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1582
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Recent applications of arene diazonium salts in organic
synthesis
Fanyang Mo,a,b Guangbin Dong,*b Yan Zhanga and Jianbo Wang*a
Received 6th December 2012,
Accepted 9th January 2013
Arene diazonium salts are common, easily prepared and highly useful intermediates in organic synthesis
due to their rich reactivity and diverse transformations. In this review, recent advances involving arene
DOI: 10.1039/c3ob27366k
diazonium salts as starting materials or active intermediates for various synthetically useful applications
www.rsc.org/obc
are summarized.
1 Introduction
Diazonium compounds, taught in almost every sophomore
organic chemistry course, represent a large group of organic
compounds with the general formula R–NuN+X−, in which R
can be alkyl or aryl and X is an organic or inorganic anion
such as a halogen. Diazonium salts, especially those where R
is an aryl group, are important intermediates and have found
wide applications in organic synthesis. Since their first discovery in 1858,1 several prominent named reactions associated
a
College of Chemistry and Molecular Engineering, Peking University, Beijing,
P. R. China. E-mail: wangjb@pku.edu.cn
b
Department of Chemistry and Biochemistry, University of Texas at Austin, Austin,
Texas 78712, USA. E-mail: gbdong@cm.utexas.edu
Fanyang Mo
Fanyang Mo was born in Liaoning Province of China in 1982.
He received his B.Sc. and M.Sc.
degrees from Beijing Institute of
Technology (P. R. of China) in
2004 and 2006 under the supervision of Professor Zhiming Zhou.
He then obtained his Ph.D. from
Peking University under the
supervision of Prof. Jianbo Wang
in 2010. He is currently a postdoctoral fellow in Prof. Guangbin Dong’s group at the
University of Texas at Austin.
1582 | Org. Biomol. Chem., 2013, 11, 1582–1593
with arene diazonium salts have evolved throughout the development of more than one century (Scheme 1).
In 1884, Sandmeyer disclosed that by treatment with
copper(I) chloride, benzenediazonium salt was converted into
chlorobenzene.2 He also showed that bromobenzene could be
formed when using copper(I) bromide, and benzonitrile was
obtained when copper(I) cyanide was used. 12 years later,
Pschorr reported a method for the preparation of biaryltricyclics by intramolecular substitution of one arene with an aryl
radical, which is generated in situ from an aryl diazonium salt
by copper catalysis.3 In 1924, Gomberg and Bachmann developed an intermolecular version of Pschorr’s radical biaryl synthesis, which is now known as the Gomberg–Bachmann
reaction.4 Only three years later, an important breakthrough
was achieved by Balz and Schiemann, who reported thermal
decomposition of aromatic diazonium tetrafluoroborates.
Guangbin Dong received his B.S.
degree from Peking University
and completed his Ph.D. degree
in chemistry from Stanford University with Professor Barry
M. Trost, where he was a Larry
Yung Stanford Graduate fellow.
In 2009, he began to research
with Prof. Robert H. Grubbs at
the California Institute of Technology, as a Camille and Henry
Dreyfus Environmental Chemistry Fellow. In 2011, he joined
Guangbin Dong
the department of chemistry and
biochemistry at the University of Texas at Austin as an assistant
professor and a CPRIT Scholar. His research interests include the
development of powerful chemical tools for addressing questions
of biological importance.
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Scheme 1
Perspective
Brief history of diazonium salts.
The reaction leads to the formation of aromatic fluorides,
which cannot be accessed by the Sandmeyer reaction.5 In
1939, Meerwein and co-workers reported an extensive study on
the reaction of aromatic diazonium salts with α,β-unsaturated
carbonyl compounds. The reaction was later known as Meerwein arylation, in which the aryl group adds across the double
bond.6
In 1977, Doyle and co-workers reported a different method
for the generation of diazonium salts in which an aqueous
acidic solution was no longer necessary.7 This development
expands the synthetic scope of diazonium salts in organic synthesis. Besides the above-mentioned classical reactions, diazonium salts also served as arylhalide surrogates, which have
been utilized in Pd-catalyzed cross-coupling reactions for
carbon–carbon bond and carbon–heteroatom bond formation.
