Solvent-free palladium-catalyzed phosphination of aryl bromides and triflates with triphenylphosphine

Article abstract of DOI:10.1016/S0040-4039(02)00582-8

Palladium-catalyzed phosphination of substituted aryl bromides and triflates using triphenylphosphine as the phosphinating agent was developed using solvent-free conditions. This operationally simple method tolerates ketone, aldehyde, ester, nitrile and e

Full text of DOI:10.1016/S0040-4039(02)00582-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3537–3539
Solvent-free palladium-catalyzed phosphination of aryl bromides
and triflates with triphenylphosphine
Fuk Yee Kwong, Chi Wai Lai and Kin Shing Chan*
Department of Chemistry, Open Laboratory of Chirotechnology of the Institute of Molecular Technology for Drug Discovery and
Synthesis,† The Chinese University of Hong Kong, Shatin, Hong Kong
Received 6 November 2001; revised 12 March 2002; accepted 21 March 2002
Abstract—Palladium-catalyzed phosphination of substituted aryl bromides and triflates using triphenylphosphine as the phosphi-
nating agent was developed using solvent-free conditions. This operationally simple method tolerates ketone, aldehyde, ester,
nitrile and ether functional groups. © 2002 Elsevier Science Ltd. All rights reserved.
Solvent-free chemical synthesis has received much
attention recently.1,2 Solvent-free processes are not only
environmentally benign but also economical.3 Since
solvent is not required, toxic wastes can be minimized
or eliminated and so the cost of solvent and waste
treatment is reduced. Furthermore, operational simplic-
ity is an attractive feature. Recent advances in this area
include, for example, aldol4 and related reactions,5
asymmetric-catalyzed addition6 and catalyzed cross-
coupling reactions.7
mides. The triflates reacted faster by 50–80% pre-
sumably due to having a better leaving group.10
Nonaflates(ONf)11 reacted at a similar rate and gave
similar yields to the triflates (Table 1, entry 5). Other
functional groups, such as aldehydes, esters, nitriles and
methyl ethers, are tolerant to this phosphination reac-
tion without the need of protecting groups12 (Table 1).
Even sterically more hindered ortho-substituted triflates
reacted (Table 1, entries 15 and 17). The (2-
cyanophenyl)diphenylphosphine product (Table 1,
entry 17) is an important starting material for the
synthesis of the optically active phosphinooxazoline
P,N ligands of the Pfaltz type.13 Nearly the same rate
was observed for electronically different non-coordinat-
ing aryl bromides or triflates (Table 1, entries 1, 2, 8
and 9). The reactions of coordinating substrates which
contained ester, aldehyde and nitrile groups (Table 1,
entries 3 and 6), required longer reaction times for aryl
bromides. Presumably the strongly coordinating sub-
strates rendered the complex coordinatively saturated
and hence with reduced catalytic efficiency.
Aryl phosphines are an important class of ligands in
transition metal-catalyzed reactions. We have recently
reported that aryl bromides8 and triflates9 are converted
into the corresponding aryl phosphines/arsines by palla-
dium-catalyzed phosphination or arsination9 with tri-
aryl phosphines or triphenylarsine without the need of
air-sensitive reagents or catalysts. We now report the
results of an improved, operationally simple catalyzed
phosphination in solvent-free conditions.
The results of this solvent-free phosphination are
shown in Table 1. The prototype substrates of 4-bro-
moacetophenone and 4-acetylphenyl triflate were
reacted with 2.3 equiv. of triphenylphosphine in the
presence of 10 mol% palladium acetate catalyst at
115°C for 1.5 days and 1 day to yield 4-(diphenylphos-
phino)acetophenone in 44 and 40% yields, respectively
(Table 1, entries 1 and 2). Consistent with earlier
reports,8,9 aryl triflates are more reactive than bro-
The rate of the reaction was nearly the same for the
bromides but much slower for the triflates in a manner
consistent with the reactions carried out in DMF.8,9
The yields of the products were, however, slightly
higher.8,9 Since anhydrous DMF and air-sensitive start-
ing materials are not required, the reaction is opera-
tionally simple and user-friendly.
A plausible mechanism for this solvent-free phosphina-
tion is similar to our earlier suggested one.8,9 Pd(OAc)2
is reduced in situ by triphenylphosphine to Pd(0).14
* Corresponding author. E-mail: ksc@cuhk.edu.hk
† The University Grants Committee Area of Excellence Scheme
(Hong Kong).
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00582-8

