Dual-catalyst engineered porous organic framework for visible-light triggered, metal-free and aerobic sp3 C[sbnd]H activation in highly synergistic and recyclable fashion

Article abstract of DOI:10.1016/j.jcat.2020.12.013

Photoredox and organo-catalysis denote powerful construction tools for new classes of carbon–carbon bonds, where incisive amalgamation of both the approaches over a single, recyclable platform can bring about synergic and eco-friendly reactions under mild

Full text of DOI:10.1016/j.jcat.2020.12.013

Journal of Catalysis 394 (2021) 40–49
Contents lists available at ScienceDirect
Journal of Catalysis
journal homepage: www.elsevier.com/locate/jcat
Dual-catalyst engineered porous organic framework for visible-light
triggered, metal-free and aerobic sp3 CAH activation in highly
synergistic and recyclable fashion
Gaurav Kumar a,b, Soumya Ranjan Dash c, Subhadip Neogi a,b,
⇑
a Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
b Inorganic Materials & Catalysis Division, CSIR-CSMCRI Bhavnagar, Gujarat 364002, India
c Physical and Material Chemistry Division, CSIR-NCL Pune, Dr. Homi Bhaba Road, Pune 411008, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Photoredox and organo-catalysis denote powerful construction tools for new classes of carbon–carbon
bonds, where incisive amalgamation of both the approaches over a single, recyclable platform can bring
about synergic and eco-friendly reactions under mild conditions. Aiming at enamine-based photoredox
catalysis for atom-economic and metal-free sp3 CAH activation, an amide-based two-dimensional (2D)
porous organic framework (POF) is devised. The pendent ANH2 groups are judiciously anchored with
two catalytic stations viz. Rose Bengal and L-proline, through stepwise variation of solid phase peptide
synthesis. The dual-catalyst engineered POF represents a fully organic material that synergistically per-
forms visible-light triggered oxidative Mannich reaction to produce biorelevant heterocycle b-amino
ketone in excellent yield at room temperature, using oxygen as clean and selective oxidant.
Importantly, activity of this bi-functionalized catalyst compares favorably well to individual homoge-
neous counterparts. The covalently modified framework demonstrates economic viability via
gram-scale synthesis besides admirable reusability, and proves to be effective for nineteen varieties of
substrates. The photocatalytic path is detailed from efficient energy transfer from host polymer to
substrate in light of experimental and theoretical studies, which provides proof-of-concept to the
photo-organo combined mechanism. The material benefits heterogenising two homogeneous catalysts,
besides excluding additional steps of conventional Mannich reactions, and offers a step-forward to smart
and green cross-dehydrogenative coupling reactions.
Received 7 October 2020
Revised 9 December 2020
Accepted 15 December 2020
Available online 6 January 2021
Keywords:
Porous organic framework
Dual-catalyst engineering
Photo-organo catalysis
Atom-economy
Metal-free reaction
CAH activation
Ó 2020 Elsevier Inc. All rights reserved.
1. Introduction
transformations have been accomplished by various photocata-
lysts [5]. Though environmentally unfriendly, organic dyes such
Recent advancement in developing unprecedented methodol-
ogy for the construction of new classes of carbon–carbon bonds
will overwhelmingly dictate synthetic efficacy of organic synthesis.
Among others, visible-light driven heterogeneous photocatalysts
rank top priority with enhanced catalytic ability. Till date, various
paths have been explored for visible-light mediated CAH bond
activation and subsequent CAC bond formation through cross-
coupling reactions, where cross-dehydrogenative coupling (CDC)
is the most powerful tool [1–3]. From economic viewpoint, light
driven CDC reaction between pronucleophiles and proelec-
trophiles, containing divergent CAH bonds will reduce the syn-
thetic steps and confer more proficiency [4]. Enroute, these
as Eosin Y and Rose Bengal (RB) are proved to be the best homoge-
neous photocatalysts [6–8]. Then again, reported catalytic systems,
are dominated by toxic and costly homogenous transition-metal
complexes, thus limiting scale up and long-term use for real-time
applications [9–11].
As a sustainable alternative, amalgamation of a photocatalyst
with an organocatalyst should be practical, but reports are rather
infrequent. Bach et al. exemplified bifunctional photo-organo cata-
lyst for cycloaddition reactions [12]. We reported merger of pho-
toredox catalyst with chiral metal complex for asymmetric
alkynylation [13]. In spite of these innovative studies, fabrication
of a system, retaining the functions of both photoredox and organo
catalysis is still in infancy. Thus, present need is to develop an effi-
cient bi-functionalized material that is highly recyclable,
metal-free and active under environmentally benign conditions.