These coupling reactions have been well established over the
past 40 years since the pioneering work of Kikukawa and
Matsuda in 1977,8 and are comprehensively documented in a
series of excellent reviews.9 In addition, diazonium salts are
also highly useful in the dye and pigment industry for the
preparation of azo-compounds.10 Regardless of the long
history, the arene diazonium compounds still attract attention
and new developments have been emerging constantly. In this
short review article, we will focus on the most recent
developments.
Arene diazonium salts have been utilized as reactive arylhalide
surrogates in Pd-catalyzed cross-coupling reactions for C–C
bond formation.9 The intrinsic electrophilicity of diazonium
salts comes from N2 being a superb leaving group, which
allows the use of mild reaction conditions, and sometimes
without an additional ligand and/or base. The first utilization
of the aryldiazonium salts as electrophiles in Pd-catalyzed
Suzuki–Miyaura cross-couplings was achieved independently
by Genêt11 and Sengupta.12 A recent example was shown by
Gras and co-workers who reported an application of diazonium salts 1 in a base-free cross-coupling reaction with selfactivated dioxazaborocanes 2 under mild and user-friendly
conditions (Scheme 2).13
In their study, Pd(OAc)2 only showed moderate efficiency
and gave homo-coupling of dioxazaborocanes 2 as the major
product, whereas Pd/C was proved to be a highly selective catalyst towards cross-coupling products.
Although arene diazonium tetrafluoroborates have been
well established as coupling partners in Pd-catalyzed reactions,
the major drawback is that they are usually not commercially
available and in many cases have to be newly prepared before
use. In this context, one-pot diazotization/cross-coupling is
obviously more attractive. Such a one-pot approach has been
Yan Zhang obtained her B.S. in
1997, and her Ph.D. in 2002
from Lanzhou University (under
the supervision of Prof. Ziyi
Zhang). She continued her
research as a postdoctoral
associate
in
Hong
Kong,
Germany, and the United States.
She began her academic career
at Peking University in 2008 in
Prof. Jianbo Wang’s group. Her
research focuses on the application of transition metal comYan Zhang
plexes of N-heterocyclic carbenes
and the synthesis of small molecules with important biological
activities.
Jianbo Wang received his B.S.
degree from Nanjing University
of Science and Technology in
1983, and his Ph.D. from
Hokkaido University (under the
supervision
of
Prof.
H.
Suginome) in 1990. He was a
postdoctoral associate at the
University of Geneva from 1990
to 1993 (with Prof. C. W.
Jefford), and at the University of
Wisconsin-Madison from 1993 to
1995 (with Prof. H. E. ZimmerJianbo Wang
man and F. A. Fahien). He began
his academic career at Peking University in 1995. His research
interests include catalytic metal carbene transformations.
This journal is © The Royal Society of Chemistry 2013
2 Carbon–carbon bond formation
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Perspective
Scheme 2 Pd-catalyzed
dioxazaborocanes.
Organic & Biomolecular Chemistry
cross-coupling
of
diazonium
salts
and
Scheme 4
Scheme 3
Pd-catalyzed one-pot diazotization/cross-coupling.
exploited previously by several groups.14 A recent example has
been shown by Wang and co-workers who have demonstrated
a convenient Pd-catalyzed base-free Suzuki–Miyaura crosscoupling for the synthesis of biaryls using arylamines 4 as the
starting materials (Scheme 3).15 The mechanism of this diazotization-coupling is proposed to be the standard oxidative
addition–reductive elimination mechanism of Pd-catalyzed
cross-coupling.16
The Heck–Matsuda reaction is the diazonium salt version
of the Heck–Mizoroki reaction, where aryl-halides or -sulfonates serve as electrophiles. Although the seminal work was
achieved by Kikukawa and Matsuda in 1977,8 the Heck–
Matsuda reaction had been overlooked until the late nineties.
In recent years, the group of Felpin has made significant contributions toward the development of the Heck–Matsuda reaction.9,17 In 2010, they demonstrated a highly efficient Heck–
Matsuda coupling of aryldiazonium salts with 2-arylacrylates
leading to cis-stilbene with good to excellent E stereoselectivity
(Scheme 4).17e
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Synthesis of stilbenes by the Heck–Matsuda reaction.
It has been shown that 2-arylacrylates 6 with one substituent on the aromatic ring at C2 coupling with diazonium salts 1
under palladium catalysis gives exclusively cis-stilbenes. Interestingly, the high stereoselectivity observed does not seem to
be related to any stereoelectronic effect on either the acrylate
or the diazonium salt. They also found that the catalyst
loading can be lowered to 0.005% in the coupling reaction of
diazonium salts with methyl acrylate.
