A powerful azomethine ylide route mediated by TiO2photocatalysis for the preparation of polysubstituted imidazolidines

Article abstract of DOI:10.1039/d0ob02277b

Lewis- and Br?nsted-acid catalyzed 1,3-dipolar cycloaddition between azomethine ylides and unsaturated compounds is an important strategy to construct five-membered N-heterocycles. However, such a catalytic route usually demands substrates with an electron-withdrawing group (EWG) to facilitate the reactivity. Herein, we report a TiO₂photocatalysis strategy that can conveniently prepare five-membered N-heterocyclic imidazolidines from a common imine (N-benzylidenebenzylamine) and alcohols along the route of 1,3-dipolaron azomethine ylide but without pre-installed EWG substituents on the substrates. Our EPR results uncovered the previously unknown mutual interdependence between an azomethine ylide and TiO₂photo-induced h_vb⁺/e_cb^?pair. This transformation exhibited a broad scope with 21 successful examples and could be scaled up to the gram level.

Full text of DOI:10.1039/d0ob02277b

Organic &
Biomolecular Chemistry
View Article Online
View Journal | View Issue
COMMUNICATION
A powerful azomethine ylide route mediated
by TiO2 photocatalysis for the preparation of
polysubstituted imidazolidines†
Cite this: Org. Biomol. Chem., 2021,
19, 2192
Received 16th November 2020,
Accepted 16th February 2021
Anan Liu, a,c Dongge Ma, *b Yuhang Qian,b Jundan Li,b Shan Zhai,b Yi Wangb
d
DOI: 10.1039/d0ob02277b
and Chuncheng Chen
rsc.li/obc
Lewis- and Brønsted-acid catalyzed 1,3-dipolar cycloaddition side). There are sparse successful reports that focused on 1,3-
between azomethine ylides and unsaturated compounds is an dipolar cycloaddition through an unstabilized azomethine
important strategy to construct five-membered N-heterocycles. ylide catalyzed by diphenylphosphate. However, in these cases,
However, such a catalytic route usually demands substrates with it is still required that another substrate, dipolarophile imines,
an electron-withdrawing group (EWG) to facilitate the reactivity. must have strong EWGs such as nosyl and tosyl groups to
Herein, we report a TiO2 photocatalysis strategy that can con- make the reaction proceed smoothly.3 Therefore, developing
veniently prepare five-membered N-heterocyclic imidazolidines methods that can accommodate common azomethine ylides
from a common imine (N-benzylidenebenzylamine) and alcohols and imines without pre-installed stabilizing EWGs is in urgent
along the route of 1,3-dipolaron azomethine ylide but without need, especially for the preparation of polysubstituted imida-
pre-installed EWG substituents on the substrates. Our EPR results zolidine compounds.4
uncovered the previously unknown mutual interdependence
between an azomethine ylide and TiO2 photo-induced hvb+/ecb
Photoredox catalysis for the purposes of organic transform-
ation has experienced a resurgence in the past decades.5
−
pair. This transformation exhibited a broad scope with 21 success- Compared with the mainstream noble metal Ru- and Ir-based
ful examples and could be scaled up to the gram level.
homogeneous photocatalysts,6 Earth-abundant and non-toxic
TiO2 nanomaterials emerged relatively late in the organic che-
mists’ toolbox. TiO2-based photocatalysis potential from the
aspect of organic synthetic chemistry has only been revisited
recently.7–13 There have been some examples in the application
Lewis- and Brønsted-acid catalyzed 1,3-dipolar cycloaddition
between azomethine ylides and imines, i.e., Hüisgen reaction,
is one of the most important methods to prepare various
N-heterocyclic molecules for natural products, pharmaceuti-
cals, pesticides and fine chemicals.1 Perfect regioselectivity
and diastereoselectivity or enantioselectivity have been
achieved by such designable azomethine ylide strategies.