⇑
Corresponding author at: Academy of Scientific and Innovative Research
(AcSIR), Ghaziabad 201002, India.
E-mail address: sneogi@csmcri.res.in (S. Neogi).
https://doi.org/10.1016/j.jcat.2020.12.013
0021-9517/Ó 2020 Elsevier Inc. All rights reserved.

G. Kumar, Soumya Ranjan Dash and S. Neogi
Journal of Catalysis 394 (2021) 40–49
Scheme 1. Schematic representation for the synthesis of precursor porous organic framework C-1.
Fig. 1. a) FT-IR and b) solid-state 13C/CP-MAS NMR spectrum of as-synthesized POF (C-1). c) FT-IR and d) solid-state 13C/CP-MAS NMR spectrum of bifunctional framework C-
7.
To overcome the separation issues, heterogenization of individual
catalytic parts over a solid support is a promising option. Zhang
et al. reported bi-functional sponge photocatalyst for CDC reactions
[14]. Post-synthetic modification (PSM) can also be achieved by
grafting the active components on pre-functionalized solid materi-
als [15–17]. In this direction, metal-organic frameworks (MOFs)
are the most intriguing candidates, where modification of these
supports are proved to be suitable for effective heterogeneous
catalysis [18–20]. However, development of metal-free photo-
organo heterogeneous catalyst is yet to be explored and challeng-
ing due to lack in (a) effective photon energy transfer from host
polymer to substrate, (b) rational protocol to blend diverse func-
tionalities over
a single platform, and (c) fabricating ideal
organic-support that bears effective pore size tunability and stabil-
ity towards a variety of PSMs. In this milieu, new-generation por-
ous organic materials, including covalent organic framework
41

G. Kumar, Soumya Ranjan Dash and S. Neogi
Journal of Catalysis 394 (2021) 40–49
Fig. 2. C1s and N1s XPS spectra of the as synthesised (C-1) (a, c) and post-modified (C-7) (b, d) POF.
Fig. 3. a) FE-SEM images of C-1 (i, ii) and C-7 (iii, iv) at different magnifications, b) TEM images of C-1 (i, ii) and C-7 (iii, iv).
(COF) [21], conjugated microporous polymer (CMP) [22], and por-
framework. The dual-catalyst engineered POF acts as a fully
organic visible-light catalyst for oxidative Mannich reaction, pro-
ducing biologically important b-amino ketones [29,30] under aer-
obic conditions. Obvious advantage of heterogenising two
homogeneous catalysts include: (a) atom-economic sp3 CAH func-
tionalization of tertiary amines through elimination of additional
steps of conventional Mannich reactions, (b) effectiveness towards
wide variety of substrates, (c) excellent multi-cyclic performances,
and (d) economic viability via gram-scale synthesis. Detailed
experimental and theoretical studies portray the photocatalytic
path and validates combined photo-organo mechanism. To our
knowledge, this is the first approach of a dual-catalyst anchored
POF for synergic, metal-free and atom-efficient reaction that sheds
ous polymer network (PPN) [23] gained immense interest due to
their easy synthesis, pore size tunability and effective pore func-
tionalization. Earlier reports demonstrated that amide based por-
ous organic frameworks (POF) serve as excellent robust
candidates for supports in heterogeneous catalysts [24].
Bearing the aforementioned challenges and rationale in mind,
we synthesised a novel ANH2 functionalized POF [25] that exhibits
high stability [26], permanent porosity [27], modifiable pore
structure [28], and structural adaptability towards wide range of
modifications. Judicious grafting of RB dye as photo-catalyst and
L-proline as organo-catalyst over stepwise solid phase peptide
synthesis (SPPS) leads to the formation of unique bifunctional
42

G. Kumar, Soumya Ranjan Dash and S. Neogi
Journal of Catalysis 394 (2021) 40–49
Fig. 4. a) N2 adsorption isotherm of C-1 and C-7 at 77 K (inset shows pore size distribution of respective materials). b) Solid state UV ꢀ vis diffuse reflectance spectra of
pristine POF (C-1: red, C-7: blue).
