Photocatalyzed Intramolecular [2+2] Cycloaddition of N-Alkyl-N-(2-(1-arylvinyl)aryl)cinnamamides

Article abstract of DOI:10.1002/chem.202003641

N-Alkyl-N-(2-(1-arylvinyl)aryl)cinnamamides are converted into natural product inspired scaffolds via iridium photocatalyzed intramolecular [2+2] photocycloaddition. The protocol has a broad substrate scope, whilst operating under mild reaction conditions. Tethering four components forming a trisubstituted cyclobutane core builds rapidly high molecular complexity. Our approach allows the design and synthesis of a variety of tetrahydrocyclobuta[c]quinolin-3(1H)-ones, in yields ranging between 20–99 %, and with excellent regio- and diastereoselectivity. Moreover, it was demonstrated that the intramolecular [2+2]-cycloaddition of 1,7-enynes—after fragmentation of the cyclobutane ring—leads to enyne-metathesis-like products.

Full text of DOI:10.1002/chem.202003641

Accepted Article
Accepted Article
Title: Photocatalyzed Intramolecular [2+2] Cycloaddition of N-alkyl-N-
(2-(1-arylvinyl)aryl)cinnamamides
Authors: Márcio Weber Paixão, Wanderson de Souza, Bianca Matsuo,
Priscilla Matos, José Tiago M. Correia Correia, Marilia S.
Santos, and Burkhard König
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.202003641
Link to VoR: https://doi.org/10.1002/chem.202003641
01/2020

10.1002/chem.202003641
Chemistry - A European Journal
FULL PAPER
Photocatalyzed Intramolecular [2+2] Cycloaddition of N-alkyl-N-
(2-(1-arylvinyl)aryl)cinnamamides
Wanderson C. de Souza,[a] Bianca T. Matsuo,[a] Priscilla M. Matos,[a] José Tiago M. Correia,[a] Marilia S.
Santos,[a,b] Burkhard König,[b] Marcio W. Paixão [a]*
[a]
MSc.Wanderson C. de Souza, MSc. Bianca T. Matsuo, Dr. Priscilla M. Matos, Dr. José Tiago M. Correia, Prof. Dr. Marcio W. Paixão
Centre of Excellence for Research in Sustainable Chemistry (CERSusChem),
Department of Chemistry, Federal University of São Carlos – UFSCar,
São Carlos, São Paulo, Brazil
E-mail: mwpaixao@ufscar.br
[b]
Dr. Marilia S. Santos, Prof. Dr. Burkhard König
Institut für Organische Chemie, Universität Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany
E-mail: burkhard.koenig@chemie.uni-regensburg.de
Supporting information for this article is given via a link at the end of the document.
Abstract: N-Alkyl-N-(2-(1-arylvinyl)aryl)cinnamamides are converted
into natural product inspired scaffolds via iridium photocatalyzed
intramolecular [2+2] photocycloaddition. The protocol has a broad
substrate scope, whilst operating under mild reaction conditions.
Tethering four components forming a trisubstituted cyclobutane core
builds rapidly high molecular complexity. Our approach allows the
design and synthesis of a variety of tetrahydrocyclobuta[c]quinolin-
3(1H)-ones, in yields ranging between 27-99%, and with excellent
regio- and diastereoselectivity. Moreover, it was also demonstrated
that the intramolecular [2+2]-cycloaddition of 1,7-enynes - after
fragmentation of the cyclobutane ring - leads to enyne-metathesis-like
products.
