Combining photoredox and silver catalysis for azidotrifluoromethoxylation of styrenes

Article abstract of DOI:10.1039/c8cc01096j

The first example of an azidotrifluoromethoxylation of styrenes has been achieved by synergistic visible-light-mediated photoredox and silver catalysis. Trifluoromethyl arylsulfonate (TFMS) and the Zhdankin reagent were used as the trifluoromethoxylation reagent and the azide source, respectively. A good functional group tolerance and mild reaction conditions of this method are applicable to late-stage azidotrifluoromethoxylation of complex small molecules. Furthermore, the mechanistic investigations indicate the single-electron transfer involved in the reaction.

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Combining Photoredox and Silver Catalysis for
Azidotrifluoromethoxylation of Styrenes
Cite this: DOI: 10.1039/x0xx00000x
Fei Cong, ‡ Yongliang Wei‡ and Pingping Tang*a
Received 00th January 2012,
Accepted 00th January 2012
The first example of an azidotrifluoromethoxylation of styrenes has been achieved by synergistic visibleꢀ
lightꢀmediated photoredox and silver catalysis. Trifluoromethyl arylsulfonate (TFMS) and the Zhdankin
reagent were used as the trifluoromethoxylation reagent and azide source, respectively. A good
functional group tolerance and mild reaction conditions of this method is applicable to lateꢀstage
azidotrifluoromethoxyaltion of complex small molecules. Furthermore, the mechanistic investigations
indicate the singleꢀelectron transfer involved in the reaction.
DOI: 10.1039/x0xx00000x
www.rsc.org/
The incorporation of a trifluoromethoxy group (OCF3) into drugs of styrenes with a photoredox system and transition metal catalysis.
and agrochemicals has received much attention due to its strongly Inspired by recent studies that •N3 was generated from the Zhdankin
electronꢀwithdrawing nature and high lipophilicity.1 Therefore, great reagent (3) with photoredox catalyst,12 we hypothesized that the
efforts have been devoted to the development of new methods for merger of visibleꢀlight photocatalysis (to generate •N3) with silver
the synthesis of trifluoromethyl ethers.2 Recently, photoredox catalysis (to generate reactive AgOCF3 species)9 might provide a
catalysis employing visible light has emerged as a valuable platform mild and general method for the azidotrifluoromethoxylation of
for the synthesis of fluorinated compounds.3 However, methods for styrenes.
Our
initial
investigations
focused
on
the
the synthesis of trifluoromethyl ethers by photoredox catalysis azidotrifluoromethoxylation of 4ꢀvinylbiphenyl in the presence of
remain extremely rare, due to the reversible decomposition of photoredox catalyst and silver salts with TFMS (2) and Zhdankin
trifluoromethoxide anion and limited trifluoromethoxylation reagent (3). As briefly illustrated in Table 1, the use of a photoredox
reagents.4 To the best of our knowledge, only two methods have
Table 1. Optimization of the reaction conditions. a
been reported by Ngai and coꢀworkers for the construction of
trifluoromethoxylated aromatic compounds by photoredox catalysis.5
Herein,
we
reported
the
first
example
of
an
azidotrifluoromethoxylation of styrenes by synergistic visibleꢀlightꢀ
mediated photoredox and silver catalysis under mild reaction
conditions, with trifluoromethyl arylsulfonate (TFMS)2v,9 and the
Zhdankin reagent6 as the trifluoromethoxylation reagent and azide
source, respectively.
The traditional methods for the trifluoromethoxylation of alkenes
have been achieved using trifluoromethyl hypofluorite or
trifluoromethyl hypochloride.7 However, the toxic and potential
explosiveness of these reagents are major drawbacks. Recently,
palladiumꢀcatalyzed intramolecular aminotrifluoromethoxylation
and intermolecular ditrifluoromethoxylation of unactivated alkenes
with AgOCF3 as the trifluoromethoxylation reagent was reported by
Liu and coꢀworkers.8 With the TFMS, our group has reported an
asymmetric silverꢀcatalyzed bromotrifluoromethoxylation of
alkenes.9 Although the progress has been made for the synthesis of
trifluoromethyl ethers from alkenes, methods for the
trifluoromethoxylation of alkenes are limited. Furthermore, the
merger of photocatalysis and transition metal catalysis (termed
metallaphotocatalysis) has recently received much attention as a
versatile platform for new methods development,10 and no example
was reported for trifluoromethoxylation with metallaphotocatalysis.
