Ortho-substitution groups promoted photo-induced E (trans) → Z (cis) isomerization

Article abstract of DOI:10.1016/j.tetlet.2020.152396

The past decades have witnessed the fast growth of ortho-directing group assisted in C[sbnd]H activation and olefination. Herein we addressed these olefination products’ photo-induced E → Z isomerization in term of various ortho-substitution groups. Initi

Full text of DOI:10.1016/j.tetlet.2020.152396

Tetrahedron Letters 61 (2020) 152396
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Ortho-substitution groups promoted photo-induced E (trans) ? Z (cis)
isomerization
a,b,
Quan Zhou a, Xi Hong a, He-Zhen Cui a, Yong Sun b, Bing Zhan a, Aikebaier Reheman b, , Xiu-Feng Hou
⇑
⇑
a Department of Chemistry, Fudan University, Shanghai 200433, China
b Key Laboratory of Toxicology, Ningde Normal University, Ningde, 352000, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The past decades have witnessed the fast growth of ortho-directing group assisted in CAH activation and
olefination. Herein we addressed these olefination products’ photo-induced E ? Z isomerization in term
of various ortho-substitution groups. Initially, we discovered ortho benzoxazolyl aryl acrylates effectively
undertook E ? Z isomerization (up to 88% yields) under 365 nm direct irradiation. Furthermore, scoping
other five directing groups in CAH activation and olefination revealed that acetylamino group also pre-
sent to be good ortho-substituted groups that enhancing E ? Z isomerization. Controlled experiment
shows the substitution position is vital for photo-induced isomerization or [2 + 2] cycloaddition.
Lastly, prevalent interesting fluorescent quenching/change phenomenon were always in accompany with
the isomerization. X-ray single crystallography disclose the isomerization process undertook significant
conjugated distortion of the aryl acrylates fragment, we proposed such change could contribute to fluo-
rescent and absorbent decrease.
Received 24 July 2020
Revised 16 August 2020
Accepted 20 August 2020
Available online 29 August 2020
Keywords:
Benzoxazolyl
Isomerization
Cis-alkenes
Ortho effect
X-ray structure
Ó 2020 Elsevier Ltd. All rights reserved.
Introduction
reversible quantitative isomerization under triplet or singlet elec-
tron manifold relaxation. [7] Moreover, acrylate naphthalenyl [8]
The alkene with two different substituents on different carbons
owns two kind isomers, stereo specially E-, Z- isomers. E- isomer
configuration, the two substituents are dispersed in most extent,
is thermodynamic favored configuration. However, methodologies
normally access to E-isomer were much more than Z-isomer, [1]
including the traditional olefin methods [2] as well as transition-
metal-catalyzed CAH oxidative olefination. [3] To fabricate ther-
modynamically disfavored Z-alkenes, special reaction reagents or
catalysts are required [4] With the photochemistry development
in recent years, much attentions have focused on the photochem-
ically driving alkene E/Z isomerization by energy uphill catalyst/
photosensitizer. For example, Weaver took use of cyclometalated
iridium(III) photo-sensitizer complex as photocatalyst in the
trans-to-cis isomerization of aryl allylamine. [5] Gilmour developed
a bio-inspired organic photo-sensitizer which especially effective
for b-substituted acrylates with electron-withdrawing groups, like
cyano, ester, carboxylic acid, more recently, energy transfer strat-
egy was also applied in aryl or alkyl acrylates double bonds E/Z iso-
merization [6]. Arthur E. Bragg reported a higher conjugated alkene
molecule (1,2-dithienyl-1,2-dicyanoethene), which could undergo
or anthracenyl [9] had undertaken the E ? Z isomerization by
direct ultraviolet excitation without energy transfer catalyst.
Additionally, ortho CAH activation for olefination have devel-
oped in full blossom with various directing groups and transition
metal catalyzed CAH activation. Up to now, directing groups that
could furnish CAH olefination with alkyl acrylate mainly comes
from oxygen-containing groups or nitrogen-containing groups
with weak coordination ability [10], for example, oxazoline [11],
ketone [12], ester [13], acetylamide [14], N-sulfonyl imine [15],
hydroxyl [16]. It is proved that the olefination of CAH bond usually
affords the E-olefins, since the key step involves thermal stable
favored b-H elimination during the conversion. Considering the
E/Z-isomers difference in structure and physical property, it is nec-
essary to develop feasible method for converting E-olefins to the
corresponding Z-isomers.
In recent years, our group have focused on the 2-aryl benzoxa-
zoles backbone construction and application in CAH activation,
organometallic catalyst [17]. In the CAH olefination study17a, we
observed an interesting phenomenon. The fluorescent light spot
of compound E-1 (see Table 1) on the TLC plate was slowly chan-
ged from sky blue to yellow when irradiated by UV-365 nm
(0.4 mW/cm2). For understanding the process deeply, in-situ
NMR experiment was conducted that exposure E-1 solution to
365 nm irradiation. To our surprised, after 8 h, the typical signal
⇑
Corresponding authors.
E-mail addresses: akbarphd@126.com (A. Reheman), xfhou@fudan.edu.cn
(X.-F. Hou).
https://doi.org/10.1016/j.tetlet.2020.152396
0040-4039/Ó 2020 Elsevier Ltd. All rights reserved.

