A unified strategy for silver-, base-, and oxidant-free direct arylation of C-H bonds

Article abstract of DOI:10.1039/c6gc03438a

Here, we report a dual catalytic approach for room temperature direct arylation of C-H bonds with aryldiazonium salts as a simple aryl group donor, also working as an internal oxidant via C-N₂ bond cleavage. This unified strategy has been achieved by the synergistic combination of visible-light metal-free photoredox and palladium catalysis under silver-, base- and/or additive-free conditions. The broad substrate scope, functional group tolerance, excellent regioselectivity and redox-neutral conditions of this process make it attractive for the effective synthesis of a wide range of important N-heterocyclic commodities such as dibenzo[b,d]azepine, carbazole and phenanthridine.

Full text of DOI:10.1039/c6gc03438a

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Unified Strategy for Silver-, Base-, and Oxidant-free Direct
Arylation of C-H Bonds†
Manoj K. Sahoo, Siba P. Midya, Vinod G. Landge, and Ekambaram Balaraman*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
Here, we report a dual catalytic approach for room temperature transition-metal catalyzed direct C-H arylation of (electron-
direct arylation of C-H bonds with aryldiazonium salts as a simple rich) arenes (Chart 1).4 Despite a few notable progress in this
aryl group donor, also working as an internal oxidant via C-N2 field over the last decade, the majority of the approaches still
bond cleavage. This unified strategy has been achieved by the suffer from harsh conditions such as operates at elevated
synergistic combination of visible-light metal-free photoredox and temperature, and the need for excess amounts (super-
palladium catalysis under silver-, base- and/or additive-free stoichiometric) of oxidants, bases and/or additives and results
conditions. The broad substrate scope, functional group tolerance, in copious waste and functional-group incompatibilities.5
excellent regioselectivity and redox-neutral condition of this Hence, it would be desriable to develop
a mild, and
process make it attractive for the effective synthesis of a wide environmentally benign C-H arylation under oxidant-, base/
range of important N-heterocyclic commodities such as additive-free conditions.
dibenzo[b,d]azepine, carbazole and phenanthridine.
In recent times, aryldiazonium salts emerge as a convenient
arylating reagent,6-7 however, their exploitation in transition-
metal catalyzed expedient C-H arylation is rare. This is due to
its high electrophilic character, reactivity towards many classes
of nucleophilic coupling partners, and sensitivity towards
ligand-additives and bases employed in the majority of C-H
bond activation and cross-coupling reactions.8 Recently,
Sanford and co-workers reported the Ru/Pd-catalyzed C-H
Development of new chemical approaches for the synthesis of
industrially relevant compounds and pharmaceutical drugs is
of great demand and fuels the efforts of the present scientific
community. In this context, the biaryl motif is an important
structural component of numerous natural products,
pharmaceutical agents, organic materials and many of them of
industrial importance.1 Classical transition-metal-catalyzed
cross-coupling reactions are the powerful methods for the
construction of the biaryl skeleton.2-3 In contrast to the well-
established cross-coupling reactions, ubiquitous C-H bond
direct arylation has recently emerged as more promising and
practical approach to access biaryl motifs with great step- and
atom-economy.3 Indeed, it circumvents the necessity of
prefunctionalization of an organic molecule and has more
advantages when the regioselective introduction of
(pseudo)halides in an organic molecule involves multistep
synthetic strategy and required harsh reaction conditions or
sometimes problematic. In particular, owing to the prevalence
of 2-arylaniline scaffolds in pharmaceuticals, agrochemicals,
and material science much attention has been paid to the
arylation of 2-phenylpridine, which is
a good substrate
because of its chelating ability, and cyclic tert-amides by using
aryldiazonium tetrafluoroborates as aryl group donor.9a
However, this reaction still requires
aryldiazonium salts and notably, the role of silver salt (Ag2CO3,
mild oxidant) used as an additive is not always
a large excess of
a
straightforward. Chang and co-workers reported Cp*Ir(III)-
catalyzed (10 mol% w.r.t to Ir atom) oxidant-free C-H arylation
of electron-deficient amides using aryldiazonium salts as an
unconventional arylating agent, also working as an internal
oxidant;9b nevertheless, often required a catalytic amount of
silver salt and a base (Scheme 1a). Gaunt and co-workers
developed a direct approach to C-H arylation of anilides at 50–
70 oC using diaryliodonium salts as the aryl coupling partner
under oxidant-free copper catalysis,10 but unfortunately, only
meta-arylation of anilides was accomplished (Scheme 1b).
