Organic semiconductor photocatalyst can bifunctionalize arenes and heteroarenes

Article abstract of DOI:10.1126/science.aaw3254

Photoexcited electron-hole pairs on a semiconductor surface can engage in redox reactions with two different substrates. Similar to conventional electrosynthesis, the primary redox intermediates afford only separate oxidized and reduced products or, more rarely, combine to one addition product. Here, we report that a stable organic semiconductor material, mesoporous graphitic carbon nitride (mpg-CN), can act as a visible-light photoredox catalyst to orchestrate oxidative and reductive interfacial electron transfers to two different substrates in a two- or three-component system for direct twofold carbon–hydrogen functionalization of arenes and heteroarenes. The mpg-CN catalyst tolerates reactive radicals and strong nucleophiles, is straightforwardly recoverable by simple centrifugation of reaction mixtures, and is reusable for at least four catalytic transformations with conserved activity.

Full text of DOI:10.1126/science.aaw3254

RESEARCH
cost of its straightforward synthesis from readily
available starting materials is only a few euros
per kg (25) (supplementary materials, materials
and methods). The available redox window upon
visible-light photoexcitation spans 2.7 V [from
approximately +1.2 V to –1.5 V versus saturated
calomel electrode (SCE) upon 460-nm illumina-
tion], and the electronic band structures can be
easily tuned through modification of the nano-
morphology or doping (13). This redox window
covers a diverse range of redox-active substrates
and is comparable to or greater than those of
widely used transition metal complexes, organ-
ic dyes, and inorganic semiconductors, such as
Ru(bpy)32+, eosin Y, and CdS, respectively (Fig. 1).
In suspension, mpg-CN is stable toward re-
active nucleophilic, electrophilic, and radical
intermediates, as well as acidic and basic con-
ditions (pH range 0 to 14) (12) and intense light
irradiation.
Figure 1 summarizes the working strategies
of arene C–H functionalizations using mpg-CN
as a heterogeneous semiconductor photocat-
alyst. In these processes, the photogenerated hole
and electron on the catalyst surface orchestrate
oxidative and reductive redox steps to yield
arene products functionalized at two distinct
C–H sites from either two or three starting
materials. We designate these reactions as type
B′ and type B″, respectively, to distinguish
them from the original process of linear radical
combinations described by Kisch (Fig. 1)
(15, 16, 18). When the substrate activation
leads to monofunctionalized arene products
by means of a coupled sacrificial redox pro-
cess, the processes are classified as oxidative
or reductive type A, depending on the redox
mode (hole or electron) for substrate activation.
Overall, these transformations include direct
one-pot dual C(sp2)–C(sp3)/C(sp2)–heteroatom
and C(sp2)–C(sp3)/C(sp2)–C(sp3) C–H function-
alizations and innate (that is, at the inherently
reactive positions) or regiospecific C(sp2)–C(sp3),
C(sp2)–C(sp2), or C(sp2)–heteroatom bond-forming
reactions resulting in the installation of more
than 20 different synthetically important func-
tionalities onto arenes and heteroarenes under
oxidative, reductive, or dual catalytic reaction
conditions, as well as in the presence of strong
nucleophiles, highly reactive sp3/sp2 C-centered
radicals, and acids or bases.
ORGANIC CHEMISTRY
Organic semiconductor photocatalyst
can bifunctionalize arenes
and heteroarenes
Indrajit Ghosh1,2, Jagadish Khamrai1, Aleksandr Savateev2, Nikita Shlapakov1,
Markus Antonietti2*, Burkhard König1*
Photoexcited electron-hole pairs on a semiconductor surface can engage in redox
reactions with two different substrates. Similar to conventional electrosynthesis, the
primary redox intermediates afford only separate oxidized and reduced products or,
more rarely, combine to one addition product. Here, we report that a stable organic
semiconductor material, mesoporous graphitic carbon nitride (mpg-CN), can act as a
visible-light photoredox catalyst to orchestrate oxidative and reductive interfacial electron
transfers to two different substrates in a two- or three-component system for direct
twofold carbon–hydrogen functionalization of arenes and heteroarenes. The mpg-CN
catalyst tolerates reactive radicals and strong nucleophiles, is straightforwardly
recoverable by simple centrifugation of reaction mixtures, and is reusable for at least four
catalytic transformations with conserved activity.
