Photocatalyst-free, Visible Light Driven, Gold Promoted Suzuki Synthesis of (Hetero)biaryls

Article abstract of DOI:10.1002/cctc.201701436

A visible-light driven Suzuki cross-coupling reaction was performed with colored and bench-stable arylazosulfones in the presence of Ph₃PAuCl (5 mol %) as the catalyst. The absence of a photocatalyst, along with the use of commercially available and easy-to-handle arylboronic acids underline the novelty and synthetic usefulness of the protocol. A reaction mechanism involving the generation of an aryl radical as the key intermediate has been proposed on the basis of experimental investigations.

Full text of DOI:10.1002/cctc.201701436

Accepted Article
Title: Photocatalyst-free, visible light driven, gold promoted Suzuki
synthesis of (hetero)biaryls
Authors: Marco Bandini, Christopher Sauer, Yang Liu, Assunta De Nisi,
Stefano Protti, and Maurizio Fagnoni
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: ChemCatChem 10.1002/cctc.201701436
Link to VoR: http://dx.doi.org/10.1002/cctc.201701436
A Journal of
www.chemcatchem.org

10.1002/cctc.201701436
ChemCatChem
COMMUNICATION
Photocatalyst-free, visible light driven, gold promoted Suzuki
synthesis of (hetero)biaryls
Christopher Sauer,[a] Yang Liu,[a] Assunta De Nisi,[a] Stefano Protti,*[b] Maurizio Fagnoni,[b] Marco
Bandini*[a]
Abstract: A visible-light driven Suzuki cross-coupling reaction was
performed with colored and bench-stable arylazosulfones in the
presence of Ph3PAuCl (5 mol%) as the catalyst. The absence of a
photocatalyst, along with the use of commercially available and
easy-to-handle arylboronic acids underlined the novelty and
synthetic usefulness of the protocol. A reaction mechanism involving
the generation of an aryl radical as the key intermediate has been
proposed on the basis of experimental investigations.
In recent decades, homogeneous gold catalysis has been
applied to an impressive variety of synthetic protocols[1] with
eminent examples in the field of total synthesis[1d] and
asymmetric catalysis.[1i] In particular, the [Au(I)/Au(III)] redox
cycle was exploited in a wide range of cascade nucleophilic
addition-oxidative coupling processes,[2] where the formation of
an alkyl-[Au(III)] intermediate is followed by its reaction with
nucleophilic species such as alkynes or boronic acids, in
Sonogashira and the Suzuki protocols, respectively.[3] In these
cases, different strategies have been proposed to facilitate the
Scheme 1.
gold/photoredox catalytic approach.
A selection of synthetic targets achieved through a dual
redox cycle, including the use of a strong external oxidant (e.g.
Selectfluor, PhI(OAc)2) or
a dual Au/Pd transition metal
system.[4a] At this regard, the development of innovative dual
catalytic systems is currently a challenge[4b] and the pioneering
works by Toste[5a] and Glorius[5b] prompted the rise of the
combination of gold and visible light photoredox catalysis in dual
Moreover, this approach was recently implemented into a
visible-light driven photocatalyst-free cross-coupling of boronic
acids and arenediazonium tetrafluoroborate salts by Hashmi and
coworkers. (pCF3-C6H4)3PAuCl was used as the catalyst, with
the isolation of biaryls in satisfactory yields (Scheme 2 path
a).[8a]
Arenediazonium salts are rather unstable and colorless
compounds, thus the species [LAu(III)](N2Ar)]+ generated in situ
was claimed for the visible light absorption.[8]
catalytic
arylation
processes.[4b,6]
In
these
cases,
arenediazonium salts were considered as the elective substrate,
that was smoothly reduced by the photoexcited catalyst PC* (a
colored inorganic complex or an organic dye) to generate, after
nitrogen loss, the corresponding aryl radical. The latter is then
involved in the [Au(I)/Au(III)] redox catalytic cycle. Therefore,
This strategy has been successfully applied to a plethora of
synthetic protocols, including the oxy- and amino arylation of
alkenes (Scheme 1, path a)[7a-c] the synthesis of cyclic ketones
A recent report by Crespi et al. focused on the wavelength
dependent photoreactivity of arylazosulfones,
compounds that can be smoothly prepared from the
corresponding anilines in
two steps procedure.[9] Such
molecules bear colored photolabile moiety (i.e.
