Benign Perfluoroalkylation of Aniline Derivatives through Photoredox Organocatalysis under Visible-Light Irradiation

Article abstract of DOI:10.1002/ejoc.201501189

In this work, we present a room- or solar-light-initiated transition-metal-free radical homolytic aromatic substitution (HAS) reaction of aniline derivatives with perfluoroalkyl moieties employing perfluoroalkyl halides as readily available perfluoroalkyl

Full text of DOI:10.1002/ejoc.201501189

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201501189
Benign Perfluoroalkylation of Aniline Derivatives through Photoredox
Organocatalysis under Visible-Light Irradiation
Sebastián Barata-Vallejo,[a] Damian E. Yerien,[a] and Al Postigo*[a]
Keywords: Radical reactions / Organocatalysis / Photocatalysis / Perfluoroalkylation / Aromatic substitution
In this work, we present a room- or solar-light-initiated tran-
sition-metal-free radical homolytic aromatic substitution
(HAS) reaction of aniline derivatives with perfluoroalkyl moi-
eties employing perfluoroalkyl halides as readily available
perfluoroalkyl sources in the presence of cesium carbonate
as base and inexpensive Rose Bengal as organophotocatalyst
in MeCN as solvent, rendering perfluoroalkyl-substituted
aniline derivatives in good-to-excellent yields, even upon
scaling up. Although the mechanism of this reaction is still
under investigation, we shall present some evidence based
on competitive substitution rate experiments that cast some
light onto the reaction intermediates.
Introduction
tion (HAS).[6] The HAS reaction with the CF3 group has
been well documented;[7] however, fewer examples have
been reported for HAS perfluoroalkylation.[8–11] HAS reac-
tions with perfluoroalkyl groups can be performed by two
methods: thermal and photoinduced. Thermal methods can
make use of transition-metal catalysis[12–16] and several per-
fluoroalkyl sources (Figure 1) or else be non-metal-cata-
lyzed: the use of the Baran reagent[17] or perfluoroalkyl sulf-
inate salts[18] in the presence of organic peroxide[19] or azo
initiators[20] (Figure 1) yield perfluoroalkyl-substituted ar-
enes efficiently. Also electrophilic perfluoroalkylating rea-
gents in the presence of metals effect C–H bond radical
substitutions with Rf groups.[15,21]
The aniline moiety is well-represented in pharmaceuti-
cals with a large array of activities. For instance, sulfa drugs
are a well-known class of antibacterial agents containing N-
substituted sulfonamide groups at the para position of an
aniline ring (NH2ArSO2NHR). Recently, halogenated de-
rivatives of N-substituted-4-aminobenzenesulfonamides, as
well as triazine sulfa drug derivatives, have shown remark-
able activity towards carbonic anhydrase isozymes[1,2] and
anticancer activity[3] as well. Compounds such as anilino
enaminones have found applications as potential anticon-
vulsant agents, and the fluoro, trifluoromethyl, and trifluor-
omethoxy derivatives have shown substantially enhanced
activity.[4] Also, largely prescribed anesthetics such as pro-
caine and benzocaine contain aminoaromatic functionali-
ties.
The introduction of a fluoroalkyl moiety into a pharma-
cophore is often known to increase its activity, resistance
to oxidation, and lipophilicity/bioavailability. However, it is
now widely accepted that compounds with certain func-
tional groups, such as anilines and hydrazines, have a much
greater associated risk towards formation of reactive metab-
olites in drug candidates than compounds that do not con-
tain such “structural alerts”. The incorporation of fluoro-
alkyl moieties into anilino substrates[5] can therefore be con-
ceived to hamper the formation of these metabolites as a
result of their unwillingness to undergo oxidation.
One general strategy to achieve fluoroalkyl-group substi-
tution is the radical homolytic aromatic substitution reac-
[a] Universidad de Buenos Aires,
Figure 1. Methods for C–H (HAS) radical perfluoroalkylation of
arenes.
Facultad de Farmacia y Bioquímica,
Departamento de Química Orgánica,
Junin 954, CP1113 Buenos Aires, Argentina
E-mail: apostigo@ffyb.uba.ar
Photoinduced methods, either through direct homolysis
of X–CnF2n+1 bonds[22,23] or by means of photoinduced
electron transfer (PET) reactions,[24] are capable of generat-
ing perfluoroalkyl radicals CnF2n+1 even in aqueous sys-
http://www.ffyb.uba.ar/
Supporting information and ORCID(s) from the author(s) for
this article are available on the WWW under http://dx.doi.org/
10.1002/ejoc.201501189.