2
Q. Zhou et al. / Tetrahedron Letters 61 (2020) 152396
Table 1
property. To demonstrate our proposal, we test other directing
groups that ever utilized in CAH activation (Table 2).
The initial discovery of ortho-benzoxazoyl aryl acrylate UV-induced E/Z isomerization a.
Initially, we tested non-conjugated oxazolinyl containing E-1a,
only 0.7% Z-isomer was observed (in-situ H NMR) when exposed
to 365 nm for 3 days. This result indicates the conjugated benzox-
azolyl fragment is crucial for the E/Z isomerization. Then, E-1b was
applied under the standard condition, the reaction present messy
to observe the apparent Z-isomer by in situ 1H NMR, which may
result from side reactions between the methyl acrylate with amine
bond (-C@N-) site [18]. After exploring the benzoxazolyl analogous
directing groups, we checked other important and simple directing
group, acetylamino (-NHAc), which was the first one utilized as the
ortho CAH activation and olefination [19]. To our delight, we found
E-1ca showed good E-Z isomerization under 365 nm irradiation,
more importantly, its Z-isomer could easily be isolated from E-iso-
mer due to large Rf differential existed. Additionally, E-1cb with
electron-withdrawing group chloro, E-1cc with electron-donating
group methyl also showed high E ? Z isomerization to give Z-
1cb (78%), Z-1cc (82%). Furthermore, low conjugated directing
groups, acetyl (Z-1d), OAc (Z-1e) and phenyl (Z-33), their low E/Z
isomerization demonstrated the importance of ortho-benzoxazolyl
and acetylamino groups.
After the initial discovery and substitution scope, benzoxazolyl
and acetylamino groups are both special and efficient chro-
mophore that could enhance the E ? Z isomerization. In this paper,
benzoxazolyl containing molecules will be further discussed in
terms of functional groups tolerance, the relative position between
benzoxazolyl and acrylate fragment for this reaction. We scope
various benzoxazolyl containing aryl acrylates. Firstly, electronic
effect and steric effect from 2-aryl benzoxazoles were scoped. Con-
sidering the 2-aryl benzoxazoles containing two aryl fragments, we
denoted two aryl rings of the molecule backbone as ring A and B
respectively for convenient discussion (Table 3).
a
CDCl3 (0.5 mL, 0.1 M), 0.4 mW/cm2 365 nm, room temperature (r.t.), 3 days,
isolated yield 73%, in-situ NMR yield 88%. The right picture shows the CDCl3 solu-
tions of E-1 (sky blue) and Z-1 (greenish yellow) when exposed to 365 nm.
(J = 16 Hz) of trans-olefin decreased, generated a new set signal
(J = 12 Hz), which demonstrated alkene take place E-Z isomeriza-
tion (For detailed H NMR spectra of time-course UV-365 nm, see
Fig. S1 in Supporting Information). Additionally, elongation of the
exposure time to 3 days, the new set signal constituted up to
88%, and after silica gel chromatography, affording Z-1 with 73%
isolated yield. For improving conversion efficiency, we tested a
more powerful UV light source (365 nm laser, 4 mW/cm2). Sur-
prised, after two hours irradiation, 64% Z-isomer 1H NMR yield