Thus, a general and efficient strategy for direct C-H arylation of
anilides under oxidant-, additive- and/or base-free conditions
is still elusive.11 Here, we report a dual catalytic approach12 by
merging of a visible-light metal-free photoredox catalysis with
a palladium catalysis to expedient C-H arylation of anilides
Catalysis & Inorganic Chemistry Division, Dr. Homi Bhabha Road, CSIR-National
Chemical Laboratory (CSIR-NCL), Pune - 411008, India. Academy of Scientific and
Innovative Research (AcSIR), New Delhi
eb.raman@ncl.res.in; balaramane2002@yahoo.com
-
110 025, India. E-mail:
†Electronic Supplementary Information (ESI) available: [details of experimental
procedure, characterization of compounds and copy of NMR data]. See
DOI:10.1039/x0xx00000x
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using aryldiazonium salts as a convenient aryl group donor, 8%) of the product were formed in the absence of photoredox
also working as an internal oxidant via C-N2 bond cleavage catalyst; no reaction was observed upon exclusion of light. No
under silver-, and base-free conditions. A consequence of this formation of 3a was observed in the absence of Pd(OAc)2
finding could be a safer and cleaner process for the effective (Table 1, entry 4), and reducing the catalytic amount of
synthesis of a wide range of important N-heterocyclic Pd(OAc)2 gave moderate yields (Table 1, entries 14-15). We
commodities.
also examined other [Pd] sources (Table 1, entries 16-20) and
also replacing the palladium catalyst with those derived from
gold, nickel or copper salts; however, only excellent yield was
obtained when Pd(OAc)2 was used, and no product was
detected with other metal catalysts. A series of solvents were
examined and among them, methanol was found to be an
optimal solvent for this transformation (Table 1, entries 1, and
8-13). Gratifyingly, these optimal conditions employ a low-
energy 3W green LED light source and proceed readily at room
temperature under silver-, base-, and external oxidant-free
F
O
O
O
F2HC
F2HC
N
H
N
N
H
N
N
Me
N
N
Me
H
N
Cl
O
N
Cl
F
F
Ts
Cl
Cl
Bixafen (Bayer CropScience)
F
Potassium channel inhibitor
Boscalid (BASF)
Fluxapyroxad (BASF)
O
Cl
Me
OH
N
O
O
HO
F
OH
HN
N
HO
O
OMe
H
O
N
O
OMe
N
H
Me
NH
Cl
conditions with no generation of copious metal waste.
Table 1. Optimization of the reaction conditions.
N
F
HO
H
Me
LY-411575 ( -secretase inhibitor)
Carbazomycin B (Alkaloid)
Rebeccamycin (Natural product)
H2
C
H
C
R
N
X
R
N
Ar
Ar
Ar
Ar
n
N
N
N
Ni
X
Photoconducting polymer
Green host material in
phosphorescent OLEDs
Brookhart-type (olefin)
polymerization catalyst
Chart 1. The importance of C-H arylated anilines.
Scheme 1. Direct C-H Bond Arylation of Arenes under Oxidant-Free Conditions.
a
Reaction conditions: 1a (0.2 mmol), 2a (0.3 mmol), eosin-Y (1.0 mol%), Pd(OAc)2 (10
mol%), MeOH (1 mL), Ar atm, 3W green LED for 12 h (R = Piv). b Isolated yields. at 80
c
oC. d Yield determined by 1H NMR. e 24 h. f 5 mol%.
We began our external oxidant-free site-selective C-H arylation
of anilides with an evaluation of a range of solvents, mol% of
the photoredox catalyst, and palladium salts in the presence of
1a as arene partner and p-chloro diazonium salt 2a as aryl
group donor (Table 1). We found that the use of light (from
3W green LED) in the presence of catalytic amounts of eosin-Y,
and Pd(OAc)2 enabled the desired ortho C-H arylated anilide 3a
in 93% isolated yield (Table 1, entry 1). The necessity of each
of the key reaction components (photoredox catalyst, Pd-
catalyst, and light source) was demonstrated through a series
of control experiments (Table 1, entries 2-4). Reactions in the
dark and at increased temperature (80 °C) gave the desired
product 3a in very poor yield (17%), which excludes homolytic
bond cleavage of the starting material to an aryl radical under
these conditions (Table 1, entry 2). While trace amounts (only
Having identified optimal condition for the room temperature
external oxidant-, base-, silver-free strategy, next sought to
define the scope of both anilides
The scope of aryldiazonium salts
1
and aryldiazonium salts
2.
