Catalyst-Free Arylation of Tertiary Phosphines with Diaryliodonium Salts Enabled by Visible Light

Article abstract of DOI:10.1002/chem.201902955

The visible-light-induced arylation of tertiary phosphines with aryl(mesityl)iodonium triflates to produce the quaternary phosphonium salts occurs under mild, metal, and catalyst-free conditions. Photo-excited EDA complexes between diaryliodonium salts an

Full text of DOI:10.1002/chem.201902955

A Journal of
Accepted Article
Title: Catalyst-Free Arylation of Tertiary Phosphines with
Diarylodonium Salts Enabled by Visible Light
Authors: Dmitry I. Bugaenko, Alexey A. Volkov, Mikhail V. Livantsov,
Marina A. Yurovskaya, and Alexander Karchava
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To be cited as: Chem. Eur. J. 10.1002/chem.201902955
Link to VoR: http://dx.doi.org/10.1002/chem.201902955
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Catalyst-Free Arylation of Tertiary Phosphines with
Diarylodonium Salts Enabled by Visible Light
Dmitry I. Bugaenko, Alexey A. Volkov, Mikhail V. Livantsov, Marina A. Yurovskaya, Alexander V.
Karchava*[a]
Abstract: The visible-light-induced arylation of tertiary phosphines
with aryl(mesityl)iodonium triflates to produce the quaternary
phosphonium salts occurs under mild, metal, and catalyst-free
conditions. Photo-excited EDA-complexes between diaryliodonium
salts and phosphines supposedly enable this transformation, that is
difficult to achieve through the traditional ground-state reactions.
Demonstrating high functional group tolerance, broad scope, and
complete selectivity of the aryl group transfer, particularly the method
is compatible with sterically congested phosphines, which are
challenging under metal-based catalytic methods.
arylphosphonium cation. Moreover, these compounds have found
application in a variety of industrially relevant areas, serving as
corrosion inhibitors,[8a] conjugated polyelectrolytes,[8b] electron
transporting materials,[8c] nonlinear optical chromophores,[8d] ionic
liquids,[8e] and antimicrobial polymeric materials.[8f]
Metal-free reactions of diaryliodonium salts are of great
practical importance as they can be used as an alternative to the
"traditional" metal-based cross-coupling reactions, thereby
eliminating heavy-metal-related issues (high cost, toxicity,
residues, etc.).[1] Initial association between a diaryliodonium salt
and a nucleophile typically produces an electron-donor-acceptor
(EDA) complex (Scheme 1), that can occasionally be isolated or
detected by spectroscopy.[1,2] The EDA-complex, normally under
thermal activation, undergoes a concerted ligand coupling at the
I(III)-center, delivering an arylation product and an iodoarene.[1]
Alternatively, the EDA-complexes could serve as photon-
absorbing species that enable the further transformation to occur
under visible light irradiation without any exogenous
photosensitizer. In this scenario, excitation of the EDA-complexes
by harvesting light induces an intrasystem single electron transfer
(SET), eventually generating aryl radicals.[3] While metal-free
arylation with diaryliodonium salts under thermal activation
represents a powerful methodology developed in the last
decade,[1] only few examples of synthetically useful light-induced
reactions of these reagents have been reported to date.[4]
However, the photo-induced reactions are of high interest
because they could provide transformations that are impossible
or difficult to occur through the traditional thermal reactions.
Quaternary phosphonium salts are an important class of
organophosphorus compounds whose applications have been
extended well beyond the classic Wittig olefination and phase-
transfer catalysis (Figure 1A).[5] Organocatalysts,[6a] arylating[7]
and other practically useful reagents[6b] include an
Scheme 1. Metal-free arylation with diaryliodonium salts: thermal and photo
activation modes.
Furthermore, delocalized lipophilic arylphosphonium cations
can readily pass through the lipid bilayer of the cell membrane
and accumulate within mitochondria inside cells.[9] Introducing an
arylphosphonium moiety into biomolecules to make them
“mitochondriotropic”[9b] is currently a widely used strategy for
developing of mitochondria-targeted drugs, agents for imaging,
probes, and sensors.[5,9]
Commonly
employed
methods
toward
quaternary
arylphosphonium salts from tertiary phosphines are based on
Pd-,[10] or Ni-catalyzed[11] arylations with haloarenes and a photo-
redox-reaction with diaryliodonium salts mediated by a Ru-based
photosensitizer (Figure 1B).[12] While mainly effective, these
methodologies raise issues related to the high cost of catalysts
and trace toxic metal contaminations present in the end products,
which limits their industrial and biomedical applications.[13]
Furthermore, multi-halogenated and sterically congested
substrates are challenging for the metal-catalyzed assembly of
CAr–P-bond.[10,11] Among metal-free methods are quaternization
with arynes[14] and the recently developed hydrogen-bonding-
assisted reaction with bromoarenes.[15] However, the
regioselectivity problems inherent to the former and high
temperature required in the latter substantially limit these
[a]
D. I. Bugaenko, A. A. Volkov, Ass. Prof. Dr. M. V. Livantsov, Prof.
Dr. M. A. Yurovskaya, Ass. Prof. Dr. A. V. Karchava
Department of Chemistry, M. V. Lomonosov Moscow State
University
methodologies.