Eur. J. Org. Chem. 2015, 7869–7875
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
7869

S. Barata-Vallejo, D. E. Yerien, A. Postigo
SHORT COMMUNICATION
tems[25] (Figure 1). Since the pioneering work of MacMillan ane as solvent at 100 °C, as shown in entry 1, Table 1, to
in the trifluoromethylation reactions of arenes by using afford a 30% combined yield of 4-perfluorobutylaniline (1)
transition-metal organophotocatalysts,[26] only a few re- and 2-perfluorobutylanilne (2) at a 1/2 ratio of 70:30. The
ports on the photocatalytic perfluoroalkylation of arenes reaction employing Na2CO3 (entry 2, Table 1) does not
have been documented.[27]
yield any product. The reaction of aniline and n-C4F9I car-
Among the reported synthetic methods described to ob- ried out in the absence of cesium carbonate in 1,4-dioxane
tain perfluoroalkyl-substituted anilines by HAS reactions, as solvent at 100 °C did not yield a substitution product
the CuI oxide-[29] and the zinc-SO2-mediated methodolo- (Table 1, entry 3). Varying the cesium salt (entry 4), the base
gies[30a,30b] afford 2- and 4-substituted perfluoroalkyl anil- (entry 5), the solvent (entries 6–8), the stoichiometry (en-
ines in moderate yields in organic solvents.[30c] These meth- tries 9, 10), or the temperature (entry 11) led to a sluggish
ods, however, lack in regioselectivity and employ harsh re- substitution of the ring with a perfluorobutyl group and
action conditions.
recovery of the starting material. Prolonging the reaction
We have employed the PET protocol in the past to effect times (entry 12) of the substitution reaction has little or no
the HAS reaction on activated aromatic amines to synthe- effect on the yield of product. The reaction of aniline,
size Ar–Rf, in water or in aqueous organic solvent mix- Cs2CO3, and n-C4F9I in 1,4-dioxane without deoxygenation
tures.[22] Compounds such as N,N-dimethylaminoaromatic (entry 13) also yields the substituted aniline, demonstrating
substrates efficiently substitute a ring H-atom by a perfluo- that air does not suppress the radical initiation and/or prop-
roalkyl group. We have postulated a PET mechanism[22] be- agation. Inspection of the crude reaction mixtures (i.e.,
tween the excited aromatic amine and n-C4F9I, which af- those from entries 1, 9, and 12, in Table 1, for example)
fords a radical ion pair (the radical cation of the amine and reveals that the methodology compromises substrate integ-
the radical anion of RfX), from which C4F9 radicals are rity, as substantial oligomeric material is formed under the
obtained, which ultimately substitute the ring systems. reaction conditions, and the mass balance is not complete
However, the PET substitution reaction of secondary and (ca. 63%).
primary aromatic amines with perfluoroalkyl moieties is
We then attempted the reaction of aniline with n-C4F9I
very sluggish, probably due to deprotonation of the re- in the presence of quercetin (Q) as photocatalyst (PC) in
sulting radical cations,[31,32] which divert the aromatic-ring MeCN as solvent in room light (60 Watt fluorescent light
Rf group substitution pathways.[33]
bulb), obtaining substitution products in 25% yield (entry
The perfluorobutylation of isonitriles leading to the syn- 14, Table 1). Encouraged by this result, we used other PCs,
thesis of Rf–phenanthridines by employing Cs2CO3 accord- such as Rose Bengal (RB)[34] (entry 15, Table 1) and eosine
ing to Scheme 1 has recently been reported.[28]
Y (EO) (entry 19, Table 1), and obtained good substitution
yields with the former (52% yield of combined 1 and 2).
However, when we added Cs2CO3 to the photocatalytic re-
action mixture of Q (entry 16, Table 1) or RB (entry 17,
Table 1), the perfluorobutylation yields improved substan-
tially, and perfluorobutyl-substituted anilines were obtained
quantitatively with RB as PC in the presence of Cs2CO3.
The illuminated reaction (60 Watt fluorescent light bulb) of
aniline and n-C4F9I in the absence of PC and in Ar-deoxy-
genated MeCN (entry 21, Table 1) affords 50% yield of
combined substitution products 1 and 2 (cf. with entry 1,
Scheme 1. Perfluorobutylation of isonitriles to form phenanthrid-
ines.