a class of
through the arylative ring expansion of allyl alcohols (path b)[5b,c]
,
a
the synthesis of oxygen- (path c)[7d] and nitrogen- based
heterocycles[7e,f] via arylative cyclization of alkynes as well as the
synthesis of allyl- (path d,)[7g] and vinylarenes,[7h] aryl alkynes[7i]
and biaryls (path e).[7j-l]
a
-
N2SO2CH3)[10,11] which undergoes, upon visible light exposition,
homolytic cleavage of the N-S bond and N2 loss, delivering the
corresponding radicals. We reported herein that such photo-
triggered, bench stable precursors of aryl radicals can be
exploited satisfyingly in the visible light promoted photocatalyst-
free Suzuki cross coupling under gold catalytic regime (Scheme
2, path b).
[a]
[b]
Mr. C. Sauer, M. Y. Liu, Ms. A. De Nisi, Prof. M. Bandini
Dipartimento di Chimica “G. Ciamician”
Alma Mater Studiorum – Università di Bologna
Via Selmi 2, 40126 Bologna, Italy
E-mail: marco.bandini@unibo.it
Prof. S. Protti, Prof. M. Fagnoni
PhotoGreen Lab, Department of Chemistry,
University of Pavia
V.le Taramelli 10, 27100 Pavia, Italy
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
This article is protected by copyright. All rights reserved.

10.1002/cctc.201701436
ChemCatChem
COMMUNICATION
Table 1. Optimization of the reaction conditions.
Entry
1
Conditions
3aa yield (%)[a]
61[b]
1a, 2a, PPh3AuCl (5 mol%), bpy (20 mol%),
NaOAc (2 equiv.)
[c]
1a, 2a, PPh3AuCl (5 mol%),
2
-
bpy (20 mol%)
[c]
3
4
1a, 2a, bpy (20 mol%), NaOAc (2 equiv.)
-
Scheme 2. a) Light induced, photocatalyst-free Suzuki coupling described by
Hashmi and co-workers (see ref. 8a). b) Visible light promoted synthesis of
substituted biaryls from arylazosulfones described in the present paper.
1a, 2a, PPh3AuNTf2 (5 mol%),[d] bpy (20
mol%), NaOAc (2 equiv.)
50
53
41
1a, 2a, PPh3AuCl (20 mol%), bpy (20 mol%),
NaOAc (2 equiv.)
5
6
At the outset of our investigation, we considered p-CN-derivative
1a and phenyl boronic acid 2a as the model reactants for the
1a', 2a, PPh3AuCl (5 mol%), bpy (20 mol%),
NaOAc (2 equiv.)
cross-coupling event and
a range of reaction parameters
(including the nature of the base and its concentration, the
solvent, the presence of additives, the stoichometric ratio
between 1a and 2a as well as the light source employed) were
assessed in order to ascertain optimal reaction conditions. The
optimization of the process has been described in detail in
Tables S1-S7.
Thus, the conditions that emerged as optimal involved the
irradiation of a mixture containing 1a (0.5 M), 2a (2 equiv.),
PPh3AuCl (5 mol%), bpy (20 mol%), NaOAc (2 equiv.),
CH3CN/MeOH (degassed 3:1) by means of a 7 W Blue-LED as
the light source. Under these conditions, biphenyl 3aa was
isolated in 61% yield along with a 20% of 4,4'-dicyanobiphenyl
(3a’) arising from the homocoupling of 1a.[12] Additionally, GC-
MS analysis of the reaction crude pointed out the presence of
traces (overall < 10% yield) of p-cyanophenyl-methyl sulfone as
well as of 4-(phenyldiazenyl)benzonitrile.
7
1a, 2a, PPh3AuCl (5 mol%), NaOAc (2 equiv.)
17
15
8[e]
1a, 2a, PPh3AuCl (5 mol%), bpy (20 mol%),
NaOAc (2 equiv.)
[a] Isolated yield. A complete conversion of 1 was observed in all cases. [b] 20% of
4,4'-dicyanobiphenyl 3a' was isolated. [c] No arylation observed. [d] Preformed gold
complex was employed [e] Blank experiment in the absence of light, rt.