Figure 1. Selected examples of pharmaceuticals and natural products bearing
the cyclobutane core moiety
Introduction
Cyclobutane containing molecules are interesting organic
molecules, frequently found in pharmaceuticals[1] and biologically
relevant natural products (Figure 1).[2] The core structure has
been exploited by numerous research groups as key reactive
In this context, visible-light photocatalysis has emerged as
an important tool for the synthesis of complex molecular
architectures through [2+2] photocycloadditions under mild and
selective redox or energy-transfer processes. Their broad
applicability is highlighted by a number of key photocatalytic [2+2]
cycloaddition reactions already reported in the literature
employing photosensitive metal complexes (ruthenium,[9]
iridium,[10] rhodium[11]) and organic dyes.[12] In 2012, Yoon and co-
workers showcased the intramolecular [2+2] styrene
cycloaddition via a triplet sensitization mechanism mediated by an
Ir(III) photocatalyst, affording a range of high value cycloadducts
(Scheme 1a).13] This approach was further expanded to 1,3-
dienes,[14] and more recently an enantioselective version was
intermediates
towards
building
complex
molecular
architectures.[3] The synthesis of cyclobutane derived compounds
has been achieved through a diverse range of approaches,[4] with
[2+2] photocycloadditions being the most versatile and well
established strategy.[5] The first examples of cyclobutane
synthesis through [2+2] photocycloadditions were reported at the
end of the 19th century and since then an immense amount of
information has been collected[6] allowing for rationally designed
transformations.[7] Beyond a better mechanistic understanding,
those
studies
culminated
in exceptional preparative
developed
using
a
chiral
hydrogen-bonding
iridium
photosensitizer (on both intra- and intermolecular systems).[15]
Meanwhile, Kwon and co-workers elegantly reported [2+2]
cycloadditions involving aromatic dienones also employing an
iridium-complex photosensitizer.[16] Contrasting with the previous
examples of straight [2+2] cycloadditions, a crossed cycloaddition
process took place to afford a family of benzobicyclo[3.1.1]-
heptanones in good to excellent yields (Scheme 1b). Very
recently, adapting the previous works from Mykhailiuk and
Cibulka groups to visible-light photocatalytic conditions,[17]
Reiser´s and Oderinde´s groups concomitantly reported the
synthesis of aryl-3-azabicyclo[3.2.0]-heptanones and aryl-3-
azabicyclo[3.2.0]heptanes employing the same photosensitizer
as reported in Yoon´s seminal works (Scheme 1a).[18],[19]
methodologies, with highly stereoselective applications in total
synthesis.[5] Nonetheless, until recently, most of the photoinduced
protocols require the use of high-energy UVC radiation[8] (ca. λ =
240–265 nm; photon energy 108-120 kcal mol-1), which is not
amenable to highly functionalized organic substrates often
present in the synthesis of bioactive small-molecules.
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10.1002/chem.202003641
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FULL PAPER
Herein, as part of our ongoing investigations towards the
development of photocatalytic strategies for the synthesis of
complex heterocyclic compounds,[20] we report our latest findings
compound 1 was obtained and characterized by X-ray structure
analysis (Scheme 2 – See supporting information for more details).
towards
the
synthesis
of
substituted
tetrahydro-
Table1. Optimization of the photocatalyzed [2+2]-cycloaddition
cyclobuta[c]quinolin-3(1H)-ones via a highly diastereoselective
intramolecular visible-light photocatalyzed [2+2] cycloaddition of
N-alkyl-N-(2-(1-arylvinyl)aryl)cinnamides (Scheme 1c). A distinct
feature of our strategy is the fact that the participating olefinic
entity is tethered by a rigid aryl-amide moiety restricting the
rotation along amide and Ar-N bonds.
Ph
Ph
Ir-1
(1 mol%)
Ph
Me
N
DMA, 50°C
O
N
O
Blue LEDs
48h
Me
1
Ph
1'
Scheme 1. Previous reports on photocatalyzed [2+2] cycloadditions on relevant
systems and our protocol.