The authors[28] propose that perfluoroalkyl radicals are
generated through thermal initiation with Cs2CO3 and that
a radical anion intermediate is formed along the reaction
pathway. We hypothesized that the use of Cs2CO3 could be
modulated to achieve direct HAS reactions with Rf
groups.[28b]
We herein report a transition-metal-free and environmen-
tally benign perfluoroalkylation of aniline derivatives with
organic dyes as visible-light organophotocatalysts in the
presence of Cs2CO3.
·
Table 1), which indicates that room light initiates n-C4F9
radical production in the presence of Cs2CO3 and in the
absence of PC (a blank experiment illuminating the reaction
mixture of aniline and C4F9I in the absence of Cs2CO3 and
RB yields 5% of substitution product). The dye-photocata-
lyzed reaction without deoxygenation (entry 22, Table 1)
also affords good yields of substitution product (78%
yield). We also attempted the reaction under exposure to
solar light and obtained 91% yield of products 1 and 2 after
15 h of accumulated solar incidence (entry 23, Table 1). We
therefore chose PC RB in the presence of Cs2CO3 in Ar-
deoxygenated MeCN as solvent for the model perfluoro-
Results and Discussion
We commenced our studies by inspecting the role of butylation reaction of aniline derivatives under irradiation
[28b]
Cs2CO3
in the radical initiation process for generating from a household fluorescent light bulb. Interestingly, when
C4F9 radicals in the dark, and their reaction with aniline, we inspected the reaction rate profiles of the production of
as summarized in Table 1.
perfluorobutyl-substituted aniline isomers as a function of
The reactions were carried out in the presence of irradiation time (Figure S4, Supporting Information), we
Cs2CO3, in vessels deoxygenated with Ar, by using 1,4-diox- observed the formation of the disubstituted 2,4-bis(per-
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Eur. J. Org. Chem. 2015, 7869–7875

Benign Perfluoroalkylation of Aniline Derivatives
Table 1. Percentage yield of combined 4- and 2-perfluorobutyl-substituted aniline products 1 and 2, from 24-hour reactions of aniline
(0.2 mmol) with n-C4F9I, unless otherwise noted, or an additive salt/catalyst, in a given solvent (3 mL), under an argon atmosphere and
different reaction conditions.
Entry
[An]/[RfI]/[additive]
Additive/catalyst (0.05 equiv.)
T [°C] /cond.
Solvent system
%(1 + 2)[a]
1
2
3
4
5
6
7
8
1:3:1.5
1:3:1.5
1:3:–
1:3:1.5
1:3:1.5
1:3:1.5
1:3:1.5
1:3:1.5
1:3:3
1:3:0.75
1:3:1.5
1:3:1.5
1:3:1.5
1:3:–
Cs2CO3/–
Na2CO3/–
–/–
100/dark
100/dark
100/dark
100/dark
100/dark
100/dark
100/dark
100/dark
100/dark
100/dark
60/dark
100/dark
100/dark
r.t./hν[d]
r.t./hν[d]
r.t./hν[d]
r.t./hν[d]
r.t./hν[d]
r.t./hν[d]
r.t./hν[d]
r.t./hν[d]
r.t./hν[d]
r.t./hν[f]
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane/H2O
THF
30
–
–
Ͻ 5
Ͻ 5
–
Ͻ 5
–
CsF/–
CsF–Na2CO3/–
Cs2CO3/–
Cs2CO3/–
Cs2CO3/–
Cs2CO3/–
Cs2CO3/–
Cs2CO3/–
Cs2CO3/–
Cs2CO3/–
–/Q
MeCN
9
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane[b]
1,4-dioxane[c]
MeCN
35
16
–
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
30
20
25
52
50
98
81
62
Ͻ 5
50
78
91
–
1:3:–
–/RB
MeCN
MeCN
1:3:1.5
1:3:1.5
1:3:1.5
1:3:1.5
1:3:1.5
1:3:1.5
1:3:1.5
1:3:1.5
1:3:1.5
Cs2CO3/Q
Cs2CO3/RB
Cs2CO3/RB
Cs2CO3/EO
Cs2CO3/RB
Cs2CO3/–
Cs2CO3/RB
Cs2CO3/RB
Cs2CO3/RB
MeCN
MeCN[e]
MeCN
H2O
MeCN
MeCN[c]
MeCN
r.t./dark
MeCN
1
[a] Yields determined by H and 19F NMR integration (combined 4-C4F9, and 2-C4F9 yields para/ortho = 70:30). [b] 64-hour reaction.
