Visible-light-induced regioselective synthesis of polyheteroaromatic compounds

Article abstract of DOI:10.1039/c6cc00562d

A method for visible-light-induced synthesis of polyheteroaromatics from 2-heteroaryl-substituted anilines and heteroarylalkynes was developed. The process, which uses fac-Ir(ppy)₃ as the photocatalyst and ^tBuONO as the diazotization reagent, is highly regioselective.

Full text of DOI:10.1039/c6cc00562d

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DOI: 10.1039/C6CC00562D
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Visible‐Light‐Induced Regioselective Synthesis of
Polyheteroaromatic Compounds
Tanmay Chatterjee,a Myung Gil Choi, a Jun Kim, a Suk‐Kyu Chang a and Eun Jin Cho a ,*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
A
method
for
visible‐light‐induced
synthesis
of polyheteroaromatic structures,6,9 few strategies have been
for synthesizing heteroaryl‐substituted
polyheteroaromatics from 2‐heteroaryl‐substituted anilines and devised
heteroarylalkynes was developed. The process, which uses fac‐ polyheteroaromatics with control of the relative locations of
t
Ir(ppy)3 as the photocatalyst and BuONO as the diazotization heteroatoms, which is an essential characteristics for a
reagent, is highly regioselective.
molecule to be used as potential bidentate type functional
materials. Herein, we designed and developed a protocol for
the direct regioselective synthesis of heteroaryl‐substituted
polyheteroaromatics, with regulations on the locations of
heteroatoms (Scheme 1). Significantly, the structure of this
series of polyheteroaromatics shows high flexibility, which is
an important feature in bidentate compounds since they can
adjust their bite angle while coordinating to metal ions.
Polyaromatic compounds1 that contain N, O, and
S
heteroatoms are useful materials that have attracted great
interest recently because of their enhanced and controllable
optoelectronic properties.1c,2 Polyheteroaromatic compounds
have many applications (Figure 1), including use in various
electronic devices3 such as organic light‐emitting diodes
(OLEDs) and organic field‐effect transistors (OFETs). These
compounds are also key components in fluorescent
bioimaging4 and in chemosensor5 systems designed to detect
metal ions and biologically relevant species. In addition, many
biologically active natural products, pharmaceuticals, and
agrochemicals have polyheteroaromatic core strutures.6
Fig. 2 Examples of bidentate ligands for organometallic
compounds.
Fig. 1 Uses of polyheteroaromatics.
Scheme 1 New strategy for synthesis of heteroaryl‐substituted
polyheteroaromatics.
Polyaromatics containing two or more heteroatoms
located within close proximity are of particular interest
because they are used as bidentate luminophores in sensing
systems7 and, more importantly, as ligands8 in transition‐
metal‐catalyzed organic transformations (Figure 2). Although
many methods have been developed for constructing various
Visible‐light photocatalysis is a powerful synthetic tool
owing to its environmental compatibility and versatility in
promoting
a large number of synthetically important
reactions.10,11 Among various processes of this type, free‐
radical addition reactions have received considerable attention,
e.g., visible‐light‐promoted reactions of aryl diazonium salts
have been employed to generate aryl radical
intermediates.12,13 However, a difficulty exists in preparing
diazonium salts from amines that contain nitrogen
heteroatoms14 because of the need for acidic conditions that
a.
Department of Chemistry, Chung‐Ang University, 84 Heukseok‐ro, Dongjak‐gu,
Seoul 156‐756, Republic of Korea. E‐mail: echo@cau.ac.kr
Electronic Supplementary Information (ESI) available: Experimental procedures,
additional experimental data, analytical data, and 1H and 13C NMR spectra of
starting
amine substrates and
polyheteroaromatic
products.
See
DOI: 10.1039/x0xx00000x
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result in the formation of N‐hydrochloride salts. In order to and 5–8). Various polypyridyl‐based Ru and Ir complexes and
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DOI: 10.1039/C6CC00562D
avoid this limitation, we utilized an amine diazotization an organic dye, eosin Y, were tested as photocatalysts. The
protocol that uses a nitrite source as part of a one‐pot,15,16 for results show that the reaction promoted by fac‐Ir(ppy)3 gave
visible‐light‐promoted synthesis of polyheteroaromatics the highest yield and degree of regioselectivity (Table 1,
(Scheme 1). Previously, the Zhou group developed a method entries 1 and 9–13). The use of isoamyl nitrite as the nitrite
for the synthesis of phenanthrenes using biaryldiazonium source gave a marginally lower yield (Table 1, entry 14).
tetrafluoroborates and alkynes in the presence of eosin Y as Further optimization studies showed that the reactant
