Synthesis of symmetrical and nonsymmetrical bisthienylcyclopentenes

Article abstract of DOI:10.1002/chem.201301645

Diarylethenes possess unique structural properties, which enabled them to find widespread applications in the field of photochromism. Nowadays, bisthienylcyclopentenes (BTCs) present the most popular subfamily of these compounds, which are widely used as P-type chromophores. This minireview summarises the main strategies for the synthesis of symmetrical and nonsymmetrical BTCs. In addition, attention is drawn to desymmetrisations achieved by monosubstitutions, which is not frequently utilised, although it can be highly advantageous. This is supported with some of the authors' latest results. Copyright

Full text of DOI:10.1002/chem.201301645

DOI: 10.1002/chem.201301645
Synthesis of Symmetrical and Nonsymmetrical Bisthienylcyclopentenes
Gyçrgy Szalꢀki* and Jean-Luc Pozzo[a]
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Chem. Eur. J. 2013, 19, 11124 – 11132

MINIREVIEW
Abstract: Diarylethenes possess unique structural prop-
erties, which enabled them to find widespread applica-
tions in the field of photochromism. Nowadays, bisthie-
nylcyclopentenes (BTCs) present the most popular sub-
family of these compounds, which are widely used as P-
type chromophores. This minireview summarises the
main strategies for the synthesis of symmetrical and
nonsymmetrical BTCs. In addition, attention is drawn
to desymmetrisations achieved by monosubstitutions,
which is not frequently utilised, although it can be
highly advantageous. This is supported with some of the
authorsꢁ latest results.
Figure 1. Distribution of the number of publications in the field.
Keywords: bisthienylcyclopentenes · diarylethenes · di-
thienylcyclopentenes · dithienylperfluorocyclopentenes ·
nonsymmetrical diarylethenes · photochromism
(based on selective monolithium–halogen exchange) as a
viable desymmetrisation method.
Introduction
Synthesis of Bisthienylcyclopentenyl Core
Bisthienylcyclopentenes (BTCs) are a subtype of diaryle-
thenes, one of the most popular P-type photochromes. Their
success lies not only in their thermal irreversibility, but also
in their high fatigue resistance and fast response times.[1] Al-
though these compounds most often called diarylethenes, di-
thienylethenes, bisthienylethenes or dithienylperfluorocyclo-
pentenes, we use the name bisthienylcyclopentenes, which in
our opinion offers the most precise structural description of
these molecules. The number of reports in the field have
shown growing tendency (Figure 1); 2257 publications have
been published up to date, of which 191 are patents and 143
are general reviews.
For the synthesis of these compounds two conceptually dif-
ferent methods exist. The majority of these syntheses are
based on the substitution of octafluorocyclopentene with
substituted thiophene derivatives (Scheme 1). In this formal
A leading review, focusing mainly on the fundamental
properties and applications of diarylethenes was published
by Irie in 2000.[2] During our work with nonsymmetrical
BTCs we observed the lack of publications dealing with the
synthesis of this successful family of compounds. This work
summarises the available synthetic approaches towards sym-
metrical and nonsymmetrical BTCs. It is not the aim of this
minireview to give an exhaustive overview of the published
literature, but rather to highlight the recent developments in
the field of BTC synthesis. In the second half of this work
we concentrate particularly on the synthesis of nonsymmet-
rical analogues and report our recent findings as well. Final-
ly, we would like to highlight monosubstitution of BTCs
Scheme 1. General conditions of the formal substitution reaction of octa-
fluorocyclopentene.
substitution reaction the preformed lithiated thiophene
reacts with octafluorocyclopentene to give F-BTCs accord-
ing to an addition–elimination mechanism.[3] The high vola-
tility (b.p.: 26–288C) of octafluorocyclopentene can account
for lower yields; however, the conditions of lithium–halogen
exchange probably play a major role in this reaction.[4] The
reaction is usually conducted in etheral solvents such as
THF or Et2O, using half equivalent of octafluorocyclopen-
tene at low temperatures (À80 to À608C). At these temper-
atures, side reactions such as heteroatom-directed metala-
tions or unwanted lithium–halogen exchange are minimised,
which otherwise might strongly deteriorate yields.