In subsequent work, the same group reported a Heck–
Matsuda reaction using a substoichiometric amount of diazonium salt through a double catalytic cycle.17g A variety of acids
were examined in order to evaluate the influence of the acidity
and the nature of the counter-ion (eqn (1)). The results showed
that although the tetrafluoroborate anion has been widely
used in the literature, it was not the most effective counter-ion
regardless of the source of the acid (i.e., HBF4 and BF3·Et2O).
Finally, MeSO3H was selected as the acid of choice based on
the cost and recoverability.
ð1Þ
This reaction is not sensitive to steric effects as some orthosubstituted diazonium salts gave even higher yields as compared with their para-substituted counterparts. Moreover, this
coupling has been utilized to complete the synthesis of quinolone 11 by their Heck-reduction–cyclization strategy
(Scheme 5).
In 2012, König and co-workers developed an efficient
visible-light mediated arylation of alkenes, alkynes and enones
with diazonium salts by photoredox catalysis (Scheme 6).18
The reaction scope comprises a range of different substituted
aryl diazonium salts and tolerates a variety of functional
groups including aryl halides. Mechanistically, a radical
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Organic & Biomolecular Chemistry
Scheme 5
Perspective
Scheme 7
salts.
Pd–Au-catalyzed Sonogashira cross-coupling of arenediazonium
Scheme 8
Sonogashira cross-coupling of aryldiazonium salts.
Scheme 9
Pd-catalyzed reaction of phenol diazonium salts with alkynes 13.
Heck–Matsuda reaction and synthesis of quinolone 11.
Scheme 6 Photocatalytic arylation of alkenes, alkynes and enones with diazonium salts.
pathway including one-electron oxidation and reduction steps
is likely for this photoredox arylation.
In early 2013, Gholinejad reported Heck–Matsuda and
Suzuki–Miyaura coupling reactions of aryl diazonium salts
catalyzed by palladium nanoparticles supported on agarose.19
By using this new catalyst, reactions could be carried out in
aqueous solution at lower temperature. Moreover, this
immobilized catalyst could be recycled and reused several
times.
Although many Pd-catalyzed cross-coupling reactions, such
as the Heck, Suzuki–Miyaura and Stille reactions, have been
developed utilizing aryldiazonium salts as aryl halide surrogates, the Sonogashira cross-coupling remained a challenge
until the first two successful examples presented by the Sarkar
group and the Cacchi group in 2010, respectively (Schemes 7
and 8).20,21 In Sarkar’s work, AuCl and PdCl2 were combined
as a catalyst and the reaction could even start with aniline
derivatives by employing an in situ diazonium formation step.
In Cacchi’s work, initial attempts with various Pd catalysts, solvents and bases did not produce the desired product. The
problem was circumvented by a sequential iododediazoniation/cross-coupling strategy.
Carbopalladation of alkynes results in the formation of
alkenyl palladium species. Phenol diazonium salts 12 have
been recently explored by Schmidt and co-workers in Pd-
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catalyzed [2 + 2 + 1] cyclization, leading to the formation of
spirocyclic ketones 14 (Scheme 9).22
Besides traditional cross-coupling reactions, arene diazonium salts can also serve as an aryl radical source in transition-metal-catalyzed C–H functionalization and metal-free
C–C bond forming reactions. For a recent example, the
Sanford group described a room-temperature ligand-directed
C–H arylation reaction using aryldiazonium salts (Scheme 10).23
The linchpin for the success of this methodology is the combination of visible-light photoredox catalysis and Pd-catalyzed
C–H functionalization. This room-temperature C–H arylation
reaction is effective for the substrates containing a wide range
of directing groups, including 2-arylpyridines, amides,
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Perspective
Scheme 10
Pd/Ru-catalyzed C–H arylation with diazonium salts.
pyrazoles, pyrimidines, oxime ethers, and free oximes. The
authors have proposed a mechanism which involves a ruthenium catalyst cycle. The diazonium salt is decomposed to an
aryl radical by Ru(bpy)32+*,24 which is formed by photoexcitation of Ru(bpy)32+. This aryl radical then participates in the Pdcatalyzed C–H functionalization cycle to oxidize Pd(II) to Pd(III),
which is further oxidized by Ru(III) to form a Pd(IV) species and
regenerate the photocatalyst. Finally, C–C bond-forming reductive elimination releases the arylated product and regenerates
the Pd(II) catalyst.
