Rh-Catalyzed annulations of: N -methoxybenzamides with ketenimines: Synthesis of 3-aminoisoindolinones and 3-diarylmethyleneisoindolinones with strong aggregation induced emission properties

Article abstract of DOI:10.1039/c6cc05456k

Rhodium-catalyzed C-H activation/annulation reactions of ketenimines with N-methoxybenzamides furnished 3-aminoisoindolin-1-ones and 3-(diarylmethylene)isoindolin-1-ones. The synthesized 3-(diarylmethylene)isoindolin-1-ones exhibited aggregation induced emissions in aqueous tetrahydrofuran solution and strong green-yellow emissions in solids.

Full text of DOI:10.1039/c6cc05456k

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DOI: 10.1039/C6CC05456K
Journal Name
COMMUNICATION
Rh-catalyzed annulations of N-methoxybenzamides and
ketenimines: Synthesis of 3-aminoisoindolinones and 3-
diarylmethyleneisoindolinones with strong aggregation induced
emission properties
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Xiaorong Zhou†, Zhixing Peng†, Hongyang Zhao, Zhiyin Zhang, Ping Lu*, Yanguang Wang*
www.rsc.org/
Rhodium-catalyzed C-H acitvation/annulations of ketenimines result (82% yield) was obtained by the reaction of 1a (0.36
with N-methoxybenzamides furnished 3-aminoisoindolin-1-ones mmol), 2a (0.3 mmol), [Cp*RhCl2]2 (0.015 mmol), Cl3CCO2Cs
o
and 3-(diarylmethylene)isoindolin-1-ones. The synthesized 3- (0.09 mmol), and 4
(diarylmethylene)isoindolin-1-ones exhibited aggregation induced hours.
Å
MS (60 mg) in DCE (2 mL) at 80 C for 10
emissions in aqueous tetrahydrofuran solution, and strong yellow
or blue emissions both in nano-particles and in solids.
With the optimized reaction conditions in hand, we
examined the substrate scope using various N-
methoxybenzamides
1
and ketenimines
2
(Table 1).
Substituent (R1) on the 4-position of N-methoxybenzamides
1
Ketenimines have been emerging as valuable and versatile
synthetic intermediates in organic synthesis.1 They can
undergo a variety of reactions, including nucleophilic additions,
could either be electron-donating (Me, MeO) or electron-
withdrawing (Cl, CF3). Thus, 3b were obtained at yields
-
e
[4+2]
and
[2+2]
cycloadditions,
and
sigmatropic
varying from 59% to 81%. Substituent on 3-position of N-
methoxybenzamide could be Cl (3f), NO2 (3g), and CH3 (3h). 2-
Fluoro-N-methoxybenzamide gave the desired product 3i in
low yield (29%). Substituent (R2) on the nitrogen atom of
rearrangements. To the best of our knowledge, applications of
ketenimine as a coupling partner in transition metal catalyzed
C-H activation/annulations have not been reported although
these reactions have been widely explored and applied in the
preparation of a variety of carbocycles and heterocycles.2
ketenimines
2
could be p-BrC6H4 (3k3), p-MeOC6H4 (3l) and
Table 1 Synthesis of 3-aminoisoindolin-1-ones 3a
Herein, we report
activation/annulation
a
Rh(III)-catalyzed cascade C-H
reaction between N-
methoxybenzamides and ketenimines, furnishing 3-
aminoisoindolin-1-ones and 3-(diarylmethylene)isoindolin-1-
ones.
To start with, we probed the reaction conditions for the
envisioned rhodium-catalyzed C-H activation/annulation of N-
methoxybenzamide (1a) with 2,2-diphenyl-N-(p-tolyl)ethen-1-
imine (2a) (see Supporting Information, Table S1). In our
primary test, the reaction of 1a with 2a under CsOAc (30 mol%)
and [Cp*RhCl2]2 (5 mol%) in dichloroethene (DCE) at 80 oC
afforded a [4+1] annulation product 3a in 46% yield. We then
screened
catalysts
([Cp*RhCl2]2,
[Cp*IrCl2]2,
and
[RuCl2(cymene)]2), solvents (DCE, CH3CN, toluene, 1,4-dioxane,
CH2Cl2, and acetone), bases (CsOAc, NaOAc, KOAc, Cl3CCO2Na,
PivOCs, Cl3CCO2Cs, and Cl3CCO2K), reaction temperature (from
o
room temperature to 100 C), atmosphere (air, N2, and O2),
the ratio of starting materials, and catalyst loading. The best
aReaction conditions:
(0.015 mmol), Cl3CCO2Cs (0.09 mmol), 4Å MS (60 mg), DCE (2
mL), N2, 80 oC, 10 h; Isolated yields refer to
1 (0.36 mmol), 2 (0.3 mmol), [Cp*RhCl2]2
Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China
† These authors contributed equally.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
2
.