[a] Dr. G. Szalꢂki, Prof. J.-L. Pozzo
Institut des Sciences Molꢃculaires, Universitꢃ Bordeaux 1
351 Cours de la Libꢃration, 33405, Talence (France)
Fax : (+33)5-40-00-69-94
E-mail: g.szaloki@ism.u-bordeaux1.fr
Yields are highly dependent on the substitution pattern of
the thiophenyl unit (Table 1). Reaction conditions may vary
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201301645.
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11125

G. Szalꢂki and J.-L. Pozzo
Table 1. Substituent effect in the formal substitution reaction of octa-
fluorocyclopentene.
Recently, Shinokubo et al. reported a novel method to
synthesise F-BTCs using Suzuki–Miyaura coupling.[10] The
method utilises 1,2-dichlorohexafluorocyclopentene which is
much less volatile (b.p.: 908C) than octafluorocyclopentene
and therefore easier to work with. Furthermore, this way or-
ganolithium species are also avoided and carbonyl or cyano
derivatives can be obtained in one step in low to moderate
Entry
1
R
Yield [%] Entry
R
Yield [%]
16
75
60
4
5
À
yields (entries 2–6, Table 2). In the course of C H function-
alisation studies (vide supra) the same group published the
synthesis of an H-BTC analogue by the same method
(entry 1).[11]
2
3
5
Another widespread method creates the cyclopentenyl
motif in an intramolecular McMurry reaction rather than
starting from a halogenated cyclopentene. In 1997, Fan pub-
lished the synthesis of a dihydrothiophene-bridged bisthien-
yl analogue using the McMurry reaction.[12] The same
method was later adapted by Feringa et al. to the synthesis
of BTCs, which were achieved in three or four steps from
readily available 2-methylthiophene (Scheme 3).[13] Many
perhydro BTC (H-BTC) analogues have since been synthes-
ised by this method. Migulinꢁs review nicely describes the
utility of McMurry reaction in the synthesis of BTCs and
other dihetarylethenes.[14]
27
6
23
slightly; however, some general considerations might be
drawn from analogues synthesised under identical condi-
tions. Thiophenyl units bearing an electron-withdrawing
group tend to give lower yields, while the presence of an
electron-donating or a conjugative group increases yields
(entries 1–5, Table 1).[3,5] Electronic effects transferred
through aromatic substituents are much less apparent.[6]
Thiophene units bearing a heteroalkyl or heteroaromatic
groups tend to give low yields (entry 6, 23%), which might
be attributed to the cumulated effect of the coordinating
groups obstructing the desired lithium–halogen exchange.[7]
It is worth noting that 4,4’-substituted analogues, such as
benzothiophenes (entry 1) or dimethylthiophenes (entry 2),
can also be obtained by this method. These compounds
have improved fatigue resistance compared to the analogous
thiophene derivatives. The substituents at the 4,4’-positions
are believed to obstruct an irreversible rearrangement,
which is the main fatigue process upon irradiation of these
compounds.[2]
Symmetrical dihalo-BTCs, such as chloride 1, are versatile
intermediates as the halogen can be converted to a great va-
riety of other moieties (vide supra). When using substituted
dihalothiophenes for preparing F-BTCs, the 4-position
always has to be accommodated with the more reactive hal-
ogen, or otherwise the sulfur atom would govern selectivity
to give preferentially the 2-substituted product, by stabilis-
ing the negative charge more efficiently at the 2-position.[8]
In terms of accessibility, stability, and selectivity chlorobro-
momethylthiophene is a useful intermediate when following
this route. It is commercially available or can be synthesised
in two steps from 2-methylthiophene (Scheme 2).[9]
Gyçrgy Szalꢀki obtained his M.Sc. degree
in Chemical Engineering from the Buda-
pest University of Technology and Eco-
nomics in 2005. After working at AMRI
Hungary for a year as a research chemist
he accepted a Marie Curie Fellowship at
the National Hellenic Research Foundation
in Athens. He received his Ph.D. from
University College London in 2012, where
he worked on the synthesis of novel ferro-
cenyl ligands and their applications in
asymmetric catalysis. Since then, he has
been working with Jean-Luc in the field of
photochemistry at the University of Bor-
deaux. In the course of this work they design and synthesise multiaddressa-
ble photochromic switches mainly based on bisthienylcyclopentenes
(BTCs).