In 2012, König and co-workers reported a metal-free,
visible-light-mediated direct C–H arylation of heteroarenes
with aryldiazonium salts (Scheme 11).25
The reaction does not require transition-metal catalysts or
bases and proceeds smoothly at room temperature. In contrast
to Sanford’s ruthenium catalyst, this protocol uses eosin Y 17
as the photoredox catalyst, and is presumed to proceed
through a radical mechanism.26 The radical mechanism is
supported by the fact that 2,2,6,6-tetramethylpiperidinoxyl
(TEMPO) effectively inhibits the reaction, and trapped intermediates can be detected.
As shown in Scheme 11, the proposed mechanism starts
with the formation of an aryl radical A by single-electron transfer (SET) from the excited state of eosin Y to the aryldiazonium
salt. Addition of the aryl radical to heteroarene gives radical
intermediate B, which is further transformed to the carbocation intermediate C by two possible pathways: (a) oxidation
of the radical intermediate B by the eosin Y radical cation to
give C or (b) oxidation of B by aryldiazonium salt in a radical
chain transfer mechanism. Finally, deprotonation of intermediate C regenerates the aromatic ring and gives the final
coupling product.
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Organic & Biomolecular Chemistry
Scheme 11 Eosin Y-catalyzed visible-light-mediated direct C–H arylation of
heteroarenes with aryldiazonium salts.
In the same year, the König group developed an eosin Y
catalyzed visible light photocatalytic reaction of o-methylthioarenediazonium salts with alkynes. The reaction affords substituted benzothiophenes through a similar radical annulation
process.27 This method provides mild and efficient access to
benzothiophenes. This method was employed to prepare
the key intermediate 21 for the synthesis of raloxifene28
(Scheme 12).
In 2012, Studer and co-workers reported a transition-metalfree oxyarylation of alkenes 23 with aryldiazonium salts and
TEMPONa (Scheme 13).29 The mechanism involves aryl radical
addition to alkenes with subsequent TEMPO trapping to
afford the corresponding oxyarylation products 24. TEMPONa
is used as a reducing reagent to convert an aryldiazonium salt
to the corresponding aryl radical through single-electron transfer. The product TEMPO-based alkoxyamines can be easily
converted to more common and useful compounds by further
chemical manipulation.
Aryldiazonium salts are typically considered as electrophiles
to participate in various Pd-catalyzed cross-coupling reactions.
However, much less attention has been paid to the synthetic
utility of the homocoupling of aryldiazonium salts for synthesizing symmetrical biaryls.30 In 2012, Song and co-workers
reported a simple and efficient FeCl2-promoted homocoupling
of aryldiazonium tetrafluoroborates to afford symmetrical
biaryls 25 with broad substrate scope and high yields
(Scheme 14).31 The authors suggest that the mechanism
involves reductive homocoupling of the aryldiazonium salt
with the oxidation of the Fe2+ ion.
Aryldiazonium salts are not only excellent precursors
for the generation of radical intermediates, but also aryl
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Perspective
Scheme 14
Scheme 12
Homocoupling of aryldiazonium tetrafluoroborates.
Benzothiophene synthesis from arene diazonium salts.
Scheme 15 Synthesis of polycyclic aromatic hydrocarbons through Friedel–
Crafts intramolecular arylation.
arylamine in high yields and are easy to handle, are widely
used as equivalents of aryldiazonium salts. In the presence of
Lewis or Brønsted acid, aryltriazenes are activated and the corresponding aryldiazonium salt is generated.
Zhou and co-workers reported a metal-free, visible lightinduced [4 + 2] benzannulation of biaryldiazonium salts 28
and alkynes with eosin Y as the photoredox catalyst.34 A variety
of 9-substituted or 9,10-disubstituted phenanthrenes 29 were
obtained via a cascade radical addition and cyclization
sequence. In general, electron deficient alkynes give higher
yields as compared with electron rich ones (Scheme 16).