However, the substrate scope is mostly limited to azomethine
ylides with an electron-withdrawing group (EWG) adjacent to
their carbanion center2 so far (see Scheme 1a, the right-hand
−
of photo-induced hvb+/ecb on the TiO2 surface to realize
single- or two-electron transfer redox reactions.14–25
Nonetheless, TiO2 photocatalysis based on the single-electron-
transfer (SET) or free-radical mechanism is seldom used in
more common acid/base catalytic reactions, although these
reactions actually have wider application scopes in organic syn-
thesis by means of nucleophilic and electrophilic reactivity.
TiO2 photocatalysts themselves, in terms of thermal catalysis,
were not believed to possess either Lewis or Brønsted acid/
base catalytic activity (pI = 6.8) at room temperature. Very
recently, we found that the photo-induced protons from
alcohol oxidation on the TiO2 surface possess strong Brønsted-
acid properties owing to the co-existent weakest conjugated
base, i.e., the delocalized conduction-band electron (ecb−) acts
as a conjugated Brønsted base.26 This photocatalytic pathway
enables a non-trivial aromatic electrophilic substitution reac-
tion coupled with photo-induced ecb−. Herein, we report
aBasic Experimental Centre for Natural Science, University of Science and Technology
Beijing, 30 Xueyuan Road, Beijing, 100083, China
bDepartment of Chemistry, College of Chemistry and Materials Engineering, Beijing
Technology and Business University, Fucheng Road 11, Beijing, 100048, China.
E-mail: madongge@btbu.edu.cn
cSchool of Chemistry and Biological Engineering, University of Science and
Technology Beijing, 30 Xueyuan Road, Beijing, 100083, China
dKey Laboratory of Photochemistry, Institute of Chemistry, Chinese Academy of
Sciences, Zhongguancun North First Street 2, Beijing, 100190, China
†Electronic supplementary information (ESI) available. CCDC 1856874. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
d0ob02277b
−
another unrevealed function of the photo-induced hvb+/ecb
pair that can catalytically transform an enamine intermediate
2192 | Org. Biomol. Chem., 2021, 19, 2192–2197
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Communication
Scheme 1 1,3-Dipolar cycloaddition to synthesize imidazolidines through the azomethine ylide intermediate.
into highly active azomethine ylide species, and these sub- tuents. Under photoirradiation, the TiO2 photocatalyst may
strates without pre-installed EWGs are readily used for 1,3- transform imine and alcohol into an active enamine inter-
dipolar cycloaddition reactions (Scheme 1b). This reactivity is mediate via the condensation of nascent aldehyde and amine
unprecedented in conventional Lewis and Brønsted acid/base delivered from photo-induced hvb+/ecb−, respectively (eqn (2)–
thermal catalytic reactions.
(4) in Scheme 2). An azomethine ylide species was in tandem
Based on our group’s constant research in TiO2-based generated by another photo-induced hvb+/ecb−, in which photo-
photocatalysis applied in organic synthesis,10–13,20,23,25 we induced hvb+/ecb did not act as a conventional redox agent
−
envisioned a possible reaction route for this transformation but as a Lewis acid/base to catalyze the formation of azo-
(as shown in Scheme 2). We selected common imines and methine ylide from in situ formed enamine (eqn (5) in
alcohols as remote precursors of azomethine ylide in place of Scheme 2). The as-formed azomethine ylide would be reactive
enamines that traditionally must have necessary EWG substi- to result in sequential 1,3-dipolar cycloaddition with excess
dipolarophile imine (eqn (6) in Scheme 2). Alcohols used here,
on the one hand, significantly expand the scope of enamines
by the introduction of alternative R5 groups (see Scheme 1b).
On the other hand, they generally have overwhelming reactivity
greater than those of other substrates and intermediates to
avoid being over-oxidized by active photo-induced hvb+. In this
way, a series of pharmaceutically important polysubstituted
1,3-dibenzylimidazolidine molecules27 could be produced
from commercially available alcohols and imines (Scheme 1b).