Jean-Luc Pozzo was awarded diplomas
from Paris VI University (1987) and the
National School of Chemistry of Paris
(ENSCP, 1989) followed by an M.Sc.
degree from Aix-Marseille II University
(1990). His Ph.D. (1993) from Universitꢁ
de la Mꢁditerranꢁe (Marseilles, France) fo-
cussed on T-type photochromes, such as
chromenes and naphthooxazines. Essilor
International—PPG Industries offered him
a grant for an industrial post-doctoral stay
on tunable ophthalmic lenses. Since 2002,
he has been full Professor at the University
of Bordeaux developing photoswitchable
NLOphores and gelators, as well as multiaddressable self-assemblies and
bi- and triphotochromics. He was appointed Dean of the Chemistry De-
partment in 2011.
Scheme 2. Synthesis of dichloro F-BTC 1.
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Organic Photochromic Compounds
MINIREVIEW
Table 2. Suzuki–Miyaura coupling of 1,2-dichloro-hexafluorocyclopen-
tene with thiophenyl boronic acids/esters.
Table 3. Electrophilic substitution of dichlorides 1 and 2.
Entry
ArB(OR)2
R
X
Pd
[mol%]
Yield
[%]
Entry
R
E+
E
Yield [%]
AHCTUNGTRENNUNG
F
95
98
96
87
68
89
88
70
75
44
85
1
2
3
DMF
CO2
I2
CHO
CO2H
I
1
2
3
4
5
6
H
F
F
F
F
F
Br
Cl
Cl
Cl
Cl
Cl
2.5
1
89[a]
88
H
H
F
H
F
H
F
H
F
4
5
6
TMSCl
PhS-SPh
ClPPh2
TMS
SPh
1
82
PPh2
10
10
10
63
H
45
though yields might be low in certain cases (entries 3, 4 and
7), symmetrical analogues with valuable functional groups
(halogen, aldehyde, hydroxyl, nitrile) can be accessed this
way. In these reactions consistently higher yields were ach-
ieved when H-BTCs were used. During our work with sym-
metrical diarylated BTCs, we
29
[a] Conditions: [Pd
ester.
ACHTUNGTRENNUNG(PPh3)4], Na2CO3, toluene/EtOH (1:1); pin=pinacol
found that nBuLi was not re-
active enough to affect com-
plete dilithium–halogen ex-
change of dichloride 2 and a
mixture of the mono- and dis-
ubstituted products was isolat-
ed. Switching to tBuLi greatly
improved the yield (from 50 to
81%, entry 8).
Transition-metal couplings
were also tested by Feringa
Scheme 3. Synthesis of symmetrical chlorides 1 and 2 using the McMurry reaction.