was observed, however, irradiation another 2 h heated the reaction
solution up to 40 0C and messed up the reaction. So, to acquire high
yield of Z-isomer, we chose 0.4 mW/cm2 365 nm light for the opti-
mal condition. In Addition, we have screened different solvents,
only slight influence was observed on this E/Z isomerization
(Table S1). Herein, we tried to disclose a feasible complement to
Z-alkenes of ortho-substitution aryl acrylates with resort to E ? Z
isomerization in the absence of energy transfer catalyst.
When ring A was substituted by methyl, ring B was substituted
with electron-withdrawing group (EWG) fluoro, or electron-donat-
ing group (EDG) methoxy, totally showed moderate to good iso-
lated yield of Z isomers (Z-2, 73%, Z-3, 62%). However, the chloro
substituted showed comparatively lower conversion (Z-4, 43%).
Then, we turned the substitution of ring B to meta position, bromo,
p-MeOC6H4 all undertook good E ? Z isomerization (Z-5, Z-7),
which demonstrated that the pseudo-heavy atom could accelerate
this conversion, while methyl shows moderate conversion (Z-6).
More interesting, when butyl acrylate fragment was anchored
between fluoro and benzoxazolyl groups, it could also isomerize
(Z-8, 80%). In our previous work, it was proved that olefinic hydro-
gen have hydrogen bond effect with nitrogen and fluoro atom in
compound E-8,17a which means no negative effect result from
hydrogen bond interaction. Lastly, para substitution substrates
show good tolerance to this conversion, albeit with moderate to
good isolated yields (Z-9 ~ Z-16). Worthy to note, EWG substituted
substrates bear high E-Z isomerization under optimized condition.
Furthermore, electronic effect for this conversion was also checked
in regard of substitution on ring A. When ring A was forged with
chloro or hydrogen substrates, Z-17 ~ Z-21 could be obtained in
moderate to good yield (50% ~ 75%). The isomerization efficiency
decreases dramatically as for difluoro anchored substrate (Z-22,
56%, 3 days) with comparison to Z-2 (73%, 50 h), Z-18 (50%,
10 h). Apart from E-Z isomerization, we observed some substrates
undertook chemo-selectively alkene [2 + 2] dimerization to give
anti-head-to-head cyclobutanyl derivatives, for example, E-23
forged Di-1 (78%) [20]. Its solid structure was disclosed by X-ray
single crystallography, and adopt thermodynamically stable con-
figuration, anti-head-to-head. (see Table S2, S3 for details) Further-
more, we addressed the relative position between benzoxazolyl
fragment and aryl acrylate. To our surprise, E-24, whose acrylate
fragment located meta to the benzoxazolyl fragment, failed to
With the initial discovery of the benzoxazolyl containing aryl
acrylate E/Z isomerization, we proposed that it’s the benzoxazolyl
fragment that play the vital role for light sensitizer and fluorescent
Table 2
a.
Scope of other ortho-directing groups for UV-induced E/Z isomerization
a
Without other notes: CDCl3 (0.5 mL, 0.1 M), 0.4 mW/cm2 365 nm, r.t., 3 days,
b
c
isolated Yield; in-situ NMR yields; 7 days.

