2-
3
O), 127.8 (d, JC,P = 7.5 Hz, 4 C, meta-C), 128.6 (s, 2 C, para-C),
2
1
134.8 (d, JC,P = 19.2 Hz, 4 C, ortho-C), 135.7 (d, JC,P = 7.1 Hz,
3
Physical Data for 4 and 5
2 C, ipso-C), 162.7 (d, JC,P = 7.8 Hz, 1 C, triazine-4), 163.5 (d,
3JC,P = 9.7 Hz, 1 C, triazine-6), 182.6 (d, JC,P = 18.3 Hz, 1 C,
1
2-(Diphenylphosphanyl)-4,6-dimorpholino-1,3,5-triazine (4a): 1H
NMR (400 MHz, CDCl3, 25 °C): δ = 3.40–3.90 (br., 16 H, -N-CH2-
CH2-O-), 7.28–7.36 (m, 6 H, arom.), 7.50–7.58 (m, 4 H, arom.)
triazine-2) ppm. 31P{1H} NMR: δ = –0.91 ppm. FABMS: 422 [M
+ H]+.
ppm. 13C{1H} NMR (100 MHz, CDCl3, 25 °C): δ = 43.3 (4 C, 2-(Diphenylphosphanyl)-4,6-dimethoxy-1,3,5-triazine (4g): 1H NMR
3
CH2-N), 66.6 (4 C, CH2-O), 127.8 (d, JC,P = 7.6 Hz, 4 C, meta- (400 MHz, CDCl3, 25 °C): δ = 3.90 (s, 6 H, -CH3), 7.35–7.41 (m,
C), 128.7 (s, 2 C, para-C), 134.6 (d, JC,P = 19.2 Hz, 4 C, ortho-C), 6 H, arom.), 7.52–7.57 (m, 4 H, arom.) ppm. 13C{1H} NMR
2
1
3
3
135.2 (d, JC,P = 6.9 Hz, 2 C, ipso-C), 163.2 (d, JC,P = 8.5 Hz, 2
(100 MHz, CDCl3, 25 °C): δ = 55.2 (2 C, -O-CH3), 128.4 (d, JC,P
3
1
C, triazine-4,6), 183.3 (d, JC,P = 16.4 Hz, 1 C, triazine-2) ppm.
= 8.0 Hz, 4 C, meta-C), 129.5 (s, 2 C, para-C), 133.5 (d, JC,P
=
31P{1H} NMR (162 MHz, CDCl3, 25 °C): δ = –0.50 ppm. FABMS:
5.4 Hz, 2 C, ipso-C), 134.9 (d, 2JC,P = 20.1 Hz, 4 C, ortho-C), 171.1
(d, JC,P = 7.6 Hz, 2 C, Tiazine-4,6), 190.3 (d, JC,P = 5.1 Hz, 1 C,
triazine-2) ppm. 31P{1H} NMR: δ = 2.50 ppm. FABMS: 326 [M +
H]+.
3
1
436 [M + H]+.
4,6-Bis(dimethylamino)-2-(diphenylphosphanyl)-1,3,5-triazine (4b):
1H NMR (400 MHz, CDCl3, 25 °C): δ = 2.90–3.12 (br., 12 H, CH3-
N), 7.28–7.34 (m, 6 H, arom.), 7.53–7.60 (m, 4 H, arom.) ppm.
2-(Diphenylphosphanyl)-4,6-bis(3-phenylpropyloxy)-1,3,5-triazine
13C{1H} NMR (100 MHz, CDCl3, 25 °C): δ = 35.8 (br., 4 C, N- (4h): 1H NMR (400 MHz, CDCl3, 25 °C): δ = 1.99 (tt, J = 7.7,
4960
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 4956–4962

Phosphanyltriazines as Ligands for Catalysts
1
2
6.5 Hz, 4 H, -CH2-CH2-CH2-), 2.67 (t, J = 7.7 Hz, 4 H, -CH2-Ph),
4.25 (t, J = 6.5 Hz, 4 H, -CH2-O), 7.12–7.28 (m, 10 H, arom.),
(d, JC,P = 6.5 Hz, 4 C, ipso-C), 134.8 (d, JC,P = 19.8 Hz, 8 C,
3
ortho-C), 163.3 (t, JC,P = 7.8 Hz, 1 C, triazine-6), 184.5 (dt, JC,P
7.30–7.37 (m, 6 H, arom.), 7.51–7.56 (m, 4 H, arom.) ppm. 13C{1H} = 11.2, 7.0 Hz, 2 C, triazine-2,4) ppm. 31P{1H} NMR (162 MHz,
NMR (100 MHz, CDCl3, 25 °C): δ = 30.1 (2 C, -CH2-CH2-CH2-), CDCl3, 25 °C): δ = 0.35 ppm. FABMS: 465 [M + H]+.
