Switching the Photochromic Activity of Acenaphthylene Derivatives through a Tandem Nucleophile-Promoted Addition Reaction

Article abstract of DOI:10.1002/chem.201602912

New acenaphthylene-based dithienylethenes have been prepared. Surprisingly they did not show photochromism. However, they readily underwent a tandem addition of a nucleophile and an electrophile, leading to a small library of dearomatized colourless analogues, which, on the contrary, were endowed with photochromic activity. In the absence of the electrophile, the intermediate obtained by C-attack readily aromatizes to give, surprisingly, a final product of direct aromatic nucleophilic substitution, which was not photochromically active.

Full text of DOI:10.1002/chem.201602912

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Accepted Article
Title: Switching the Photochromic Activity of Acenaphthylene Derivatives through a
Tandem Nucleophile Promoted Addition Reaction
Authors: Chiara Lambruschini; Luca Banfi; Giuseppe Guanti
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Switching the Photochromic Activity of Acenaphthylene
Derivatives through a Tandem Nucleophile Promoted Addition
Reaction
Chiara Lambruschini,[a] Luca Banfi,*[a] and Giuseppe Guanti*[a]
Abstract: New acenaphthylene based dithienylethenes have been
prepared. Surprisingly they did not show photochromism. However,
they readily underwent a tandem addition of a nucleophile and an
electrophile, leading to a small library of dearomatized colourless
analogues, which, on the contrary, were endowed with photochromic
activity. In the absence of the electrophile, the intermediate obtained
by C-attack readily aromatizes to give, surprisingly, a final product of
direct aromatic nucleophilic substitution, which was not
photochromically active.
Diarylethenes, and in particular, dithienylethenes 1, are a well-
studied and promising class of molecular photochromic
Scheme 1. Dithienylethenes and acenaphthylene
switches.[1] Upon irradiation of the open form of
a
dithienyllethene with UV light, a 6-π photocyclization reaction
occurs, leading to ring closed adducts 2 and to a bathochromic
shift of light absorption. On the other hand, upon irradiation with
visible light of the closed isomer 2, the reverse ring opening
reaction occurs. When the cyclization process is thermally
irreversible, but photochemically reversible, the systems are
particularly useful, especially when the open form is colourless
whereas the closed one absorbs in the visible range. In order to
improve the properties of the photochromic materials
approaching the ideal features,[1c] several authors have studied
the effect of R1 or R2 groups.[2] In particular, compounds 3 and 4
characterized by a cyclopentene or a perfluorocyclopentene,[2]
have emerged as the most favourable in terms of stability of the
cyclized form. In acenaphthylene 5, the five membered ring is
known to have a rather small aromatic character.[3] Therefore we
thought that it could be interesting to synthesize 1,2-
dithienylacenaphthylene derivatives and to test their
photochromic properties.
The subsequent metalation of these bromides followed by
the addition to acenaphthenequinone 6 affords diols 9 and 10 in
good yield. The relationship between substrate and solvent has
a strong effect in this reaction, in fact when THF was employed
as solvent the addition product was obtained with 8 as substrate
but not with 7. It is worth noting that the diols show a single set
of signals at 1H NMR. This rules out the presence of rotamers in
solution and reveals that the addition step occurs with complete
diastereoselectivity. In order to understand the stereochemistry
of the diols, compound 10 was treated with 1,1’-
thiocarbonyldiimidazole, but the corresponding thionocarbonate
was not observed. Therefore, we concluded that the relative
configuration of the OH groups is trans according to a steric
control in the addition of the second thienyl moiety.
In order to obtain the dithienylacenaphthylene derivatives
compounds, we tried different approaches. Diol 10 was
subjected to the McMurry reaction[5b, 6] under different conditions
(i.e. TiCl4/Zn and TiCl3(THF)3/Zn), but the desired alkene 16 was
obtained in unsatisfactory yields and with scarce reproducibility.
Then we tried the Zn/HCl system in AcOH, that was expected to
promote a domino process involving a pinacol rearrangement,
followed by ketone reduction and by a Wagner-Meerwein-type
rearrangement.[7] However, in our hands, these conditions
afforded ketones 11 and 12 as the only products. Therefore we
decided to split the transposition and reduction steps,[8]
employing HCl in AcOH to promote both the rearrangements
and LiAlH4 to reduce the ketone. These reactions are fast and
clean and afforded the alkenes 15 and 16 in excellent overall
yield without the need to isolate the intermediates.
At the outset of this research, this class of compounds was
unprecedented. However, a recent paper of Kawai et al. dealing
with some derivatives of this type,[4] prompted us to publish our
own results in this field.
We started our studies with the synthesis of compounds 15
and 16 (Scheme 2). Bromides 7 and 8 were easily prepared
from 2-methylthiophene and 2,5-dimethylthiophene, respectively,
following in part reported procedures.[5]
[a]
Dr. Chiara Lambruschini, Prof. Luca Banfi, Prof. Giuseppe Guanti
Department of Chemistry and Industrial Chemistry
University of Genova
Compounds 15 and 16 are orange-coloured foams (see the
UV-visible spectrum of 16 reported in Figure 1) but,
unfortunately, showed no photochromic activity even upon
prolonged UV light irradiation (300 nm).[4] They are also quite
stable under visible light.[9] This result is somehow unexpected,
Via Dodecaneso 31, 16146 Genova (Italy)
E-mail: banfi@chimica.unige.it
Supporting information for this article is given via a link at the end of
the document.