entry
1
deviation from standard conditions
none
1 [%]
a) Yoon et al (2012/2014) / Reiser et al (2019) / Oderinde et al (2020)
97
10
R1
O
R3
R1
R2
2
3
4
5
6
7
8
R3
[Ir{dF(CF3)ppy}2(dtbbpy)]PF6
Ru-1 instead of Ir-1
Ir-2 instead of Ir-1
Ir-3 instead of Ir-1
MeCN instead of DMA
DMSO instead of DMA
24-36h
O
X
DMSO ou MeCN
visible light,
94
X
R4
R4
R2
93
X = O, NTs, NBn, NBoc, NAc or C(R5)2
36
b) Kwon et al (2017)
R2
90
R1
R1
R2
R3
83-86
nr
[Ir{dF(CF3)ppy}2(dtbbpy)]PF6
O
CH2Cl2, 25°C
White LEDs
no cat or in darkness
R3
O
CF3
PF6
(PF6)2
PF6
F
tBu
R
R
N
Ru
N
N
Ir
N
Ir
N
c) This work - aryl-amide tethered olefinic moieties
N
N
N
N
N
N
N
F
F
R2
N
R3
R2
N
tBu
R1
[Ir(ppy)2(dtbbpy)]PF6
R1
F
NR4
DMA, 50°C
Blue LEDs
CF3
N
O
R4
O
Ir-1
Ru-1
Ir-2 - R=H
Ir-3 - R=t Bu
48h
R3
27 examples
27-99% yield
high diastereoselectivity
Reaction conditions: 1'
(0.1 mmol) and photocatalyst (1.0 mol%) in sol-
vent (0.5 mL) at T= 50 °C (no fan) under household blue LEDs irradiation
(34 W) during 48 h.
Ar-N and N-CC=O rotational
barriers to be overcome
With the optimized conditions in hand, we turned our
attention to investigate the substrate scope of the transformation
(Scheme 2). Based on the excellent yield obtained for 1, we first
evaluated the influence of different functional groups at the para
position in the aniline portion (R1) of the styrene moiety.
Gratifyingly, the reaction tolerated a range of functionalities
including halides (Cl, Br = 2, 4, 76% and 78% yield respectively),
and electron donating groups, including methoxy (3), methyl (5),
and thiomethyl (6) in yields ranging between 63-80%. When the
dimethylamine group (7) was introduced however, the target
product was accessed in only 23% yield, likely owing to the
competing photosensitizer quenching by this functional group
under the reaction conditions. Substituents at other positions also
gave the desired cyclobutane products. A trimethoxy-derivative
was tested, affording the desired product (8) in moderate yield
(53%). Replacing the aniline moiety by a naphthalen-2-amine
group led to a detrimental change in product yield (9, 27%).
Next, the phenyl moiety at R2 was modified to incorporate
para-halide substituents (10 and 11) and a para-methyl group (12)
- the corresponding cyclobutaquinolinones were obtained in 56%,
85% and 84% yield respectively. Replacing the phenyl ring with a
thiophenyl or a methyl group were also tolerated, affording the
desired products in excellent isolated yields (13, 82% and 14,
80%). When an ortho-methyl-phenyl derivative was attempted,
Results and Discussion
To begin our studies, we chose to optimize the [2+2]
cycloaddition reaction conditions starting with substrate 1’ in the
presence of 1 mol% of the photocatalyst Ir-1. (ET = 49.2 kcal/mol).
Under these conditions, we were pleased to observe that
cyclobutane 1 could be accessed in 97% yield and excellent
diastereoselectivity (Table 1, entry 1). Changing to the ruthenium-
based photocatalyst Ru-1 (ET = 46.5 kcal/mol) led to a significant
drop in the product yield (10%, entry 2). Using higher triplet
energy photocatalysts, Ir-2 (ET = 62 kcal/mol) and Ir-3 (ET = 61.8
kcal/mol) afforded the desired product in 94% and 93% yield
respectively (entries 3 and 4). To further investigate the influence
of the polar solvent, dimethyl acetamide was replaced by
acetonitrile or dimethyl sulfoxide, but a decrease in yields were
observed (entries 5 and 6). Shortening the reaction time from the
48 hours to 24 hours or 36 hours led to a significant drop in yield
(83% and 86% respectively, entries 7 and 8). Additionally, control
experiments revealed that the combination of both Ir-1
photocatalyst and blue LED light irradiation is essential for the
reaction outcome. In order to determine the structure of the
diastereoisomer in this transformation, a crystal structure of
2
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no product was detected when the cinnamide moiety was
replaced by a crotylamide or an acrylamide. However, reactivity
could be restored when Ir-3 was employed in lieu of Ir-1, affording
the desired products 30 and 31 in 20% and 53% yield,
respectively.