et al. in order to obtain diary-
lated analogues.[13a] Kumada
coupling gave the monosubsti-
Derivatisation of the Bisthienylcyclopentenyl Core
tuted product in low yield (40%). The double Kumada cou-
pling was achieved later by Branda in moderate to good
yields.[26] On the other hand, diarylation by Suzuki coupling
was not successful. Since then, there have been a few inde-
pendent reports on successful Suzuki–Miyaura coupling of
H- and F-BTC dihalogenides in low to good yields (38–
81%).[27] In 2009 Hermes et al. reported the Suzuki–
Miyaura coupling reaction of dichloride 1 and aromatic bor-
onic acids/esters with high yields (Table 5).[9a]
During our work we were unable to reproduce the same
yields starting from dichloride 1. Under identical conditions
the yields were lower for phenyl (entry 1, Table 6) and mod-
erate for the other functionalised analogues. Therefore, the
more reactive dibromide 3 and diiodide 4 were synthesised
in good yields (76 and 87%, respectively) according to liter-
ature precedents.[15a,26] These analogues showed highly im-
proved reactivity, which resulted in shorter reaction times
(entries 2 and 3 Table 6). It is worth noting that bromide 3
The 2,2’-dichloro BTCs can be further derivatised by elec-
trophilic substitution giving access to a wide range of com-
pounds in moderate to excellent yields (Table 3).[15] The al-
dehyde moiety proved to be particularly useful as it can be
functionalised in many different ways to extend the p conju-
gation of the BTC system. To achieve this, Wittig[16] and
Knoevenagel[17] reactions have been most frequently ap-
plied. Other interesting structures, containing imidazole,[18]
triazole,[19] rhodanine,[20] indolinooxazolidine[21] or phenan-
throline[22] groups have also been reported.
When using borates as electrophiles, diboronic acid and
ester derivatives can be isolated; however, they undergo
rapid deboronation.[23] Borononic esters can be reacted in
situ with aryl bromides in a Suzuki reaction to give diarylat-
ed products (Table 4).[24] This one-pot procedure is the most
common way of arylating H- and F-BTC analogues.[24b,25] Al-
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G. Szalꢂki and J.-L. Pozzo
Table 4. One-pot electrophilic substitution/Suzuki–Miyaura coupling of
dichlorides 1 and 2.
Table 6. Comparison of the reactivity of dihalogenides 1, 3 and 4 in
Suzuki–Miyaura coupling.[a]
Entry
1
R
F
Ar
Yield [%]
55
2
3
F
F
52
23
Entry
SM[b]
X
t [h]
Yield [%]
mono, 0
mono, 0
mono, 0
1
2
3
1
3
4
Cl
Br
I
18
3
2
di, 72
di, 75
di, 95
4
5
6
7
8
F
42
H
H
H
H
83
[a] General conditions: ArB(OH)2 (2.2 equiv), [PdACHTNUGTRNEUGN(PPh3)4], (10 mol%),
Na2CO3, DME/H2O (4:1), reflux. [b] SM=starting material.
76
(Scheme 4). The only example of H-BTC gave a lower yield
than the corresponding F-BTC analogue.
35
81[a]
Diiodide-substituted H-BTC analogues can also be deri-
vatised using Sonogashira coupling (Table 7).[15c,28]
[a] tBuLi was used in first step.
Table 5. Double Suzuki–Miyaura coupling of dichloride 1 with different
aryl boronic acids/esters.
À
Scheme 4. Diarylation of simple bisthienylcyclopentene using C H func-
tionalisation.
Entry
1
Ar
R
H
Yield [%]
91
Table 7. Sonogashira coupling of diiodide.
2
3
4
pin
H
85
86
94
Entry
1
Ar
Yield [%]
75
Entry
2
Ar
Yield [%]
95
H
5
pin
84
Synthesis of Nonsymmetrical BTCs
Several groups have made attempts to tune the photochro-
mic properties of these compounds; therefore, the number
of synthesised nonsymmetrical BTCs has increased over the
last decade. To form nonsymmetrical BTCs, a highly selec-
tive reaction is needed to allow desymmetrisation to occur
at some point during the synthesis. In 1995 Irie published a
protocol to synthesise a monosubstituted F-BTC analogue,
using only an equimolar amount of thiophene derivative
and octafluorocyclopentene.[29] Since then, this approach has
been applied to the synthesis of many nonsymmetrical F-
was reactive enough in Suzuki–Miyaura couplings to make
this approach feasible towards aryl-substituted BTCs. This
was later exploited in our desymmetrisation studies (vide
supra).