2
was initially explored using
N-(m-tolyl)pivalamide 1a as a benchmark substrate at room
temperature. As shown in Table 2, the present direct C-H
arylation strategy displayed a high functional-group tolerance
and proved to be a general method for the preparation of
mono-selective ortho C-H arylated anilides in good to excellent
yields (up to 94%) under very mild conditions. Aryldiazonium
salts bearing electron-donating groups at the meta and para
position of the phenyl ring, such as methyl and methoxy,
proceeded smoothly and gave the corresponding ortho-
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arylated anilides in 89%-94% isolated yields (products 3e, and Next, the scope of our C-H arylation strategy extended to cyclic
3j-3k). Indeed, electron-withdrawing group substituted (-CF3, - systems. Thus, under optimized conditions, indoline
NO2, -CN, and -F) aryldiazonium salts, such as 3f-3h, 3l, and 3n- derivatives (products 4q in 81% and 4r in 89% isolated yields)
3o were also well tolerated and afforded the corresponding C- and tetrahydroquinolines (products 4s in 84% and 4t in 92%
H arylated products in good yields (66%-89%) (Table 2). These isolated yields) gave the corresponding C-H bond arylated
results indicate that the electronic nature of the aryldiazonium products in excellent yields. The effect of substituent on the
salts has little influence on the room-temperature external acyl group of anilides was further studied by changing N-
oxidant-free C-H arylation reaction. However, a substituent at pivaloyl to N-acetyl and gave the expected ortho-aryl N-
the ortho position of the phenyl ring gave the desired product phenylacetamide (4u) in 65% yield.13 However, under optimal
with a slightly decreasing yield (products 3c in 78% yield and conditions N-methylaniline and N,N-dimethylaniline didn’t
3d in 70% yield) which could be explained by steric reasons.
yield the ortho-arylated products.14 We have also successfully
shown the scalability and practical viability of this catalytic
protocol under standard conditions (products 4a in 82%, and
4n in 87% isolated yields). Notably, the present catalytic
system can be reusable. Thus, after the first catalytic run
between 1a and 2a in the presence of catalytic amounts of
eosin-Y and [Pd] source under standard conditions, the yield of
the ortho-arylated product 3a observed was 95% (GC yield). In
the same reaction vessel were placed a fresh 1a and 2a, and
the reaction was continued further without the addition of
catalysts. After 18 h, the yield of 3a determined for the second
cycle was 91%.
Table 2. Scope of aryldiazonium salts.a,b
Table 3. Scope of anilides 1 a,b
.
a
Reaction conditions: 1a (0.2 mmol), 2 (0.3 mmol), eosin-Y (1 mol%), Pd(OAc)2 (10
mol%), MeOH (1 mL), Ar atm, 3W green LED for 12 h (R = Piv). b Isolated yields.
We next focused our attention on the scope of the anilide
coupling partner. As exemplified in Table 3, electron-donating,
as well as electron-withdrawing groups on the N-phenyl ring,
gave the desired mono-selective arylated products in excellent
yields (up to 97%). Thus, N-phenylpivalamide
1 with electron-
donating substituents such as o-isoPr, o-OMe, m-OMe, p-Et,
and p-OMe afforded the corresponding site-selective ortho-
arylated products in very good yields (Table 3, products 4b in
84%, 4c in 87%, 4f in 97%, 4k in 85%, and 4l in 93% isolated
yields). Under optimized conditions,
1 with electron-
withdrawing substituents (p-F and m-NO2) on the phenyl group
successfully reacted with 2a and yielded the corresponding C-
H arylated products in 91% and 49% respectively. Halide
substituents are also well tolerated and gave the expected C-H
arylated products in good yields (up to 94%). It is noteworthy
that the corresponding O-phenylpivalamide failed to undergo
C-H arylation. Thus, the reaction of 1m with 2a under
optimized conditions selectively gave 4m in 79% isolated yield.
a
Reaction conditions: 1 (0.2 mmol), 2a (0.3 mmol), eosin-Y (1 mol%), Pd(OAc)2 (10
mol%), MeOH (1 mL), Ar atm, 3W green LED for 12 h (R = Piv). b Isolated yields. c Gram-
scale synthesis.