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m-MeC6H4
(
3m). Two aryls on the terminal carbon of AgNTf2 (see Supporting Information, Scheme S1, eq 1). We
View Article Online
DOI: 10.1039/C6CC05456K
ketenimines could be altered, and 3n and 3o were prepared at isolated a simple addition product
6 (96% yield), which is
37% and 40% yields, respectively. The reaction of N-methoxy- stable to the standard annulation conditions. In this case, the
2-naphthamide (1b) with 2a was also examined. In this case, rhodium catalyst functioned as a Lewis acid and the C-H
3pa (31% yield) and 3pb (33% yield) were obtained without activation was effectively inhibited. When the reaction of 1a
regioselectivity (Scheme 1).
was conducted with the addition of D2O and in the absence of
ketenimine, a deuterium incorporated product was obtained,
indicating a reversible C-H activation (Scheme S1, eq 2). Kinetic
isotope effect (KIE) was carried out in a parallel experiment
(Scheme S1, eq 3). By treatment of 1a or 1a-d5 under standard
reaction conditions for 30 min, KIE of the [4+1] reaction was
determined to be 1.3. This result indicated that the C-H
activation was not the rate determining step. When D2O was
added to the reaction of 1a and 2a, Ha and Hb were
incorporated with deuterium in 22% and 18% ratios,
respectively (Scheme S1, eq 4). The fact that Hb was
incorporated with deuterium implies that metal-H exchange
occurred during the reaction.
Scheme 1 Formation of 3pa and 3ph
.
When N-methoxy-1-naphthamide
substrate, [3+2] annulation
(diarylmethylene)isoindolin-1-one 4a 3
was isolated in 74%
yield (Table 2). Under the established reaction conditions,
products 4b
j3 (46-93% yields) were prepared by the reaction
(
1c
)
was used as
product, 3-
a
,
-
of 1c with a variety of ketenimines. The substituent on
naphthalene substrate could be 4-Br (4k) and 4-ethoxy (4l).
Then, we compared the reactivity of N-methoxy-2-
chlorobenzamide (1d), N-methoxy-2-methyl-benzamide (1e),
N-methoxy-2-phenylbenzamide (1f), and N-methoxy-5,6,7,8-
Scheme 2 Preperation of 5a-d
On the basis of these results, a possible reaction mechanism
is proposed in Scheme 3. In the presence of Cl3CCO2Cs,
.
tetrahydro-1-naphthamide
(
1g). Their reactions with 2a
in 24-61% yields.
afforded the corresponding products 4m
-
p
Table 2 Synthesis of 3-(diarylmethylene)isoindolin-1-ones 4a
[Cp*RhCl2]2 is activated to species
and subsequent coordination with
A
. Then, the activation of
I
2
afford -complex

C, which
undergoes migration insertion to C=N bond to form complex
D
.
When the ortho position of benzamide is occupied by H or F
with less steric hindrance, the C=C bond in can coordinate to
center metal to form undergoes a migration insertion and
metal-H exchange to generate in a [4+1] annulation manner.
In the cases where the ortho position of benzamide is occupied
by a bulky group (i.e., R H or F), it is difficult for the
coordination of the C=C bond to metal to form due to more
steric hindrance between R and amido groups, but can
undergoes an intramolecular nucleophilic substitution to
D
E. E
3

E
D
produce
4
in a [3+2] annulation manner.
aReaction conditions:
(0.015 mmol), Cl3CCO2Cs (0.09 mmol), 4Å MS (60 mg), DCE (2
mL), N2, 80 oC, 10 h; Isolated yields refer to
1 (0.36 mmol), 2 (0.3 mmol), [Cp*RhCl2]2
2
.
The resulted 3-aminoisoindolin-1-ones
converted into 3-(diarylmethylene)isoindolin-1-ones. For
example, n the presence of trifluoroborane etherate, 3a could
be converted into 5a in 83% yield. Similar eliminations could
be done to produce 5b in 76-86% yields (Scheme 2).
3 could also
i
-
d
To probe the reaction mechanism, the reaction of 1a with
2a was examined using 5 mol % [Cp*RhCl2]2 and 15 mol %
Scheme 3 Proposed mechanism.
