Synthesis of quaternary aryl phosphonium salts: Photoredox-mediated phosphine arylation

Article abstract of DOI:10.1039/c6cc00556j

We report a synthesis method for the construction of quaternary aryl phoshonium salts at ambient temperature. The regiospecific reaction involves the coupling of phosphines with aryl radicals derived from diaryliodonium salts under photoredox conditions.

Full text of DOI:10.1039/c6cc00556j

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: R. M. Denton, J.
An, A. Fearnley, M. Jackson and P. Lindovska, Chem. Commun., 2016, DOI: 10.1039/C6CC00556J.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/chemcomm

Please do not adjust margins
ChemComm
Page 1 of 4
View Article Online
DOI: 10.1039/C6CC00556J
ChemComm
COMMUNICATION
Synthesis of Quaternary Aryl Phosphonium Salts: Photoredox-
Mediated Phosphine Arylation
Received 00th January 20xx,
Accepted 00th January 20xx
a*
A. F. Fearnley, J. An, M. Jackson, P. Lindovska and R.M. Denton
DOI: 10.1039/x0xx00000x
www.rsc.org/
1
1
We report a synthesis method for the construction of subsequently revisited by Kampmeier, could meet the above
1
2
quaternary aryl phoshonium salts at ambient temperature. criteria. The latter non-preparative
mechanistic study
The regiospecific reaction invovles the coupling of corroborated a redox radical chain process involving aryl and
1
3
14
phosphines with aryl radicals derived from diaryliodonium phosphoranyl radicals and, despite being overlooked since,
salts under photoredox conditions.
suggested that a synthetically useful phosphine arylation
reaction could be developed. Herein we report a photoredox-
initiated arylation reaction between aryliodonium salts and
phosphines under ambient reaction conditions (Scheme 1C).
Quaternary phosphonium salts are a fundamentally important
class of organophosphorus compounds, which have been
1
applied as synthesis reagents phase-transfer catalysts, ionic
2
3
4
5
liquids, anti-cancer agents as well as in drug delivery. More Figure 1. A and B Current methods for phosphine arylation. C This study:
photoredox-initiated phosphine arylation using diaryliodonium salts.
recently, phosphonium salts have begun to be explored as
6
Lewis acids as a result of their low lying
σ
* orbitals, opening
up an exciting new class of organocatalysts.
(A) Transition metal-catalysed coupling
Despite this diverse range of applications methods for the
construction of aryl-substituted phosphonium salts are limited.
7
Transition metal-mediated couplings of phosphines and aryl
Ar
(dba)
X
Ar
Pd
2
3
1 mol%
P
X
R1
R
3
xylenes, 125 o
C
P
R3
R1
R2
R2
halides, such as the palladium-catalysed reactions reported by
7
b,c
Charette and co-workers (Scheme 1A)
,
are known but
(B) Arylation via aryne intermediates
TMS
typically take place at high temperatures. An important
alternative method was recently reported by Juge and co-
workers (Scheme 1B) and involves the interception of in situ-
R4
Ar
OTf
OTf
P
3
P
R1
R
R3
MeCN, room temp.
R1
R2
R2
8
generated arynes with phosphines at room temperature. This
(C) THIS WORK: radical arylation
method is limited somewhat by the availability of 2-
(
trimethylsilyl)aryl triflates and poor the regioselectivities
X
I
Ar1
Ar2
6H
obtained during the coupling of unsymmetrical arynes with
phosphines.
Ar
Ru(bipy)
3
Cl
2
2
O
P
X
R1
R3
P
visible light
MeCN, room temp.