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A consequence of the present direct C-H arylation strategy reaction kinetics (Figure. 1). Thus, continuous sampling was
could be a safer and cleaner process for the effective synthesis undertaken with the different time intervals, and the
of a wide range of important N-heterocyclic commodities such conversion of anilide (1a) and the yield of ortho-aryl anilide
as phenanthridine, carbazole, and dibenzo[b,d]azepine. The
removal of the directing group (pivaloyl group) was easily line, indicating a constant reaction rate.13 To find the order of
accomplished under mild reaction conditions to access ortho- reaction in each component (1a 2a, and catalyst) of the
(3a) were determined. The formation of 3a followed a linear
,
aryl anilines in excellent yields (products 5a in 93%, and 5b in current dual catalytic approach to direct arylation of anilides
94% yields; Scheme 2). The intramolecular cyclization of ortho- with aryldiazonium salts was determined individually by using
aryl anilides proceeded smoothly in the presence of POCl3, the initial rate approximation. The progress of the reaction
yielding phenanthridine derivatives 6a and 6b in 94%, and 89% studied with the kinetic analyses and revealed that the
yields, respectively. In addition, ortho-aryl anilines were arylation reaction is fractional order in anilide, aryldiazonium
converted into carbazole derivatives 7a-c in good yields in the salt, and the catalyst concentration.
presence of catalytic amounts of [Cp*IrCl2]2 (2 mol %) and
Cu(OAc)2 (20 mol %) as well as PivOH (1 mmol) under air.4d
A
palladium(II)-catalyzed [5+2] oxidative annulations of o-
arylanilines with alkynes to access to an imine-containing
dibenzo[b,d]azepines (8; 72% isolated yield) with great
stereoselectivity was demonstrated.4f
tBu
NH2
N
R'
Intramolecular
cyclization
R'
R
=
P
i
v
v
i
P
=
5a
R' = Cl,
(93%)
6a
R' = OMe,
(94%)
R
Figure 1. Reaction profile for the formation of 3a.
= CH3, 5b (94%)
NHR
= Cl, 6b (89%)
R'
Ph
Ph
H
N
R
H
=
=
H
R
N
R
'
=
C
R'
l
Cl
7a
R' = H,
(75%)
= Me, 7b (67%)
= Cl, 7c (73%)
8
(72%)
Scheme 2. Diversification of ortho-arylaniline derivatives.
To our delight, a potential synthetic application of the ortho C-
H bond arylated anilides was successfully shown in Scheme 3.
Treatment of 5a with
9 in the presence of a catalytic amount
of 4-dimethylaminopyridine (DMAP) led to Boscalid (10) in
81%, which is used as a potent fungicide.4c A copper powder
mediated N-arylation of carbozole
(
7a
)
with 4,4’-
diiodobiphenyl (11) to access 12, a green host material in
phosphoroscent OLEDs was also shown.4e
O
O
NH2
10 mol% DMAP
Et3N, DCM
Cl
N
(a)
+
H
N
Cl
N
Cl
0
oC to RT, 12 h
9
Cl 5a
10
Cl
(81%)
Boscalid (BASF)
I
Figure 2. Time-dependent formation of 3a at different initial concentrations of
(A) 1a, (C) 2a, and (E) metal-free photoredox catalyst. (B) Plot of log(rate) vs
log(equiv of 1a), (D) 2a, and (F) metal-free photoredox catalyst. The rates are the
Cu powder
N
(b)
N
+
anhy.K2CO3
o-dichlorobenzene
reflux, 24 h
N
H
12
(71%)
7a
11
average of three independent measurements
.
Green host material in
phosphorescent OLEDs
I
Performing the reaction in the presence of the radical
scavenger 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), the
reaction was completely inhibited (Scheme 4a). Indeed, the O-
arylated-TEMPO product was detected on GC-MS, indicating
that the radical reaction pathway could be involved in the
Scheme 3. Synthetic applications of ortho C-H arylated anilines.
Time-dependent experiments on external oxidant-free direct
C-H arylation of anilides were also conducted to study the
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catalytic cycle. Furthermore, the yield of 3a was completely followed by an acetate ion coordination regenerates the
dropped when no photocatalyst was present in the reaction palladium catalyst.
and/or under dark conditions (Table 1, entry 3). A “light/dark”
experiment clearly indicates that a radical chain process in the
present dual catalytic system may be operative.15 Notably, the
C-H arylation of the isotopically labeled substrate [D]-1d was
not accompanied by H/D exchange reactions, which is
indicative of a kinetically relevant C-H palladation step
(Scheme 4b). In a preliminary experiment, the formation of
palladacycle intermediate 14 was identified by the
stoichiometric reaction of 1a with Pd(OAc)2.13,16
Scheme 5. A plausible catalytic cycle for C-H arylation of 1.