In contrast, traditional Lewis- or Brønsted-acid and noble
metal-based catalysis always requires activating EWG substitu-
ents in either azomethine ylide or imine (Scheme 1a).
Using N-benzylidenebenzylamine (NBBA) and ethanol as
the model substrates, ethanol itself as the solvent and P25
TiO2 as the photocatalyst under an anaerobic Ar atmosphere,
the aimed imidazolidine product with almost quantitative
98% yield was dramatically produced under 300 W Xe lamp
irradiation. The product structure was confirmed by X-ray
single-crystal diffraction, 1H-NMR, 13C-NMR and HR-ESI-MS
characterization techniques (see ESI sections VII, IX, and X
and CCDC-1856874.cif†). A number of control and optimiz-
ation experiments were conducted to screen the optimum con-
ditions. The results are shown in Table 1 and Tables S1–S3.†
Both UV irradiation and the TiO2 photocatalyst were the pre-
requisites for successful transformation (see Table S1†). Other
Scheme 2 Proposed route of TiO2 photocatalyzed 1,3-dipolar cyclo-
addition between NBBA and alcohols.
visible-light responsive photocatalysts could not provide the
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 2192–2197 | 2193

View Article Online
Communication
Organic & Biomolecular Chemistry
Table 1 Control and optimization of TiO2 photocatalytic 1,3-dipolar
cycloaddition between NBBA and ethanol
Entry
Photocatalyst
Irradiation
Atmosphere
Yielda (%)
1
2
3
4
P25 TiO2
None
P25 TiO2
P25 TiO2
P25 TiO2
P25 TiO2
P25 TiO2
Yes
Yes
No
Yes
Yes
Yes
Yes
Ar
Ar
Ar
N2
O2
Air
Ar
98
8
ND
85
Trace
Trace
91c
5
6
7b
Reaction conditions: 1 mmol NBBA, 32 mg P25 TiO2, 3 mL ethanol,
300 W Xe lamp, 5 h. a GC yield. b For the gram scale synthesis: NBBA,
7.6 mmol; P25 TiO2, 80 mg; ethanol, 10 mL; 300 W Xe lamp; 48 h.
c Isolated yield.
aimed imidazolidine product (see Table S2†). Changing the
atmosphere to 1 atm O2 or air led to only a trace amount of the
product, indicating the necessity of an anaerobic atmosphere
(see Table 1). Furthermore, the transformation could be scaled
up to the gram level, providing a nearly unreduced isolated
yield of 91% with 1.17 g aimed product after column purifi-
cation (see ESI section VI†). The TiO2 photocatalyst after
several recycles and reuse still retained high activity. By simple
centrifugation and washing of the catalyst after each use, an
almost undiminished yield of 95% after 5 cycles was achieved
(Fig. S1†). Until now, the P25 TiO2 photocatalyst did not experi-
ence an apparent morphology change (Fig. S2†). As shown in
Table S3,† changing the solvent from ethanol to MeCN led to a
decrease in the yield from 98% to 75%. Other polar aprotic sol-
vents such as DMF and DMSO also showed further decreased
yields (45% and 38%, respectively). When non-polar solvents
toluene and n-hexane were used, much lower yields were
obtained. The dependence of the yield on the solvent polarity
suggested that the photocatalytic reaction probably proceeds
through a charged intermediate (the most probable being azo-
Fig. 1 TiO2 photocatalytic 1,3-dipolar cycloaddition between different
alcohols and imines.