3 Carbon–boron bond formation
Scheme 13 Transition-metal-free oxyarylation of alkenes with aryldiazonium
salts and TEMPONa.
cations.32 One of the latest examples is shown in Scheme 15,
which was reported by Ren and co-workers in 2012.33 It has
been shown that the reaction of aryltriazenes 26 with BF3·OEt2
leads to the formation of polycyclic aromatic hydrocarbons 27
through a Friedel–Crafts intramolecular arylation. Aryltriazenes, which can be readily prepared from the corresponding
This journal is © The Royal Society of Chemistry 2013
Since the discovery of diazonium salts by Griess in 1858,
carbon–halogen, carbon–carbon, carbon–nitrogen, carbon–
oxygen, carbon–sulfur bond formation have been achieved by
utilizing intrinsic reactivity of diazonium salts. Although
numerous efforts have been made in Pd-catalyzed cross-coupling reactions using aryldiazonium salts since the pioneering
work of Kikukawa and Matsuda reported in 1977, in terms of
mechanism, diazonium salts in these reactions only serve as
“super” electrophiles and surrogates of aryl halides. Thus, it is
not unexpected that aryldiazonium salts can also be used in
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Scheme 18
Scheme 16 Eosin Y-catalyzed visible light-induced [4 + 2] benzannulation of
biaryldiazonium salts and alkynes.
Scheme 17
Cu(I)-catalyzed borylation of aryldiazonium salts.
the Pd-catalyzed Miyaura borylation reaction, which is an
important approach towards aromatic boronates.35
A recent example of transition-metal-catalyzed borylation
of diazonium salts was shown by Yu and co-workers. They
reported Cu(I)-catalyzed cross-coupling reactions of aryl diazonium salts with B2pin2 [bis( pinacolato)diboron] 30 in MeCN–
H2O at room temperature, providing the corresponding arylboronates 31 in good to high yields (Scheme 17).36 They found
that CuBr is superior to other inorganic salts and water in an
organic solvent is helpful to the reaction. Most of the substrates presented are those with electron withdrawing groups
on the aromatic ring. However, the reaction tolerates halo and
acidic substituents.
Recently, transition-metal-free methods for C–B bond formation reactions involving aryldiazonium salts as key intermediates have been reported.37–40 In 2010, Mo and Wang
reported novel metal-free C–B bond formation by directly
1588 | Org. Biomol. Chem., 2013, 11, 1582–1593
Direct conversion of arylamines to pinacol boronates.
converting arylamines into pinacolboronates 31 at room temperature. The starting material arylamine is first converted into
the corresponding diazonium ion by reaction with tert-butylnitrite 32, and then the diazonium ion reacts with the diboron
reagent B2pin2 30 to deliver the final product (Scheme 18).37
The reaction occurs smoothly with meta- and para-substituted arylamines, while the reactions with ortho-substituted
arylamines give diminished yields. In general, substrates with
electron-withdrawing groups at the para- and meta-positions
exhibit good reactivity. It is noteworthy that substrates bearing
halo substituents can also be employed in this reaction, providing the possibility of multiple transition-metal-catalyzed
cross-coupling. Since arylamines are inexpensive and ubiquitous starting materials, this borylation method is expected to
find wide applications in organic synthesis.
More recently, the substrate scope of the reaction was
further expanded, especially to heterocyclic amine derivatives,
for which the corresponding boronate products are highly
important in both academic research and the pharmaceutical
industry (Scheme 19).38 It was found that electron-deficient
heterocyclic amines exhibit high reactivity with nearly complete conversion of B2pin2. However, electron-rich heterocyclic
amines are prone to be oxidized in the presence of t-BuONO,
resulting in diminished yields of the borylation products.
Based on the experimental observations, a possible reaction
pathway involving radical species is proposed for this borylation reaction as shown in Scheme 20. First, the tert-butoxide
anion interacts with B2pin2 to form a tetra-coordinated boron
complex A. Single electron transfer (SET) between the ate
complex A and the aryldiazonium ion then affords an aryl
radical D through N2 extrusion from radical B. Finally, reaction
of aryl radical D with intermediate C gives the borylation
product.
Scheme 19
Heterocyclic boronates from heterocyclic amines.
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Scheme 20
Scheme 21
Perspective
Proposed mechanism for borylation of arylamine.
Scheme 23
Borylation of aryltriazene mediated by BF3·OEt2.
Scheme 24
Proposed mechanistic for borylation of aryltriazene.
Metal-free, visible-light-induced borylation of aryldiazonium salts.