Conclusions
In conclusion, a dual catalytic approach by successfully
merging visible-light photoredox catalysis with palladium
Scheme 4. Mechanistic studies.
catalysis to room temperature external oxidant-free direct C-H
arylation of anilides by using aryldiazonium tetrafluoroborates
Although the complete mechanistic details of this
as a convenient aryl group donor, also working as an internal
transformation are not clear at this moment, based on above
oxidant via C-N2 bond cleavage has been reported. The unified
experimental findings and literature precedent12,15-17
a
approach operates under extremely mild conditions; silver-,
additive-free, and redox-neutral conditions, and no generation
of copious metal waste, and can thereby be scaled up in gram-
scale synthesis. A consequence of this finding could be a safer
and cleaner process for the effective synthesis of a wide range
of important N-heterocyclic commodities such as
dibenzo[b,d]azepine, carbazole, and phenanthridine. In
addition, a potential synthetic application of ortho C-H bond
arylated anilides in agrochemical and material science has
been successfully demonstrated. The broad substrate scope,
functional group tolerance, and excellent selectivity of this
process make it attractive for the facile construction of C-H
arylated compounds of high utility in various research areas.
plausible mechanism for external-oxidant free C-H arylation of
is shown in Scheme 5. Initially, eosin Y (EY) absorbs visible
1
light in the green light region (λmax = 539 nm) to give a
photoexcited singlet state, 1EY*, which undergoes rapid
3
intersystem crossing to its lowest long-lived triplet state EY*
3
with a lifetime of 24µs.15d This photoexcited EY* is a strong
reductant (E1/2(3EY*/EY·+) = -1.15 V vs SCE)15d-e and undergoes
oxidative quenching followed by reducing the ArN2BF4. (the
standard reduction potential of different ArN2BF4 are very
close to SCE varying from a small positive to negative values;
red
E1/2
=
−0.1
V
vs SCE for phenyldiazonium
tetrafluoroborate)15f to the corresponding electrophilic aryl
radical with the concomitant generation of dinitrogen. Then
the electrophilic aryl radical (Ar·) reacts with palladacycle 14
(generated by the carboxylate assisted C-H bond activation of
Acknowledgements
1
) to afford the intermediate 15 18
. Single electron oxidation of
15 by EY·+ (strongly oxidizing, E1/2(EY·+/EY) = +0.78 V vs SCE)15
This research is supported by the SERB (SB/FT/CS-065/2013)
and EMR/2015/30 and 12FYP ORIGIN program (CSC0108).
MKS, SPM, and VGL thanks the CSIR for the research
fellowship.
to regenerate the photocatalyst (EY) and forms intermediate
16. The mechanistic studies show that a significant
contribution of a radical chain process in the present catalytic
system is operative.13,15a,15f Therefore, a second SET process
between palladacycle 14 with another equivalent of the
aryldiazonium salt contributes to the formation of 15 may also
feasible. Finally, the reductive elimination of 17 leads to an
Notes and references
1
(a) J.-P. Corbetand G. Mignani, Chem. Rev., 2006, 106, 2651-2710; (b)
E. R. Kay, D. A. Leigh and F. Zerbetto, Angew. Chem., Int. Ed., 2007,
ortho-arylated anilide
3 or 4 via the C-C bond formation and
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46, 72-191; (c) R. A. Hughes and C. J. Moody, Angew. Chem., Int. Ed.,
2007, 46, 7930-7954; (d) L. Ackermann, Modern Arylation Methods,
Wiley-VCH, Weinheim, 2009; (e) G. Bringmann, T. Gulder, T. A. M.
Gulder and M. Breuning, Chem. Rev., 2011, 111, 563-639.
(a) M. Beller and C. Bolm, Transition Metals for Organic Synthesis, 2nd
ed., Wiley-VCH, Weinheim, 2004; (b) A. de Meijere and F. Diederich,
Metal-Catalyzed Cross-Coupling Reactions; Wiley-VCH, Weinheim,
2004.
6
7
Recent reviews on the utilization of aryldiazonium salts as an arylating
agent, see:(a) J. G. Taylor, A. V. Moro and C. R. D. Correia, Eur. J. Org.