[c] Without deoxygenation. [d] 60 Watt fluorescent light bulb. [e] 18-hour reaction. [f] 15-hour accumulated sunlight exposure.
fluorobutyl)aniline product 3 at the expense of the pro- scope of the photocatalytic reaction with different aniline
duction of the 2-perfluorobutylaniline (2) isomer, demon- derivatives, bearing electron-withdrawing and electron-do-
strating that the p-isomer [i.e., 4-perfluorobutylaniline (1)] nating groups at the ortho and para positions of the aniline
is formed first, and disubstitution ensues from the ortho- ring (Table 2).
C4F9-substituted aniline 2. A control of the regioselectivity
For the 2-substituted anilines with the CH3O, CH3, F,
of the photocatalytic reaction (HAS) of aniline was at- Br, and NO2 groups, major perfluorobutylated products
tempted by changing the substrate/C4F9I ratio to 3:1. How- (Table 2, products 12, 14, 15, 16, and 17, respectively) arise
ever, the p/o isomer ratio remains almost identical (i.e., from homolytic substitution at the 4-position of the ring
70:30). The reaction of aniline with n-C8F17I affords prod- with less or no substitution encountered at the 6-position
ucts 4-perfluorooctylaniline 4 and 2-perfluorooctylaniline 5 of the ring (except for F and NO2 groups, where the major
in 80% yield (4/5 = 60:40, Table 2). The reactions of sec- substitution occurs at the 6-position). Disubstitution with
ondary and tertiary aromatic amines lead to substitution the C4F9 moiety is encountered for 2-anisidine (13) (see
products 7–9 in very good yields (Table 2). Employing an- Supporting Information). For the 4-substituted aniline de-
other perfluoroalkyl source, such as I(CF2)4I, we obtained rivatives with CH3O, CH3, Br, I, and 2,4-I2 groups, major
the 4-(1,1,2,2,3,3,4,4-octafluoro-4-iodobutyl)aniline deriva- perfluoroalkyl-group substitutions take place at the 2- and
tive 10 and 2-(1,1,2,2,3,3,4,4-octafluoro-4-iodobutyl)aniline 6-positions for 2,4-I2 of the aniline ring (products 18, 19,
derivative 11 with retention of the iodine atom, in a 65:35 21, 22, and 23, respectively, Table 2). It is observed in
isomeric ratio (Table 2). No ring-closure product was en- Table 2 that the presence of halides on the aniline moiety
countered (cf. ref.[34c]). We then proceeded to evaluate the does not preclude the occurrence of a HAS reaction, and
Eur. J. Org. Chem. 2015, 7869–7875
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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7871

S. Barata-Vallejo, D. E. Yerien, A. Postigo
SHORT COMMUNICATION
Table 2. Perfluoroalkylation yields of aniline derivatives by Rose Bengal photoredox organocatalysis.
the perfluorobutylated products keep the bromine/iodine drug prescribed world-wide}, leads to product 24 in 25%
atom(s) intact (reactions of 2-bromoaniline, 4-bromoanil- yield (Table 2). The perfluorobutylation of anesthetic ben-
ine, 4-iodoaniline, and 2,4-diiodo-aniline, affording prod- zocaine (i.e., ethyl-4-amino-benzoate) leads to 45% yield of
ucts 16, 21, 22, and 23, respectively, Table 2). This is quite ethyl-4-amino-3-(1,1,2,3,3,4,4,4-octafluoro-2-methyl-
interesting, since an orthogonal reactivity is observed for butyl)benzoate 25. We attempted a large-scale (0.01 mol) re-
haloarenes, as no ipso substitution of the bromine/iodine action of benzocaine, and successfully obtained 30% yield
atom(s) is encountered under photocatalytic conditions. of 25. In order to cast some light onto the nature of the
Strong electron-withdrawing groups on anilines, such as the transition state or intermediate of the photocatalytic reac-
2-nitro group, can also render the perfluorobutylated sub- tion, we attempted to measure the ratio of rate constants
stitution product 17 (Table 2); however, the 4-nitro-aniline for the photocatalytic (RB) perfluorobutylation of anilines
derivative is unreactive even after prolonged reaction times substituted at the para-position with substituents of dif-
(Table 2). Di-C4F9-substitution is encountered for p-tolu- ferent electronic nature, such as electron-withdrawing and
idine (product 20, Supporting Information). Electron-rich electron-releasing groups.