A
highly specific metal-free method for
introducing the Ph3P-moiety on the pyridine ring has also been
developed recently.[7c] Although quaternary arylalkylphosphonium
salts are traditionally available via alkylation reaction, both active
alkylating agents and
119234 Moscow, Russia
E-mail: karchava@org.chem.msu.ru
Supporting information for this article is given via a link at the end of
the document.
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at different positions of the phenyl ring in 44–94% yields and with
excellent selectivity of the aryl group transfer. The reaction
exhibits a good functional group compatibility; methyl (2d-f, k),
trifluoromethoxy (2j), trifluoromethyl (2l,m), cyano (2p),
methoxycarbonyl (2q), sulfamide (2s), nitro (2k,r) groups and the
pyridine ring (2t) were well tolerated. Halo-substituted
phosphonium salts 2n,o could also be obtained in good yields,
which would be challenging using most current methods.[17]
Remarkably, ortho-substituted iodonium salts, regardless of the
electronic nature of the substituents, were successfully reacted
giving 2e,k,l in 85–90% yields. For all aryl(mesityl)iodonium salts
tested, aryls with substituents of different electronic nature are
exclusively transferred, while the mesityl group serves as a
"dummy" group. Notably, the reaction required prolonged
irradiation time to reach synthetically useful yields when electron-
rich aryls were transferred (2b,f,g,i). Arylation with 4-
methoxyphenyl(mesityl)iodonium triflate (1i) produced 2i as the
only detectable outcome, though in a moderate (44%) yield
achieved in 5h. When di(mesityl)iodonium triflate (1f) was
employed, however, 2f was obtained in 72% yield despite the
steric
hindrance.
Reaction
of
(pyridine-3-yl)(4-
methoxyphenyl)iodonium triflate (1t) gave 2t exclusively in 87%
yield. The chemoselectivity observed allows us to assume the
reaction shows electronic preferences, suggesting that the more
electron-deficient aryl group should be transferred. Considering
the result obtained for 1i, however, one could conclude that steric
interactions probably also contribute to the reaction outcome,
though do not prevent the reaction from occurring.
Figure 1. Examples of useful molecules featuring arylphosphonium moiety (A),
current status of methods for arylation of tertiary phosphines (B).
sterically innocent phosphines are normally required for the
reaction to proceed with high efficiency.[16]
We report here on the employing aryl(mesityl)iodonium triflates,
bearing a variety of substitution patterns, for a broadly applicable
visible-light-driven arylation of tertiary phosphines under mild,
metal-, and photocatalyst-free conditions. The new protocol
circumvents the above issues and is suitable for the late-stage-
diversification of tertiary phosphines to make valuable quaternary
arylphosphonium salts.
We began our investigation by exploring the reaction of
Ph(Mes)IOTf (1a) and Ph3P under different conditions (Scheme
2).[17] When 1a and Ph3P were reacted in a 1:1.5 ratio in MeCN at
80 °C for 12 h a poor conversion was observed and the expected
Ph4POTf (2a) was obtained in only 19% yield. Inspired by an early
report from Reutov and co-workers[18a] and other isolated
reports,[12,18b] we next examined the ability of light to drive the
reaction to full conversion. After evaluating a wide set of reaction
parameters,[17] we found that 90% yield of 2a was achieved when
1a (1 equiv) and Ph3P (1.5 equiv) in MeCN were irradiated with a
6 W blue LED (400–410 nm) for 2 h at. Importantly, arylation with
1a lead to the exclusive formation of 2a; while a transfer of the
mesityl-group is also possible, the corresponding phosphonium
salt was not detected.
After establishing the optimal reaction conditions, we applied
this new protocol to a series of substituted aryl(mesityl)iodonium
triflates 1a-t having diverse electronic and steric effects (Scheme
3A). A variety of 1a-t reacted smoothly with Ph3P, producing the
corresponding aryltriphenylphosphonium triflates bearing either
electron-donating (2b–2i) or electron-withdrawing (2k–2s) groups
Scheme 2. Selected optimization results. [a] Yields by 1H NMR, isolated yield
in parentheses.
Our next challenge was to apply this method to different tertiary
phosphines (Scheme 3B). All tested phosphines reacted
efficiently delivering 2u–z in 66–91% isolated yields. Importantly,
tert-butyl[bis(o-tolyl)]phosphine readily produced 2x in 91% yield,
highlighting the utility of the developed method for arylation of
sterically demanding phosphines in sharp contrast to the previous
metal-based protocols.[17] Notably, the steric hindrances do not
necessitate to alter the established reaction conditions.