To complement the previous substrates, we were
successfully able to modify the N-methyl group with N-benzyl (26,
93%), N-allyl (26, 80%) and N-propargyl (27, 77%) groups,
affording the desired products in high yields (Scheme 2). When
attempting to access the cyclobutachromen-3-one 32 and NH-
cyclobutaquinolinone 33, only decomposition of the starting
materials was observed, highlighting the requirement of an N-
protected aryl-amide moiety (Scheme 2).
Scheme 2. Exploring the reaction scopea
only the isomerization product was obtained, possibly due to
steric hinderance of the ortho- donating group. The same
replaced by a naphthyl moiety (29).
The scope and limitations in terms of the the R3 substituent
on the cinnamide moiety were also investigated. A wide range of
functionalities were well tolerated, including ortho- and para-
substituted methoxy, methyl and bromo, as well as di-fluoro and
methylenedioxy groups in good to excellent yields between 49-
98% (15-22). Additionally, heteroaromatics also underwent this
transformation, providing the cyclobutaquinolinones 23 and 24 in
30% and 47% yield, respectively. Under the optimized conditions,
With the success of the styrenyl-derived substrates
undergoing
a
smooth
reaction
to
the
desired
3
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cyclobutaquinolinones, we investigated replacing the pendant
alkene functionality with an internal alkyne group (34’). To our
delight, instead of the expected cyclobutene product, the diene 34
could be accessed in 96% yield using iridium catalyst Ir-1 (1
mol%) in DMA at 50 °C using blue LEDs for five hours (Scheme
3 – see SI for full table of optimization conditions).[21] Satisfied by
this result, we moved onto investigating the scope of the
transformation, firstly by modifying the enyne moiety R2 aryl
substituent. Incorporation of an electron rich methyl group at the
para-position gave the desired diene product 35 in 95% yield,
whilst an ortho-methyl substituent led to a noticeable drop in yield,
presumably due to steric hinderance (36, 63%). Methoxy
substituents on the aryl ring in the para-position were also
tolerated in the reaction, giving rise to product 37 in 82% yield;
however, incorporation of an electron deficient bromine atom at
the para-position resulted in a lower yield of 39% for diene product
38. Furthermore, we were pleased to see that an aryl ring could
be replaced with a heteroaryl ring system, a 2-thiophene, which
yielded diene 39 in a respectable 57% yield. We then moved onto
investigating the scope of the cinnamic moiety – substituted aryl
rings incorporating either a methoxy or bromide substituent gave
the required diene products 40 and 41 in 85% and 80% yield,
showing a good tolerance to electronic changes on this part of the
starting materials. A final inclusion of a 2-furan heterocycle, in
place of an aryl ring, gave diene 42 in 84% yield.
these experiments, two reducing potentials were found (E1/2= -
2.06, -2.49 V vs SCE), which are outside of the reachable redox
window of Ir-1 (supporting information). These findings indicate
that the reaction is not triggered by PET, but by an EnT
photosensitization. To further corroborate this evidence, a set of
additional experiments were performed using different
photocatalysts which were selected based on their triplet energies
(Table S2, supporting information).5,22 As observed, catalysts with
lower triplet energy than Ir-1, such as Eosin Y and Ru(bpy)3(PF6)2
were ineffective for the transformation (Table S2, entries 2 and 3,
respectively), whilst the photosensitizers with higher triplet energy
afforded the corresponding products (Table S2, entries 4-7).
When the reaction was performed under aerobic conditions, a
decrease to 75% was observed, which could be explained by the
quenching of the triplet state of the Ir-1 by oxygen (Table S2, entry
8). Additionally, it is noteworthy that the reaction also worked in
the absence of the photocatalyst in the presence of more
energetic radiation (UVA) – (Table S2, entries 9 and 10).