ver the past decade, transition metal com-
plexes (1–3) and organic dyes (4, 5) have
been investigated extensively as visible
light–absorbing catalysts in a wide range
of photoredox transformations (4, 6). None-
reduced catalyst. In the latter case, the reactive
catalyst intermediate may also engage in un-
wanted chemical reactions, leading to catalyst
decomposition (4, 17). The stability and the
aligned interfacial oxidation and reduction,
without the generation of reactive catalyst re-
dox intermediates, bestow semiconductor pho-
tocatalysts easy control over the primary redox
intermediates, which, depending on semicon-
ductor redox reaction modes, affords the final
product. Kisch has earlier proposed two differ-
ent semiconductor reaction modes in visible-
light photocatalysis (15, 16, 18): In semiconductor
type A photoredox reactions, the intermedi-
ates generated by oxidation and reduction
lead to two separate products, whereas in semi-
conductor type B, photocatalysis orchestrated
oxidative and reductive redox reactions, al-
lowing both intermediates to participate in
yielding the final product. However, a broader
appreciation of such semiconductor photocata-
lytic reaction modes in synthesis was attenuated
by the use of toxic metal sulfides as semicon-
ductor photocatalysts, which are photocorro-
sive (15, 19) under synthetic organic reaction
conditions, and only linear sequences of ra-
dical or radical ion addition reactions were
realized.
We report here the application of organic
semiconductor mesoporous graphitic carbon
nitride (mpg-CN) as a heterogeneous photoredox
catalyst for synthetically important functionaliza-
tions of arenes and heteroarenes. Even though
the first synthesis of mpg-CN dates back to 1834
(20), its applications as a photocatalyst have
only recently received attention, owing to its
capacity to split water under visible-light illu-
mination (12, 21, 22). The metal-free, nontoxic
(23), straw-yellow powder (24) is easily synthe-
sized in multigram quantities. Although mpg-
CN is not commercially available as of yet, the
O
theless, their use is restricted on account of in-
compatibility with strong acidic or basic reaction
media (7), strong nucleophiles, electrophiles, or
reactive radical intermediates (4) exemplified by
fac-Ir(ppy)3, which reacts with C(sp3) radicals,
leading eventually to catalyst deactivation (8, 9).
The photophysical properties of organic photo-
catalysts, such as eosin Y, drastically change with
changing pH of the solution (7), and acridinium,
triarylpyryliums, and quinolinium dyes are de-
activated in the presence of nucleophiles such
as amines, acetates, phosphates, or cyanide ions
(4, 10, 11).
Organic semiconductor materials are photo-
and chemically stable toward otherwise reactive
radicals and nucleophiles and have a suitable
bandgap between valence band maxima and
conduction band minima (12, 13) for controlled
oxidation and reduction of many practical
substrates. Light absorption by heterogeneous
semiconductor photocatalysts generates sur-
face redox centers as electron-hole pairs (14–16).
As such, a semiconductor photocatalyst, upon
photoexcitation, accomplishes two aligned re-
dox transformations on the same particle sur-
face (14–16), whereas a molecular photocatalyst,
after electron transfer to one reaction partner,
completes the overall redox process through a
subsequent redox reaction of the oxidized or
Bifunctionalization of arenes and
heteroarenes by mpg-CN
The synthetic examples of semiconductor photo-
catalytic arene C(sp2)–C(sp3)/C(sp2)–heteroatom
bifunctionalizations at two distinct C–H sites are
shown by using alkyl bromides as the source of
two different functional groups (Fig. 2). Upon
single-electron reduction, the C(sp3)–bromine
bond in alkyl bromides breaks spontaneously,
generating the relevant alkyl radical and a bro-
mide anion (26) for such bifunctionalizations. In
the presence of mpg-CN (27), blue-light irradia-
tion for 4 hours of a reaction mixture con-
taining arene and alkyl bromide [in this case,
1-phenylpyrrole and diethyl bromomalonate as
1Fakultät für Chemie und Pharmazie, Universität Regensburg,
93040 Regensburg, Germany. 2Department of Colloid
Chemistry, Max-Planck Institute of Colloids and Interfaces,
Research Campus Golm, 14424 Potsdam, Germany.