Subsequently, Yan and co-workers reported photoredoxmediated reduction of aryldiazonium salts, providing free aryl
radicals that are borylated in the presence of B2pin2
(Scheme 21).39 Both electron poor and electron rich aromatics
are tolerated and provided the corresponding borylated compounds in moderate to good yields.
In the proposed mechanism, an aryl radical is formed by
single electron transfer (SET) from the excited state of eosin Y
to aryldiazonium salt (Scheme 22). The aryl radical then reacts
with complex A, which is generated in situ from the B2pin2
coordination tetrafluoroborate anion, affording borylation
product 31 and the radical anion intermediate B. Oxidation of
B to C by the eosin Y radical cation completes the catalytic
cycle. This transformation provides supportive evidence for the
involvement of aryl radical species in the borylation with
B2pin2 as shown in Scheme 20.
More recently, Yamane and Zhu described a related arylboronate synthesis via direct borylation of aryltriazene mediated by
BF3·OEt2 (Scheme 23).40 The aryltriazenes, which are
considered as protected diazonium salts, can be easily prepared from the corresponding arylamines in high yields.41 The
reaction proceeds smoothly for a variety of aryltriazenes 35
and provides moderate to high yields of arylboronates.
For the reaction mechanism, it is proposed that the formation of triazene–BF3 complex A is followed by the generation of aryldiazonium salt B (Scheme 24). Then the fluoride
anion transfers from the trifluoroborate anion onto B2pin2 to
generate C. Finally, nucleophilic substitution affords the borylation product and releases N2 and F–Bpin. Although this borylation is closely related to those shown in Scheme 18, a
mechanism involving radical species has been ruled out based
on the trapping experiment.
4 Carbon–sulfur bond formation
Direct chlorosulfonylation of diazonium salts to build carbon–
sulfur bonds was first reported by Meerwein and co-workers in
1957.42 In their original paper, the diazonium salt, formed
from aniline using aqueous NaNO2 in a mixture of concentrated aqueous HCl and acetic acid, is added to a saturated
solution of SO2 in acetic acid in the presence of a catalytic
amount of CuCl2. The reaction affords the corresponding aryl
sulfonyl chloride (eqn (2)).
ð2Þ
Scheme 22
Proposed reaction mechanism.
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Scheme 28 Proposed
dithiocarbamates.
Scheme 25
in CS2.
Formation of diaryldisulfides by electrolyses of aryldiazonium salts
Scheme 26
Proposed reaction mechanism for 36.
Recently, Batanero and co-workers developed an electrolytic
method towards diaryldisulfides synthesis by cathodic
reduction of aryldiazonium tetrafluoroborates in CS2–EtOH
and Bu4NClO4 (Scheme 25).43 In their previous paper,44 they
had already demonstrated that the aryldiazonium salts are
easily reduced to the corresponding aryl radicals under electrolysis, which can further react with solvents such as acetonitrile,
DMF, or 1,2-dichloroethane to produce the dimethylaminocarbonyl, cyanomethyl, or 1,2-dichloroethyl radicals, respectively.
As shown in Scheme 26, the aryl radical, once generated in a
low concentration, can react with CS2 forming intermediate A,
which further decomposes to give carbon monosulfide and
aryl sulfur radical B. Dimerization of intermediate B releases
the final diaryldisulfide product.
In 2011, Ranu and co-workers reported a transition-metalfree procedure for the synthesis of S-aryl dithiocarbamates 37
using water as a solvent at room temperature.45 The reaction is
a one-pot multi-component condensation of aryldiazoniumtetrafluoroborate, carbon disulfide and an amine without
metal catalysts (Scheme 27).
Scheme 27 Transition-metal-free reaction of aryldiazonium salts with dithiocarbamate anions.
1590 | Org. Biomol. Chem., 2013, 11, 1582–1593
Scheme 29
reaction
mechanism
for
the
formation
of
Zn-mediated synthesis of diarylchalcogenides 40.
Mechanistically, it was found that CS2 underwent a very fast
reaction with piperidine in water at 0–5 °C to form piperidine1-dithiocarbamic acid 38, which could be isolated and fully
characterized. Compound 38 could react with aryldiazonium
tetrafluoroborate to give the corresponding dithiocarbamate
product (Scheme 28).