Scheme 2. Stepwise route for the construction of dual-catalyst engineered framework C-7 via solid phase peptide synthesis (structural details of C-4 to C-6 are provided in
the Supporting Information).
light on tailor-made fabrication of smart functional material for
promising catalytic applications via environmentally benign route.
in turn disseminate the positive effects of amide-based porous
organic frameworks (POFs) [31,32]. Extended -cloud delocaliza-
p
tion over the two-dimensional (2D) sheets allow nearly planar con-
formation to the structure (Scheme 1) [33] and reinforce textual
properties like stability and porosity. We also attempted N-Boc
protected ATC to synthesize C-1 and achieved almost same yield
after deprotection that ruled out any possibility of self-
condensation reaction of ATC. C-1 is insoluble in water and com-
mon organic solvents. The FT-IR spectrum displays sharp bands
2. Results and discussion
2.1. Synthesis and characterization of amide-based porous organic
framework (C-1)
The chemical assembly of precursor material (C-1) includes
base-catalysed reaction between precursors 1,3,5-Tris(4-aminophe
nyl)benzene (TAB) and 2-aminoterephthaloyl dichloride (ATC) that
at 1661 cmꢀ1 and 3262 cmꢀ1 that correspond to
(NAH) stretching vibrations of amide-I band, respectively.
m(C@O) and m
43

G. Kumar, Soumya Ranjan Dash and S. Neogi
Journal of Catalysis 394 (2021) 40–49
Scheme 3. a) Energy Diagram for Photocatalytic Oxidative Mannich Reaction of 1a to 3a using the RB Grafted C-7 (energy levels of the orbitals are arbitrary to scale). b)
Pictorial Representation of HOMO and LUMO Orbitals and their Energy Levels for Sole RB Moiety.
Peaks belonging to 1516 cmꢀ1 and 1398 cmꢀ1 are attributed to
(NAH) in-plane bending and (CAN) stretching vibrations of
t–Teller (BET) surface area 405 m2/g with a pore volume of
0.5 cm3/g (Fig. 4a). Though, the nature of isotherm is fairly similar
to the reported once [35], these values are superior because of the
larger C3 symmetric core unit. The pore size of the POF, calculated
by fitting non-linear density functional theory (NLDFT) model to
the N2 sorption isotherm, were centred at 1.31 nm (Fig. 4a).
m
m
amide groups (Fig. 1a). Existence of amide bond is further con-
firmed by a peak at 166.57 ppm in cross polarization magic angle
spinning (CP-MAS) 13C NMR, where other peaks ranging from
156 to 120 ppm correspond to the aromatic carbon network
(Fig. 1b). To further supplement molecular composition of C-1,
the range of bonding patterns were observed from X-ray photo
electron spectroscopy (XPS). The survey spectrum clearly showed
the presence of carbon, oxygen, and nitrogen (Fig. S6a). The C1s
spectrum (Fig. 2a) is deconvoluted into four peaks with diverse
binding energies (BEs), where peak at 284.3 eV is endorsed to
CAH and C@C carbon, and the other peak at 285.4 eV corresponds
to carbon of amide bond. The weakest deconvoluted peak at
286.2 eV is associated with NAC@O bond, while carbon of CAN
bond is found at 287.4 eV. Similarly, the N1s spectrum (Fig. 2c) is
deconvoluted into two peaks, having BEs 399.3 and 400.0 eV. The
former peak corresponds to the free amine group of ATC, and the
latter is ascribed to amide nitrogen.