Q. Zhou et al. / Tetrahedron Letters 61 (2020) 152396
3
Table 3
functional groups, like ester, halogen, methoxy group. Several care-
ful attempts for Z-isomer suitable single crystal failed. Strategy of
increasing molecular polarity, either shortening the flexible alkyl
linkage (Z-21) or direct hydrolysis acrylate ester into acrylate acid
(Z-210) both successfully forged Z-isomer single crystals. Mean-
while, we are lucky to get a single crystal of E-17, which has the
same molecular skeleton as E-21, only the ester group is slightly
different. The X-ray diffraction showed that Z-21 and E-17 pos-
sessed structural characteristics of olefins trans /cis isomerism
(Fig. 1) and disclosed cis-configuration Z-21 and Z-210 owns
58°and 40° torsion angle respectively between acrylate fragment
and Ring B (Table S5, S6), and the acrylate fragment adopted the
cis-configuration as expected [21].
The scope of ortho-benzoxazolyl substituted aryl acrylates under 365 nm irradiation a.
Interesting, exclusively significant fluorescent change was
accompanied by these efficient ortho chromophores assisted
E ? Z isomerization (benzoxazolyl containing substrates). For
example, Fig. 2 showed E-21 bore apparent 365 nm fluorescent
emission property, presenting strong fluorescent quantum yield
(UE-21 = 0.61), however, after E ? Z isomerization, the fluorescent
intensity of Z-21 decreased 32-folds (UZ-21 = 0.02), which may
result from aryl acrylate co-plane distortion (vide supra).
The excited triplet lifetimes of some typical E-isomers were
tested. Preliminary results showed that the ortho effect will elon-
gate the excited triplet lifetime (s) (Table 5 and Figs. S2-S5), nearly
three times as long as lifetimes of ortho E-9 in comparison to meta
E-24 and para E-25. Meanwhile the short lifetime of E-23 (0.8 ns)
may result from thiophene’s sulfur heavy atom spin–orbit effect
and not be facilitate E/Z isomerization.
In summary, we discovered ortho-benzoxazolyl/ acetylamino
substituted aryl acrylate could undertake E ? Z isomerization
without uphilled or energy transfer catalyst. This approach makes
a
Without other notes: CDCl3(0.5 mL, 0.1 M), 0.4 mW/cm2, r.t., isolated yield,
exposure to 365 nm, 3 days; b in-situ NMR yields; c 2 days; d 1.5 days; e 0.5 days; f Z-
21 hydrolysis by 2.0 eq NaOH in THF/H2O (1 mL/0.2 mL), r.t., 6 h.
Table 4
The comparison of meta, para to ortho-benzoxazolyl aryl acrylates on the UV-induced
a.
E/Z isomerization
Fig. 1. The structures of E-17 (left) and Z-21(right).
a
b
CDCl3 (0.1 M, 0.5 mL), 0.4 mW/cm2 365 nm, r.t., 3 days, isolated Yield; in-situ
observed NMR yields.
observe effective conversion. In contrast, E-25 was exclusively con-
verted [2 + 2] to dimer product (Di-2) in 50% NMR yield without
detectable Z-isomer. Hence benzoxazolyl fragment substituted
position was vital to determine aryl acrylates behaviors under
direct 365 nm irradiation. Similar relative position effect was also
observed in ortho (Table 2, E-1ca ~ 1cc)/para (Table 4, E-1cd)-
acetyl amide differential: the former afforded at least 76% yield,
while the later undertook only 28% isomerization, outline the vital
role of substituted special chromophore for direct E/Z
isomerization.
To disclose the E/Z isomers spatial distribution, several
attempts were focused on the molecules with relatively high polar
Fig. 2. Emission spectra of E/Z-21 at in dichloromethane (10ꢀ4 M) at 298 K.

4
Q. Zhou et al. / Tetrahedron Letters 61 (2020) 152396
Table 5
along with the manuscript and graphic files to the appropriate edi-
torial office. Supplementary data to this article can be found online
at https://doi.org/10.1016/j.tetlet.2020.152396.
The excited triplet lifetimes of some E-isomers.
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Declaration of Competing Interest
The authors declare that they have no known competing finan-
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Appendix A. Supplementary data
Supplementary material that may be helpful in the review pro-
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