Additionally, arylation of other organophosphorus (III) compounds,
namely phosphinous and phosphonous amides, also lead
smoothly to 2aa,bb in 86% and 71% isolated yields respectively
with no traces of the N-quaternization products. Conversely, 2aa
was formed in only 17% yield with a low conversion of starting
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Scheme 3. Scope of the reaction. [a] (Pyridine-3-yl)(4-methoxyphenyl)iodonium triflate (1t) was used.
materials when a mixture of reagents was refluxed in MeCN for
12 h,[17] thereby highlighting the difference between ground- and
excited-state reactions of the EDA-complex.
Combining the above results and literature precedents, we
propose the following rationale for the reaction (Scheme 5).
Initially, the interaction between a tertiary phosphine and an
aryl(mesityl)iodonium salt leads to the formation of an EDA-
complex, serving as a photo-absorbing species. This complex is
characterized by only a weak absorption band; however, it has
been previously reported that the strong absorption of an EDA-
complex is not mandatory for a successful reaction induced by
visible light.[19] Next, an excited EDA-complex is formed upon
photo-irradiation. The following single electron transfer from the
phosphorous atom to the iodonium center brings about
decomposition of the above complex to form the aryl radical and
the phosphorous radical cation with the simultaneous elimination
of MesI. Eventually, combination the above radical species leads
to the resulting phosphonium salts. In the presence of oxygen, the
excited EDA*-complex changes its duty and acts as an energy
transfer (EnT) agent.[20] The energy transfer process occurs
between the excited EDA*-complex and triplet oxygen 3O2 to give
a singlet oxygen 1O2., which reacts with Ph3P finally furnishing
Ph3PO as the product.[21] The addition of Co(acac)3, a singlet
oxygen quencher,[22] completely suppresses the formation of
Ph3PO [Eq. (5), Scheme 4], thereby supporting our assumption
on the key role of 1O2 in this oxidation process.
To obtain information about the reaction mechanism we
performed several experiments (Scheme 4). Mixing starting
compounds in different combinations and ratios did not result in
the appearance of the EDA complex that could be determined by
1H or 31P NMR. In a UV-Vis experiment, however, the mixture of
1p and Bu3P (1:1) exhibited a weak but notable absorption
between 350 and 450 nm compared to the separated
compounds,[17] which can be attributed to the formation of the
EDA-complex. The addition of TEMPO (1 equiv) completely
suppressed the formation of 2a, implying that this reaction
involved radical pathway [Eq. (1)]. In this case, similarly to the
reaction performed under air conditions (Scheme 2c), Ph3PO was
produced as the main product, with 1a being quantitatively
recovered. Importantly, neither air nor TEMPO were able to
oxidize Ph3P to Ph3P=O in the absence of 1a under otherwise
identical conditions [Eq. (2, 3)]. However, loading even only 0.1
equiv of 1a gave Ph3P=O in 13% yield after 5 h, and in 51% yield
after 15 h irradiation [Eq. (4)], thus pointing to the key role of 1a
in the oxidation process. Notably, 1a turned out fully stable upon
exposure to visible light under both argon and air atmosphere [Eq.
(6, 7)]. Irradiation of a mixture of iodobenzene and Ph3P (3 equiv)
did not lead to the phosphonium salt in any detectable amount
[Eq. (8)]. Finally, an on/off visible-light-irradiation experiment
demonstrated that the continuous irradiation is necessary for the
reaction completion.[17]
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In summary, we have developed a general method for
producing quaternary arylphosphonium salts employing a visible-
light-driven reaction of aryl(mesityl)iodonium triflates and tertiary
phosphines. The possibility of introducing aryl groups of different
electronic and steric nature and applicability to sterically
congested tertiary phosphines are the features of this protocol. In
contrast to thermal reaction, the photo-induced transformation
occurs with good to excellent yields under mild, metal- and
catalyst-free conditions with an exceptional selectivity of the aryl
group transfer governed by electronic factors.
Acknowledgements
D.I.B. thanks the Russian Foundation of Basic Research (Grant
No. 18-33-01100) for partial support of this work. The NMR
equipment used in this research was purchased under the
Moscow State University Program of Development. Thermo
Fisher Scientific, MS Analytica (Moscow, Russia) and Professor
A. Makarov (Thermo Fisher Scientific) are acknowledged for
providing the MS equipment.
Scheme 4. Control experiments.
Keywords: diaryliodonium salts • hypervalent compounds •
phosphonium salts • photochemistry• synthetic methods
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Dmitry I. Bugaenko, Alexey A. Volkov,
Mikhail V. Livantsov, Marina A.
Yurovskaya, Alexander V. Karchava*
Page No. – Page No.
Catalyst-Free Arylation of Tertiary
Phosphines with Diaryliodonium
Salts Enabled by Visible Light
Just a light is enough! Arylation of tertiary phosphines with aryl(mesityl)iodonium
salts occurs under visible light irradiation without any catalyst or additives. The new
protocol allows for an easy access to valuable quaternary arylphosphonium salts,
bearing substituents of different electronic and steric nature, including those
challenging to current catalytic methods.
This article is protected by copyright. All rights reserved.
[a]
D. I. Bugaenko, A. A. Volkov, Dr. M. V. Livantsov, Prof. Dr