2 | J. Name., 2012, 00, 1-3
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During the preparation of 3-(diarylmethylene)isoindolin-1-
ones 4, we serendipitously found that this class of compounds
exhibited strong aggregation-induced emissions (AIE)4
properties. Delighted by the potential applications of AIE
active molecules in optoelectronic devices, luminescent
sensors, biomedical imaging and smart materials,5 and as an
continuation of our work on developing new AIE
fluorophores,6 we investigated the photophysical properties of
these compounds. The results are summarized in Table S2 (see
Supporting Information).
View Article Online
DOI: 10.1039/C6CC05456K
Fig. 1 (a) Emission spectra of 4d in THF/water mixtures. (b)
Fluorescence intensity of 4h in THF/water mixtures. Excited
width = 3 mm, emission width = 10 mm.
Absorption of the selected compounds 4a
measured in dilute solution of THF in a concentration scale of
10-5 M. Compounds 4a
absorbed light at about 375 nm with
-p and 5a-d were
-
e
molar absorptivities varying from 17800 to 23700. By installing
substituent on para-position of 3-diarylmethylene, electron-
donating group (MeO) could tune the maximum absorption
wavelength. 4i and 4f absorbed light at 405 nm and 412 nm,
respectively. The highest absorptivity was achieved when the
substituent is phenyl (4h). Either electron-withdrawing (Br, 4k
)
or electron-donating (EtO, 4l) on 4-position of naphthalene
influenced the absorption and gave rise to a blue-shifted
absorption. Compounds 4m
with molar absorptivities ranging from 18100 to 19500.
Compared with , the absorption of 5a shifted to about 346
-p absorbed light at about 370 nm
Fig. 2 Magnified folds of quantum yields by AIE effect.
4
-b
nm. Theoretical HOMO and LUMO orbitals were calculated by
B3LYP/6-31G+ method on Guassian 09 program. The
calculated HOMO-LUMO gaps were in good agreement with
the experimental observations based on the relative errors
shown in Table S3 (see Supporting Information).
Dilute solutions of compounds 4a
quantum yields up to 0.077% (4h) referring to the standard of
quinine sulfate (Φ =0.54 in 0.1M H2SO4). Quantum yields of 5a
were slightly higher up to 0.514% (5a). The situation changed
-p were not emissive with
-
d
by just adding water. For example, solutions of 4d were not
emissive as the water fraction gradually changed to 80% (Fig.
1). Further tuning the water fraction to 85%, the solution was
lit up under UV-irradiation. As water fraction increased to 95%,
the quantum yield increased to 87.3 times the initial quantum
yield. The results indicated that all of these compounds were Fig. 3 The size distribution and shape of nano-particles of
AIE active. The quantum yields of 4a could be magnified in a compound 4d in H2O-THF (99;1, 95:5, 90:10, and 85:15, v/v). (a)
-
p
range of 18 to 163 folds. In comparison with the reported AIE- Particle size distribution. (b) Particle size in peak value and
active molecules, such as tetraphenylethene (40 folds),7 9- relationship of particle size in peak value and the
(diphenylmethylene)-9H-fluorene (35 folds)8 and 3,4- corresponding maximum fluorescence intensity. (c)-(f) TEM of
diphenylisoquinolin-1(2H)-one (8 folds)9, the AIE effect of the particles in 99;1, 95:5, 90:10, and 85:15 H2O-THF, respectively
synthesized compounds 4a and 4h was obvious (Fig. 2).
Adding water to the solution of 4d in THF resulted in the
aggregation of solutes and the formation of nano-particles.
(Scare bar = 1 μm)
The stronger emission in nano-suspension could be
The shape and size distribution of nano-particles were explained by aggregation induced emission.4 The restriction of
determined by TEM and DLS (Fig. 3). As the water fraction intramolecular rotation (RIR) of phenyl and phenylene rings in
increased from 85% to 99%, the diameter of nano-particles aggregates might be the main reason.11 Because 4h has two
changed from 164 nm to 72 nm. As a result, a smaller diameter more phenylene rings conjugated by sigma bonds, the
corresponds to a stronger emission.10
quantum yield of 4h was magnified to 163 folds. Compounds
4a and 5a are strong emissive not only in nano-suspension
but also in solids. Comparative figures, before and after UV-
irradiation on 4a 4d 4h 4n, and 5c, are shown in Fig. 4. These
compounds are shining in solids.