Morphology of C-1 was confirmed from field-emission scanning
electron microscopy (FE-SEM) (Fig. 3a) and high-resolution trans-
mission electron microscopy (HR-TEM) (Fig. 3b). The FE-SEM
images display spherical particles clustered together with homoge-
nous distribution, which are typical to reported porous organic
polymers [34,35]. TEM analysis showed extended network struc-
ture with similar spherical shape. Powder X-ray diffraction (PXRD)
of C-1 shows a broad peak and corroborates amorphous nature of
the material (Fig. S1) [33]. Thermogravimeric analysis (TGA) under
N2 environment (heating rate: 10 °C/min) shows 2.30% weight loss
up to 110 °C (Fig. S3), which is associated with the moisture in the
porous structure. A large 60% weight loss in the temperature range
350-420 °C suggests decomposition of the framework. Permanent
porosity, pore volume and pore size were checked through N2
adsorption isotherm at 77 K up to relative pressure (P/P0) 1.0. Prior
to the measurement, C-1 was activated at 120 °C for 4 h to remove
the pore occluded solvents. The material shows Brunauer–Emmet
2.2. Synthesis and characterization of dual-catalyst engineered
framework (C-7)
The unbound ANH2 moieties in C-1 allow covalent modification
to this framework. A route to stepwise formation of dual-catalyst
grafted POF (C-7) through varying protocols of SPPS [36] is mapped
in Scheme 2, while detailed discussions on synthesis (Scheme S4)
and characterization of intermediates (C-2 to C-6) are presented
in the Supporting Information. Thorough characterizations of C-7
are accomplished from FTIR, 13C/CP MAS NMR, TGA, and XPS anal-
ysis. FT-IR of C-7 displays sharp bands at 1660, 1775 cmꢀ1 and
3270 cmꢀ1 that correspond to
(NAH) stretching vibrations of amide-I band, respectively. Peaks
belonging to 1515 cmꢀ1 and 1401 cmꢀ1 are attributed to
(NAH)
in-plane bending and (CAN) stretching vibrations of amide
m(C@O) amide, m(C@O) ester and m
m
m
groups (Fig. 1c). Presences of two amide functional groups in C-7
are confirmed from peaks at 166.01 and 161.31 ppm in the solid-
state 13C/CP MAS NMR (Fig. 1d). The other ester group with proline
moiety generates peak at 170.08 ppm, and all other peaks ranging
from 137 to 120 ppm correspond to aromatic carbons. Remaining
peaks in the aliphatic region (range: 42.04–24.07 ppm) belong to
the combined aliphatic carbons of proline and RB moiety
(Fig. 1d). The TGA profile of C-7 shows (Fig. S3) a weight loss of
2.97% up to 110 °C due to loss of moisture. The second weight loss
(27.03%) results from partial disruption of linked organic moieties,
while further weight loss relates to overall decomposition of the
framework. The C1s XPS spectrum of C-7 is shown in Fig. 2b, which
depicts peaks at 285.00, 285.70, 286.30, 288.20 and 288.80 eV,
belonging to C@C, C@O (ester and amide), CAN, NAC@O, and
44

G. Kumar, Soumya Ranjan Dash and S. Neogi
Journal of Catalysis 394 (2021) 40–49
Table 1
OAC@O types of bonding, respectively. Two peaks at 398.5 and
400.0 eV in the deconvoluted N1s spectra (Fig. 2d) originate from
nitrogen of CANH and NAC@O bonds. Further, Cl and I XPS spectra
were also recorded (Fig. S7), which prove grafting of RB to the poly-
mer network. Changes in the absolute morphology are monitored
by FE-SEM and TEM analyses. SEM images of C-7 shows (Fig. 3a)
agglomeration of irregular morphology with moderate alteration
in spherical shape at low magnification that may originate from
post-synthetic covalent modifications. The catalyst(s) loading on
C-7 was 0.022 mmol/g, as determined by elemental analysis [37].
The N2 adsorption isotherm of the POF after hooking of two cat-
alytic stations reflects a sharp reduction (195 m2/g) in BET surface
area (Fig. 4a), and alternatively confirm grafting of RB and L-proline
moieties [20]. It may be noted that we also measured BET surface
areas for the intermediates (C2–C4), which clearly indicated grad-
ual reduction of values (Fig. S4a,b) to that of C-1 [38].
The optical energy gaps for the photocatalyst loaded C-7 is cal-
culated from Tauc plot (Fig. S9), using UV ꢀ vis diffuse reflectance
spectra (DRS) [39]. The spectra shows broad absorption in the vis-
ible region with two peaks at 535 and 580 nm (Fig. 4b), as also
appears for sole RB molecule [40]. The energy difference between
highest occupied and lowest unoccupied molecular orbitals
(HOMO and LUMO) of RB (Scheme 3b), obtained from density func-
tional theory (DFT) calculation [41,42], is higher than experimen-
tally observed value of C-7. Nevertheless, the visible light
absorption capacity of C-7 is still ideal for activating a tertiary
amine for photo-induced oxidative Mannich reaction with ketone
(Scheme 3a). In comparison to the precursor C-1 (kmax = 400 nm)
the photo response of the C-7 was markedly extended due to func-
tionalization with the RB (Fig. 4b), which should be advantageous
for visible-light catalysis. The photo luminescent (PL) spectra of
dispersed solution of C-7 (in acetonitrile) shows emission band
at 550 nm upon exciting at 525 nm (Fig. S13), which is ascribed
to the emission from excited state of RB. The redox behaviour of
C-7 as well as RB were determined from cyclic voltammetry (CV)
using glassy carbon as working electrode, and Ag/AgCl as reference
electrode. The results showed (Fig. S14) similar types of curves
with oxidation and reduction peaks of C-7 at ꢀ0.77 V and
+0.93 V, respectively, inferring that RB hooked catalyst delineates
both electron donor and acceptor attributes.