Entry
1
Photocatalyst
fac-Ir(ppy)3
Silver salts
AgF
Yield(%)d
2
2
2
[Ir(ppy)2(dtbbpy)](PF6)2
Eosin Y
AgF
3
AgF
0
4
Fluorescein
AgF
0
5
[Ru(bpz)3](PF6)2
[Ru(phen)3](PF6)2
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
none
AgF
0
6
AgF
36
52
5
7
AgF
8
AgOTf
AgOAc
AgF
9
39
63
1
10b
11
12
13c
none
AgF
2
[Ru(bpy)3](PF6)2
AgF
0
Therefore, the development of
trifluoromethoxylation of alkenes by metallaphotocatalysis is highly
desirable.
a
new method for the
a General conditions: 1a (0.05 mmol), 2 (0.15 mmol), 3 (0.10 mmol),
photocatalyst (1 mol%) , silver salts (50 mol%), tBu3tpy (30 mol%), degassed
CH3CN, 10 °C, 4 h, 14 W blue LED. b 5.0 equiv of TFMS (2) was used. c In
the dark, temperature is 60ºC. d Yields were determined by 19F NMR with
benzotrifluoride as a standard.
Considering the importance of the azide group as a stable
precursor of amines,11 we envisioned an azidotrifluoromethoxylation
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Table 2. Substrate scope for Ag/Ruꢀcatalyzed azidotrifluoromethoxylation of styrenes a
a Reaction conditions: 1 (1.0 equiv), 2 (2.0 equiv), 3 (5.0 equiv), [Ru(bpy)3](PF6)2 (1 mol%) , AgF (50 mol%), tBu3tpy (30 mol%), CH3CN, N2 atmosphere, 10
°C, 4 h, 14 W blue LED. Yields of isolated products are given. tBu3tpy = 4,4',4''ꢀtriꢀtertꢀbutylꢀ2,2':6'2''ꢀterpyridine.
catalyst is crucial for achieving an efficient transformation in the revealed that product 4a could be obtained in the highest yield when
presence of AgF, and [Ru(bpy)3](PF6)2 was found to give the highest the reaction of 1a was conducted with 1.0 mol% [Ru(bpy)3](PF6)2,
yield (entries 1ꢀ7). Changing the photocatalyst to facꢀIr(ppy)3, 50 mol% AgF and 30 mol% tBu3tpy, 5.0 equiv of TFMS (2), 2 equiv
[Ir(ppy)2(dtbbpy)](PF6)2 or other organic photocatalysts resulted in of Zhdankin reagent (3) in MeCN under N2 atmosphere at 10°C
less than 5% yield of desired product formation. Next, different under 14W blue LED light irradiation for four hours.
silver salts were evaluated and AgF was found to give the highest
yield (entries 7ꢀ9). A further improvement was observed when 5.0
equiv of TFMS was used (entry 10). Importantly, photoredox
catalyst, silver salt, and visible light were all critical for this
transformation. Significantly reduced yields of 4a (<1%) were
observed in the absence of these components. Also, no desired
Adopting the optimum conditions, we explored the substrate
scope of the transformation (Table 2). First, styrene derivatives 1aꢀ
1v bearing electronꢀdonating to electronꢀwithdrawing substituents on
aryl rings were successfully converted to the desired products with
isolated yields ranging from 32% to 80%. In general, styrenes with
electronꢀdonating groups gave higher yields compared to styrenes
products were found in the dark and thermal conditions (entry 11 to
with electronꢀwithdrawing groups. It was worth mentioning that
13). Finally, extensive optimization with various solvents, ligands
bulky orthoꢀsubstituents such as the mesityl derivative 1b yielded
and temperatures (See more details in the supporting information),
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the desired product 4b in 80% yield. Notably, thianaphthene When the LED lamp was switched off, the reaction didn’t proceed
analogues (1y) and quinolone analogues (1z) could be employed to during the “off” periods, which suggested the visible light was
provide the corresponding products (4y, 4z). This method could also essential. Moreover, the quantum yield of this photocatalytic
be applied to the azidotrifluoromethoxylation of an amino acid reaction was determined. The value of Φ was estimated to be 0.55.