methine ylide) rather than a neutral radical intermediate. With to sterically crowded 3,5-di-tert-butyl benzyl alcohol (1s). To
the optimized conditions in hand, we began to explore the broaden the substrate scope of this photocatalytic method, we
scope of substrate alcohols. Short-chain primary alcohols pro- changed another reactant NBBA with EWG and EDG substitu-
vided excellent yields (see Fig. 1; 1a, 1b, and 1c), while long- ents at the para-position of its benzylamine ring (1t and 1u,
chain alcohols such as n-butanol and n-octanol (see Fig. 1; 1d respectively). As a result, both cases showed very satisfactory
and 1e) also achieved fair yields. Branched primary alcohols yields (78% for 1t and 62% for 1u) and supported the validity
(1f and 1g) provided moderate yields. This method was also of this strategy. In addition, since the two phenyl groups
suitable for aromatic primary alcohols, but the solvent should linked to the C4 and C5 positions of the imidazolidine product
be changed from neat alcohol to MeCN (Table S3†). Benzyl generally resulted in a diastereoisomeric mixture of two
alcohol and 4-methyl and 2-methylbenzyl (1h, 1i, and 1j) alco- couples (i.e., trans-4S,5S and -4R,5R; cis-4S,5R and -4R,5S), the
hols were all feasible substrates. Electron-rich 4-methoxyl and relative configuration of each diastereoisomer was determined
4-N,N′-dimethylamino benzyl alcohols provided moderate to through comparing the tendency of chemical shifts in the
good yields (1k and 1l). Compared with electron-rich alcohols, 1H-NMR spectra of each couple diastereomers and their coup-
electron-poor alcohols gave lower yields. 4-Trifluoromethyl, ling patterns with those of 1b since 1b was obtained as an
4-cyano, 4-F, 4-Cl, 4-Br and 4-methyl benzoate substituted almost single isomer and its XRD structure showed the trans-
benzyl alcohols (1m, 1n, 1o, 1p, 1q, and 1r) showed moderate configuration (see ESI section X†). Fig. 1 shows the ratios of
but synthetically useful yields. This method could be extended the trans- : cis-configuration of every product. Most of the ratios
2194 | Org. Biomol. Chem., 2021, 19, 2192–2197
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Communication
of trans- to cis- were in the range of 2 : 1 ∼ 1 : 1, except for 1b, EWG ester group as eqn. (8) in Table 2, we obtained almost the
indicating that this pathway had little diastereoselectivity. same yield as reported in the literature under Lewis-acid
To further demonstrate the significance of this method, we AgOAc (entry 4) and Cu(CH3CN)4BF4 (entry 7) or Brønsted-acid
conducted the 1,3-dipolar cycloaddition experiments of either DPP (entry 10) catalysis conditions.1,28,29 The control experi-
the unactivated or the activated azomethine ylide precursor to ments shown in Table 2 adequately demonstrated that the 1,3-
compare TiO2 photocatalysis with typical Lewis-1,28 and dipolar cycloaddition of imines both without (entry 1 in
Brønsted-acid3,29 catalysis. As shown in Table 2, when exposed Table 2) and with the activated group such as the –COOMe
to the TiO2 photocatalysis system, the azomethine ylide precur- group (entry 11 in Table 2) can be carried out smoothly by our
sor imines bearing either unactivated phenyl as eqn (7) (entry TiO2 photocatalysis strategy. TiO2 photocatalysis exhibit power-
1 in Table 2) or the activated EWG ester group as eqn (8) (entry ful Lewis-acid catalytic activity besides its common photo-
11 in Table 2) reacted with ethanol to form the imidazolidine redox property.
product in almost perfect quantitative yield (∼95% and ∼92%,
To shed light on the cascade reaction of the azomethine
respectively). However, when the azomethine ylide precursor ylide precursor imine and alcohol assisted by TiO2 photocata-
imine NBBA with the unactivated phenyl group was applied lysis, off-line GC-MS tracing experiments were performed.
under either typical Lewis-acid (AgOAc (entries 2 and 3 in From the experimental results shown in Fig. 2, two key inter-
Table 2) and Cu(CH3CN)4BF4 (entries 5 and 6 in Table 2)) or mediates were identified. Dibenzylamine with m/z = 197 and
Brønsted-acid (DPP) (entries 8 and 9 in Table 2) catalysis con- N,N′-dibenzylethenamine with m/z = 223 were confirmed by
ditions, no aimed cycloaddition product was observed using GC-MS analysis against irradiation times.
either ethanol or previously reported successful THF or DCM
Dibenzylamine is generated from the reduction of NBBA
as the solvent.28,29 Instead, using imines with the activated imine by photo-induced ecb (eqn (3) in Scheme 2), while
−
+
photo-induced hvb oxidizes primary alcohol to aldehyde (see
Scheme 2, eqn (2) and (3)). The N,N′-dibenzylethenamine inter-
mediate is generated from the consecutive condensation
between dibenzylamine and aldehyde (see Scheme 2, eqn (4)).
