A novel synthesis of functionalised tertiary phosphines by palladium catalysed phosphination with triarylphosphines

Article abstract of DOI:10.1016/S0040-4039(00)01850-5

The palladium catalysed Pd-aryl/P-aryl exchange was applied in the synthesis of various functionalised phosphines from their corresponding substituted aryl triflates using triarylphosphines as the phosphinating agents. This method tolerated many functional groups including ketone, aldehyde, ester, nitrile, methyl ether, pyridyl and chloride groups. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01850-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 10285–10289
A novel synthesis of functionalised tertiary phosphines by
palladium catalysed phosphination with triarylphosphines
Fuk Yee Kwong, Chi Wai Lai, Yuan Tian and Kin Shing Chan*
Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong
Received 25 August 2000; revised 13 October 2000; accepted 19 October 2000
Abstract
The palladium catalysed Pd-aryl/P-aryl exchange was applied in the synthesis of various functionalised
phosphines from their corresponding substituted aryl triflates using triarylphosphines as the phosphinat-
ing agents. This method tolerated many functional groups including ketone, aldehyde, ester, nitrile,
methyl ether, pyridyl and chloride groups. © 2000 Elsevier Science Ltd. All rights reserved.
1
Tertiary phosphines are an important type of ligands in transition metal catalysed reactions.
Functional group incorporation is necessary for modified catalysis. However, the synthetic
methods available are limited in scope for the synthesis of functionalised phosphines. The
preparation of phosphines from the literatures can be divided into two categories. The reaction
2
of halophosphines with organometallic reagents; or transition metal catalysed couplings of
3–7
primary or secondary phosphines with aryl halides/sulfonate esters. The former methodology
is not compatible with base-sensitive compounds since organo-lithium/magnesium reagents are
used. Easily reducible functional groups such as the aldehyde group are not tolerated in the
4
latter transition-metal catalysed category because reducing zinc metal is used. Although
palladium catalysed phosphination using (trimethylsilyl)diphenylphosphine tolerates many func-
tional groups, it is mainly limited to aryl iodides and incompatible with the aldehyde functional
5
group. Besides, the complementary palladium-catalysed phosphination using diphenylphos-
6
7
phine oxide or diphenylphosphine–borane requires subsequent reduction or deprotection steps.
Ph P
Ar
Ph P
Ph
3
3
Pd
Pd
(1)
X
PPh3
X
PArPh2
X = Br, I, OTf
*
Corresponding author.
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01850-5

10286
In order to seek a functional group tolerant phosphination, the interesting aryl–aryl exchange
reaction of the palladium bound aryl ring with the phosphorus bound phenyl ring was used (Eq.
8
,9
10
(
1)). However, the application of this reaction in synthesis remains limited. Herein, we report
the application of the catalytic aryl–aryl exchange for the synthesis of substituted aryl phosphi-
nes using economical triarylphosphines as the phosphinating agents (Eq. (2)). This method was
found to be compatible with many functional groups such as ketone, aldehyde, ester, nitrile,
methoxy and pyridyl groups (Eq. (2)).
PPh3
OTf
PPh2
Fn
Pd cat.
Fn
(2)
Fn = COMe, CHO, COOMe, CN, OMe, Cl, py
In a typical experiment, 4-acetylphenyl triflate was transformed to 4-(diphenylphos-
11
phino)acetophenone 1 with 10 mol% of Pd(OAc) , 2.3 equiv. of triphenylphosphine in DMF
2
for 2 hours at 110°C (Table 1, entry 1). Besides, the 4-formylphenyl triflate underwent smooth
Table 1
Palladium catalysed phosphination of various functionalised aryl triflates using triphenylphosphine
Entry
Substrates
Products
Time/h %yielda
O
O
1
OTf
PPh2
2
37
1
2
3
OHC
NC
OTf
OTf
OTf
OHC
NC
PPh2
PPh2
PPh2
3
3
31
32
2
3
4
O
O
4
5
30
MeO
MeO
OTf
PPh2
N
N
5
6
72
24
45
5
6
20 (33)b
OTf
OTf
PPh2
PPh2
N
N
27b
51b
7
7
16
4
OTf
PPh2
8
9
8
MeO
Cl
OTf
OTf
OTf
MeO
Cl
PPh2
6
5
20 (25)b
45b
9
10
PPh2
1
0
tBu
tBu
PPh2
50b
11
6
11
a
b
Isolated yield.
GC yield using anthracene as the internal standard.