-
p
-d
,
,
,
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Notes and references
1
View Article Online
For recent reviews on ketenimines, DsOeIe::10(.a10)39P/.C6LuCCa0n54d56YK.
Wang, Synlett 2010, 2010, 165; (b) S. H. Kim, S. H. Park, J. H.
Choi and S. Chang, Chem. Asian J. 2011, 6, 2618; (c) P. Lu and
Y. Wang, Chem. Soc. Rev. 2012, 41, 5687; (d) M. Alajarin, M.
Marin-Luna and A. Vidal, Eur. J. Org. Chem. 2012, 2012, 5637.
For recent reviews on RhIII-catalyzed C-H activation: (a) T.
Satoh and M. Miura, Chem. Eur. J. 2010, 16, 11212; (b) D. A.
Colby, R. G. Bergman and J. A. Ellman, Chem. Rev. 2010, 110,
624; (c) D. A. Colby, A. S. Tsai, R. G. Bergman and J. A. Ellman,
Acc. Chem. Res. 2012, 45, 814; (d) F. W. Patureau,J.Wencel-
Delordand and F. Glorius, Aldrichimica Acta 2012, 45, 31; (e)
G. Song, F. Wang and X. Li, Chem. Soc. Rev. 2012, 41, 3651; (f)
2
Fig. 4 Image of compounds 4a (a), 4d (b), 4h (c), 4n (d), and 5c
(e) before (top) and after (bottom) UV-irradiation.
Mechanochromic fluorescent materials have attracted
much attention due to their promising applications. They can
be applied in fields including mechanosensors,12 security inks13
and optical storage.14 Therefore, compound 4h was tested for
such possibilities. As showed in Fig. 5 , 4h in crystal shown
green with emission at 525 nm. However, it changed colour
from green to yellow with emission at 541 nm after grounding.
Fluorescence spectra agreed well with the pictures. The
different phenomenon may be ascribed to the change of
configuration. After grounding, it altered from crystal to
amorphous state. SXRD also verified the assumption.
N. Kuhl, N. Schröder and F. Glorius, Adv. Synth. Catal. 2014
,
356, 1443; (g) G. Song and X. Li, Acc. Chem. Res. 2015, 48,
1007; (h) B. Ye and N. Cramer, Acc. Chem. Res. 2015, 48,
1308; (i) Z. Chen, B. Wang, J. Zhang, W. Yu, Z. Liu and Y.
Zhang, Org. Chem. Front. 2015, 2, 1107.
3
4
For ORTEPs of products 3k, 4a, and 4h please see the
SupportingInformation. CCDC 1405389 (3k), 1405393 (4a),
and 1436545 (4h) contain supplementary crystallographic
data for this paper.These data can be obtained free of
charge from The Cambridge CrystallographicData Centre via
www.ccdc.cam.ac.uk/data_request/cif
J. Luo, Z. Xie, J. W. Y. Lam, L. Cheng, B. Z. Tang, H. Chen, C.
Qiu, H. S. Kwok, X. Zhan, Y. Liu and D. Zhu, Chem. Commun.
2001,1740.
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J. Mei, Y. Hong, J. W. Y. Lam, A. Qin, Y. Tang and B. Z. Tang,
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Fig. 5 Fluorescent images of compound 4h in crystalline (a) and
amorphous (b). (c) Emission spectra of 4h in crystalline and
amorphous. (d) SXRD patters of 4h in crystalline and
amorphous
Z. Li, B. Z. Tang, J. Sun and H. S. Kwok, Appl. Phys. Lett. 2007
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In conclusion, we have developed a rhodium-catalyzed C-H
activation/annulation
of
ketenimines
with
N-
methoxybenzamides. Two types of annulations have been
revealed based on the structure variation of N-
methoxybenzamides. Thus, 3-aminoisoindolin-1-ones and 3-
(diarylmethylene)isoindolin-1-ones were constructed through
[4+1] and [3+2] annulation manners, respectively.
Furthermore, the synthesized 3-(diarylmethylene)isoindolin-1-
ones were found to exhibit strong aggregation-induced
emission effect. Strong yellow or blue emissions were
observed for these compounds existing both in nano-particles
and in solids.
13 A. Kishimura, T. Yamashita, K. Yamaguchi and T. Aida, Nat.
Mater. 2005, 4, 546.
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We thank the National Natural Science Foundation of China
(Nos. 21272204, 21272203 and J1210042) for finacial support.
4 | J. Name., 2012, 00, 1-3
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