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F. Y. Kwong et al. / Tetrahedron Letters 43 (2002) 3537–3539
Table 1. Catalytic, solventless phosphination of aryl bromides, triflates and nonaflate
2.3 eq. PPh3
10 mol% Pd(OAc)2
X
PPh2
115 oC
Fn
Fn
solvent-free
X = Br, OTf
Entry
Substrate
X
Product
Time/d
%Yield
O
O
1
2
X = Br
X = OTf
1.5
1.0
44
40
X
X
PPh2
PPh2
O
O
3
4
5
X = Br
X = OTf
X = ONf
2.5
1.5
1.5
40
42
43
MeO
MeO
6
7
X = Br
X = OTf
2.5
1.0
38
38
NC
X
X
X
X
NC
PPh2
PPh2
PPh2
PPh2
1.0
0.8
33
26
8
9
X = Br
X = OTf
MeO
OHC
MeO
OHC
2.5
2.5
40
42
10
11
X = Br
X = OTf
2.5
1.5
34
38
12
13
X = Br
X = OTf
OHC
OHC
14
15
X = Br
X = OTf
After 7 days, no reaction
3.5 27
X
OMe
X
PPh2
OMe
PPh2
16
17
X = Br
X = OTf
After 7 days, no reaction
2.5 37
CN
CN
Subsequent oxidative addition with an aryl bromide or
triflate yields an aryl Pd(II) species. Reductive elimina-
tion with triphenylphosphine then gives an aryl-
triphenylphosphonium salt15 which undergoes oxida-
tive addition of a CꢀP bond16 with the palladium
species to generate the coordinated phosphine product.
Finally ligand substitution by triphenylphosphine
regenerates the Pd(0) species and substituted phos-
phine product.
needed to determine the physical state of the reaction
to gain further understanding of the solvent-free
phosphination.
In conclusion, an operationally simple and environ-
mentally benign solvent-free catalyzed phosphination
of aryl bromides and triflates with triphenylphosphines
has been developed.
Experimental procedure: 4-Bromoacetophenone (100
mg, 0.5 mmol), Pd(OAc)2 (11 mg, 0.05 mmol) and
PPh3 (301 mg, 1.15 mmol) were placed in a Teflon
stopcock flask. The flask was then evacuated and re-
filled with nitrogen three times. The mixture was
heated to 115°C and the reaction was monitored by
GC MS or TLC. After completion, the reaction mix-
ture was cooled down and the crude product was
purified by column chromatography on silica gel using
a solvent mixture of hexane/ethyl acetate (20/1) as the
eluent to give 4-(diphenylphosphino)acetophenone in
44% yield as white solids.
The exact physical state of the reaction is not clear at
this stage. The reaction occurs either in the molten or
solid state. While the reaction took place at 110°C,
Ph3P with a melting point of 80°C, is a liquid while
tetraphenylphosphonium salts melt above 160°C.15
However, the intermediate aryltriphenylphosphonium
salt and aryldiphenylphosphine may be in the solid or
liquid state depending on substituents. The reaction
mixture did appear to be in the solid state by visual
inspection. The reaction might occur in the interfacial
molten state.17 However, further experiments are

F. Y. Kwong et al. / Tetrahedron Letters 43 (2002) 3537–3539
3539
Acknowledgements
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The work described in this paper was supported by the
Areas of Excellence Scheme established under the Uni-
versity Grants Committee of the Hong Kong Special
Administrative Region, China (Project No. [AoE/P-10/
01]).
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