32.0 (2 C, -CH2-Ph), 67.6 (2 C, -CH2-O), 126.1 (s, 2 C, -CH2-Ph:
2,4-Bis(diphenylphosphanyl)-6-[(R)-1-phenylethylamino]-1,3,5-tri-
3
para-C), 128.44 (d, JC,P = 8.8 Hz, 4 C, P-Ph: meta-C), 128.48 (s,
azine (5d): 1H NMR (400 MHz, CDCl3, 25 °C): δ = 1.33 (d, J =
8 C, -CH2-Ph: ortho, meta-C), 129.5 (s, 2 C, -P-Ph: para-C), 133.7
7.2 Hz, 3 H, -CH3), 4.86 (quintet, J = 7.2 Hz, 1 H, CH), 5.52 (br.
1
2
(d, JC,P = 5.6 Hz, 2 C, -P-Ph: ipso-C), 134.9 (d, JC,P = 20.0 Hz, 4
d, J = 8 Hz, 1 H, NH), 7.02 (dd, J = 5.6, 1.6 Hz, 2 H, arom.),
7.18–7.45 (m, 23 H, arom.) ppm. 13C{1H} NMR (100 MHz,
CDCl3, 25 °C): δ = 21.9 (1 C, -CH3), 50.0 (1 C, CH), 126.1 (s, 2 C,
phenethyl-ortho-C), 127.1 (s, 1 C, phenethyl-para-C), 128.00 (d,
3JC,P = 14.0 Hz, 2 C, meta-C), 128.06 (d, 3JC,P = 6.9 Hz, 4 C, meta-
C), 128.2 (s, 2 C, para-C), 128.4 (s, 2 C, phenethyl-meta-C), 128.8
3
C, P-Ph: ortho-C), 141.2 (s, 2 C, -CH2-Ph: ipso-C), 170.8 (d, JC,P
1
= 7.7 Hz, 2 C, Tiazine-4,6), 190.1 (d, JC,P = 5.7 Hz, 1 C, triazine-
2) ppm. 31P{1H} NMR (162 MHz, CDCl3, 25 °C): δ = 2.46 ppm.
FABMS: 534 [M + H]+.
2-(Diphenylphosphanyl)-4-morpholino-6-(2-phenylethoxy)-1,3,5-tri-
azine (4i): 1H NMR (400 MHz, CDCl3, 25 °C): δ = 2.96 (t, J =
7.6 Hz, 2 H, -CH2-Ph), 3.55–3.85 (br., 8 H, -N-CH2-CH2-O-), 4.40
(t, J = 7.6 Hz, 2 H, PhCH2-CH2-O), 7.08–7.29 (m, 5 H, arom.),
7.30–7.37 (m, 6 H, arom.), 7.51–7.57 (m, 4 H, arom.) ppm. 13C{1H}
NMR (100 MHz, CDCl3, 25 °C): δ = 35.2 (1 C, -O-CH2-CH2-Ph),
43.5 (1 C, -CH2-N-), 43.9 (1 C, -CH2-N-), 66.58 (1 C, -NCH2-CH2-
O-), 66.63 (1 C, -NCH2-CH2-O-), 67.8 (1 C, PhCH2-CH2-O-), 126.5
2
(d, JC,P = 12.5 Hz, 2 C, meta-C), 129.0 (s, 2 C, para-C), 134.2 (d,
1JC,P = 6.0 Hz, 3 C, ipso-C), 134.3 (d, JC,P = 7.3 Hz, 1 C, ipso-C),
1
134.6 (d, 2JC,P = 18.8 Hz, 2 C, ortho-C), 134.75 (d, 1JC,P = 19.1 Hz,
1
2 C, ortho-C), 134.78 (d, JC,P = 19.9 Hz, 2 C, ortho-C), 134.9 (d,
1JC,P = 19.5 Hz, 2 C, ortho-C), 143.0 (s, 1 C, phenethyl-ipso-C),
3
161.4 (t, JC,P = 6.5 Hz, 1 C, triazine-6), 183.4 (dd, JC,P = 7.6,
6.2 Hz, 1 C, triazine-2/4), 184.3 (dd, JC,P = 8.2, 5.0 Hz, 1 C, tri-
azine-2/4) ppm. 31P{1H} NMR (162 MHz, CDCl3, 25 °C): δ = 0.58,
0.05 ppm. FABMS: 569 [M + H]+.