Optimization of Reaction Conditions.a
Entry
Catalyst
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
C-7
C-7
C-7
C-7
C-7
C-7
C-7
C-7
C-7
C-7
TAB
ATC
C-1
C-2
C-4
C-7
C-7
C-7
DMF
65 (10 h)
35 (10 h)
30 (10 h)
35 (10 h)
25 (10 h)
25 (9 h)
Acetone
MeCN
DCM
Toluene
CHCl3
Water
Dioxane
EA
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
50 (10 h)
35 (10 h)
43 (10 h)
98 (6 h)
9
10
11
12
13
14
15
16
17
18
n.r. (18 h)
n.r. (18 h)
n.r. (18 h)
10 (18 h)
45 (18 h)
60c, 70d, n.re,f (18 h)
45g, n.r.h (18 h)
20i (6 h)
a
Reactions were performed using 1a (0.2 mmol) and 2a (2.0 mmol) in 2 mL
solvent with 1 mol % C-7 using molecular oxygen as oxidant at room temperature
with a 24 W household lamp for 6–18 h.
b
Isolated yields.
12 W blue LED.
12W Green LED.
In the absence of visible light irradiation.
c
d
e
f
In dark.
g
Thermal conditions at 60 °C or open air.
Under inert atmosphere.
TEMPO as radical scavenger (0.2 mmol) (n.r.: no reaction).
h
i
To further check the synergism in photo-organo reaction, RB
hooked C-4, together with L-proline as external Lewis base, was
tested for enamine catalysis, which furnished inferior yield of the
product (Table S3, entry 1) compared to C-7. Also, pyrrolidine
(pKa = 11.27) as stronger external Lewis base did not improve
the yield (Table S3, entry 2), signifying potential of in-situ hooked
base in the photo-organo catalysis. To more effectively generate
the enamine nucleophiles from acetone, we even used the combi-
nation of trifluoroacetic acid and pyrrolidine along with C-4, which
still exhibits inferior yield (Table S3, entry 3). These control exper-
iments mutually demonstrates the synergism between two cat-
alytic stations in C-7.
Notably, present synthetic route is atom-economic compared to
conventional Mannich reaction [43–47], where an additional step
is associated to prepare the iminium ion intermediate, which is
in situ generated here (Scheme 4). Variation of catalyst amount
divulged that 1 mol % of C-7 is most effective for the reaction
(Table S2). The reaction does not proceed when conducted in pres-
ence of improper light sources (Table 1, entry 16) or in absence of
household fluorescent lamp (24 W) and/or in dark (Table 1, entry
16). Also, the reaction showed only 45% product yield under ther-
mal conditions or in open air (Table 1, entry 17), while no product
formed while conducting the reaction in absence of O2 (Table 1,
entry 17). Collectively, the present heterogeneous system unveils
first-ever combination of dual photo-organo catalysis that works
in highly synergistic and atom-economic manner under metal-
free and mild reaction conditions, using molecular oxygen as selec-
tive oxidant.
2.3. Visible-light triggered, metal-free and aerobic sp3 CAH activation
by C-7
Surmising on promising photoredox property and visible-light
absorption capacity of C-7, we determined its photo-organo cat-
alytic activity towards sp3 CAH activation reaction between 2-(phe
nyl)-1,2,3,4-tetrahydroisoquinoline (1a) as electrophile, and ace-
tone (2a) as nucleophile. The influences of different reaction
parameters, including solvents, catalyst amount, oxidants, and
light sources (visible-light irradiation) were thoroughly checked
(Tables S1-S3). Among other solvents (DMF, acetone, MeCN,
DCM, toluene, CHCl3, water, dioxane, and ethyl acetate), MeOH
was found to be most suited (Table 1, entry 1–10), producing the
desired product (3a) in 98% yield. Using 1 mol % catalyst, molecular
oxygen proved to be the best oxidant (Table 1). In fact, the activity
of other oxidants (Fig. 5) including H2O2 (30 wt% in water), TBHP
(70 wt% in water), chloranil, hypervalent iodine, N-
hydroxyphthalimide (NHPI) and meta-chloroperoxybenzoic acid
(mCPBA) were checked and found to be less for this reaction
(Table S1). No catalytic reaction ensues using precursor ligand moi-
eties (TAB & ATC) and/or pristine POF, while C-2 and C-4 gave 10
and 45% yields, respectively (Table 1, entry 11–15). These observa-
tions vividly point that proline moiety on C-7 plays synergistic role
to accelerate the enamine based oxidative Mannich reaction with
ketones.