*Corresponding author. Email: markus.antonietti@mpikg.mpg.
de (M.A.); burkhard.koenig@ur.de (B.K.)
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model substrates (Fig. 2)] yielded the C(sp2)–C(sp3)
product 1a-1 and C(sp2)–Br bond-forming pro-
duct 1a-2 (Fig. 2 and fig. S10) (26, 28). Gas chro-
matography (GC)–mass spectrometry analysis
of the crude reaction mixture revealed the for-
mation of C(sp2)–C(sp3)/C(sp2)–Br bifunction-
alized product 1a. Irradiation of the reaction
mixture for longer times led to the formation of
the bifunctionalized product 1a in 63% isolated
yield, along with the formation of synthetically
important dibrominated arene (1a-3, in 27%
isolated yield) and C(sp2)–C(sp3)/C(sp2)–C(sp3)
bifunctionalized product 1a-4 as minor product
(Fig. 2). The formation of such bifunctionalized
arenes that were obtained in excellent overall
yield required only mixing of heteroarene, alkyl
bromide, and mpg-CN in dimethyl sulfoxide
(DMSO) and irradiation under nitrogen with a
blue light-emitting diode (LED). Control reac-
tions (without mpg-CN or no visible-light irradia-
tion) confirmed that photocatalysis by mpg-CN
is imperative for the formation of 1a. Although
complex, a likely mechanism for the forma-
tion of bifunctionalized product 1a involves
the initial redox-neutral C–H arene alkylation
and net oxidative bromination of the arene gen-
erating the monofunctionalized products 1a-1
and 1a-2 (chemical structures in Fig. 2), respec-
tively, which upon further redox-neutral or net
oxidative redox transformations generate the
bifunctionalized products. The net reaction,
generating the bifunctionalized product 1a,
can be viewed as the formal insertion of the
heteroarene onto a C(sp3)–Br bond releasing
dihydrogen, which, however, was not detected
in the head space GC analysis, suggesting the
role of excess diethyl bromomalonate as redox
and proton balance in the overall transforma-
tion (supplementary materials). A molecular
photocatalyst can mediate heteroarene bifunc-
tionalization reactions through the generation
of oxidized or reduced catalyst species, and we
2+
demonstrated this by using Ru(bpy)3 as a
photocatalyst yielding product 1a in approxi-
mately 40% GC yield (experimental details in
the synthetic procedures section in the supple-
mentary materials). However, the photochem-
ical reaction using eosin Y as a photocatalyst
did not give the desired product 1a. The design
of photoredox transformations using a molec-
ular photocatalyst leading to bifunctionalized
heteroarenes and the yields of the reaction
depend on the stability of the oxidized or re-
duced photocatalyst after the initial electron
transfer in the presence of different reactive
intermediates and under photoirradiation, their
respective lifetimes, and associated electron
Fig. 1. Schematic representations of semiconductor photoredox catalytic reaction modes in C–H arene functionalizations. The type B′ mode can
also combine oxidative and reductive photocatalytic steps. Chemical structure, absorption and luminescence spectra, and relative band positions and
redox potentials of mpg-CN with respect to commonly applied photocatalysts are shown.