Palladium-catalysed direct arylation of simple bisthienyl-
cyclopentene has also been reported by Shinokubo et al.[11]
The method was tested on a wide range of analogues, which
gave good yields (63–78%) under optimised conditions
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Organic Photochromic Compounds
MINIREVIEW
BTC derivatives (Table 8).[15a,30] The analogues are synthes-
ised in a stepwise manner, using previously synthesised thio-
phene units (A and B). As in the first step, monosubstitu-
tion is the aim and excess of the octafluorocyclopenetene
also been published that follow a different approach. Wuest
reported the synthesis of a nonsymmetrical cyclopentene an-
alogue by two consecutive Suzuki–Miyaura couplings using
1,2-dibromocyclopentene (Scheme 5).[32] Although, this ana-
logue is not a BTC derivative, Wuestꢁs protocol was later
adapted by Shinokubo to the synthesis of symmetrical BTCs
(see Table 2). This example also implies that stepwise
Suzuki coupling is feasible towards the synthesis of nonsym-
metrical BTCs as well.
Table 8. Synthesis of nonsymmetrical F-BTCs 6 using stepwise substitu-
tion.
À
Shinokubo et al. tested their C H functionalisation proto-
col (vide infra) on simple bisthienylcyclopentenes.[11] The
first monosubstitution gave monofunctionalised F-BTCs in
low yields (32–36%, Scheme 6). In this case they planned to
achieve monosubstitution by using one equivalent of the ar-
yliodide coupling partner, which might had been responsible
for the low yields. In the second arylation an excess
(3.9 equiv) of aryliodides were used; however, possibly due
to increased steric hinderance, the yields were only slightly
higher (37–40%) then in the first steps. Doucet and Guer-
chais independently reported a protocol using the same
strategy under modified conditions.[33] In the course of their
work they synthesised 13 nonsymmetrical analogues from
low to excellent yields (21–94%).
Entry
1
A
Yield
of 5 [%]
B
Yield
of 6 [%]
97
67
2
3
4
75
81
81
60
(4 analogues)
(3 analogues)
75–85
32–73
The McMurry reaction has also been applied to the syn-
thesis of
a nonsymmetrical H-BTC, by Migulin et al.
(Scheme 7).[34] This way, a versatile intermediate was ob-
tained, which was selectively derivatised in the following
step.
5
54
70
Unsymmetrically functionalised F-BTCs can be obtained
from dihalogenides as well, such as 1, 3 or 4, by using
Suzuki–Miyaura coupling. We were interested to see wheth-
can be used. Unfortunately, the utilisation of organolithium
reagents limits this method to protected carbonyls/hydroxyls
and nonhalogenated aromatics.
In addition, only F-BTCs can
be synthesised by this method.
The yields of the second sub-
stitutions are generally lower
than the first ones. Yoshida
et al. sucessfully adapted inte-
Scheme 5. Synthesis of a nonsymmetrical H-BTC using Suzuki–Miyaura coupling.
grated flow microreactor sys-
tems to this approach.[31] These
systems have proven efficient
in controlling selectivity in re-
actions of highly reactive inter-
mediates, such as lithiated spe-
cies.
This stepwise method is
widely used; however, a few
other isolated reports have
À
Scheme 6. Stepwise arylation of simple bisthienylcyclopentene using C H functionalisation.
Scheme 7. Synthesis of a nonsymmetrical H-BTC using the McMurry reaction.
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11129

G. Szalꢂki and J.-L. Pozzo
er monosubstitution can be achieved by using only a small
excess (1.2 equiv) of the boronic acid. The results of mono
Suzuki coupling of dihalogenides 1, 3, and 4 with phenylbor-
onic acid are depicted in Table 9. The yields are unoptimised
results were obtained (Table 10, entries 1–3), which led us to
believe that this ratio (selectivity) does not depend on the
nature of the electrophile but only on the stability of the
lithiated species. Perhydro analogue 2 was more reactive
compared to perfluoro analogue 1 (entries 1 and 4). Not
only the monoaldehyde 10 was isolated in higher yield
(73%), but the starting material 2 was completely con-
sumed. A doubly substituted by-product 11 was also isolated
upon purification.