45

G. Kumar, Soumya Ranjan Dash and S. Neogi
Journal of Catalysis 394 (2021) 40–49
Fig. 5. Bar diagram for reaction optimization conditions.
Scheme 4. Synergic Mechanistic Path for Oxidative Mannich Reaction of Tetrahydroisoquinoline with Ketone by Dual-catalyst Engineered Framework.
2.4. Substrate scope for oxidative Mannich reaction
methyl ketone having two enolizable positions reacts exclusively
at the less substituted side to offer product in moderate yield
(Table 2, entry 6). 3,3-dimethoxyylbutan-2-one as well as 4-
phenyl-2-butanone revealed moderate yield of respective products
(Table 2, entry 7, 8). Besides, cyclopropyl-ketone and acetyl ketone
were also used to build CAC bonds in decent yields (Table 2, entry
9, 10). Notably, aromatic ketones proved to be less promising
nucleophiles and rendered inferior yields compared to aliphatic
counterparts as a consequence of conjugation between phenyl ring
and acetone group. For example, acetophenone and its 4-methoxy
Considering aforesaid optimum reaction conditions, we next
pursued substrate scope for sp3 CAH activation reaction. As such,
no trend of reducing the yield of products was observed even with
long chain aliphatic ketones (Table 2, entry 2,3), providing an
excellent opportunity for vast spectrum of derivatization. For
instance, 3-pentanone provided 78% yield (Table 2, entry 4) while
inert 3,3-dimethylbutan-2-one could be coupled in satisfactory
yield with slight longer reaction duration (Table 2, entry 5). Ethyl
46

G. Kumar, Soumya Ranjan Dash and S. Neogi
Journal of Catalysis 394 (2021) 40–49
Table 2
Substrate Scope for the Oxidative Mannich Reactions between Diverse N-aryl Tetrahydroisoquinoline and Ketones under Optimised Conditions.a
Entry
1
3° amine (R1 & R2)
Ketone (R3 & R4)
Products
Yieldb (%)
98
(2a) R3 = ꢀH, R4 = ꢀH
(1a) R1 = ꢀH, R2 = ꢀH
(3a) R1 = ꢀH, R2 = ꢀH, R3 = ꢀH, R4 = ꢀH
(3b) R1 = ꢀH, R2 = ꢀH, ꢀCH2CH3CH3, R4 = ꢀH
(3b) ꢀH, R2 = ꢀH, ꢀCH2CH3CH3CH3, R4 = ꢀH
(3d) ꢀH, R2 = ꢀH, ꢀCH2CH3, R4 = ꢀCH3
(3e) ꢀH, R2 = ꢀH, R3 = ꢀCH(CH3)2, R4 = ꢀH
(3f) ꢀH, R2 = ꢀH, ꢀCH2CH3, R4 = ꢀH
(3 g) ꢀH, R2 = ꢀH, ꢀCH(OMe)2, R4 = ꢀH
(3 h) R1 = ꢀH, R2 = ꢀH, ꢀCH2CH2C6H5, R4 = ꢀH
(3i) R1 = ꢀH, R2 = ꢀH, ꢀcyclopropyl, R4 = ꢀH
(3j) ꢀH, R2 = ꢀH, ꢀacetyl, R4 = ꢀH
2
3
4
5
6
7
8
9
(1a) R1 = ꢀH, R2 = ꢀH
(1a) R1 = ꢀH, R2 = ꢀH
(1a) R1 = ꢀH, R2 = ꢀH
(1a) R1 = ꢀH, R2 = ꢀH
(1a) R1 = ꢀH, R2 = ꢀH
(1a) R1 = ꢀH, R2 = ꢀH
(1a) R1 = ꢀH, R2 = ꢀH
(1a) R1 = ꢀH, R2 = ꢀH
(1a) R1 = ꢀH, R2 = ꢀH
(1b) R2 = ꢀ4OMe, R1 = ꢀH
(1c) R2 = ꢀ3OMe, R1 = ꢀH
(1d) R2 = ꢀ2OMe, R1 = ꢀH
(1e) R2 = ꢀ4Me, R1 = ꢀH