Chem., 2011, 1403-1428; (b) F. Mo, G. Dong, Y. Zhang and J. Wang,
Org. Biomol. Chem., 2013, 11, 1582-1593; (c) D. P. Hari and B. König,
Angew. Chem., Int. Ed., 2013, 52, 4734-4743; (d) D. P. Hari, T. Hering
and B. König, ChimicaOggi-Chemistry Today, 2013, 31, 59-63.
2
3
(a) E. W. Werner and M. S. Sigman, J. Am. Chem. Soc., 2011, 133
,
9692-9695; (b) E. W. Werner, T.-S. Mei, A. J. Burckle and M. S.
Sigman, Science, 2012, 338, 1455-1458; (c) D. P. Hari, P. Schroll and
B. König, J. Am. Chem. Soc., 2012, 134, 2958-2961; (d) M. Hartmann,
Y. Li and A. Studer, J. Am. Chem. Soc., 2012, 134, 16516-16519; (e) P.
For representative reviews of direct C-H arylation, see: (a) D. Alberico,
M. E. Scott and M. Lautens, Chem. Rev., 2007, 107, 174-238; (b) L.
Ackermann, Top. Organomet. Chem., 2007, 24, 35-60; (c) F. Kakiuchi
and T. Kochi, Synthesis, 2008, 3013-3039; (d) B.-J. Li, S.-D. Yang and
Z. J. Shi, Synlett, 2008, 949-957; (e) G. P. McGlacken and L. Bateman,
Chem. Soc. Rev., 2009, 38, 2447-2464; (f) X. Chen, K. M. Engle, D.-H.
Wang and J.-Q. Yu, Angew. Chem., Int. Ed., 2009, 48, 5094-5115; (g)
Schroll, D. P. Hari and B. König, ChemistryOpen, 2012, 1, 130-133; (f)
B. Sahoo, M. N. Hopkinson and F. Glorius, J. Am. Chem. Soc., 2013,
135, 5505-5508; (g) X.-Z. Shu, M. Zhang, Y. He, H. Frei and F. D.
Toste, J. Am. Chem. Soc., 2014, 136, 5844-5847; (h) C. C. Oliveira, M.
V. Marques, M. N. Godoi, T. Regiani, V. G. Santos, E. A. F. dos Santos,
M. N. Eberlin, M. M. Sá and C. R. D. Correia, Org. Lett., 2014, 16, 5180-
5183; (i) D. Xue, Z.-H. Jia, C.-J. Zhao, Y.-Y. Zhang, C. Wang and J.
Xiao, Chem. -Eur. J., 2014, 20, 2960-2965; (j) B. Verbelen, S. Boodts, J.
O. Daugulis, H. Q. Do and D. Shabashov, Acc. Chem. Res., 2009, 42
,
1074-1086; (h) L. Ackermann, R. Vicente and A. R. Kapdi, Angew.
Chem., Int. Ed., 2009, 48, 9792-9826; (i) T. W. Lyons and M. S.
Sanford, Chem. Rev., 2010, 110, 1147-1169; (j) O. Daugulis, Top. Curr.
Chem., 2010, 292, 57-84; (k) G. P. Chiusoli, M. Catellani, M. Costa, E.
Motti, N. D. Ca and G. Maestri, Coord. Chem. Rev., 2010, 254, 456-
469; (l) J. Yamaguchi, A. D. Yamaguchi and K. Itami, Angew. Chem.,
Int. Ed., 2012, 51, 8960-9009.
Hofkens, N. Boens and W. Dehaen, Angew. Chem., Int. Ed., 2015, 54
,
4612-4616; (k) H. M. Nelson, B. D. Williams, J. Miró and F. D. Toste, J.
Am. Chem. Soc., 2015, 137, 3213-3216; (l) L. Huang, D. Hackenberger
and L. J. Gooßen, Angew. Chem., Int. Ed., 2015, 54, 12607-12611; (m)
J. Um, H. Yun and S. Shin, Org. Lett. 2016, 18, 484-487.
4
(a) O. Daugulis, A. H. R. MacArthur, F. C. Rix and J. L. Templeton, ACS
Catal., 2015,
L. Ackermann, ACS Catal., 2015,
Himmler, L. Rodefeld and L. Ackermann, Adv. Synth. Catal., 2015, 357
6
, 1518-1532; (b) J. Hubrich, T. Himmler, L. Rodefeld and
8
9
S. Kim, J. Rojas-Martin and F. D. Toste, Chem. Sci., 2016, 7, 85-88.
5
, 4089-4093; (c) J. Hubrich, T.