Based on our findings and on previous studies by Reiser
and Kwon,[16][18] the mechanistic considerations for the reaction
are shown below in Scheme 4. We also considered a strong
dependence between the reaction outcome and conformation
adopted by the aryl-cinnamide, since the rotational barriers
around the amide (15–20 kcal/mol) and the (ortho-substituted)
Ar–N (~20-30 kcal/mol) bonds need to be overcome to achieve a
conformation, in which the olefin moieties are close enough to
react (Scheme 4, center).[23] As previously described, we
postulate the iridium photocatalyst (Ir-1) absorbing blue LED
irradiation is excited to the *Ir(III) singlet excited state.[5b] Inter-
R1
R2
Ir-1
(1 mol%)
R1
Me
system crossing converts the singlet into the long-lived triplet-
N
[24]
DMA, 50°C
state,
which undergoes an intermolecular energy-transfer
O
Blue LEDs
5h
(EnT) process to give a conformationally distinct biradical species,
depending on the conformation of the starting substrate. An EnT
to conformer trans-1’-1, in which the olefinic moieties are distant
N
O
R2
34' - 42'
Me
34 - 42
from each other, leads to biradical 1’-1* (not shown) that can
rotate along the C-C bond axis and return to the ground state to
afford isomer cis-1’-1 (Scheme 4, bottom right). This pathway is
consistent with the results obtained when bulky aryl moieties were
placed in R2 position (28 and 29, Scheme 2). On the other hand,
Enyne moiety
Ph
Ph
R1
Ph
Ph
S
an EnT to conformer trans-1’-2 leads to biradical 1’-2* (Scheme
4, top-center) that can, due the proximity of the olefinic moieties,
undergo two different cyclization pathways. According to the
results obtained, the cyclization through a 6-exo-trig process is
faster and two new conformationally distinct biradical species (int-
2-cis and int-2-trans) are possible (Scheme 4, left). In order to
minimize the repulsion between the aryl moieties, the biradical
int-2-trans is formed exclusively, leading to the observed product
1 through a radical-radical coupling event. Moreover, this
mechanistic proposal does not rule out the possibility of the
isomerization product cis-1’-1 to adopt a suitable conformation to
also undergo the cycloaddition pathway towards 1 after a second
photoexcitation event.
N
O
N
O
N
O
Me
Me
Me
35 - R1 = p-MeC6H4, 95%, E/Z = 3:1
36 - R1 = o-MeC6H4, 63%, E/Z = 3:1
34 - 96%
E/Z = 2.4:1
39 - 57%
E/Z = 2:1
37 - R1 = p-OMeC6H4, 82%, E/Z = 2.3:1
38 - R1 = p-BrC6H4, 39%, E/Z = 2.5:1
Cinnamic moiety
O
R2
Ph
Ph
N
O
N
O
Me
Me
40 - R2
41 - R2 = p-BrC6H4, 80%, E/Z = 3.9:1
=
-MeOC H , 85%,
= 2:1
E/Z
p
42 - 84%, E/Z = 1:1
6
4
Reaction conditions: Enyne 34'-42' (0.1 mmol) and Ir-1 (1.0 mol%) in
DMA (0.5 mL) at T= 50 °C (no fan) under household blue LEDs
irradiation (34W) during 5h.
Scheme 3. Synthesis of dienes using an Iridium photocatalyzed approach.
In order to evaluate whether the intramolecular
cycloaddition proceeds via EnT or photoinduced electron transfer
(PET) mechanism, we performed the cyclic voltammetry of 1’ to
determine its redox properties (See supporting information). From
4
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Ph
Ph
Ph
Ph
(a)
(b)
N
O
N
O
O
from 26
from 27
Bn
N
N
N
43, 90%
44, 83%
Ph
Ph
R1
(c)
from 1
(d)
from 3
N
R2
O
Ph- -OCH
p
Ph
3
Ph
Ph
H
N
S
N
H
Me
Me
45, 50%
46, 44%
Reagents and conditions: (a) CuSO4.5H2O, sodium ascorbate, benzyl azide, DCM/H2O, 3
h; (b) PdCl2, CuCl2, THF:H2O (20 equiv.), O2 (baloon); (c) DIBAL, toluene, reflux; (d)
Lawesson’s reagent, toluene, reflux
Scheme 5. Late-stage diversification of cyclobutaquinolinones
Scheme 4. Postulated reaction mechanism for the Iridium-photocatalyzed [2+2]
cycloaddition reaction of 1.