R1
R
3
R2
With these limitations in mind we sought a method that
could be conducted at ambitent temperature and was
regiospecific with respect to carbon-phosphorus bond
formation. We reasoned that the arylation of tervalent
R2
We began by establishing a new method for the initiation
of the putative radical chain at ambient temperature under
1
5
photoredox conditions. To this end the combination of visible
light with Ru(bpy) Cl was explored (Table 1). Gratifyingly, the
9
organophosphorus compounds with iodonium salts, first
1
reported by Reutov and co-workers in 1965
3
2
0
and
photo-redox initiated arylation of triphenylphosphine with
diphenyliodonium triflate (entry 1) gave the corresponding
phosphonium salt in good conversion. Next, the analogous
reaction without the 10W lamp was investigated (entry 2) and
gave a much-reduced 23% conversion. The arylation reaction
did proceed in the presence of visible light without
Ru(bpy)
entry 3).
3
Cl
2
, albeit more slowly (12% conversion after 20 mins,
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please d Co hn eo mt aC d oj um s mt margins
Page 2 of 4
View Article Online
DOI: 10.1039/C6CC00556J
Journal Name
COMMUNICATION
Table 1. Survey of initiation methods.
Table 2. Scope of the arylation reaction.
OTf
Ph
I
OTf
I
Ar
Ph
initiator
Ar1
2
6H O 2 mol%
Ph
P
Ar
P
Ru(bipy)
3
Cl
2
OTf
OTf
P
P
Ph
Ph
Ph
R3 10 W lamp, MeCN, room temp.
Ph
Conversion
R1
R3
MeCN, room temp.
R
1
Ph
Ph
2
R2
R
1
a
2
Entry
1
Initiator
mol%)
10 W lamp
Ru(bpy) Cl
mol%
Time
(min)
20
Isolated
yield (%)
Entry
Product
(
PPh
19
3
PPh
10
3
O
PPh
73
4
Ph
3
2
OTf
Ph
1
2
2a
2b
P
85
74
2
Ph
Ph
Ph
2
3
4
Ru(bpy)
mol%
3
Cl
2
20
71
84
100
0
6
23
12
0
OTf
Ph
P
2
Me
Ph
Ph
Ph
OTf
10 W lamp
None
20
6
N
3
4
2c
P
82
57
Ph
Ph
OTf
120
0
P
2d
MeO
OMe
5
AIBN (80 °C) 240
50
50
1
0 mol%
31
Determined via P NMR analysis of the crude the reaction mixture.
OMe
Ph
a
OTf
P
Finally, in the absence of both ruthenium and visible light
entry 4) no conversion to phosphonium salt was obtained
5
6
2e
69
F
F
(
after 120 minutes. These experiments demonstrate that
Ru(bpy) Cl in combination with visible light from a 10 W lamp
serve as an effective radical initiator in this system at ambient
F
3
2
Ph
OTf
P
1
6
temperature. For comparison initiation using AIBN proved to
o
be less efficient (entry 5) giving 23% conversion at 80 C after
2f
51
Cl
Cl
two hours. Having established that the combination of
Cl
Ph
Ru(bpy)
3
Cl
2
and visible light was effective for initiating a
OTf
Ph
radical-based coupling reaction we proceeded to examine the
scope of this room temperature arylation protocol.
P
7
8
9
2g
2h
2i
63
65
71
Cl
N
We began by arylating a range of triarylphosphines with
diphenyliodonium triflate (Table 2, entries 1,3,4,5 and 6) to
Ph
afford the corresponding phosphonium salts
2
in moderate to
OTf
Ph
P
excellent isolated yield following flash chromatography and
recrystallization. The arylation of methyldiphenylphosphine
Ph
Cl
Cl
Ar
P
(entry 2) was also efficient.
OTf
Ar
Next we sought to prepare further phosphonium salts
Ar
bearing functional groups that would facilitate further
transformations after arylation. To this end we prepared two
chlorophenyl(mesityl)iodonium triflates and carried out
arylation reactions with a range of phosphines (entries 7-11).
The phosphonium salt products were obtained in good to
moderate yields and are suitable for further functionalization
Ar=4-fluorophenyl
Ar
OTf
P
Ar
1
0
2j
57
46
Ar
Cl
Ar=4-methoxyphenyl
7
b
Ph
via cross coupling. In each case selective transfer of the
7
chlorophenyl group over the mesityl group was observed.