(a) D. Kalyani, K. B. McMurtrey, S. R. Neufeldt and M. S. Sanford, J.
Am. Chem. Soc., 2011, 133, 18566-18569; (b) K. Shin, S.-W. Park and
S. Chang, J. Am. Chem. Soc., 2015, 137, 8584-8592.
,
474-480; (d) C. Suzuki, K. Hirano, T. Satoh and M. Miura, Org. Lett.,
2015, 17, 1597-1600; (e) S. Choi, T. Chatterjee, W. J. Choi, Y. You and
10 R. J. Phipps and M. J. Gaunt, Science, 2009, 323, 1593-1597.
11 A photoredoxIr/Pd-catalyzed arylation of anilide (only one substrate)
with aryldiazonium salt gave very poor yield (38%). Reaction conditions:
E. J. Cho, ACS Catal., 2015,
5, 4796-4802; (f) Z. Zuo, J. Liu, J. Nan, L.
Fan, W. Sun, Y. Wang and X. Luan, Angew.Chem., Int. Ed., 2015, 54
,
+
15385-15389; (g) M. Feng, B. Tang, H.-Xi Xu and X. Jiang, Org. Lett.,
2016, 18, 4352-4355.
PhN2 (2 equiv.), Pd(NO3)2 (0.10 equiv.), Ir(ppy)2(dtbbpy)PF6 (0.05
equiv.). See: S. R. Neufeldt and M. S. Sanford, Adv. Synth. Catal.,
2012, 354, 3517-3522.
5
(a) S. J. Tremont and H. Rahman, J. Am. Chem. Soc., 1984, 106, 5759-
5760; (b) D. Kalyani, N. R. Deprez, L. V. Desai and M. S. Sanford, J.
Am. Chem. Soc., 2005, 127, 7330-7331; (c) O. Daugulis and V. G.
12 (a) J. Xuan and W.-J. Xiao, Angew. Chem., Int. Ed., 2012, 51, 6828-
6838; (b) J. W. Tucker and C. R. J. Stephenson, J. Org. Chem., 2012,
77, 1617-1622; (c) C. K. Prier, D. A. Rankic and D. W. C. MacMillan,
Chem. Rev., 2013, 113, 5322-5363; (d) M. N. Hopkinson, B. Sahoo, J.-
L. Li and F. Glorius, Chem. -Eur. J., 2014, 20, 3874-3886; (e) M. D.
Zaitsev, Angew. Chem., Int. Ed., 2005, 44
, 4046-4048; (d) D.
Shabashov and O. Daugulis, J. Org. Chem., 2007, 72, 7720-7725; (e) Z.
Shi, B. Li, X. Wan, J. Cheng, Z. Fang, B. Cao, C. Qin and Y. Wang,
Angew. Chem., Int. Ed., 2007, 46, 5554-5558; (f) S. Yang, B. Li, X. Wan
and Z. Shi, J. Am. Chem. Soc.,2007, 129, 6066-6067; (g) G. Brasche, J.
García-Fortanet and S. L. Buchwald, Org. Lett., 2008, 10, 2207-2210;
Levin, S. Kim and F. D. Toste, ACS Cent. Sci., 2016,
L. Skubi, T. R. Blum and T. P. Yoon, Chem. Rev., 2016, 116, 10035-
10074; (g) N. A. Romero and D. A. Nicewicz, Chem. Rev., 2016, 116
2, 293-301; (f) K.
,
(h) B. Li, S. Tian, Z. Fang and Z. Shi, Angew. Chem., Int. Ed., 2008, 47
,
10075-10166; (h) I. Ghosh, L. Marzo, A. Das, R. Shaikh and B. König,
Acc. Chem. Res., 2016, 49, 1566-1577.
1115-1118; (i) N. R. Deprez and M. S. Sanford, J. Am. Chem. Soc.,
2009, 131, 11234-11241; (j) T. Nishikata, A. R. Abela and B. H.
Lipshutz, Angew. Chem., Int. Ed., 2010, 49, 781-784; (k) T. Nishikata,
A. R. Abela, S. Huang and B. H. Lipshutz, J. Am. Chem. Soc., 2010,
132, 4978-4979; (l) X. Zhao, C. S. Yeung and V. M. Dong, J. Am.
Chem. Soc., 2010, 132, 5837-5844; (m) C. S. Yeung, X. Zhao, N.