The scope of the photocatalyst-free, gold-catalyzed Suzuki-type
cross coupling was then investigated by carrying out the reaction
of a range of arylazosulfones 1a-g with aryl boronic acids 2a-f
(Chart 1) under the reaction conditions previously optimized.
The obtained results were depicted in Scheme 3.
Any deviation from the above-described conditions caused
either a marked drop in reaction performances or no significant
changes (see results depicted in Table 1). Indeed, the presence
of the gold(I) complex as well as of a base proved to be
mandatory for the success of the titled cross-coupling reaction
(entries 1-3), while attempts to improve the efficiency of the
process by catalytic modulation (i.e. PPh3AuNTf2, or higher
loading) did not result in a significant change of the final
outcomes (entries 4,5).[13] Finally, when the tosyl derivative 1a’
was employed instead of 1a no significant improvements were
obtained (yield = 41%, entry 6).
The positive role played by the bpy (20 mol%) in aryl-gold
mediated coupling processes has been documented in
literature.[14] This effect was also proven in our methodology, as
a matter of fact, the absence of bpy was detrimental for the final
chemical outcome (entry 1 vs entry 7). Although a conclusive
explanation for this effect is not defined yet, bpy could act as an
acidity scavenger of for the stabilization of organo-gold adducts
(e.g. ligand assistance) during the catalytic cycle.
Chart 1. Substrates employed in the present work.
Isolated yields were commonly from moderate to good, no
significant effect of the electronic properties of the aromatic
substituents was observed. Interestingly, functionalized
terphenyls (e.g. 3ad and 3bd) were obtained in satisfactory
yields up to 55%. Ortho-substitution on the arylazosulfone (1f)
was also tolerated, though the desired compound (e.g. 3fc) was
isolated only in modest amounts (28% yield). Noteworthy,
hetero-aromatic boronic acids such as C(3)-benzothiophene (2f)
underwent arylation with diversely substituted arylazosulfones,
This article is protected by copyright. All rights reserved.

10.1002/cctc.201701436
ChemCatChem
COMMUNICATION
providing the corresponding cross-coupling products 3af-3cf in
acceptable yields (40-48%).
Remarkably, the protocol also allows the persistence in the final
product of an arylhalide bond (see compounds 3da, 3dc, 3ec
and 3fc), enabling further chemical manipulations under
complementary reaction conditions, possible.
A reaction mechanism was suggested on the basis of both the
experimental data and what reported by Fouquet and co-
workers on dual photoredox/Au catalyzed arylation processes.[7l]
Scheme 4. Proposed mechanism for the visible light/[Au(I)] catalyzed Suzuki
cross-coupling described herein.
Oxidative addition occurring on the [Au(I)] catalyst by the
photogenerated Ar• resulted in the formation of the [Au(II)]
species
I
(path b), which is further oxidized by the
•
methanesulfonyl radical (CH3SO2 ), thus forming the
triphenylphosphine [Au(III)] species/methanesulfinate ion pair II.
The activation of boronic acid 2 by a base allowed for an
enhanced polarisation of the boron-carbon bond, which
facilitated the transmetallation with II (path d) to form the
intermediate III. Following reductive elimination resulted in the
release of the coupling products (3, path e) while affording the
starting [Au(I)] catalyst.
Competitively to path c, a second aryl radical might concur to the
oxidation of the [Au(II)] intermediate I (path c'), resulting in a
[Au(III)] species III’ that could release side-product Ar-Ar 3’ via
reductive elimination.[15]
The key role of the aryl radical was also pointed out through
experiments carried out in the presence of 2,2,6,6-
tetramethylpiperidin-1-yl)oxyl (TEMPO) as the radical trap.[10] In
the present case, irradiation of 1a and 2a under the optimized
conditions with 1.2 equiv. of TEMPO resulted in a significant
decrease in the efficiency of the desired cross-coupling reaction
(See Table S5 for further details).
In conclusion, an unprecedented [Au(I)] catalysed Suzuki
cross-coupling between arylazosulfones and boronic acids has
been documented under visible-light assisted regime. The
colored and photolabile properties of the sulfonyl partners
enabled a photocatalyst-free protocol to be implemented under
mild reaction conditions. Experimental evidences account for a
dual metal-photoredox catalytic cycle involved in the Ar-C bond
forming process.
Scheme 3. Scope of the photocatalyst-free gold catalyzed Suzuki reaction.[a]
Blue led 1 W was used (CH3CN:H2O = 3:1).