3
(s, 1 C, -CH2-Ph: para-C), 128.2 (d, JC,P = 7.8 Hz, 4 C, P-Ph:
meta-C), 128.5 (s, 2 C, -CH2-Ph: meta-C), 129.0 (s, 2 C, -CH2-Ph:
1
ortho-C), 129.2 (s, 2 C, -P-Ph: para-C), 134.5 (d, JC,P = 6.2 Hz, 2
2,4-Bis(diphenylphosphanyl)-6-methoxy-1,3,5-triazine (5e): 1H
NMR (400 MHz, CDCl3, 25 °C): δ = 3.74 (s, 3 H, -OCH3), 7.24–
7.48 (m, 20 H, arom.) ppm. 13C{1H} NMR (100 MHz, CDCl3,
25 °C): δ = 54.7 (1 C, -O-CH3), 128.2 (d, 3JC,P = 8.1 Hz, 8 C, meta-
2
C, -P-Ph: ipso-C), 134.9 (d, JC,P = 19.7 Hz, 4 C, P-Ph: ortho-C),
3
137.6 (s, 1 C, -CH2-Ph: ipso-C), 164.5 (d, JC,P = 7.5 Hz, 1 C, tri-
3
1
azine-4), 169.2 (d, JC,P = 8.9 Hz, 1 C, triazine-6), 186.6 (d, JC,P
= 11.1 Hz, 1 C, triazine-2) ppm. 31P{1H} NMR: δ = 1.02 ppm.
FABMS: 471 [M + H]+.
1
C), 129.1 (s, 4 C, para-C), 133.4 (d, JC,P = 5.7 Hz, 4 C, ipso-C),
2
3
134.7 (d, JC,P = 19.9 Hz, 8 C, ortho-C), 167.4 (t, JC,P = 6.3 Hz, 1
C, triazine-6), 187.2 (dd, JC,P = 4.2, 2.9 Hz, 2 C, triazine-2,4) ppm.
31P{1H} NMR (162 MHz, CDCl3, 25 °C): δ = 1.83 ppm. FABMS:
480 [M + H]+.
6-(PEG-600)-Substituted 2-(Diphenylphosphanyl)-4-morpholino-
1
1,3,5-triazine (4j): H NMR (400 MHz, CDCl3, 25 °C): δ = 3.55–
3.82 (br., -N-CH2-CH2-O-, O-CH2-CH2-O-), 4.34 (br. t, 2 H, -OH),
7.24–7.58 (m, 10 H, arom.) ppm. 31P{1H} NMR (162 MHz,
CDCl3, 25 °C): δ = 0.89 ppm. FABMS: 895 [M]+ (n = 12).
2,4-Bis(diphenylphosphanyl)-6-(3-phenylpropyloxy)-1,3,5-triazine
(5f): 1H NMR (400 MHz, CDCl3, 25 °C): δ = 1.91 (tt, J = 8.0,
6.8 Hz, 2 H, -CH2CH2CH2-), 2.59 (t, J = 8.0 Hz, 2 H, -CH2Ph),
4.15 (t, J = 6.8 Hz, 2 H, -CH2-O), 7.08–7.46 (m, 25 H, arom.) ppm.