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Fig. 2. C–H bifunctionalization of arenes
using contemporary type B′ and type B″
semiconductor photocatalysis. Het, hetarene.
transfer kinetics to substrates or intermedi-
ates. The organic semiconductor mpg-CN, upon
photoexcitation, naturally generates electron
and hole pairs, and its stability and associated
electron-hole transfer kinetics enable easy exe-
cution of such bifunctionalizations, with cat-
alyst recoverability and reuse as a practical
advantage.
Biologically relevant pyrrole derivatives con-
taining different substituents, such as haloarene,
alkyl, or –CN functionalities, were compatible
with the reaction conditions, yielding the re-
spective products (1a–1d) in moderate-good yields.
Commodity chemicals, such as bromoform,
were also applicable in these bifunctionaliza-
tion reactions, affording 1e, which contains
both an aldehyde group and a newly formed
C–Br bond.
The formation of such bifunctionalized hetero-
arenes is an exciting development in photoredox
catalysis. Although photocatalytic multitransfor-
mations have recently been attempted (29–32),
challenges remain in developing methods that
allow for a one-pot orchestrated sequential trans-
formation, as established in homogeneous me-
tal, organo-, or enzyme catalysis (33). The few
reported examples of photocatalytic tandem
and cascade reactions often involve combining
photo- and enzymatic catalysis or using cas-
cades that combine different activation modes.
Difficulties arise predominantly from poor
photocatalyst compatibility under diverse reac-
tion conditions. The mpg-CN photocatalytic pro-
tocol tolerates oxidative and reductive reaction
sequences.
synthesis (34),” the primary redox intermediates
(radicals or radical ions) that are generated by
oxidative and reductive redox steps combine
to give coupled end products. Our reaction,
described as semiconductor type B″, orches-
trated the reaction of two redox intermediates
with one arene, forming two new chemical
bonds (Fig. 2). Although the isolated yields of
the bifunctionalized products are only moder-
ate to good, the clean conversion, simple op-
eration, and facile separation and isolation of
the products recommend the mpg-CN catalyzed
arene C(sp2)–C(sp3)/C(sp2)–C(sp3) bond-forming
bifunctionalization protocol for applications
in organic synthesis. Among other investigated
substrates, ethyl bromodifluoroacetate, bromo-
acetonitrile, a-bromo-g-butyrolactone, substituted
a-bromo-g-butyrolactone, and phenacyl bro-
mide were effective precursors of functionally
important alkyl, (substituted) g-butyrolactone,
and phenacyl radicals. Reactions with these radi-
cals yielded the corresponding bifunctionalized
products 2a-g in moderate to good isolated yields
considering two new C–C bond-forming reac-
tions. Similarly, using this mpg-CN photoredox
catalytic protocol, the scope of oxidative part-
ners was easily extended, allowing installation
of medicinally relevant –CH2CF3 (2h) and di-
fluoromethyl (–CF2H, 2i) groups. The –CH2CF3
group is slightly electron withdrawing and an
The C–H bifunctionalization reaction was ex-
tended in scope to C(sp2)–C(sp3)/C(sp2)–C(sp3)
bond-forming reactions when we activated the
functional groups of different reaction partners
by means of complementary redox processes
(type B″) in a tricomponent system. In this pro-
cess, we envision arene bifunctionalizations using
two different C(sp3)-centered radicals accessed
through oxidative and reductive photoredox trans-
formations. Sodium triflinate has an oxidation
potential of approximately +1.1 V (versus SCE,
table S4) and is oxidized by photoexcited mpg-
CN, generating the CF3SO2 radical that, upon re-
leasing SO2, generates a •CF3 (trifluoromethyl)
radical. When a reaction mixture containing
arene (in this case, 1-phenylpyrrole as a model
substrate), alkyl bromide ethyl bromodifluoro-
acetate, sodium triflinate, and mpg-CN was illu-
minated using a blue LED, the twofold C–H
functionalized product 2a was obtained in 36%
isolated yield along with synthetically impor-
tant monofunctionalized products (separate
trifluoromethylated arene and alkylated arene:
fig. S12). In typical semiconductor type B photo-
catalysis (15) or in conventional “paired electro-
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excellent bioisostere of an ethyl group, and the
–CF2H group is a lipophilic hydrogen bond donor
and acts as a bioisostere for alcohol and thiol
functional groups.