Cl
OTf
P
1
11
2k
Ph
Ph
In summary the arylation protocol provides access to a
range of functionalised aryl phosphonium salts under ambient
conditions.
a
Typical procedure: iodonium salt (1.0 equiv, 0.7-0.8 mmol), phosphine (1.5
equiv) and Ru(bpy) Cl •6H O (10 mol%). Yields are for isolated phosphonium
salts following normal phase flash chromatography and recrystalisation.
3
2
2
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 2
Please do not adjust margins

Page 3 of 4
Please d Co hn eo mt aC d oj um s mt margins
View Article Online
DOI: 10.1039/C6CC00556J
Journal Name
COMMUNICATION
Ru(bipy) initiated pathway
3
Ph
P
(A)
(B)
2+
[
Ru(bipy)3]
Ph
I
Ph
visible
light
P
Ph
R3
R1
R3
R1
R2
R2
Ph
Ph
PhI
Ru(bipy)3] 2+*
[
P
R3
I
OTf
R1
R2
Ph
P
(
C)
Ph
[
Ru(bipy)3] 1+
P
Ph
P
Ph
P
I
OTf
R1
R3
R1
R3
R3
R1
R2
R2
R2
Ph
Background arylation reaction
(D)
P
R1
R
3
Ph
I
OTf
Ph
visible light
R3
Ph
I
OTf
Ph
OTf
Ph
Ph
I
R1
P
R2
R3
R1
R2
R2
C.T. complex
Scheme 1. Plausible pathways for the arylation process.
In terms of the mechanism our experimental observations, as
Ph
I
OTf
Ph
1
8
Ph
1 equiv.
O 2 mol%
Ph
well as those of others are consistent with the pathways
depicted in Scheme 1 Visible light-induced excitation of
Ru(bpy) Cl results in population of the excited state, which is
reductively quenched by the phosphine resulting in the
Ph
P
.
OTf
Ph
Ru(bipy) Cl
3
2
6H
2
P
(
A)
Ph
Ph
Ph
3
2
10 W lamp, MeCN, 30 min
Ph
Ph
room temp.
1
6% conversion
1
9
corresponding phosphoniumyl radical cation. The derived
ruthenium (I) species now reduces the iodonium salt, resulting
in fragmentation to afford an aryl radical and iodobenzene as a
by-product. Formation of the product phosphonium salt can
now occur through two pathways. Either, the phosphoniumyl
radical cation combines with the phenyl radical (Scheme 1B),
or a radical chain process intervenes (Scheme 1C). The radical
chain reaction involves addition of a phenyl radical to
triphenylphosphine to afford an intermediate phosphoranyl
3 2 2
Ru(bipy) Cl 6H O 2 mol%
(B) Ph
I
OTf
Ph
X
Ph
I
PhH
10 W lamp, MeCN, 60 min
room temp.
NEt 1 equiv.
3
3 2 2
Ru(bipy) Cl 6H O 2 mol%
(
C) Ph
I
OTf
Ph
Ph
I
PhH
1
0 W lamp, MeCN, 30 min
room temp.
>95% conversion
1
3
radical. Subsequent oxidation of this radical by the iodonium
salt affords the phosphonium salt product and propagates the
radical chain. Support for above proposal comes the following
experiments depicted in Scheme 2. An arylation reaction
conducted in the presence of 1,1-diphenylethylene resulted in
significantly reduced conversion to the product phosphonium
Ph
I
OTf
Ph
Ru(bipy) Cl 6H O 2 mol%
Ph
OTf
P
P
3
2
2
Ph
Ph
(D)
Ph
Ph
Ph
Ph
10 W lamp 3 min
MeCN, 20 min
room temp.
2
6% conversion
salt (16% compared to 73% under standard conditions, entry 1 Scheme 2. Experiments corroborating the pathways depicted in Scheme 1.