1
2,4-Bis(diphenylphosphanyl)-6-morpholino-1,3,5-triazine (5a): H
NMR (400 MHz, CDCl3, 25 °C): δ = 3.54 (br. s, 8 H, -N-CH2-
CH2-O-), 7.20–7.33 (m, 12 H, arom.), 7.42–7.47 (m, 8 H, arom.)
ppm. 13C{1H} NMR (100 MHz, CDCl3, 25 °C): δ = 43.1 (2 C,
-CH2-N-), 66.4 (2 C, -CH2-O-), 128.0 (d, 3JC,P = 7.8 Hz, 8 C, meta-
13C{1H} NMR (100 MHz, CDCl3, 25 °C):
δ = 29.9 (1 C,
-CH2CH2CH2-), 31.9 (1 C, -CH2-Ph), 67.4 (1 C, -O-CH2-), 125.9
(s, 1 C, -CH2-Ph: para-C), 128.3 (d, JC,P = 8.1 Hz, 8 C, P-Ph:
3
1
C), 128.8 (s, 4 C, para-C), 134.4 (d, JC,P = 6.7 Hz, 4 C, ipso-C),
meta-C), 128.4 (s, 4 C, -CH2-Ph: ortho, meta-C), 129.2 (s, 4 C, -P-
Ph: para-C), 134.6 (d, 1JC,P = 5.8 Hz, 4 C, -P-Ph: ipso-C), 134.8 (d,
2JC,P = 19.9 Hz, 8 C, P-Ph: ortho-C), 141.1 (s, 1 C, -CH2-Ph: ipso-
C), 167.2 (t, 3JC,P = 6.7 Hz, 1 C, triazine-6), 187.2 (t, JC,P = 4.0 Hz,
2 C, triazine-2,4) ppm. 31P{1H} NMR (162 MHz, CDCl3, 25 °C):
δ = 1.76 ppm. FABMS: 480 [M + H]+.
2
3
134.7 (d, JC,P = 19.5 Hz, 8 C, ortho-C), 160.7 (t, JC,P = 6.4 Hz, 1
C, triazine-6), 183.5 (dd, 1JC,P = 8.4, 5.5 Hz, 2 C, triazine-2,4) ppm.
31P{1H} NMR (162 MHz, CDCl3, 25 °C): δ = 0.18 ppm. FABMS:
535 [M + H]+.
1
6-(Butylamino)-2,4-bis(diphenylphosphanyl)-1,3,5-triazine (5b): H
NMR (400 MHz, [D6]DMSO, 25 °C): δ = 0.74 (t, J = 7.4 Hz, 3
H, -CH3), 1.08 (sextet, J = 7.6 Hz, 2 H, -CH2-CH3), 1.20–1.30 (m,
2 H, -CH2-CH2-CH2-), 2.97 (q, J = 6.7 Hz, 2 H, -N-CH2-), 7.28–
7.44 (m, 20 H, arom.), 8.01 (t, J = 6.0 Hz, 1 H, NH) ppm. 13C{1H}
NMR (100 MHz, [D6]DMSO, 25 °C): δ = 14.0 (1 C, -CH3), 19.9
(1 C, -CH2-CH3), 31.0 (1 C, -CH2-CH2-CH2-), 40.6 (1 C, N-CH2-
Procedure for the Preparation of the Pd-4a Complex:
PdCl2(CH3CN)2 (50 mg, 0.19 mmol) and phosphanyltriazine 4a
(0.52 mmol) were dissolved in THF (7.5 mL) at room temp. under
Ar. After the mixture was stirred for 1 h, it was concentrated in
vacuo. The yellow solid residue was then recrystallized from
CH2Cl2/Et2O to give the single crystal of the Pd-4a suitable for X-
ray analysis.
3
3
), 128.7 (d, JC,P = 7.7 Hz, 4 C, meta-C), 128.9 (d, JC,P = 7.9 Hz,
4 C, meta-C), 129.5 (s, 2 C, para-C), 129.6 (s, 2 C, para-C), 134.7
1
2
Procedure for the Preparation of the Pd-5c Complex:
PdCl2(CH3CN)2 (106 mg, 0.41 mmol) and diphosphanyltriazine 5c
(0.43 mmol) were dissolved in CH2Cl2 (10 mL) at room temp. un-
der Ar. After the mixture was stirred for 1 h, the precipitate formed
was collected by filtration. The yellow solid was then recrystallized
from DMF/Et2O to give the single crystal of the Pd-5c complex
suitable for X-ray analysis.