the photocatalyst.17 However, the method is not efficient for concentrations critically affected the efficiency and
the synthesis of heteroaryl substituted polyheteroaromatic regioselectivity of this process. The yield and regioselectivity of
compounds mainly due to the difficulty of synthesis of the reaction forming 3aa significantly increased and the yield
diazonium substrates with N‐heterocycles and relatively lower of the deamination product 4a decreased as the
reactivity of the organic photocatalyst.
concentrations of 1a and 2a increased (Table 1, entries 10 and
15–20). Moreover, the respective amounts of tBuONO and fac‐
Ir(ppy)3 can be lowered to 1.5 equiv. and 0.3 mol% without
affecting the yield or regioselectivity (Table 1, entries 17 and
21–24). The use of at least 1.5 equiv. of 2a is required to
obtain reproducibly high efficiencies (Table 1, entry 25).
Table 1 Optimization of Reaction Conditionsa
Table 2 Reaction Scopea,b
tBuONO (1.5 equiv)
NH2
0.3 mol% fac-Ir(ppy)3
+
H
MeCN (1.0 M)
blue LEDs (7 W)
10-15 h, r. t.
H
H
1
2
H
3
n
n
n
n
n = 1 or 2
entry amine (1) alkyne (2)
product (3)
entry amine (1) alkyne (2) product (3)
NH2
1
7
8
9
1c
2c
2c
2a
S
N
N
N
S
N
N
1a
2a
3aa, 84%
3cc, 53%
NH2
2
3
1a
S
N
S
N
S
S
2b
1d
3dc, 52%
3ab
,
80%c
NH2
1a
N
N
N
O
S
O
3ac, 75%d
2c
2a
1e
3ea, 70%
NH2
4
5
10
11
1e
2c
2a
aConditions: 1a (0.1 mmol) and 2a (0.15 mmol) were used in each
reaction unless otherwise stated; byield determined using gas
chromatography; c3 equiv. of alkyne used; d1.2 equiv. of alkyne used.
N
N
S
O
N
1b
1b
3ba
,
3ec
65%
,
65%
NH2
2c
Initially, the investigation was commenced using 2‐
(pyridin‐3‐yl)aniline (1a) and 2‐ethynylthiophene (2a) as model
substrates in MeCN (0.2 M) under LED irradiation at room
temperature in the presence of 3 equiv. of tert‐butyl nitrite
N
S
S
N
N
S
N
3bc
,
1f
3fa
61%
,
63%
(tBuONO)15 and
1
mol% Ru(bpy)3Cl2. 5‐(Thiophen‐2‐
NH2
6
2a
12
1f
2c
N
N
yl)benzo[f]quinolone (3aa) was obtained in 51% yield along
with 10% of its regioisomer 3aa’, and the corresponding
deamination product 4a in 30% yield (Table 1, entry 1). Control
experiments showed that visible light, the photocatalyst, and
the nitrite source are required to achieve this transformation
S
N
N
N
S
N
1c
3ca, 60%
3fc, 61%
aReaction scale:
cregioisomer ratio (91:9); dregioisomer ratio (3ac
1
(0.5 mmol),
2
(0.75 mmol); bisolated yield;
3ac' = 73:27).
:
(Table 1, entries 2–4). Among various solvents (MeCN,
dichloromethane, THF, DMF, and DMSO) tested, MeCN was
the best for this reaction in terms of yield (Table 1, entries 1
Next, the substrate scope was investigated. Under the
optimized conditions, reactions of anilines containing five‐
1
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and six‐membered electron‐rich and electron‐deficient pyridine ring to form the corresponding radical 11V.iSewETArtficrloemOnl1in1e
IV
+
DOI: 10.1039/C6CC00562D
heteroaryl substituents with thiophene‐ and pyridine‐based to [Ir (ppy)3] reforms the photocatalyst and produces cation
alkynes
2 provided a wide variety of polyhetoraromatic 12, which undergoes deprotonation to generate the
products
3 in moderate to high yields, along with low yields polyheteroaromatic product. Formation of deamination
(5–20%) of deamination products (Table 2).18 These processes product 4a is likely a result of hydrogen atom abstraction by
are highly regioselective, as shown by the fact that reactions of the initially formed aryl radical 9a from one of a number of
1d and 1e with alkynes, which can potentially produce two possible H‐atom donors.
regioisomeric products, form single polyheteroaromatic
compounds 3dc 19
3ea, and 3ec (Table 2, entries 8–10).
,
Although the reactions of pyridylaniline 1a with
ethynylthiophenes 2a and 2b are also highly regioselective, the
reaction between 1a and 2c produces a mixture of 3ac and its
regioisomer 3ac’ in a ratio of 73:27 (Table 2, entry 3). The
conditions that give increased levels of regioselectivity in the
reaction between 1a and 2c were further identified by
determining the effects of reagent concentrations and
stoichiometries, and the results were included as Table S2 and
Figure S1 in ESI.
Scheme 3 Proposed reaction mechanism.
Scheme 2 Reactions of benzo‐fused heterocycle‐substituted
anilines and heteroaryl‐substituted heterocyclic amines.
Benzo‐fused heterocycle‐substituted anilines were also
tested as possible substrates for the synthesis of tetracyclic
polyheteroaromatic compounds. The reaction between 1g and
2a generated the corresponding tetracyclic heteroarene
product 3ga [Scheme 2,(1)], but the conversion was low.
Figure 3. (a) UV‐vis and fluorescence spectra of 3aa, 3ca, and 3ea,
respectively represented by blue, red, and black dotted (absorption)
and dashed (fluorescence) lines. (b) Photograph of UV‐illuminated 3aa
3ca, and 3ea. [3aa] = [3ca] = [3ea] = 1.0
10−5 M in dichloromethane,
ex = 300 nm.
,