substrate), mpg-CN, and the commercially avail-
able trifluoromethanesulfinic acid sodium salt
under air led to the formation of the corre-
sponding trifluoromethylated product 3a in
87% isolated yield. Trifluoromethyl radical cou-
plings to boronic acids (36) or unactivated arenes
(37, 38) are typically performed using difficult-
to-handle trifluoroiodomethane (a toxic gas)
or trifluoromethanesulfonyl chloride (a corro-
sive low-boiling liquid). These reactions are
performed under strictly inert conditions by
using transition metal catalysts. Alternatively,
sodium triflinate reactions have required an
excess of peroxides as radical initiators that
Although a detailed mechanistic picture of
these transformations remains to be elucidated,
the experimental results suggest that sodium tri-
flinate, in addition to being the source of the
•CF3 radical, competed effectively with other
oxidation processes. Irradiation of arene sub-
strates (for example, 1-phenylpyrrole and 1,3,5-
trimethoxybenzene) in the presence of only ethyl
bromodifluoroacetate yielded monofunctional-
ized C–C (examples 6d and 6a in Fig. 3) and
brominated arenes (by means of C–Br bond for-
mation; chemical structures in table S5) as se-
parate products. However, in the presence of
sodium triflinate, the bifunctionalized products
2a and 2b were obtained in 36% and 52% iso-
lated yields, respectively (Fig. 2). Similar obser-
vations were found for other oxidative partners
in their respective reactions.
Direct C–H monofunctionalizations of
arenes and heteroarenes by mpg-CN
The mpg-CN semiconductor photocatalysis is
highly effective for direct C–H functionaliza-
tions of arenes in the presence of “sacrificial”
electron donors or acceptors, operating then
through a more conventional type A reaction
mode (Fig. 1). Whereas C–H functionalizations of
arenes are reported using conventional photo-
catalysts (4, 6, 10, 11, 35), the photocatalyst
selection and synthetically demanding catalyst
modification for a given transformation (11)
still remain a fundamental challenge in pho-
toredox catalysis. Photocatalyst deactivation
(8, 11) limits the direct use of many unpro-
tected strong nucleophiles in arene C–H func-
tionalizations (10), catalyst reuse in large-scale
synthetic transformations, or orchestrated se-
quential transformations under diverse redox
reaction conditions using different reagents (for
example, nucleophiles and reactive radicals in
a sequence, Fig. 5) in one-pot sequential cat-
alytic reactions. As we discuss in the following
sections, mpg-CN semiconductor photocataly-
tic reactions proceed through the generation
of reactive C-centered sp3 or sp2 radicals from
the respective radical precursors under both
oxidative and reductive reaction conditions
(Fig. 3) or in the presence of reactive nucleo-
philes, ideally bulk chemicals such as alkali
metal salts (Fig. 4).
C–H arene functionalizations using
radical precursors
Examples of C–H arene functionalizations
using C(sp3)- and C(sp2)-centered radicals un-
der oxidative and reductive semiconductor type
A photoredox reaction conditions are shown
in Fig. 3. In particular, the •CF3, •CH2CF3, •CF2H,
or pentafluoro aryl •C6F5 radical sources have
been recently used extensively for late-stage
functionalizations of medicinally relevant mol-
ecules (36–39). Irradiation of a reaction mixture
containing 1,3,5-trimethoxybenzene (model
Fig. 3. Direct C–H trifluoromethylations, difluoromethylations, perfluoroarylations of
arenes, and medicinally relevant molecules by means of oxidative or reductive radical
reactions. *NMR yield by 19F NMR. †The bifunctionalized product was obtained in 14% isolated
yield. ‡Respective bromoarene was formed as the major by-product (table S5). NMR, nuclear
magnetic resonance.