(1f) R2 = ꢀ3Me, R1 = ꢀH
(1 g) R2 = ꢀ2Me, R1 = ꢀH
(1a) R1 = ꢀH, R2 = ꢀH
(2b) R3 = ꢀCH2CH3CH3, R4 = ꢀH
(2c) R3 = ꢀCH2CH3CH3CH3, R4 = ꢀH
(2d) R3 = ꢀCH2CH3, R4 = ꢀCH3
(2e) R3 = ꢀCH(CH3)2, R4 = ꢀH
(2f) R3 = ꢀCH2CH3, R4 = ꢀH
(2 g) R3 = ꢀCH(OMe)2, R4 = ꢀH
(2 h) R3 = ꢀCH2CH2C6H5, R4 = ꢀH
(2i) R3 = ꢀcyclopropyl, R4 = ꢀH
(2j) R3 = ꢀacetyl, R4 = ꢀH
92
86
78
75
88
65
75
85
84
96
89
86
94
92
75
80
85
10
11
(2a) R3 = ꢀH, R4 = ꢀH
(3 k) R2 = ꢀ4OMe, R3 = ꢀH, R4 = ꢀH
(3 l) R2 = ꢀ3OMe, R3 = ꢀH, R4 = ꢀH
(3 m) R2 = ꢀ2OMe, R3 = ꢀH, R4 = ꢀH
(3n) R2 = ꢀ4Me, R3 = ꢀH, R4 = ꢀH
12
13
(2a) R3 = ꢀH, R4 = ꢀH
(3o) R2 = ꢀ3Me, R3 = ꢀH, R4 = ꢀH
(3p) R2 = ꢀ2Me, R3 = ꢀH, R4 = ꢀH
(3q) R1 = ꢀH, R2 = ꢀH, R5 = ꢀ4OMe
(3r) R1 = ꢀH, R2 = ꢀH, R5 = ꢀH
(2 k) R5 = ꢀ4OMe
(2 l) R5 = ꢀH
14
(1 h) R2 = ꢀ4Br, R1 = ꢀH
(2a) R3 = ꢀH, R4 = ꢀH
(3 s) R2 = ꢀ4Br, R3 = ꢀH, R4 = ꢀH
90
a
Reactions were performed using 1a (0.2 mmol) and 2a (2.0 mmol) in 2 mL of MeOH and C-7 catalyst (1 mol%), using molecular oxygen, at room temperature with a 24 W
visible-light for 6ꢀ18 h.
b
Isolated yields.
derivative react with 1a to give moderate yields (Table 2, entry 13).
Reaction performances of ketones with diverse N-aryl-
tetrahydroisoquinoline derivatives, containing both electron-
donating and electron-withdrawing groups were also examined.
Yet, no prominent trends were found based on the electronic effect.
In general, methoxy and/or methyl group at the para position of
the aryl ring in 1a furnished the corresponding products with sat-
isfactory yield (Table 2, entry 11 and 12). Bromo substitution at the
para position of 1a also gave good yield of the final product
(Table 2, entry 14). However, coupling products with these groups
at ortho positions lead to a decrease in the yield (Table 2, entry 11
and 12) that may be a consequence of steric constrain.
separation of the catalyst, which indicated no material/dye leach-
ing during the course of reaction. Additional leaching test was car-
ried out by separating the catalyst from reaction mixture via
centrifugation after 3-hour, which yielded 40% conversion (based
on GC). Exposing this reaction mixture to visible-light under con-
tinuous stirring condition did not reveal any further conversion
and affirms that covalently hooked catalytic stations are intact.
To check the real-time efficiency of this photo-organo catalyst,
we tested the model reaction in gram (10 mmol) scale under the
optimized conditions. To our delight, 96% isolated yield was
achieved within 8 h, providing the suitability of C-7 towards
large-scale synthesis as well.