(d, JC,P = 6.2 Hz, 2 C, ipso-C), 134.87 (d, JC,P = 19.5 Hz, 4 C,
ortho-C), 134.98 (d, 1JC,P = 6.5 Hz, 2 C, ipso-C), 134.99 (d, 2JC,P
20.0 Hz, 4 C, ortho-C), 162.1 (t, JC,P = 7.6 Hz, 1 C, triazine-6),
=
3
182.6 (dd, JC,P = 6.3, 11.4 Hz, 1 C, triazine-2/4), 183.3 (dd, JC,P
=
4.9, 11.3 Hz, 1 C, triazine-2/4) ppm. 31P{1H} NMR (162 MHz,
[D6]DMSO, 25 °C): δ = –1.53, –1.41 ppm. FABMS: 521 [M + H]+.
1
6-Amino-2,4-bis(diphenylphosphanyl)-1,3,5-triazine (5c): H NMR
(400 MHz, CDCl3, 25 °C): δ = 5.42 (br., 2 H, NH2), 7.23–7.44 (m, Typical Procedure for the Mizorogi–Heck Reaction Using Pd-4a:
20 H, arom.) ppm. 13C{1H} NMR (100 MHz, CDCl3, 25 °C): δ =
Aryl halide (0.50 mmol), NaOAc (0.55 mmol), Pd(OAc)2
128.2 (d, 3JC,P = 8.0 Hz, 8 C, meta-C), 129.1 (s, 4 C, para-C), 134.1 (0.01 mmol, 2 mol-%) and phosphane ligand 4a (0.04 mmol, 8 mol-
6
Eur. J. Org. Chem. 2009, 4956–4962
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4961

M. Hayashi, T. Yamasaki, Y. Kobayashi, Y. Imai, Y. Watanabe
FULL PAPER
[3] For reviews, see: a) P. Gamez, J. Reedijk, Eur. J. Inorg. Chem.
2006, 29–42; b) T. J. Mooibroek, P. Gamez, Inorg. Chim. Acta
2007, 360, 381–404.
%) were mixed in DMA (1 mL) at room temp. under Ar for 20 min.
To the mixture, butyl acrylate 7 (0.70 mmol) was added, and the
mixture was stirred for 10 min at room temp. and 1 h at 140 °C.
The conversion of the reaction was determined by 1H NMR by
using a portion of the reaction mixture.
[4] B. Hoge, W. Wiebe, Angew. Chem. Int. Ed. 2008, 47, 8116–8119.
[5] The synthesis of phosphanyltriazines by capping all reactive
sites in triazine derivatives with phosphane nucleophiles has
been reported: a) W. Hewertson, R. A. Shaw, B. C. Smith, J.
Chem. Soc. 1963, 1020–1026; b) J. Zhang, M. Nieuwenhuyzen,
J. P. H. Charmant, S. L. James, Chem. Commun. 2004, 2808; c)
P. W. Miller, M. Nieuwenhuyzen, S. L. James, CrystEngComm
2004, 68, 408–412; d) M. Pietraszkiewicz, A. Kłonkowski, K.
Staniszewski, J. Karpiuk, S. Biankettia, J. Alloys Compd. 2004,
380, 241. Only one example of mono-substitution has been re-
ported: e) J. McMurran, J. Kouvetakis, D. C. Nesting, J. L.
Hubbard, Chem. Mater. 1998, 10, 590–593.
Typical Procedure for the Suzuki–Miyaura Coupling Reaction in
Aqueous Media Using Pd-4j: p-Bromotoluene (0.41 mmol), phen-
ylboronic acid (0.61 mmol), Cs2CO3 (0.81 mmol), Pd2(dba)3·
CHCl3 (0.0041 mmol) and phosphane ligand 4j (0.016 mmol) were
mixed in water (2 mL) at room temp. under Ar for 30 min and at
100 °C for 3 h. The product was extracted with ethyl acetate, dried
and concentrated. The residue was purified by chromatography on
silica gel to afford the coupling product (69 mg, 100%).