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need careful controlled addition at a larger
scale. In contrast, trifluoromethylation reac-
tions using mpg-CN work in the presence of
air, and the catalyst is easily recovered for reuse
(Fig. 5). Control reactions confirmed that the
presence of mpg-CN and light irradiation were
crucial for successful direct C–H transforma-
tions of arenes (table S2). Under the optimized
reaction condition, a range of five- and six-
membered heteroarenes, such as pyrimidines
(3b), pyrroles (3d to 3g), indoles (3h and 3i),
pyridines (3j), thiophenes (3k), 7-deazapurine
(3n), and medicinally relevant arenes [for ex-
ample, veratraldehyde (3t), widely used as a
flavorant or odorant], were cleanly converted to
their respective trifluoromethylated products in
good to excellent yields. Pharmaceuticals, hor-
mones, and bioactive molecules, including the
RNA base uracil (3o), 1,3-dimethyluracil (3p),
theophylline (3q, respiratory disease medica-
tion), allopurinol (3r, uric acid medication),
caffeine (3s), melatonin (3u, hormone), 4-methyl-
2-(methylthio)pyrimidine (3v, oral antidiabetic
sulfonylureas agent’s precursor), pentoxifyl-
line (3w, muscle pain medication), uridine
(3y), and tryptophan (3z), all showed excel-
lent reactivity toward trifluoromethylation,
Fig. 4. C–H and C–X (where X = Br, Cl) functionalizations of arenes
at room temperature using alkali metal salts and ligand-free
mpg-CN/Ni dual photoredox catalytic protocols, respectively.
The reactions were carried out using mpg-CN as a heterogeneous
photocatalyst and a blue LED. *The bisubstituted product was
obtained in 12% isolated yield. †Positional isomers: 16:1. ‡Ipso
substitution product. §The bifunctionalized product was obtained
as a major product. ¶The bisubstituted product (7l') was formed
in minimal amount. 7l:7l' = 16:1. #The bisubstituted product
was obtained in 11%.
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yielding the respective products, including the
synthesis of trifluridine (3x), in good to excel-
lent yields. Similar reactivity and product yields
were obtained when the reactions were per-
formed on gram scales (examples 3o, 3q, 3s in
Fig. 3). Similarly, the installation of difluoro-
methyl (–CF2H) and –CH2CF3 groups onto caf-
feine (4a, 4d), theophylline (4b), pentoxifylline
(4c), and pyrrole derivatives (4e-4f) yielded
the desired products in good to excellent yields
(Fig. 3).
The C–H arene functionalizations using
C(sp2)-centered radicals under reductive type A
photocatalytic reaction conditions was demon-
strated through synthetically important direct
C–H perfluoroarylations of arenes through the
activation of C(sp2)–bromine bonds in perfluoro-
arylbromides. Upon photoexcitation, mpg-CN
has a reduction potential of approximately –1.5 V
(versus SCE) and can therefore assist mesolytic
cleavage of the C(sp2)–Br bonds in polyfluoroaryl
bromides (reduction potentials in table S4)
through a single-electron transfer, catalyzing
direct C–H perfluoroarylations of arenes (5a
to 5f). When triethylphosphite was present
in the reaction mixture, reductive formation
of C(sp2)–P bonds was observed (5g, Fig. 3, 51%
isolated yield).
picted in Fig. 4. Simple inorganic or organic
alkali metal salts served as precursors for the
desired functional groups for direct C–H func-
tionalizations of arenes that encompassed
brominations, relatively less explored thio-
cyanations, and in particular cyanations. These
reactions involve just mixing of substrates,
the respective alkali metal salts, and mpg-CN,
followed by solvent addition and blue-light
illumination of the reaction mixture under
air (or with an oxygen balloon; materials and
methods). Previously described methods for
arene cyanations required slow-releasing cya-
nide precursors, such as trimethylsilyl cyanide
in photocatalytic reactions using acridinium
(10) and palladium catalysts (40), as the cyanide
ion deactivates both palladium(II) and palla-
dium(0) species in the catalytic cycle (40). These
limitations are not observed when mpg-CN is
used. Conducting the reactions in the absence
of light, oxygen, or mpg-CN did not afford the
desired products in reasonable yields (table S3).