Moreover, the same group has succeeded in using aryldiazonium fluoroborates and diaryldichalcogenides 39 to access
unsymmetrical diarylchalcogenides 40 under microwave conditions (Scheme 29).46
It is known that diaryldichalcogenide could be reduced by
Zn dust via homo-cleavage to form Zn(Xaryl)2 species.47 This
Zn(Xaryl)2 species then reacts with aryldiazonium tetrafluoroborate to provide the final product with extrusion of N2.
5 Miscellaneous reactions
The stability of aryldiazonium salts depends on the aromatic
substituents and the nature of their counter-anion. The diazonium salts of tetrafluoroborates, tosylates and disulfonimides
represent the most stable ones. Recently Kachanov and coworkers have reported a modified method that introduces
1,1,2,3,3-pentacyanopropenide as the anion of aryldiazonium
salts.48 A number of aryldiazonium salts possessing the
1,1,2,3,3-pentacyanopropenide anion have been prepared by
means of the exchange reaction between aryldiazonium chlorides and pyridinium 1,1,2,3,3-pentacyanopropenide49 in water
(Scheme 30).
Although aryldiazonium salts have been widely investigated
as sources of aryl radicals in the Sandmeyer, Meerwein,
Gomberg–Bachmann, and Pschorr reactions, their use and
application as nitrogen-centered radical surrogates has only
been marginally explored so far.50 In 2010, Heinrich and coworkers reported an iron(II)-mediated three-component reaction of hydroperoxides, olefins and aryldiazonium salts to give
azo compounds as products.51 The reaction starts with a
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Scheme 30
Perspective
Preparation of aryldiazonium 1,1,2,3,3-pentacyanopropenide.
Scheme 33
Reductive deamination protocol using a Zn–EtOH system.
Scheme 34
Formation of electrophilic vinyl boranes.
fragmentation liberating acetic acid from hydroperoxide compound 41 to give radical A, which is trapped by olefin to give
another radical B. The last step involves nucleophilic attack of
B by a diazonium ion via a reductive process to furnish the
final product (Scheme 31).
Cyclization of the diazonium ion to form a heterocycle is
another common application of diazonium salts chemistry.
In 2010, Flynn and co-workers reported a modified Richter
cyclization52 by using 2-alkynylaryltriazene 43 as masked diazonium salts, affording chemoselective access to 4-bromocinnoline 44, cinnolinones 45, ring-fused cinnolines 46 and
indazoles 47 (Scheme 32).53
Scheme 31 Synthesis of the azo compound via iron(II)-mediated olefin functionalization with aryldiazonium salts.
Deamination of aromatic amines is one of the important
transformations in organic chemistry. Very recently, Müller
and co-workers reported an efficient and mild deamination
procedure for 1-aminoanthraquinones 48 by using a zinc–
ethanol system (Scheme 33).54
Recently, FLP (frustrated Lewis pair) has attracted attention.55 The chemistry of diazonium salts has also been combined with the reaction of FLP. In 2012, Stephan and coworkers described a new and facile approach for the preparation of electrophilic vinyl boranes 52 starting from diazonium salts and alkynylborate salts 50 (Scheme 34).56a
Alkynylborate salts 50 are easily prepared from the reaction of
FLP tBu3P–B(C6F5)3 with a terminal alkyne by the same
group.56b,c This methodology to electrophilic vinyl boranes can
be conveniently expanded to various alkynylborates and diazonium salts. The authors proposed a mechanism in which the
interaction of the electron-deficient cation derived from the
diazonium salt and the alkyne fragment of the alkynylborate
generates a transient carbocation adjacent to the borate centre.
This promotes the migration of the –C6F5 group from
–B(C6F5)3 to the carbon cation to afford the vinyl borane.
6 Conclusions
Scheme 32
Cyclization of 2-alkynylaryl triazenes 43.
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In this review we have shown a number of synthetic applications of aryldiazonium salts developed in recent years. The
reactive manner of the aryldiazonium salts in all these
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reactions can be summarized in three categories, namely aryl
radical precursors, aryl cation precursors, and “super” electrophiles in transition-metal-catalyzed cross-coupling reactions.
Although the history of aryldiazonium salts can be dated back
to the nonage of organic chemistry, from the selected
examples shown in this review, it can be expected that aryldiazonium salts, which are readily derived from inexpensive and
ubiquitous aromatic anilines, will continue to attract the attention of synthetic chemists as valuable reactants in the coming
years.
Acknowledgements
Financial support from the 973 Program (No. 2012CB821600)
and the National Natural Science Foundation of China is gratefully acknowledged.
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