[6] a) Y. Matsuura, T. Yamasaki, Y. Watanabe, M. Hayashi, Tetra-
hedron: Asymmetry 2007, 18, 2129–2132; b) M. Hayashi, Y.
Matsuura, T. Yamasaki, Y. Watanabe, J. Org. Chem. 2007, 72,
7798–7800; c) M. Hayashi, Y. Matsuura, Y. Watanabe, J. Org.
Chem. 2006, 71, 9248–9251; d) M. Hayashi, Y. Matsuura, K.
Kurihara, D. Maeda, Y. Nishimura, E. Morita, M. Okasaka,
Y. Watanabe, Chem. Lett. 2007, 36, 634–635; e) M. Hayashi,
Y. Matsuura, Y. Watanabe, Tetrahedron Lett. 2005, 46, 5135–
5138; f) M. Hayashi, Y. Matsuura, Y. Watanabe, Tetrahedron
Lett. 2004, 45, 9167–9169.
[7] When Ph2PH was used instead of silylphosphane 2, only mono-
phosphanyltriazine was formed, even when excess diphenyl-
phosphane was used. The use of LiPPh2 (2.2 equiv.) caused de-
gradation of the intermediate to give tetraphenyldiphosphane
as a main product.
Procedure for the Suzuki–Miyaura Coupling Reaction by Polymer-
Supported Catalyst: p-Bromotoluene (1.00 mmol), phenylboronic
acid (1.50 mmol), Cs2CO3 (2.00 mmol), Pd2(dba)3·CHCl3
(0.05 mmol) and phosphane ligand 4k (0.40 mmol) were mixed in
dioxane (1 mL) at 100 °C under Ar for 3 h. The conversion of the
reaction was determined by 1H NMR by using a portion of the
reaction mixture. After the reaction was complete, the catalyst was
filtered off and washed three times with water and acetone. The
collected solid was dried in vacuo for 2 h before the next use. The
recovered catalyst was mixed with the substrates and base as above
for reuse.
Acknowledgments
[8] Et3N reacted with the intermediates when used instead of DI-
PEA.
This work was partly supported by Ehime University Grant (Re-
search for Promoting Technological Seeds). We also thank Venture
Business Laboratory (VBL) and the Institute for Cooperative Sci-
ence (INCS) of Ehime University for NMR and X-ray crystallo-
graphical analyses. We would like to thank Prof. H. Uno at INCS,
Ehime University, for X-ray structure determination.
[9] Complex formation of ligands with similar P–N and P–N–P
substructure, where the N of the aromatic core is coordinated,
have been reported: a) J. Zhang, P. W. Miller, M. Nieuwen-
huyzen, S. L. James, Chem. Eur. J. 2006, 12, 2448–2453; b) Q.-
S. Li, C.-Q. Wan, F.-B. Xu, H.-B. Song, Z.-Z. Zhang, Inorg.
Chim. Acta 2005, 358, 2283–2291; c) I. O. Koshevoy, M.
Haukka, T. A. Pakkanen, S. P. Tunik, P. Vainiotalo, Organome-
tallics 2005, 24, 3516–3526.
[1] a) M. L. Clarke, M. J. Williams, in: Organophosphorus Reagents
(Ed.: P. J. Murphy), Oxford University Press, New York, 2004,
chapter 2; b) D. G. Gilheany, C. M. Mitchell, in: The Chemistry
of Organophosphorus Compounds (Ed.: F. R. Hartley), John
Wiley & Sons, Chichester, 1990, vol. 1, p. 151–190.
[2] a) G. Blotny, Tetrahedron 2006, 62, 9507–9522; b) C. A. M.
Afonso, N. M. T. Lourenço, A. A. Rosatella, Molecules 2006,
11, 81–102, and references cited therein.
[10] CCDC-719707 (for Pd-4a) and -719708 (for Pd-5c) contain the
supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[11] TONs were calculated from the reactions using 0.002 mol-% of
Pd catalyst.
Received: April 18, 2009
Published Online: September 2, 2009
4962
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 4956–4962