Several substituted arenes (including naphtha-
lene, 7k) and various functionalized six- or
five-membered heteroarenes—such as pyridine
(7h, 7l) or thiophenes (7i to 7j, 7q) and pyrroles
(7r and 7s), which are prone toward polymer-
ization under oxidative reaction conditions—
proceeded under our conditions to afford the
respective C–H functionalized products in good
to excellent yields (Fig. 4). Arenes could also
be substituted by using small molecules with
relatively acidic protons such as succinimide
or phthalimide (7m and 7n, through the for-
mation of C–N bonds) or salts such as acetate
(7o, through the formation of C–O bond). The
succinimide group serves as a versatile amine
equivalent, as the respective products can be
easily transformed into the corresponding amines
(41). The chlorination reaction using NH4Cl
led to the formation of product 7t (Fig. 4).
These reactions are easily performed on large
scales (gram-scale reaction in examples 7a, 7l,
and 7q in Fig. 4), and the mpg-CN catalyst also
withstood high-power blue-light illumination
when the reaction was performed in a high–
light-intensity photoreactor with radiant flux
of 2.0 0.3 W (for comparison, the radiant flux
of a typical commercial single-spot LED is 0.5
0.1 W. Entry 3 in table S3 and fig. S1 present
the respective photochemical reaction yield
and high–light-intensity reaction setup), un-
der which many conventional photocatalysts
bleach (42).
C–X arene functionalizations
The examples discussed so far (Figs. 2 to 4)
showcase C–H arene functionalization at their
inherently reactive positions. Slightly altered
semiconductor/Ni dual catalytic reaction con-
ditions allow the regiospecific arene function-
alization through the activation of C(sp2)–X
(where X = Br, Cl) bonds in electron-poor aryl
halides. Dual photo-nickel catalysis with conven-
tional photocatalysts, typically iridium complexes
(43, 44), has evolved over the past several years
C–H arene functionalizations
using nucleophiles
Examples of direct C(sp2)–H arene function-
alizations using reactive nucleophiles are de-
Fig. 5. Sequential reactions and evaluation of catalytic recycling.
(A and B) Evaluation of catalyst recycling either for the same (in this
case a bromination reaction yielding product 7a) or different reactions
(in this case, consecutive bromination, thiocyanation, cyanation, and
C–H amination reactions performed in a sequence yielding products
7a, 7c, 7b, and 7n, respectively). (C) Kinetic profile of a photocatalytic
transformation (in this case, the thiocyanation reaction yielding product 7i)
over four catalytic cycles. The simplicity of the synthetic gram-scale
reactions (in this case trifluoromethylation of caffeine) using mpg-CN
as a photcatalyst are depicted in (D, E, and F): (D) required reagents and
reaction setup; (E) photochemical reaction setup under visible-light
illumination; (F) isolated product (product 3s) and the recovered photocatalyst.
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into a valuable synthetic tool for cross-coupling
(45). The use of mpg-CN as a semiconductor
photocatalyst allows catalyst recoverability and
reuse as a distinct advantage. The reaction con-
ditions require no additional ligands for nickel
complexation, the reactions proceed at room
temperature, and the chemical and photosta-
bilty of mpg-CN allows easy scalability to gram
quantities (example 8a). Once dissolved in di-
methylacetamide (DMA), ethyl 4-bromobenzoate
irradiated with blue light in the presence of
morpholine (a heterocycle featuring both amine
and ether functional groups), mpg-CN, and a
catalytic amount NiBr2•glyme was converted
into the corresponding C–N functionalized pro-
duct in 81% isolated yield. The use of o-/m-/p-
substituted aryl bromides (or even chlorides,
example 8h) yielded the corresponding regio-
specific functionalized products in good to ex-
cellent yields, and different functional groups,
such as ester, aldehyde, ketone, amide, trifluo-
romethyl, and cyano, were tolerated under the
reaction condition. The mpg-CN/Ni dual cata-
lytic reactions are effective for various nitrogen
nucleophiles (examples 8a to 8q), including sub-
stituted benzenesulfonamide providing the cor-
responding N-aryl sulfonamide (8r) [a motif
present in pharmaceuticals (46)], in good to ex-
cellent yields.
bifunctionalized product 9a in 74% yield (Fig. 5).