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but it should be noted that a similar outcome was experienced
by Kawai et al.[4] on compound similar to 16 (with R = phenyl and
a Me in position 4 of the thiophene unit).
Scheme 3. Unexpected result of attempted formylation of 15
Very interestingly, while the substitution product 18, similarly
to 15 and 16, did not show any photochromic effect, addition
product 19 displayed a photochromic effect upon irradiation at
300 nm. Evidently, dearomatization of one of the two benzene
ring is fundamental for allowing photocyclization.
Puzzled by this outcome, we tried to thoroughly optimize the
synthesis of 19. We found out that it was not possible to
completely suppress the formation of the direct substitution
product 18.[12] Moreover, this class of compounds are really
apolar and we encountered a lot of difficulties in their purification.
These are the main reasons for the moderate isolated yields of
these new reactions. A large excess of electrophile (3.0 eq.) was
necessary for a better yield (table 1, entry 2), while increasing
the time before the addition of allyl bromide was detrimental
(table 1, entry 3 and 4), mainly due to the spontaneous
aromatization of the intermediate to give 18. We also studied the
effect of the temperature and we found out the optimal value of –
50 °C (table 1, entry 5, 6).
Scheme 2. Synthesis of the dithienylacenaphthylene derivatives.
With the purpose to explore the effect on the photochromism
of other R groups in -position on the thienyl moiety, we decided
to prepare dialdehyde 17, starting from 15. However, by
treatment of 15 with n-butyllithium followed by DMF,[10] no
halogen-lithium exchange took place and the main isolated
product was 18 corresponding to
a direct nucleophilic
In order to explore the scope of this tandem reaction, we
tested different nucleophiles and electrophiles (scheme 4). Only
primary alkyl bromides and iodides were able to afford the
addition product; on the other hand chlorides were not
sufficiently reactive and only the substitution product or the
starting material were recovered. Compounds 15 and 16 were
reactive toward other C-nucleophiles (i.e., nBuLi, BnMgBr) and
N-nucleophiles (lithium piperidide), but we observed a different
outcome of the reaction, depending on the nature of the
nucleophile. With C–nucleophiles conversion is always complete,
substitution in position 3 of the acenaphthylene moiety (Scheme
3). A possible explanation of this unexpected result could be the
involvement of a stepwise mechanism with the addition of nBuLi
to the aromatic system in the first step, followed by
a
spontaneous rearomatization, through a still unclear oxidative
mechanism. The driving force of this transformation is likely the
formation of a highly stabilized carbanion (a fluorenyl anion)
further stabilized by several limit structures, also involving the
thienyl groups. It is worth noting that direct nucleophilic
substitutions on homocyclic aromatic systems are unknown,
unless a stoichiometric oxidant is added.[11]
affording
3,4-addition
products
(with
complete
diastereoselectivity favouring the trans adduct) and 3-
substitution derivatives in a ratio depending on the reactivity of
the electrophile; on the other hand, with lithium piperidide, only
1,4-addition products where isolated, along with some unreacted
starting material, and no substitution product was detected.
Moreover, in this case, the reaction showed virtually no
stereoselectivity.
Considering the peculiarity of this reaction, we envisaged the
opportunity to trap the supposed carbanion with an electrophile
in order to isolate a stable addition product.[7] We started using
allyl bromide as electrophile and we were pleased to observe
the formation of the hypothesized compound 19, along with 18
(Table 1, entry 1).