Table 1). This is consistent with covalent trapping of phenyl
radicals, as is the production of increased amounts of Ru(I)-mediated reduction of the iodonium salt depicted in
triphpenylphosphine oxide from the reaction of the Scheme 1A. Finally, an arylation reaction in which irradiation
2
0
intermediate phosphoniumyl radical cation with water.
Secondly, diphenyliodonium triflate is stable with respect to suggests that the arylation process is weighted more towards
was stopped after 3 minutes resulted in 26% conversion. This
2
1
reductive fragmentation in the presence of Ru(bpy)
visible light (Scheme 2B). This rules out an alternative
photoredox initiation involving oxidative quenching of excited but absence of Ru(bipy)
ruthenium(II) by the iodonium salt. In a third experiment this arylation proceeds through a charge transfer complex
Scheme 2C) diphenyliodonium triflate was converted into (Scheme 1D) from which electron transfer from phosphine to
3
Cl
2
and Scheme 1B than the radical chain process (Scheme 1C) .
The reaction also proceeds in the presence of visible light
(Table 1, entry 3). We speculate that
3
9
f
(
iodobenzene and benzene in the presence of Ru(bpy)
3
Cl
2
and iodonium salt may occur in the presence of visible light to
provide the phosphoniumyl radical cation and phenyl radical.
triethylamine. These two observations are congruent with the
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please d Co hn eo mt aC d oj um s mt margins
Page 4 of 4
View Article Online
DOI: 10.1039/C6CC00556J
Journal Name
COMMUNICATION
In conclusion we have developed synthesis method for the
construction of aryl-substituted phosphonium salts under mild
8
E. Redmund, A.R. Leroux, J. Bayardon, S. Juge, Org. Lett. 2010, 12,
conditions. This protocol opens up a valuable new route to 1568.
9
For reviews, see (a) M.S. Yusubov, A.V. Maskaev, V.V. Zhdankin,
Arkivoc, 2011, 380; (b) V. V. Zhdankin and P.J. Stang, Chem. Rev.
008, 108, 5299; (c) E. A. Merritt and B. Olofsson, Angew. Chem.,
Int. Ed. 2009, 48, 9052. For relevant examples, see (d) S.R. Neufeldt,
M.S. Sanford, Adv. Synth. Catal. 2012, 354, 3517; (e) Y.-X. Liu, D.
Xue, J.-D. Wang, C.-J. Zhao, Q-Z. Zou, C. Wang and J. Xiao, Synlett
functionalised aryl phosphonium salts and demonstrates the
2
2
utility of photoredox-mediated arylation reactions in the
area of organophosphorus chemistry.
2
Notes and references
We are grateful to Dr. Mick Cooper, Graham Coxhill, Shazad
2
013, 24, 507; (f) M. Tobisu, T. Furukawa and N. Chatani, Chem.
Aslam and Kevin Butler for analytical support.
Lett. 2013, 42, 1203; (g) J. Heng, Y. Cheng, R. Wang, Y. Zhang and S.
Yu, Chem. Commun. 2014, 50, 6164; (h) G. Fumagalli, S. Boyd, and
1
(
a)R.W. Hoffman, Angew. Chem. Int. Ed. 2001, 50, 1411; (b) L.K. M. F. Greaney, Org. Lett., 2013, 15, 4398.
1
0
Hwang, Y. Na, J. Lee, Y. Do, S. Chang, Angew. Chem. Int. Ed. 2005,
A. Ptitsyna, M.E. Pudwva, A. Reutov, Dokl. Akad. Nauk SSSR, 1965,
4
4, 6166.
166, 582.
2
11
For a recent reviews, see (a) D. Enders, T.V. Nguyen, Org. Biomol.
J.A. Kampmeier and T.W. Nalli, J. Org. Chem. 1993, 58, 943.
This mechanistic study involved two substrates, namely,
1
2
Chem. 2012, 10, 5327; (b) K. Manabe, Tetrahedron Lett., 1998, 39,
807; (c) R. He, K. Maroua, Synthesis, 2009, 13, 2289; (d) C.-L. Zhu, triphenylphosphine and trimethylphosphite. The reactions were
F.-G. Zhang, W. Meng, J. Nie, D. Cahard, J.-A. Ma, Angew. Chem. Int. non-preparative and conducted in NMR tubes.