13 See the ESI.†
14 (a) S. W. Youn and E. M. Lee, Org. Lett., 2016, 18, 5728-5731
(Reaction of ArN2BF4 with N-methylaniline); (b) S. Chng, E. M. Parker,
J.–P. Griffiths, M. G. Moloney, Appl. Surf. Sci., 2017, 401, 181-189
(Reaction of ArN2BF4 with N,N-alkyllaniline).
Borduas and V. M. Dong, Chem. Sci., 2010,
1
, 331-336; (n) J. J.
15 For selected examples of photoredox catalysis by eosin-Y and radical
chemistry, see: (a) M. Neumann, S. Füldner, B. König and K. Zeitler,
Angew. Chem.,Int. Ed.,2011, 50, 951-954; (b) P. Hari and B. König,
Chem. Commun., 2014, 50, 6688-6699; (c) M. Majek, F. Filace and A.
J. von Wangelin, Beilstein J. Org. Chem., 2014, 10, 981-989; (d) M. A.
Mousseau, F. Vallee, M. M. Lorion and A. B. Charette, J. Am. Chem.
Soc., 2010, 132, 14412-14414; (o) T. Truong and O. Daugulis, Org.
Lett., 2012, 14, 5964-5967; (p) J. Wencel-Delord, C. Nimphius, H. Wang
and F. Glorius, Angew. Chem., Int. Ed., 2012, 51, 13001-13005; (q) L.-
Y. Jiao and M. Oestreich, Chem. -Eur. J., 2013, 19, 10845-10848; (r) F.
Cismesia and T. P. Yoon, Chem. Sci., 2015, 6, 5426-5434; (e) A. Studer
Yang, F. Song, W. Li, J. Lan and J. You, RSC Adv., 2013,
3
, 9649-
and D. P. Curran, Angew. Chem., Int. Ed., 2016, 55, 58-102; (f) P. Xu,
G. Wang, Y. Zhu, W. Li, Y. Cheng, S. Li and C. Zhu, Angew. Chem., Int.
Ed., 2016, 55, 2939-2943.
9652; (s) Y.-X. Liu, D. Xue, J.-D. Wang, C.-J. Zhao, Q.-Z. Zou, C. Wang
and J. Xiao, Synlett, 2013, 507-513; (t) N. Uhlig and C.-J. Li, Chem. -
Eur. J., 2014, 20
,
12066-12070; (u) R. A. Chinnagolla and M.
16 Cyclopalladatedanilides can exist as dimer, see: ref. 5d and T. Xiong, Y.
Li, Y. Lv and Q. Zhang, Chem.Commun., 2010, 46, 6831-6833.
Jaganmohan, Chem. Commun., 2014, 50, 2442-2444; (v) D. Li, N. Xu,
Y. Zhang and L. Wang, Chem. Commun., 2014, 50, 14862-14865; (w)
R. Haridharan, K. Muralirajan and C.-H. Cheng, Adv. Synth. Catal.,
2015, 357, 366-370; (x) P. Gao, W. Guo, J. Xue, Y. Zhao, Y. Yuan, Y.
Xia and Z. Shi, J. Am. Chem. Soc., 2015, 137, 12231-12240; (y) P.
Gao, L. Liu, Z. Shi and Y. Yuan, Org. Biomol. Chem., 2016, 14, 7109-
7113; (z) P. Nareddy, F. Jordan, S. E. Brenner-Moyer and M. Szostak,
17 G. Maestri, M. Malacria and E. Derat, Chem. Commun., 2013, 49
,
10424-10426.
18 An alternative mechanism involving binuclear Pd species that may
result in completely different catalytic cycle can’t be rolled out. For
seminal work on high oxidation state bimetallic Pd species, see: (a) D.
C. Powers and T. Ritter, Nat. Chem., 2009,
1, 302-309; (b) D. C.
ACS Catal., 2016,
6
, 4755-4759.
Powers, M. A. L. Geibel, J. E. M. N. Klein and T. Ritter, J. Am. Chem.
Soc., 2009, 131, 17050-17051.
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Green Chemistry
View Article Online
DOI: 10.1039/C6GC03438A
Table of Contents:
An external oxidant-free, base-free direct C-H arylation of (electron-rich) arenes by visible-light
mediated metal-free photoredox catalysis in tandem with palladium catalysis is reported. The
reaction operates under very mild conditions; at room temperature, without a silver-salt
activator, and additives, and no generation of copious metal waste. The broad substrate scope,
functional group tolerance and excellent regioselectivity of this process make it attractive for
effective synthesis of a wide range of N-heterocyclic moieties.