Table 9. Monoarylation of dihalogenides 1, 3 and 4.
Our results are in accordance with a previous report on
monoformylation of H-BTC and monoarylations of F-BTC
analogues.[13a,35] The latter gives access to monoarylated
products in good yields (Table 11). Although monoarylation
Entry
SM[a]
Yield[b] [%]
Entry
3
SM[a]
Yield[b] [%]
5/22/49
1
2
1
3
17/44/34
9/31/43
4
Table 11. Mono- and diarylation of dichlorides 1 and 2.
[a] SM=starting material. [b] Isolated yields of SM/monoproduct/diprod-
uct, respectively.
and only serve as a comparison of the reactivity of the dif-
ferent dihalogenides 1, 3, and 4. Dichloride 1 gave the best
selectivity, where the product was isolated in moderate yield
(44%, entry 1). The results also showed that by using the
more reactive dibromide 3 or diiodide 4 the major product
became the disubstituted analogue (entries 2 and 3).
Following this, we focused on other desymmetrisation
methods, such as electrophilic substitution using mono lithi-
um–halogen exchange. We conducted a series of experi-
ments where dichlorides 1 and 2 were treated with with a
slight excess (1.05 equiv) of nBuLi and quenched with differ-
ent electrophiles (Table 10).[37] The corresponding monolithi-
ated species were formed in good yield in each case, which
was confirmed by TLC. In addition, the NMR analysis of
the crude reaction mixtures showed the presence of only the
starting material, mono- and disubstituted products. When
using different electrophiles such as water or TMSCl similar
Entry
R
Ar1
Yield
of 12
[%]
Ar2
Yield
of 13
[%]
1
2
H
F
77
71
63
45
3
4
H
F
37
47
32
–
–
–
5
H
22
–
yields may vary but some high yielding cases (entries 1 and
2) imply that in situ formation of borate ester is complete.
Lower yields (entries 3–5) are probably the result of a less
efficient Suzuki reaction between the borate ester and the
aryl bromide. The yields of the second arylations are usually
somewhat lower than those of the first ones (entries 1–3).
The H-BTC analogues tend to give slightly higher yields
than the corresponding F-BTCs. In the second step usually
tBuLi is used to promote lithiation as in some cases nBuLi
or sBuLi proved to be ineffective.[13a] This one-pot method
(substitution followed by Suzuki coupling) can be successful-
ly applied to the synthesis of nonsymmetrical aryl-substitut-
ed BTCs.
Functionalisation, using organolithium reagents, offers a
good starting point for desymmetrisation, due to its high se-
lectivity (see Tables 10 and 11). On the other hand, for the
functionalisation of the second thiophene unit, milder transi-
tion-metal coupling reactions are advised. This would
extend the scope of this approach to functionalised deriva-
tives, such as aldehydes, ketones, nitriles, esters, halogenides,
Table 10. Substitution study of dichlorides 1 and 2.
Entry Product SM[a]
R
E+
E
Ratio
Yield [%]
1
2
3
4
7
8
9
1
1
1
2
F
F
F
H
DMF
H2O
TMSCl TMS
DMF
CHO 12/74/14[b] 7/65/7[c]
H
11/74/15[b] N.A.[e]
14/73/13[b] N.A.
10
CHO 6/78/16[d]
1/73/15[f]
[a] SM=starting material. [b] Ratio of SM/monoproduct/diproduct re-
spectively (based on crude NMR spectroscopic data). [c] Isolated yields
of SM/monoproduct/diproduct respectively. [d] Ratio of byproduct/mo-
noproduct/diproduct, respectively (based on crude NMR spectroscopic
data). [e] N.A.= not available (separation was not possible). [f] Isolated
yields of byproduct/monoproduct/diproduct respectively.
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Organic Photochromic Compounds
MINIREVIEW
Table 13. Suzuki–Miyaura coupling of monoaldehydes 7 and 14.
amides, which might be sensitive to organolithiums other-
wise. As monochloride 7 was not sufficiently reactive in
Suzuki coupling, halogen derivatives 14 and 15 were syn-
thesised (Table 12).[37] Selectivity of the lithium–halogen ex-
Table 12. Monoformylation study of dibromide 3 and diiodide 4.