10287
reaction to give 2 in 31% yield which showed that this phosphination tolerated a redox sensitive
functional group (Table 1, entry 2). In contrast, the previous synthesis of aldehyde phosphine 2
1
2
involved an acetal protective pathway. Moreover, the traditional synthesis of 4-(diphenylphos-
phino)benzonitrile 3 and methyl 4-(diphenylphosphino)benzoate 4 required several steps and the
13
overall yields were approximately 11% and 21%, respectively. In contrast, the phosphines 3
and 4 were obtained in 32% and 30% yield, respectively, in one step (Table 1, entries 3, 4).
The transformation of quinolyl and pyridyl triflates to their corresponding phosphines 5 and
6
required much longer reaction times (Table 1, entries 5 and 6). Presumably, the chelating
heteroatom coordinated to the palladium centre and rendered the complex coordinatively
saturated, hence the catalytic activity was reduced. The quinolyl phosphine 5 was found to be
a useful ligand precursor for asymmetric catalysis. The naphthyl derivatives were successfully
1
4
15
phosphinated to yield the naphthyl phosphines 7 and 8 (Table 1, entries 7 and 8). The
1
-naphthyl triflate reacted slower than the 2-napthyl substrate probably due to an increase in
steric hindrance at the ortho-position (Table 1, entries 7 and 8). In fact, this phosphination also
tolerated other functional groups such as methoxy and chloride (Table 1, entries 9 and 10). The
low yield of the phosphine product 9 was due to the partial oxidation of the product during
purification. Although palladium-catalysed phosphination using triphenylphosphine as the
reagent tolerated many functional groups, it was found to be incompatible with p-nitrophenyl
triflate. Initial experiments revealed that the nitro group was reduced to an amino group when
16
the reaction mixture was heated at 110°C for 2 days.
Although both tetrakis(triphenylphosphine) palladium(0) and palladium(II) acetate catalysed
phosphination and gave similar yield of the products, Pd(OAc) was the catalyst of choice
2
because other triarylphosphines, such as trixylylphosphine, tri(4-methoxyphenyl)phosphine and
tri(4-tolyl)phosphine could be used as the phosphinating reagents instead of just PPh only
3
(
Table 2, entries 1–3). Therefore, an array of tailor-made phosphines can be prepared easily
through this direct methodology in combination with suitable substrates containing different
triarylphosphines.
Table 2
Palladium catalysed phosphination of 4-acetylphenyl triflate using triarylphosphines.
Entry
PAr3
Products
Time/h %yielda
O
O
O
1
P
P
8
28
2
3
1
1
1
2
2
MeO
P
3
P
OMe
6
8
24
30
2
3
3
P
3
P
2
4
a
Isolated yield.
A plausible mechanism for this phosphination starts with in situ reduction of palladium(II)
17
acetate by triphenylphosphine to palladium(0) (Fig. 1). The substituted aryl triflate undergoes
oxidative addition with Pd(0) to afford an aryl palladium(II) species. The facile aryl–aryl

10288
Pd(OAc)2
PPh3
PPh4OTf
TfO
Pd(PPh3)2
Fn
PPh3
PPh3
Ph
Fn
Pd
OTf
Ph P
3
Ph3P
Pd
Ph2P
TfO
PPh3
Fn
Fn
Fn
PPh3
Ph
Ph3P
Ph2P
OTf
Pd
Pd
OTf
Ph3P
PPh3
PPh3
Pd(PPh3)2
PPh3 OTf
2 PPh + Ar-OTf
Ph P-Ar + Ph POTf
2 4
3
Fn
Figure 1. Suggested mechanism for palladium catalysed phosphination
exchange occurs by reductive elimination between PdꢀAr with triphenylphosphine to give a
1
8
phosphonium salt, which subsequently undergoes CꢀP bond oxidative addition with Pd(0) to
generate the coordinated phosphine product, and phenyl–palladium species. Finally, ligand
substitution affords the functionalised phosphine and reductive elimination of palladium bound
phenyl group with triphenylphosphine regenerates the catalytic active Pd(0) species and
Ph POTf which was isolated in 72% yield (Fig. 1). In fact, the aryldiphenylphosphine was
4
observed as the major product and only a trace amount of diarylphenylphosphine was detected
by GC–MS analysis with extended reaction time. Therefore, arylphenylphosphination by further
exchange is very slow.
In conclusion, a variety of functionalised phosphines were prepared by palladium catalysed
phosphination of aryl triflates using economical triarylphosphines as the phosphinating agent.
This methodology tolerated many functional groups including ketone, aldehyde, ester, nitrile,
methoxy and pyridyl groups.
Acknowledgements
We thank the Research Grants Council of Hong Kong (MF/rgcgrant/rgccav/564/98) for
financial support.