2.5. Catalyst recyclability and gram-scale synthesis
2.6. Synergetic photo-organo mechanism
Besides excellent catalytic activity and wide substrate scope,
regenerable attribute of C-7 is found noteworthy. The details of
catalyst recycling process are provided in the Supporting Informa-
tion, which shows that dual-catalyst engineered POF is able to per-
form ten successive catalytic reactions between 1a and 2a without
significant loss in activity (Fig. S8). Further, BET surface area
(Fig. S4c, d), FT-IR spectra (Fig. S10), SEM and TEM (Fig. S11) anal-
ysis as well as XPS spectra (Fig. S12) of the recycled catalyst
revealed maintenance of original structural features of C-7. We
also checked the UV–vis spectroscopy of the reaction medium after
Combining the results of control experiments (Table 1) and
mechanistic insights from other related reports [48–50], a plausi-
ble synergistic pathway for present oxidative Mannich reaction is
proposed in Scheme 4. Upon irradiation of visible-light, the hooked
RB in C-7 undergoes a change to photoexcited RB* that is reduc-
tively quenched by substrate 1a via a single electron transfer
(SET), producing radical cation (1b) and radical anion (RBÅꢀ). The
generated RBÅꢀ is subsequently quenched by oxidant (molecular
O2) to form the superoxide radical anion (OÅ2ꢀ) and simultaneously
regenerate RB. To crosscheck the above mechanistic conduit, we
47

G. Kumar, Soumya Ranjan Dash and S. Neogi
Journal of Catalysis 394 (2021) 40–49
endeavoured to trap the superoxide radical anion by 2,2,6,6-tetra
methylpiperidin-1-yl)oxidanyl (TEMPO) as scavenger.10 As clearly
revealed in entry 18 of Table 1, the product yield sharply decreased
to 20%. Furthermore, TEMPO ꢀ Oꢁ2ꢀ adduct could be detected by
electron spin resonance (ESR) spectroscopy (Fig. S15), which pro-
vided clear indication of superoxide radical anion generation, and
confirms the radical pathway. This OÅ2ꢀ successively abstracts a pro-
ton from 1b to produce hydroxide anion (OHꢀ) and intermediate
1c. As also stated above, in contrast to conventional Mannich reac-
tion, this iminium ion intermediate is in situ generated here, pro-
viding a way to atom-economic oxidative Mannich reaction. In a
parallel manner, the hooked L-proline moiety catalyses the ketone
(2a) to generate enamine (2a0). Finally, nucleophilic enamine
undergoes addition reaction with 1c to afford the desired product
b-amino ketone (3a).
Declaration of Competing Interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
Acknowledgements
S.N. acknowledges the CSIR (grant no. MLP-0028). G.K. thanks
the CSIR, New Delhi, India, for a research fellowship. S.R.D
acknowledges the Centre of Excellence in Scientific Computing
(COESC), CSIR-NCL, Pune for providing computational facilities.
The analytical support from ADCIF is greatly acknowledged.
CSMCRI Communication no. 004/2020.
Appendix A. Supplementary material
3. Conclusions
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.jcat.2020.12.013.
In Conclusion, a two-dimensional, amide-based porous organic
framework (POF) is constructed surmising on astute combination
of rigid struts, where pendent ANH2 moieties are strategically
hooked with Rose Bengal and L-proline moieties over stepwise
solid phase peptide synthesis to develop a metal-free, photo-
organo catalyst. Installation of dual catalytic stations in the post-
modified framework allows highly synergistic, visible-light medi-
ated, enamine-based sp3 CAH functionalization of tertiary amines
with ketones to produce biologically important b-amino ketones in
excellent yield at room temperature, using molecular oxygen as
clean oxidant. To the best of catalytic system, atom economic
oxidative Mannich reaction is realized in a way that iminium ion
intermediate is in situ generated, diminishing additional steps of
conventional Mannich reactions. What is more, the activity of this
dual-catalyst engineered POF compares favorably well to individ-
ual homogeneous counterparts, while separation difficulty as well
as adverse environmental effects of photocatalyst are excluded.
Importantly, this post-modified POF demonstrates ten cycles of
reusability and proved to be effective for a wide variety of sub-
strates along with satisfactory product yield over gram-scale reac-
tion. Effective modulation of energy gap in the catalyst, backed
through experimental and theoretical evidences, validates the
combined photo-organo mechanism. Given significant attention
is focused towards atom-economic sp3 CAH activation under envi-
ronmentally benign condition, the present results demonstrate
tremendous potential of bi-functionalized POF as a new generation
metal-free, and synergistic photo-organo catalyst that opens up a
new avenue for tailor-made fabrication of contemporary materials
for important reactions in sustainable manner.
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