anilines, substituted with OCH3 and CH3 groups, render
perfluorobutylated aniline derivatives in excellent yields pict the competition experiments and the relationship
(products 12, 14, 18, and 19, 81–95%). logkp-toluidine/kArNH , showing clearly that the substitution
Tables S3A and S3B in the Supporting Information de-
2
The perfluorobutylation of mefenamic acid {i.e., 2-[(2,3- reaction is accelerated by electron-donating X groups on
dimethylphenyl)amino]benzoic acid, an anti-inflammatory the aniline ring, which implies that a stabilization of the
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Benign Perfluoroalkylation of Aniline Derivatives
transition state is achieved with more electron-rich nuclei. fluoroalkyl-substituted anilines. A reaction of aniline, RB,
The reaction of N,N-dimethylaniline in the presence of 1,4- and C4F9I in MeCN monitored by turning the lamp on and
dinitrobenzene (p-DNB, a radical anion scavenger) is not off at different intervals (Figure 2) reveals that the reaction
suppressed, observing product 5 in yields as reported in is photocatalytic, and RB and light are needed through the
Table 2. The photoreaction of aniline/RB/C4F9I in the pres- entire reaction for the substitution product to accumulate.
ence of TEMPO does not yield the substitution product.
Instead, the TEMPO-C4F9 adduct is obtained, indicating
the intervention of C4F9 radicals. The negative result ob-
tained with p-DNB does not rule out the intermediacy of a
radical anion, as this latter could be very short-lived. A pos-
·
sible mechanism would take into account the C4F9 radical
attack at an electron-rich position of the aniline derivative,
generating a C4F9-substituted cyclohexadienyl-type radical
A, which upon deprotonation by the base (PT, Cs2CO3) af-
fords a radical anion of the C4F9-substituted product B.
The fate of this radical anion could be: (1) dissociation (in
the case of Ar–I–·),[35] (2) electron transfer (ET) to n-I–C4F9
(to propagate the chain) and thermoneutral product C, or
(3) ET to the substrate (chain termination), as shown in
Scheme 2.
Figure 2. Plot of % product vs. irradiation time. The lamp is kept
off for the shaded areas. (᭿) % of isomer 1, (᭹) % of isomer 2, (᭡)
% of disubstitution.
A mechanism such as that proposed in Figure 3, where
Scheme 2. Proton-transfer/electron-transfer (PT/ET) mechanism
a positively charged intermediate/transition state develops,
for the re-aromatization.
would account for these differences in reaction rates. Room-
However, we observed acceleration of the C4F9-substitu- light excitation of PC RB leads to RB*, which transfers an
·
tion reaction rates of anilines bearing electron-donating electron to n-C4F9I, generating C4F9 radicals and the radi-
groups (Tables S3A and S3B, Supporting Information), cal cation of RB·+[36] (Figure 3).
which indicates that, in addition to the enthalpy factor for
The ground and excited redox states of RB, an electron-
the formation of Ar–Rf bonds (A, Scheme 2), there seems transfer mediator, are important for the formation of the
·
to be a substituent effect on the rates of formation of per- electron-deficient perfluorobutyl radical (C4F9 ), which
Figure 3. Proposed mechanism for the RB-photocatalyzed perfluoroalkylation of aniline derivatives.
Eur. J. Org. Chem. 2015, 7869–7875
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7873

S. Barata-Vallejo, D. E. Yerien, A. Postigo
SHORT COMMUNICATION
functions as an oxidant of the substrate and an active spe- complex (PC/Cs2CO3/RfI), the substrate, and the RfX de-
cies for the formation of perfluorobutylated anilines. The pendence.