5
1
3
Ed. 2011, 50, 5869; (e) S. Shirakawa, A. Kasai, T. Tokuda, K.
Maruoka, Chem. Sci. 2013, 4, 2248; (f) S. Shirakawa, T. Tokuda, A. Chem. Res. 1982, 15, 117.
For a review on phosphoranyl radicals, see W.G. Bentrude, Acc.
1
4
Kasai, K. Marouka, Org. Lett. 2013, 15, 3350; (g) B. Wang, Y. Liu, C.
Sun, Z. Wei, J. Cao, D. Liang, Y. Lin, H. Duan, Org. Lett. 2014, 16, and P-OH bonds using iodonium salts, see (a) J. Xu, P. Zhang, Y. Gao,
432.
Y. Chen, G. Tang, and Y. Zhao, J. Org. Chem., 2013, 78, 8176; (b) B.
a) H. Coa, L. McNamee, H. Apler, J. Org. Chem. 2008, 73, 3530. (b) Xiong, X. Feng, L. Zhu, T. Chen, Y. Zhou, C.T. Au and S-F. Yin, ACS
For recent related coupling reactions involving arylation of P-H
6
3
(
J. McNulty, A. Capretta, J. Wilson, J. Dyck, G. Adjabeng, A.J.J. Catal., 2015, 5, 537; (c) M. Fañanás-Mastral and B.L. Feringa, J. Am.
Robertson, Chem. Soc., Chem. Commun. 2002, 1986; (c) D.A. Chem. Soc. 2014,136, 9894; (d) Y. He, H. Wu and F.D. Toste, Chem.
Gerritsma, A.J. Robertson, J. McNulty, A. Capretta, Tetrahedron Sci., 2015, 6, 1194.
1
5
Lett. 2004, 45, 7629; (d) J. McNulty, A. Capretta, S. Cheekoori, J.A.C.
For selected reviews, see (a) K.P. Prier, D.A Rankic and D.W.C.
Clyburne, A. Robertson, J. Chemica Oggi 2004, 22, 13; (e) J. MacMillan, Chem. Rev., 2013, 113, 5322; (b) Y. Xi, H. Yi and A. Lei,
McNulty, S. Cheekoori, J.J. Nair, V. Larichev, A. Capretta, A.J. Org. Biomol. Chem., 2013, 11, 2387 and (c) J.W. Tucker and C.R.J.
Robertson, Tetrahedron Lett. 2005, 46, 3641; (f) J. McNulty, J.J. Nair, Stephenson, J. Org. Chem. 2012, 77, 1617.
1
6
S. Cheekoori, V. Larichev, A. Capretta, A.J. Robertson, Chem. Eur. J.
Given the proximity of the lamp to the reaction vessel the
2
006, 12, 9314; (g) J. McNulty, S. Cheekoori, T.P. Bender, J.A. internal temperature was monitored and found to be 32 °C. A
Coggan, Eur. J. Org. Chem. 2007, 9, 1423; (h) J. McNulty, J.J, Nair,
further 1 h control experiment between Ph P and Ph IOTf at 32 °C
3
2
A.J. Robertson, Org. Lett. 2007, 9, 4575.
resulted in the formation of Ph
3
PO (6 %) and Ph
4
POTf (3%) with 92%
4
(
a) D.C. Rideout, T. Calogeropoulou, J.S. Jworksi, R. Dagnino, R.M.
of Ph P remaining.
3
1
7
McCarthy, Anti-Cancer Drug Des. 1989, 4, 265; (b) D.C. Rideout, A.
Bustmante, J. Patel, Int. J. Cancer, 1994, 57, 247.