derivative and provided the corresponding product (4bb) in 40% Furthermore, to probe the detail electron transfer among the catalyst
yield. In addition, the reaction was compatible with a good range of and substrates, a series of luminescence quenching experiments were
functionalities, including ether, ester, amide, nitrile, sulfonyl, fluoro, conducted. The Zhdankin reagent (3) is the only molecular entity in
chloro, bromo, and even iodo. Encouraged by these results, more the reaction system that quenches the excited photocatalyst.
complex substrates were employed and gave the corresponding
products (4dd to 4ff) with moderate yields. For example, artemisinin
derivative (1ff), which contains a peroxide bridge, proceeded
successfully to provide the desired product 4ff in 28% isolated yield.
Furthermore, in order to demonstrate scalability of this method, we
prepared 4a on a gram scale under the standard reaction conditions
in 67% isolated yield. The limitation of this method was that low
yields were observed with aliphatic alkenes.
Scheme 2. Mechanism studies and proposed mechanism.
Scheme 1. Further transformation of the azidotrifluoromethoxylated
products.
Based on these mechanistic studies, we proposed the mechanism
depicted in Scheme 2c, under visibleꢀlight irradiation, the
Further transformation of the azidotrifluoromethoxylated prodꢀ
photocatalyst [Ru(bpy)3]2+ is exited providing [Ru*(bpy)3]2+, which
ucts were investigated (Scheme 1). For instance, click reaction was
employed to yield trifluoromethoxylated triazole 5 in 95% yield. In
addition, the azide 4a could be reduced and protected to deliver
is then oxidatively quenched by the Zhdankin reagent (3) to deliver
an oxidizing [Ru(bpy)3]3+ and the azide radical (•N3) via single
electron transfer. The azide radical subsequently react with styrene
trifluoromethoxylated amine derivatives
7 in excellent yield.
generated a benzyl radical intermediate (A), which was further
oxidized to benzyl carbocation intermediate (B) by the [Ru(bpy)3]3+.
Concurrently, the ligated Ag(I) trifluoromethoxide, which is
generated in situ via ligated Ag(I) and TFMS (2), was intercept
benzyl carbocation intermediate (B) to give the desired product 4.
The intermediate (B) could be captured by 2ꢀiodobenzoate remaining
from the Zhdankin reagent to form the 2ꢀazidoꢀ1ꢀphenyl 2ꢀ
iodobenzoate as the major byproduct.
Furthermore, compound 8, an analogue to drug Midodrine
hydrochloride, which is a vasopressor/antihypotensive, was afforded
via the reduction of the azide and subsequent amidation. These
representative transformations demonstrated the versatilities of the
azidotrifluoromethoxylated compounds in organic chemistry.
To get some insight into the mechanism, some preliminary studies
were conducted (See more details in the supporting inforꢀmation).
Firstly, (E) and (Z)ꢀcinnamyl acetate E-9 and Z-9 were evaluated
under the standard conditions, providing the same diaꢀ
stereoselectivities (3:2) and similar yields (Scheme 2a). In addition,
Conclusions
when
2.0
equiv
of
TEMPO
was
added,
no
In conclusion, we have developed a novel silver and visibleꢀlightꢀ
mediated photoredox dualꢀcatalytic system, which has been applied
to the azidotrifluoromethoxylation of styrene with trifluoromethyl
arylsulfonate (TFMS) and the Zhdankin reagent. This new method
takes advantage of visibleꢀlight photoredox catalysis to generate the
azide radical under mild conditions and merges it with silverꢀ
catalyzed trifluoromethoxylation reaction. This method tolerates a
azidotrifluoromethoxylated product was observed, the TEMPOꢀN3
adduct 11 was isolated in 6% yield and 90% of styrene was
recovered. In the absence of TFMS, 72% yield of TEMPOꢀN3 adduct
11 was isolated (Scheme 2b).13 These results indicated that a N3
radical was involved in the reaction, and a benzyl radical species was
formed through the addition of N3 radical to styrene. To verify the
effect of photo irradiation, light/dark experiments were investigated.
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DOI: 10.1039/C8CC01096J
wide range of functional groups and is applicable to lateꢀstage
azidotrifluoromethoxylation of complex small molecules.
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