photoinduced downhill electron transfer from the excited
state of RB* to C4F9I (RB*, excited state singlet energy ES
= 2.17 eV, excited state triplet energy ET = 1.8 eV,[37a,37b] in
Conclusions
·
MeCN) is expected to efficiently generate the C4F9 and
We have developed a photocatalytic CAr–Rf bond forma-
RB·+ radical cations on the basis of their redox potentials
tion reaction (HAS) with an inexpensive organic dye, Rose
(ERB·+
= –0.68 V vs. SCE in MeCN,[37b] EC F I/C F
·
=
/RB*
–1.27 V[37c]), the ΔGET for this process is –1.53 4eV, which
suggests a quite favorable spontaneous ET (see Table S4,
Supporting Information). The expectation that an electron
from C4F9I is turned over during the photocatalytic elec-
tron-transfer cycle is based solely on the driving force pre-
dicted by the redox potentials (vide supra, Table S4, Sup-
porting Information). At this stage, no detailed mechanistic
data on the twofold reaction of aniline with C4F9· are avail-
able, but it is rationally considered that a likely reaction
9
4
9
Bengal, in the absence of transition metals, through irradia-
tion at ambient temperature with a household fluorescent
light bulb (visible light) or under exposure to solar light
and with use of readily available perfluoroalkyl iodides.
This method was applied to the synthesis of a variety of
perfluoroalkyl-substituted aniline derivatives, and work is
in progress towards the application of this methodology to
other families of organic compounds such as heteroarom-
atic compounds. As far as we know, this is the first report
on a high-yielding, almost quantitative perfluoroalkylation
reaction of aniline derivatives in which a photoredox
organocatalyst functions as an ET reductant.
·
pathway includes the radical addition of C4F9 to an elec-
tron-rich position of the aniline moiety, generating interme-
diate A (Figure 3), which is followed by oxidation to the
Wheland intermediate B (rate-determining step). This is
supported by the acceleration of the substitution reactions
of anilines bearing electron-donating groups. This proposal
(A Ǟ B C4F9I oxidation) can propagate the chain. Depro-
tonation (PT, Figure 3) affords the perfluorobutyl-substi-
tuted aniline derivative. Markovic and collaborators[38] have
found that the radical cation of the PC quercetin, Q·+, will
spontaneously be transformed into Q in the presence of
bases whose HOMO energies are higher than the SOMO
energy of Q·+ in a given medium, implying that Q cannot
undergo the ET/PT mechanism which would lead to the
quercetin radical (Q·) and a proton (H+). Therefore, it is
proposed that, in our photocatalysis by Q (entries 14, 16,
Table 1), Q·+ accepts an electron from the base (Cs2CO3)
and therefore forms thermoneutral Q (regenerating the
Experimental Section
General Procedure for the Perfluoroalkylation Reaction: A mixture
of the aniline derivative (0.6 mmol), RfX (3 equiv.), photocatalyst
(0.05 equiv.), and Cs2CO3 (1.5 equiv.) in Ar-deoxygenated MeCN
(3 mL) was irradiated (24 h) with a fluorescent light bulb (60 Watt)
under constant stirring. The mixture was extracted with CH2Cl2/
H2O thrice, and the organic layers were gathered and dried with
anhydrous Na2SO4, filtered, reduced under vacuum, separated, and
purified by column chromatography. Detailed procedures for prep-
arations, purifications, compound characterization, and spectra can
be found in the Supporting Information.
Acknowledgments
.–/CO3
PC) and carbonate radical anion (ECO
2– = +1.23
+/–0.15 V[36a]) on the basis of the HOM3O energy of the
carbonate anion. We hypothesize that the RB·+[36b] radical
cation also accepts an electron from Cs2CO3 in a fashion
analogous to that of Q·+ to regenerate RB PC. The fact that
addition of Cs2CO3 to the photocatalytic reactions (entries
17 and 18, Table 1) significantly improved the perfluoro-
butylation yields could support the role of the base as an
electron-donor adjuvant to regenerate the catalyst. Further-
more, the photoinduced activation observed in the presence
of Cs2CO3 and in the absence of PC suggests the role of
this base as an ET (photo)mediator (entry 21, Table 1). Al-
though we have demonstrated that RB functions as a pho-
Thanks are extended to Concejo Nacional de Investigaciones Ci-
entíficas y Técnicas (Conicet) and Universidad de Buenos Aires for
financial support. S. B.-V. and A. P. are research members of Con-
icet. We also thank Dr. Lucas Fabián from IQUIMEFA-Conicet-
FfyB-UBA for acquiring 600 NMR spectra.
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that step A Ǟ B (Figure 3) also generates C4F9 radicals
must be an indication that this step is a rate-determining
step. At this point, we are confident that aniline is not act-
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Received: September 12, 2015
Published Online: November 18, 2015
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