This sequential reaction simply required the ad-
dition of KBr and continuous irradiation once
the trifluoromethylation reaction was complete.
Likewise, when sodium triflinate was added post
cyanation (examples 9b and 9c), the bifunction-
alized products containing –CF3 and –CN groups
were obtained.
Considering all of these results in aggregate,
the organic semiconductor mpg-CN stands out
as one of the most versatile visible light–activated
photocatalysts, providing an inexpensive, non-
toxic alternative to classical transition metal cat-
alysts and organic dyes.
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ACKNOWLEDGMENTS
Recoverability and reuse of mpg-CN
We thank R. Vasold, R. Hoheisel, and J. Zach for GC-MS,
CV measurements, and technical assistance, respectively, and
R. Lahmy for proofreading the manuscript. Funding: We thank
the Deutsche Forschungsgemeinschaft (GRK 1626 and DFG An 156
13-1) for financial support. This project also received funding
from the European Research Council (ERC) under the European
Union’s Horizon 2020 research and innovation program (grant
agreement no. 741623). Author contributions: B.K. and M.A.
conceived and directed the project. I.G., B.K., M.A., J.K., A.S.,
and N.S. designed the experiments. I.G., J.K., A.S., and N.S.
performed and analyzed the experiments. I.G., B.K., M.A., J.K.,
and A.S. prepared the manuscript. Competing interests: The
authors declare no conflicts of interest. Data and materials
availability: Crystallographic parameters for compound 7c are
available free of charge from the Cambridge Crystallographic Data
Centre under CCDC 1880753. Data are available in the
supplementary materials.
The use of insoluble heterogeneous semicon-
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filtration (fig. S14). The recovered catalyst could
be reused for multiple transformations with
conserved activity, as specifically appraised by
determining the product yields over four cata-
lytic cycles either for the same reaction (Fig. 5A)
or for different reactions performed in a se-
quence (Fig. 5B); rates of photocatalytic trans-
formations (47, 48) over four catalytic cycles were
also conserved (Fig. 5C). The photocatalyst's high
stability enables one-pot sequential type A oxi-
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arenes in the presence of reactive C(sp3) radicals
and strong nucleophiles. This is exemplified by
consecutive trifluoromethylation and bromina-
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SUPPLEMENTARY MATERIALS
science.sciencemag.org/content/365/6451/360/suppl/DC1
Materials and Methods
Figs. S1 to S23
Tables S1 to S7
References (49–105)
9 December 2018; accepted 3 June 2019
10.1126/science.aaw3254
Ghosh et al., Science 365, 360–366 (2019)
26 July 2019
7 of 7

Organic semiconductor photocatalyst can bifunctionalize arenes and heteroarenes
Indrajit Ghosh, Jagadish Khamrai, Aleksandr Savateev, Nikita Shlapakov, Markus Antonietti and Burkhard König
Science 365 (6451), 360-366.
DOI: 10.1126/science.aaw3254
Two-for-one approach to photoredox
In photoredox catalysis, an excited chromophore typically activates a single reactant either by oxidizing or
reducing it. Ghosh et al. used a semiconductor catalyst to activate two reactants at once by quenching both an excited
electron and the residual positive hole (see the Perspective by Swift). As such, two different reactive carbon or halide
fragments could be appended to separate sites on an aryl ring. The catalyst also tolerated strong nucleophiles such as
cyanide and could be recovered easily and reused.
Science, this issue p. 360; see also p. 320
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