In the first step (Scheme 4, path a) visible light irradiation of
arylazosulfones
1
resulted in the generation of the
corresponding aryl radical (Ar•) via homolysis of the S-N bond
1
from the nπ* state of the arylazosulfone followed by dinitrogen
loss.
Experimental section
General procedures for the synthesis of (hetero)biaryls
To a solution (200 µL, CH3CN:MeOH = 3:1, reagent grade) of
arylazosulfone 1 (0.1 mmol, 0.5 M) was added the boronic acid
2 (0.2 mmol, 2 equiv.), NaOAc (0.2 mmol), PPh3AuCl (5 mol%)
This article is protected by copyright. All rights reserved.

10.1002/cctc.201701436
ChemCatChem
COMMUNICATION
[5]
a) X.-Z. Shu, M. Zhang, Y. He, H. Frei and F. D. Toste, J. Am. Chem.
Soc. 2014, 136, 5844-5847; b) M. N. Hopkinson, A. Tlahuext-Aca, F.
Glorius, Acc. Chem. Res. stefano2016, 49, 2261-2272; c) M. Zidan, T.
McCallum, L. Thai-Savard, L. Barriault, Org. Chem. Front. 2017, DOI:
10.1039/c7qo00590c.
and bpy (20 mol%) in sequence. The resulting mixture was then
degassed via N2-bubbling and the vial exposed to blue LED (1 or
7 W) until the complete consumption of 1 (TLC monitoring). The
solvent was then removed under vacuum and the reaction crude
purified via flash chromatography.
[6]
[7]
For recent review articles and examples see: a) M. Zhang, C. Zhu, L.-W.
Ye, Synthesis, 2017, 49, 1150-1157;b) H. Li, C. Shan, C.-H. Tung, Z.
Xu, Chem. Sci., 2017, 8, 2610-2615.
a) B. Sahoo, M. N. Hopkinson, F. Glorius, J. Am. Chem. Soc. 2013, 135,
5505-5508; b) M. N. Hopkinson, B. Sahoo, F. Glorius, Adv. Synth. Catal.
2014, 356, 2794-2800; c) Q. Zhang, Z.-Q. Zhang, Y. Fu, H.-Z. Yu, ACS
Catal. 2016, 6, 798-808; d) Z. Xia, O. Khaled, V. Mouriès-Mansuy, C.
Ollivier, L. Fensterbank, J. Org. Chem., 2016, 81, 7182-7190; e) C. Qu,
S. Zhang, H. Du, C. Zhu, Chem. Commun., 2016, 52, 14400-14403; f)
Z.-S. Wang, T.-De Tan, C.-M. Wang, D.-Q. Yuan, T. Zhang, P. Zhu, C.
Zhu, J.-M. Zhou, L.-W. Ye, Chem. Commun., 2017, 53, 6848-6851; g)
M. O. Akram, P. S. Mali, N. T. Patil, Org. Lett. 2017, 19, 3075-3078; h)
D. V. Patil, H. Yun, S. Shin, Adv. Synth. Catal. 2015, 357, 2622-2628; i)
S. Kim, J. Rojas-Martina, F. D. Toste, Chem. Sci., 2016, 7, 85-88; j) V.
Gauchot, D. R. Sutherland, A.-L. Lee, Chem. Sci.,2017, 8, 2885-2889;
k) V. Gauchot, A.-L. Lee, Chem. Commun.,2016, 52, 10163-10166; l) T.
Cornilleau, P. Hermange, E. Fouquet, Chem. Commun., 2016, 52,
10040-10043.
Acknowledgements
Acknowledgements are made to University of Bologna for
financial support. We are also grateful to Lombardy region/
Cariplo Foundation, Italy, project 2015-0756 “Visible Light
Generation of Reactive Intermediates from Azosulfones”. Y.L.
thanks Chinese Scholarship Council N° 201609120008 for
funding support.
Keywords: Suzuki cross-coupling • Gold catalysis • Aryl radicals
• Visible light • Photocatalyst-free process • Arylazosulfones
[1]
a) A. S. K. Hashmi, G. J. Hutchings, Angew. Chem. 2006, 118, 8064-
8105; Angew. Chem. Int. Ed. 2006, 45, 7896-7936; b) A. Fürstner, P. W.