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Table 1. Optimization of the multicomponent reaction.[a]
Time before
bromide
add. (min)
eq. of
nBuLi
eq. of
bromide
Yield of 19
Entry
T (°C)
(%)[b], [c]
1
2
3
4
5
6
1.2
2.0
2.0
2.0
2.0
2.0
1.2
3.0
3.0
3.0
3.0
3.0
-50
-50
-50
-50
0
5
5
28
46
45
22
-
10
40
5
-78
5
40
[a] Reaction conditions: To a solution of 15 (0.23 mmol) in dry THF (5 mL)
under Ar was added nBuLi (1.6 M in hexanes) and, after the amount of time
indicated, allyl bromide was added. [b] Yield of isolated product. [c] The
substitution product is always present as co-product.
We speculate that this different behaviour may depend on
the reversible formation of C–N bond (compared to an
irreversible C-C bond formation), that leads to an uncomplete
addition and to a thermodynamic control in the anion formation.
Attack at position 3 would be kinetically favoured, whereas
attack at position 1 would be thermodynamically favoured either
for steric effects and for electronic reasons.[13]
Scheme 4. Products obtained from the new MCR on dithienylacenaphthylene
derivatives
The photochromic behaviour was also analysed by HPLC-
DAD (Figure 2). After UV irradiation the chromatogram clearly
shows the decrease of 20 (open form) and the formation of two
new peaks that can be detected at 450 nm (closed form). In our
case, the cyclized products are two 3,4-trans diastereoisomers
due to the presence of the stereocenters on the
dihydroacenaphthylene moiety. Upon visible light irradiation
these peaks disappear, bringing back the open form. We also
observed the presence of two other peaks that do not vanish
after visible irradiation, which are supposed to be degradation
by-products formed upon UV irradiation, especially when it is
prolonged. We also preliminary investigated the fatigue life of 20
in two solvents (hexane and MeCN) and, although we performed
only 10 cycles, the compound showed good results. Limiting UV
irradiation to 30 sec, the absorbance at 483 nm remained
unvaried after 10 cycles.[9]
All adducts 20–27 are pale-yellow foam and show a
photochromic behaviour,[9] but we focused our efforts on the
study of compound 20 (figure 1). UV-Vis spectrum of this
compound is substantially different from the spectrum of 16,
which has, apart from the absolute maximum at 235 nm, other
local maxima at around 260, 313 and 430 nm, justifying its
orange colour. On the contrary 20 lacks the maximum in the
visible region and shows a different pattern in the UV region. We
started with the optimization of the irradiation conditions and it
was found out that the optimal values to obtain a nearly
quantitative cyclization of 100 nmol of 20 were 30 sec at 300 nm
with an 8 W monochromatic lamp. The quantum yield was
determined to be an appreciable 49%.[9] The closed form is
characterized by a visible absorption at 483 nm (orange), but
also the UV part of the spectrum changes, with an intensity
increase of the 310 nm band. We also proved that the closed
form was thermally stable keeping the solution for 30 min in the
dark and checking the UV-Vis spectrum, which remained
unchanged. On the other hand, irradiation for 2 min with a white
In conclusion, our investigation has disclosed two important
evidences: a) the simple acenaphthylene based dithienylethenes
are, unexpectedly, not good substrates for UV-promoted 6-π
photocyclization reaction, thus not showing photochromic
behaviour; b) on the contrary, removing the aromaticity from one
of the two benzenoid rings by an addition reactions, the typical
photochromic behaviour of dithienylethenes is fully restored.
light (60
W light bulb) led to a spectrum completely
superimposable with the one of uncyclized 20 (Figure 1). In this
case the quantum yield was not determined.

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Most interestingly, the multicomponent approach[14] followed for
synthesizing this new class of photochromic substances opens
the way for a potential combinatorial synthesis of analogues, in
order to finely tune the colour and other properties. Moreover,
the addition reaction, which is fully regio- and stereoselective
with carbon nucleophiles, will allow the introduction of
functionalities (handles) to be exploited for binding these
compounds to other photoactive molecules or to solid supports.
Researches on this field are in development and the results will
be reported in due course.
Acknowledgements
We thank Prof. Davide Comoretto and Dr. Massimo Ottonelli for
useful advice, Dr. Carlo Scapolla for HPLC spectra, Dr. Luca
Bono for HRMS, and Compagnia San Paolo for help in
purchasing NMR and HPLC instruments.
Figure 1. UV-Vis spectra of compound 20 (50 μM, hexane): before irradiation
(solid line); after UV irradiation at 300 nm for 30 sec with a 8 W lamp (quantum
yield = 0.49) (dotted line); after visible irradiation with a standard white lamp
(60 W) for 2 min (dashed line).
Keywords: Photochromism; Multicomponent reactions;
Aromaticity; Nucleophilic Addition; Direct Aromatic Nucleophilic
Substitution
Figure 2. HPLC-DAD of compound 20 (430 μM) before irradiation (A), after UV irradiation at 300 nm for 30 sec with a 8 W lamp (quantum yield = 0.49) (B) and
after visible irradiation with a standard white lamp (60 W) for 2 min (C) Left: chromatogram at 256 nm, right: chromatogram at 450 nm (note that the vertical scale
is different in A and C compared to B).
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[4]
[5]
S. Fukumoto, T. Nakagawa, S. Kawai, T. Nakashima, T. Kawai, Dyes
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[12] Compound 18 is formed even under strict exclusion of air from the
reaction mixture and with an excess of allyl bromide. Therefore we
believe that its formation is due to a protonation of the carbanion that
takes place before work-up, followed by air promoted aromatization
after work-up.
[13] In the anion derived from attack at position 1 there are two limit
structures that leave intact the fluorene system, while only one can be
drawn if attack takes place at position 3.
[14] Although, strictly speaking, in a multicomponent reactions, all
components should be present from the beginning, from a practical
point of view this protocol allows the union of three diversity inputs as in
typical 3-component reactions. It is worth noting that the electrophile is
added after a very short time, without changing any other condition.

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Entry for the Table of Contents
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Chiara Lambruschini, Luca Banfi,* and
Giuseppe Guanti*
Page No. – Page No.
Switching the Photochromic Activity
of Acenaphthylene Derivatives
through a Tandem Nucleophile
Promoted Addition Reaction
New acenaphthylene based dithienylethenes (R = Me, Cl) were not photochromic.
However, they readily underwent a diastereoselective nucleophilic addition reaction,
giving photochromic adducts with good fatigue resistance.