Entry
Product
R
X
T
[8C]
t
Yield
[%]
[h]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
16
17
18
19
20
21
22
23
16
17
18
19
20
21
22
23
NMe2
Cl
OMe
CHO[b]
CN
CO2Me
COMe
H
NMe2
Cl
OMe
CHO[b]
CN
CO2Me
COMe
H
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Br
Br
Br
Br
70
50
70
70
70
70
70
50
70
50
50
70
70
70
70
50
20
20
20
20
20
20
20
2
2
2
2
2
12(61)[a]
5(37)[a]
31(31)[a]
17(43)[a]
18(54)[a]
15(47)[a]
10(47)[a]
99/1[c]
97
96
94
88
76
Entry
SM[a]
X
Product
RLi
Yield [%]
1
2
3
4
3
3
4
4
Br
Br
I
14
14
15
15
nBuLi
tBuLi
nBuLi
tBuLi
64
59
49
20
I
[a] SM=starting material.
change was somewhat lower. To improve selectivity, the lith-
ium–halogen exchange was conducted at low temperatures
(À788C), while the reaction was monitored by TLC. Under
these conditions, bromoaldehyde 14 was isolated in good
(Table 12, entry 1, 64%) while the iodoaldehyde 15 in a
moderate yield (entry 3, 49%). Using the more reactive
tBuLi led to lower yields in both cases (entries 2 and 4).[36]
As it was expected, bromoaldehyde 14 showed highly im-
proved reactivity compared to
2
2
2
2
72
63
13/87[c]
[a] Yields in parentheses refer to the recovered starting material. [b] In
the case of aldehyde analogue 2.2 equivalents of boronic acid was used.
[c] Ratio of starting material/product (based on crude NMR spectroscop-
ic data).
chloroaldehyde 7 (entries 1–8,
Table 13).[37] A range of novel
functionalised derivatives 16–
23 were synthesised in good to
excellent yields (entries 9–16).
In general, the enhanced reac-
tivity of bromide 14 enabled us
to conduct the reactions under
Scheme 8. Synthesis of nonsymmetrical aldehyde 25.
milder conditions. The temper-
atures could be decreased to
50 or 708C instead of the usual reflux temperature (1058C)
and the amount of boronic acid could be reduced from 2.2
to 1.5 equivalents. Under these conditions the increased re-
activity of bromide 14 resulted in shorter reaction times, yet
higher yields compared to those reactions starting from
chloride 7. An additional result also nicely supports this vast
difference in reactivity. In the reactions of chloride decom-
position took place due to increased reaction times, while a
great part of the starting material stayed unreacted (en-
tries 1–8). On the other hand, in reactions using bromide 14
the usual byproduct was the protonated aldehyde 24, which
implies that oxidative addition occurred and the palladium
species was formed to a greater extent that can be assumed
purely from the yields.
mide, which had good reactivity in the following Suzuki cou-
pling (Scheme 8).[36]
Summary
This review examined the syntheses of symmetrical BTCs, a
group of compounds with promising photochromic proper-
ties. In addition, key synthetic approaches towards nonsym-
metrical analogues were also discussed. We also reported
our recent findings concerning the desymmetrisation strat-
egies of symmetrical BTCs. It highlights the great selectivity,
which can be achieved by monosubstitutions of dichloride 1.
In order to further improve this approach bromoaldehyde
14 was synthesised, which showed a significantly improved
reactivity in consecutive Suzuki–Miyaura couplings. It is our
belief that this approach is generally superior to other de-
symmetrisation methods in terms of versatility and overall
At the same time with our desymmetrisation studies,
Branda et al. reported the synthesis of H-BTC derivative 25,
according to the same strategy. The title compound 25 was
synthesised in two steps via the corresponding monobro-
Chem. Eur. J. 2013, 19, 11124 – 11132
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
11131

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