The observations of these two crucial intermediates were in
Table 2 Comparison of TiO2 photocatalysis with Lewis/Brønsted acid
catalysis in 1,3-dipolar cycloaddition of imine and the azomethine ylide
precursor with either an stabilizing EWG (eqn. (8)) or an electron-neutral
group (eqn. (7))
excellent agreement with the proposed process of the 1,3-
dipolar cycloaddition reaction in Scheme 2.
To demonstrate that the azomethine ylide intermediate was
generated in the cascade reaction along the reaction pathway:
alcohol oxidation to acetaldehyde and imine reduction to
amine catalyzed by photo-induced hvb+/ecb−, respectively (eqn
(2) and (3) in Scheme 2), we conducted the control experi-
ments starting with dibenzylamine, NBBA imine and acet-
aldehyde instead of alcohol. As shown in Table 3, in the
absence of either TiO2 (entry 2) or irradiation (entry 3), the
aimed cycloadduct product was not detected, while only a
small amount of the condensation product enamine was
obtained. Instead, under TiO2 photocatalysis conditions, the
Entry Catalyst
Eq. Solvent
Conv. (%) Yieldb (%)
aimed imidazolidine product could be obtained with a high
yield (entry 1). This definitely showed that the 1,3-dipolar
1a
2c
P25 TiO2
AgOAc
AgOAc
7
7
7
8
7
7
8
7
7
8
8
Ethanol
Ethanol
THF
THF
Ethanol
DCM
DCM
Ethanol
DCM
DCM
MeCN/EtOH 100
100
5
95
ND
3c
73
100
48
28
100
98
∼0
4c
AgOAc
94 (3b)
∼0
5d
6d
7d
8e
Cu(CH3CN)4BF4
Cu(CH3CN)4BF4
Cu(CH3CN)4BF4
DPP
DPP
DPP
∼0
95 (3b)
∼0
9e
99
99
∼0
10e
11f
93 (3b)
92 (3c)
P25 TiO2
a Reaction conditions: 1 mmol NBBA, 32 mg P25 TiO2, 3 mL ethanol,
300 W Xe lamp illumination for 5 h at 5 cm distance. b Conversion and
yield are based on 1H-NMR with 1,3,5-trimethoxybenzene as the
internal standard. c 5 mol% catalyst. d 3 mol% catalyst and 20 mol%
Et3N additive. e 20 mol% catalyst. Lewis-acid and Brønsted-acid cata-
lyses were conducted strictly according to the literature for 1,3-dipolar
cycloaddition between the azomethine ylide precursor with stabilizing
EWGs and imines. f Reaction conditions as [a] but with 20% ethanol/
MeCN as the cosolvent; its product was 3c. Its characterization and
NMR data are listed in the ESI.†
Fig. 2 Key intermediate formation and depletion against the reaction
time. The red line represents dibenzylamine and the black line rep-
resents N,N’-dibenzylethenamine.