Davies, Angew. Chem. 2007, 119, 3478-3519; Angew. Chem. Int.
Ed.2007, 46, 3410-3449; c) A. Arcadi, Chem. Rev.2008, 108, 3266-
3325; d) A. S. K. Hashmi, M. Rudolph, Chem. Soc. Rev., 2008, 37,
1766-1775; e) M. Bandini, Chem. Soc. Rev. 2011, 40, 1358-1367; f) T.
C. Boorman, I. Larrosa, Chem. Soc. Rev. 2011, 40, 1910-1925; g) C.
Obradors, A. M. Echavarren, Chem. Commun. 2014, 50, 16-28; h) R.
Dorel, A. M. Echavarren, Chem. Rev., 2015, 115, 9028-9072; i) W. Zi, F.
D. Toste, Chem. Sci. 2016, 45, 4567-4589.
[8]
[9]
a) S. Witzel, J. Xie, M. Rudolph, A. S. K. Hashmi, Adv. Synth. Catal.
2017, 359, 1522-1528; b) L. Huang, F. Rominger, M. Rudolph, A. S. K.
Hashmi, Chem. Commun. 2016, 52, 6435-6438; C) L. Huang, M.
Rudolph, F. Rominger, A. S. K. Hashmi, Angew. Chem. 2016, 128,
4888-4893; Angew. Chem. Int. Ed. 2016, 55, 4808-4813.
S. Crespi, S. Protti, M. Fagnoni, J. Org. Chem. 2016, 81, 9612-9619.
[10] M. Malacarne, S. Protti, M. Fagnoni, Adv. Synth. Cat. 2017, DOI
10.1002/adsc.201700619
[11] J. Yoshida, K. Kataoka, R. Horcajada, A. Nagaki, Chem. Rev. 2008,
108, 2265-2299.
[2]
[3]
[4]
For pioneering works see: a) L. T. Ball, G. C. Lloyd-Jones, C. A.
Russell, Science, 2012, 337, 1644-1648; b) L. T. Ball, G. C. Lloyd-
Jones, C. A. Russell, J. Am. Chem. Soc. 2014, 136, 254-264; c) A. J.
Cresswell, G. C. Lloyd-Jones, Chem. Eur. J. 2016, 22, 12641-12645.
a) T. de Haro, C. Nevado, Synthesis 2011, 16, 2530-2539; b) C.
González-Arellano, A. Abad, A. Corma, H. García, M. Iglesias, F.
Sánchez, Angew. Chem. 2007, 119, 7966-7968; Angew. Chem., Int.
Ed.,2007, 46, 1536-1538.
[12] The formation of the homo-coupling product of the aryl radical-
congener has been observed also in analogous protocols involving
arenediazonium salts (see refs. 7k,l).
[13] For a complete list of reaction conditions screening see Tables S1-6.
[14] R. Cai, M. Lu, E. Y. Aguilera, Y. Xi, N. G. Akhmedov, J. L. Petersen, H.
Chen, X. Shi, Angew. Chem. 2015, 127, 8896-8900; Angew. Chem., Int.
Ed. 2015, 54, 8772-8776.
[15] To investigate the role of the metal catalyst in the side-product
formation, we irradiated 1a in absence of boronic acid and PPh3AuCl.
Under these conditions, the homo-coupling compound 3a’ was not
observed.
a) M. N. Hopkinson, A. D. Gee, V. Gouverneur, Chem. Eur. J. 2011, 17,
8248-8262; b) J. Twilton, C. Le, P. Zhang, M. H. Shaw, R. W. Evans, D.
W. C. MacMillan, Nature Rev. Chem. 2017, 1, DOI: 10.1038/s41570-
017-0052.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201701436
ChemCatChem
COMMUNICATION
COMMUNICATION
C. Sauer,Y. Liu, A. De Nisi, S. Protti,* M.
Fagnoni, M. Bandini*
Page No. – Page No.
Photocatalyst-free, visible light
driven, gold promoted Suzuki
synthesis of (hetero)biaryls with
arylazo-sulfones
So free so good. A version of Suzuki cross-coupling is documented in by merging
visible photoredox catalysis and [Au(I)] catalysis.The employment og coloured and
photolibile arylazosulfone as reaction parnters enables the biaryl forming protocol to
be performed under photocatalyst-free conditions.
This article is protected by copyright. All rights reserved.