10289
References
1
2
. Kosolapoff, G. M.; Maier, L. Organic Phosphorus Compounds, Vol. 1, Wiley-Interscience: New York, 1972.
. (a) Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayaashi, H.; Taketomi, T.; Akutagawa, S.; Noyori,
R. J. Org. Chem. 1986, 51, 629–631. (b) Takaya, H.; Akutagawa, S.; Noyori, R. Org. Synth. Coll. Vol. VIII 1993,
5
7–62.
. (a) Cai, D.; Payack, J. F.; Bender, D. R.; Hughes, D. L.; Verhoeven, T. R.; Reider, P. J. J. Org. Chem. 1994, 59,
180–7181. (b) Cai, D.; Payack, J. F.; Bender, D. R.; Hughes, D. L.; Verhoeven, T. R.; Reider, P. J. Org. Synth.,
Coll. Vol. 76, 1999, 6–11. (c) Herd, O.; Hebler, A.; Machnitzki, P.; Tepper, M.; Stelzer, O. Catalysis Today 1998,
2, 413–420.
3
7
4
4
5
6
. Ager, D. J.; East, M. B.; Eisenstadt, A.; Laneman, S. Chem. Commun. 1997, 2359–2360.
. Tunney, B. H.; Stille, J. K. J. Org. Chem. 1987, 52, 748–753.
. For recent references, see: (a) Gelpke, A. E. S.; Kooijman, H.; Spek, A. L.; Hiemstra, H. Chem. Eur. J. 1999, 5,
2
472–2482. (b) Ding, K.; Wang, Y.; Yun, H.; Liu, J.; Wu, Y.; Terada, M.; Okubo, Y.; Mikami, K. Chem. Eur.
J. 1999, 5, 1734–1737. (c) Vyskocil, S.; Smrcina, M.; Hanus, V.; Polasek, M.; Kocovsky, P. J. Org. Chem. 1998,
3, 7738–7748. (d) Martorell, G.; Garcias, X.; Janura, M.; Sa a´ , J. M. J. Org. Chem. 1998, 63, 3463–3467. (e)
6
Bringmann, G.; Wuzik, A.; Vedder, C.; Pfeiffer, M.; Stalke, D. Chem. Commun. 1998, 1211–1212.
. Lipshutz, B. H.; Buzard, D. H.; Yun, C. S. Tetrahedron Lett. 1999, 40, 201–204.
. Garrou, P. E. Chem. Rev. 1985, 85, 171–185.
. For mechanistic studies of Pdꢀaryl/P-aryl exchange using stoichiometric amount of palladium complexes, see: (a)
Kong, K. C.; Cheng, C. H. J. Am. Chem. Soc. 1991, 113, 6313–6315. (b) Goodson, F. E.; Wallow, T. I.; Novak,
B. M. J. Am. Chem. Soc. 1997, 119, 12441–12453. (c) Grushin, V. V. Organometallics 2000, 19, 1888–1900.
7
8
9
10. For the first synthetic application, see: (a) Kwong, F. Y.; Chan, K. S. Organometallics 2000, 19, 2058–2060. (b)
Kwong, F. Y.; Chan, K. S. Chem. Commun. 2000, 1069–1070.
1
1
1. Triphenylphosphine was used as received and without recrystallisation.
2. (a) Hoots, J. E.; Rauchfuss, T. B.; Wrobleski, D. A. Inorg. Synth. 1982, 21, 175–177. (b) Schiemenz, G. P.;
Kaack, H. Leibigs. Ann. Chem. 1973, 1494–1497.
13. (a) Chou, W. N.; Pomerantz, M. J. Org. Chem. 1991, 56, 2762–2769. (b) Schiemenz, G. P.; Siebeneich, H. U.
Chem. Ber. 1969, 102, 1883–1886. (c) Aexandrovich, P. S.; DeMejo, L. P.; Jadwin, T. A.; Wilson, J. C. US Patent
4
,837,394.
1
1
1
1
1
4. Hu, W. H.; Chen, C. C.; Xue, G. P.; Chan, A. S. C. Tetrahedron: Asymmetry 1998, 9, 4183–4192.
5. Francio, G.; Faraone, F.; Leitner, W. Angew. Chem., Int. Ed. 2000, 39, 1428–1430.
6. Unpublished results.
7. Amatore, C.; Jutand, A.; M’Barki, M. A. Organometallics 1992, 11, 3009–3013.
8. (a) Hinkle, R. J.; Stang, P. J.; Kowalalski, M. H. J. Org. Chem. 1990, 55, 5033–5036. (b) Kowalalski, M. H.;
Hinkle, R. J.; Stang, P. J. J. Org. Chem. 1989, 54, 2783–2784. (c) Migita, T.; Nagai, T.; Kiuchi, K.; Kosugi, M.
Bull. Chem. Soc. Jpn. 1983, 56, 2869–2870.
.