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 2192–2197 | 2195

View Article Online
Communication
Organic & Biomolecular Chemistry
Table 3 Control experiments for the TiO2 photocatalytic synthesis of
imidazolidine from intermediates acetaldehyde, dibenzylamine and
NBBA
Entry
Catalyst
Irradiation
Yielda (%) (1b, 4b)
1
P25 TiO2
None
P25 TiO2
Yes
Yes
None
85, 4
14, 70
5, 72
2
3b
Reaction conditions: 1 mmol dibenzylamine, 1 mmol NBBA, 1 mmol
acetaldehyde, 3 mL anhydrous acetonitrile as the solvent, 32 mg P25
TiO2, Ar atmosphere, under 300 W Xe lamp illumination for 8 hours at
5 cm distance. a GC yield. b Heating at 40 °C.
cycloaddition mechanism, if it was true, must be a photocata-
lyzed process. In other words, in this case, the photo-induced
hvb+/ecb pair neither plays a redox role nor promotes the con-
−
Fig. 3 (Top) EPR spectra measured at 90 K of P25 TiO2 under UV
irradiation in the CH3CN solution of acetaldehyde and amine (0.005 M,
0.05 M and 0.1 M) and of acetaldehyde, amine and NBBA (0.005 M, 0.05
M and 0.1 M). (Bottom) Controlled ESR spectra measured at 90 K under
UV irradiation of P25 TiO2; P25 + CH3CN; P25 + CH3CN + dibenzyla-
mine; P25 + CH3CN + acetaldehyde; P25 + CH3CN + NBBA; P25 +
CH3CN + ethanol; and P25 + CH3CN + p-benzoquinone (1 ml CH3CN;
the organic substrate concentration is 0.1 M).
densation of aldehyde and amine into enamine; it plays a
totally novel role to generate and stabilize the azomethine
ylide intermediate for the 1,3-dipolar cycloaddition (as pro-
posed in eqn (5) and (6) in Scheme 2).
As the key azomethine ylide species either with or without
EWG groups is too transient to detect by off-line GC-MS or
NMR analysis, alternatively, we sought to exploit the low-temp-
erature 90 K electron paramagnetic resonance (EPR) technique
to in situ characterize the other key species in the photocataly-
sis reaction, i.e., photo-induced hvb and ecb−. Traditionally, before.30 Generally, the photo-induced hvb+ signal appears only
+
−
−
due to the competing fast recombination processes between when photo-induced ecb is eliminated by the ecb scavenger
photo-induced hvb and ecb species, it is necessary to add such as dioxygen,31 or the signal of photo-induced ecb
+
−
−
+
hole or electron sacrificial reagents to quench one of them to appears only when the hvb scavenger such as alcohols is
lengthen the lifetime of the other species for observations by present.23,32 Both species cannot be observed simultaneously
EPR.9,14 As proposed above, in this case, TiO2 photo-induced in the EPR determination (at 90 K) because of the fast recombi-
hvb+/ecb may also play a different role from the conventional nation between each other. The co-existence and enhancement
−
+
−
redox view. Besides alcohol oxidation to aldehyde by photo- of EPR signals of photo-induced hvb and ecb together in our
+
induced hvb and imine reduction to amine by photo-induced system have to be attributed to the stabilizing effect of photo-
ecb (see Scheme 2, eqn (2) and (3)), we argued that photo- induced hvb+/ecb species by azomethine ylide formation as
−
−
induced hvb+/ecb facilitates and stabilizes the azomethine shown in Scheme 2. It should be noted that in the absence of
−
+
−
ylide intermediate and thereby shows different EPR features. NBBA, the signals of both photo-induced hvb and ecb dra-
We took acetaldehyde, dibenzylamine and NBBA as substrates matically decreased in comparison with those in the presence
to perform the photocatalysis reaction in P25 TiO2 suspension of NBBA under otherwise identical conditions (Fig. 3, top).