However,
(benzo[b]thiophen‐3‐yl)aniline,
2‐(quinolin‐8‐
yl)aniline, and 2‐(isoquinolin‐4‐yl)aniline did not yield the
desired annulated products, but resulted in deamination and
mono‐addition, respectively (see Scheme S1, ESI).
Heteroarylamines also participate in this process, e.g., the
None of the polyheteroaromatic products (
3 and 6)
generated in these reactions has been prepared previously. In
addition, as mentioned above, the polyheteroaromatic
compounds prepared using this new method contain
heteroatoms such as N, S, and O in close proximity to one
another. The UV‐vis and fluorescence spectra of the
polyheteroaromatic compounds in dichloromethane were
obtained (Table S3 and Figure S2, ESI). All these substances
reaction of
6
6
5
with 2b yields the polyheteroaromatic compound
(45%) [Scheme 2,(2)]. Despite its low yield, the formation of
demonstrates the potential for application of this method to
the preparation of unique heteroaromatic substances.
A plausible mechanism for the reactions is outlined in Scheme
3, using 1a and 2a as substrates. The process is initiated by
tBuONO‐mediated diazotization of 1a to form the
corresponding diazonium salt 8a in situ. Subsequent single‐
electron transfer (SET) to 8a from the metal‐to‐ligand‐charge
transfer excited state [IrIV(ppy)2(ppy)•−]*, formed by visible‐
light irradiation of fac‐Ir(ppy)3, followed by nitrogen loss,
generates aryl radical 9a. Addition of 9a to 2‐ethynylthiophene
display strong absorption bands centered at 244289 nm, but
they have different fluorescence emission properties. For
example, 3ea, with O and S heteroatoms in the appended
heteroaryl ring, shows strong emission, with a maximum at
375 nm (quantum yield Φ = 0.36). In contrast, 3aa, with N and
S heteroatoms in the appended ring, emits at 421 nm (Φ =
0.16), and 3ca, with N in the pyrazine ring, and compounds
with S heteroatom rings, emit at 485 nm (Φ = 0.35), with
higher Stokes shifts (Figure 3).
(
2a) gives the corresponding vinyl radical 10, which undergoes
cyclization by facile intramolecular addition to C‐2 of the
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heteroatoms in these ring systems affect the fluorescence
properties. Compounds 3aa and 3ca, which have N and S in syn
orientations, display strong emission, but 3ab and 3ba have
diminished emission efficiencies (Figure 4).
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preparation of heteroaryl‐substituted polyheteroaromatic
compounds. The process, which is based on in situ generation
of diazonium salts and visible‐light photocatalysis, transforms
readily accessible heteroaryl‐substituted anilines and
heteroarylalkynes into the target products. These reactions,
which occur under mild, room‐temperature conditions and
require 0.3 mol% of fac‐Ir(ppy)3 as the photocatalyst, are
highly regioselective. The compounds produced from these
reactions may easily form a bidentate‐type metal coordination
complex since they bear two heteroatoms that can come to
close proximity through C‐C single bond rotation.
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quantum yields and Stokes shifts. We believe that these new
polyheteroaromatics, which have not been prepared
previously, have great potential as materials in many
applications, including use as bidentate ligands for
organometallic transformations.
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