The selective transfer of electron deficient aryl groups over the
relatively electron rich mesityl group has been observed previously
non-catalysed nucleophilic arylation reactions, see (a) J. Malmgren,
S, Santoro, N, Jalalian, F. Himo and B. Olofsson, Chem. Eur. J. 2013,
5
R.A.J. Smith, C.M. Porteous, A.M. Gane, M.P. Murphy, Proc. Natl.
Acad. Sci. USA, 2003, 100, 5407.
6
For reviews, see: (a) T. Werner, Adv. Synth. Catal. 2009, 351, 1469;
1
2
9, 10334; (b) S. K. Sundalam and David R. Stuart , J. Org. Chem.
015, 80, 6456. We observed no arylation between
(b) J.M. Bayne and D.W. Stephan, Chem. Soc. Rev.,
DOI:10.1039/C5CS00516G. For recent examples, see (c) N. Dunn ,
M.Ha and A. Radosevich, J. Am. Chem. Soc. 2012, 134, 11330; (d) L.
J. Hounjet, C. B. Caputo and D. W. Stephan, Angew. Chem. Int. Ed.
triphenylphosphine and 4-methoxyphenyl(mesityl)iodonium triflate
under the reaction conditions depicted in Table 2.
1
8
R. Muneer and T.W. Nalli, Macromolecules, 1998, 31, 7976
1
9
2012, 51,4714; (e) C. B. Caputo, L. J. Hounjet, R. Dobrovetsky and
For recent work involving phoshonium radical cations, see K.D.
D.W.Stephan, Science 2013, 341,1374; (f) M. Pérez, L. J. Hounjet, C.
B. Caputo, R. Dobrovetsky and D.W.Stephan, J.Am. Chem. Soc. 2013
Reichl, D.H. Ess, and A.T. Radosevich, J. Am. Chem. Soc. 2013, 135,
0354.
9
2
,
135, 18308; (g) M. Perez, C. B. Caputo, R. Dobrovetsky and
For electrochemical generation of the trimesityl phosphoniumyl
D.W.Stephan, Proc. Natl. Acad. Sci. 2014, 111, 10917; (h) M. Pérez,
T. Mahdi, L.J. Hounjet and D.W. Stephan, Chem. Comm., 2015, 51,
radical and subsequent reaction with water to afford the
corresponding phosphine oxide, see: B. Merzougui, Y. Berchadsky
and P. Tordo, G. Gronchi, Electrochimica Acta 1997, 42, 2445.
1
1301; (i) T. vom Stein, M. Pérez, R. Dobrovetsky, D. Winkelhaus,
C.B. Caputo and D.W. Stephan, Angew. Chem. Int. Ed., 2015 54,
0178; (j) J.M. Bayne, M.H. Holthansen and D.W. Stephan, Dalton
2
1
We are grateful to a reviewer for suggesting this experiment.
There are several other methods for the generation of aryl
2
2
1
Trans. 2015, 44, 12256-12264
For a recent review on transition-metal catalyzed C-P cross
coupling, see (a) F.M.J. Tappe, V.T. Trepohl, M. Oestreich, Synthesis,
radicals under photoredox conditions, for example from diazonium
salts, see (a) H. Cano-yelo and A. Deronzier, J. Chem. Soc., Perkin
Trans. 2, 1984, 16, 1093; (b) H. Cano-yelo and A. Deronzier,
Tetrahedron Lett. 1984, 25, 5517; (c) D. Kalyani, K.B. McMurtrey,
S.R. Neufeldt and M.S. Sanford, J. Am. Chem. Soc., 2011, 133,
7
2010, 18, 3037; (b) D. Marcoux, A.B. Charette, J. Org. Chem. 2008,
73, 590; (c) D. Marcoux, A.B. Charette, Adv. Synth. Catal. 2008, 350,
2967. For Ni-mediated coupling, see (d) L. Horner, G. Mummenthey,
1
8566. It is likely that further arylation reactions of tervalent
H. Moser, and P. Beck, Chem. Ber. 1966, 99, 2782.
phosphorus compounds will be developed along these lines.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 4
Please do not adjust margins