under UV irradiation as the case of entry 1 in Table 3 (that pro- That is, in the absence of dipolarophile imine, the formed
ceeded successfully to obtain the aimed imidazolidine product enamine would not be smoothly converted into the final imi-
+
1b), in which we observed the in situ EPR signals of hvb and dazolidine product through the azomethine ylide intermediate
ecb (see Fig. 3, top). Upon increasing the concentration of (as shown in Scheme 2, eqn (5) and (6)). At this moment, no
−
+
−
dibenzylamine, acetaldehyde and NBBA from 0.005 M to 0.1 appearance of hvb and ecb signals somewhat suggested the
M, we observed the gradual enhancement of both photo- relation of interdependence between azomethine ylide and
induced hvb signals corresponding to g1 = 2.014, g2 = 2.011, photo-induced hvb+/ecb−. To further verify the unusual hvb
+
+
−
−
and g3 = 2.003 and photo-induced ecb signals corresponding and ecb co-existence and enhancement together, we carried
to g = 1.990, g = 1.982 and g = 1.945 together (Fig. 3, top). Such out a series of controlled EPR experiments (Fig. 3, bottom). As
−
simultaneous occurrence and enhancement of photo-induced expected, only the photo-induced ecb signal appeared when
hvb+/ecb signals in our experiment are rather unexpected and we added ethanol in the photocatalysis system to eliminate
−
significantly different from nearly all photocatalytic events photo-induced hvb+, while we observed only the photo-induced
2196 | Org. Biomol. Chem., 2021, 19, 2192–2197
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Communication
+
hvb signal when we added p-benzoquinone to eliminate 10 D. Ma, A. Liu, S. Li, C. Lu and C. Chen, Catal. Sci. Technol.,
photo-induced ecb−. More certainly, when there were no sca-
2018, 8, 2030–2045.
+
vengers available to eliminate either photo-induced hvb or 11 Y. Wang, A. Liu, D. Ma, S. Li, C. Lu, T. Li and C. Chen,
ecb−, we indeed did not observe any obvious EPR signals attrib-
Catalysts, 2018, 8, 355.
+
uted to hvb or ecb−. Thus, our EPR results indicated that an 12 D. Ma, S. Zhai, Y. Wang, A. Liu and C. Chen, Molecules,
interaction exists between azomethine ylide and TiO2 photo-
2019, 24, 330.
−
induced hvb+/ecb species. A portion of TiO2 photo-induced 13 D. Ma, S. Zhai, Y. Wang, A. Liu and C. Chen, Front. Chem.,
−
hvb+/ecb species acts as the redox agent and the other part
2019, 7, 636.
acts as the Lewis acid/base catalyst to dictate the high yields of 14 A. L. Linsebigler, G. Lu and J. T. Yates, Chem. Rev., 1995,
1,3-dipolar cycloaddition reactions. To the best of our knowl- 95, 735–758.
edge, this is the first time that such a unique activity in TiO2 15 S. Yurdakal, G. Palmisano, V. Loddo, V. Augugliaro and
photocatalysis is revealed. L. Palmisano, J. Am. Chem. Soc., 2008, 130, 1568–1569.
In summary, we have demonstrated that as a cheap, stable, 16 S. Füldner, R. Mild, H. I. Siegmund, J. A. Schroeder,
Earth-abundant and non-toxic heterogeneous photocatalyst, M. Gruber and B. König, Green Chem., 2010, 12, 400–406.
P25 TiO2, could realize challenging non-activated 1,3-dipolar 17 M. Cherevatskaya, M. Neumann, S. Fueldner, C. Harlander,
cycloaddition for the preparation of polysubstituted imidazoli-
dines without numerous traditional auxiliaries and ligands.
S. Kuemmel, S. Dankesreiter, A. Pfitzner, K. Zeitler and
B. Koenig, Angew. Chem., Int. Ed., 2012, 51, 4062–4066.
This method demonstrated a fairly broad substrate scope and 18 X. J. Lang, W. H. Ma, Y. B. Zhao, C. C. Chen, H. W. Ji and
functional group tolerance. More importantly, it is revealed for J. C. Zhao, Chem. – Eur. J., 2012, 18, 2624–2631.
the first time that radically different from its well-known 19 M. Rueping, J. Zoller, D. C. Fabry, K. Poscharny,
common redox transformation, the TiO2 photocatalyst can
also act as a powerful Lewis- and Brønsted-acid/base catalyst to
R. M. Koenigs, T. E. Weirich and J. Mayer, Chem. – Eur. J.,
2012, 18, 3478–3481.
realize important 1,3-dipolar cycloadditions without additional 20 D. G. Ma, Y. Yan, H. W. Ji, C. C. Chen and J. C. Zhao, Chem.
EWGs in substrates.
Commun., 2015, 51, 17451–17454.
21 Y. Liu, M. Zhang, C.-H. Tung and Y. Wang, ACS Catal.,
2016, 6, 8389–8394.
22 D. C. Fabry, Y. A. Ho, R. Zapf, W. Tremel, M. Panthofer,
M. Rueping and T. H. Rehm, Green Chem., 2017, 19, 1911–
1918.
Conflicts of interest
There are no conflicts to declare.
23 D. Ma, A. Liu, C. Lu and C. Chen, ACS Omega, 2017, 2,
4161–4172.
24 X. Qiao, S. Biswas, W. Wu, F. Zhu, C.-H. Tung and Y. Wang,
Tetrahedron, 2018, 74, 2421–2427.
25 J. Li, A. Liu, Y. Wang, S. Zhai, D. Ma and C. Chen, Catal.
Sci. Technol., 2020, 10, 4917–4922.
26 W. Chang, C. Sun, X. Pang, H. Sheng, Y. Li, H. Ji, W. Song,
C. Chen, W. Ma and J. Zhao, Angew. Chem., Int. Ed., 2015,
54, 2052–2056.
Notes and references
1 H. Xie, J. Zhu, Z. Chen, S. Li and Y. Wu, J. Org. Chem.,
2010, 75, 7468–7471.
2 Y. Saima, S. Khamarui, K. S. Gayen, P. Pandit and
D. K. Maiti, Chem. Commun., 2012, 48, 6601–6603.
3 C. Izquierdo, F. Esteban, J. L. G. Ruano, A. Fraile and
J. Alemán, Org. Lett., 2016, 18, 92–95.
4 R. Xu, R. Xia, M. Luo, X. Xu, J. Cheng, X. Shao and Z. Li, 27 V. Sharma and M. S. Y. Khan, Eur. J. Med. Chem., 2001, 36,
J. Agric. Food Chem., 2014, 62, 381–390. 651–658.
5 F. Parrino, M. Bellardita, E. I. García-López, G. Marcì, 28 Q.-H. Li, L. Wei, X. Chen and C.-J. Wang, Chem. Commun.,
V. Loddo and L. Palmisano, ACS Catal., 2018, 8, 11191–
11225.
6 C. K. Prier, D. A. Rankic and D. W. C. MacMillan, Chem.
Rev., 2013, 113, 5322–5363.
7 G. Palmisano, E. Garcia-Lopez, G. Marci, V. Loddo,
S. Yurdakal, V. Augugliaro and L. Palmisano, Chem.
Commun., 2010, 46, 7074–7089.
2013, 49, 6277–6279.
29 W.-J. Liu, X.-H. Chen and L.-Z. Gong, Org. Lett., 2008, 10,
5357–5360.
30 N. Siemer, A. Lüken, M. Zalibera, J. Frenzel, D. Muñoz-
Santiburcio, A. Savitsky, W. Lubitz, M. Muhler, D. Marx and
J. Strunk, J. Am. Chem. Soc., 2018, 140, 18082–18092.
31 J. M. Coronado, A. J. Maira, J. C. Conesa, K. L. Yeung,
V. Augugliaro and J. Soria, Langmuir, 2001, 17, 5368–5374.
8 L. Palmisano, V. Augugliaro, M. Bellardita, A. Di Paola,
E. G. Lopez, V. Loddo, G. Marci, G. Palmisano and 32 Y. Yan, W. Shi, Z. Yuan, S. He, D. Li, Q. Meng, H. Ji,
S. Yurdakal, ChemSusChem, 2011, 4, 1431–1438.
9 H. Kisch, Angew. Chem., Int. Ed., 2013, 52, 812–847.
C. Chen, W. Ma and J. Zhae, J. Am. Chem. Soc., 2017, 139,
2083–2089.
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 2192–2197 | 2197