Conclusion
To showcase the utility and importance of our
cyclobutaquinolinone products, we subjected some of the
obtained analogues to late-stage structural modification reactions
(Scheme 5). Initially, the cyclobutaquinolinone 27 bearing an N-
The synthesis of a broad range of highly substituted and
complex cyclobutane-derived dihydroquinoline products has been
realized utilizing an iridium photocatalyzed approach. The [2+2]
cycloaddition reaction tolerated a diverse range of functional
groups at four key positions of the molecular scaffold. The
reaction generates tricyclic molecules of high value add, with 29
examples isolated in yields ranging between 19-98%. The
mechanism of the reaction was postulated based on some
preliminar experiments and recent literature precedents, which
suggest that transformation proceeds via an intermolecular
energy transfer process (EnT) between the photocatalyst and
alkenyl substrate. Moreover, replacing the alkenyl moiety for an
alkynyl group in the starting materials, we could extend the scope
of the iridium photocatalyzed approach to access diene products.
The synthetic utility of these molecules was further demonstrated
by five derivatizations in different positions of the heterocyclic
scaffold. Current research in our group is looking to expand
further on this photocatalytic transformation upon new substrates
for the synthesis of complex organic structures.
alkynl moiety underwent
a copper-catalysed azide-alkyne
cycloaddition reaction with phenyl azide, affording the 1,2,3-
triazole product 43 in excellent yield (90%).[25] Following this
success, N-allyl derived cyclobutaquinolinone 26 underwent a
smooth palladium-catalysed oxidation of the carbon-carbon
double bond, furnishing ketone 44 in 83% chemical yield.[26] To
conclude the late-stage structural modifications, we focused on
modifying the carbonyl substituent at C2 on the quinolinone core
– DIBAL reduction of 1 gave tetrahydroquinoline 45 in acceptable
yield (50%),[27] whilst conversion of the carbonyl moiety into a
thiocarbonyl group was realized using Lawessons reagent on
cyclobutaquinolinone 3, providing cyclobutaquinolinthione 46 in
modest yield (44%).[28]
Experimental Section
Full experimental details along with NMR spectra can be found in the
supplementary information.
Acknowledgements
We are grateful to CNPq (INCT Catálise), FAPESP (14/50249-8,
15/17141-1, 17/10015-6 and 20/00556-2) for financial support.
GSK is also acknowledged for the financial support. This study
was financed in part by the Coordenação de Aperfeiçoamento de
Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001
5
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[12] For
selected
examples
on
non-metal
catalyzed
[2+2]
and the German Science Foundation (DFG, KO 1537/18-1). We
are also grateful to Michael Murgu from Waters Technologies of
Brazil for the HRMS analysis and to João Honorato (DQ-UFSCar)
e Eduardo Castellano (IFSC-USP) for the X-ray crystallography.
photocycloadditions, please see; (a) M. H. Wahl, C. Jandl, T. Bach, Org.
Lett. 2018, 20, 7674-7678. (b) Y. A. Skalenko, T. V. Druzhenko, A. V.
Denisenko, M. V. Samoilenko, O. P. Dacenko, S. A. Trofymchuk, O. O.
Grygorenko, A. A. Tolmachev, P. K. Mykhailiuk, J. Org. Chem. 2018, 83,
6275-6289. (c) R. Davenport, M. Silvi, A. Noble, Z. Hosni, N. Fey, V. K.
Aggarwal, Angew. Chem. Int. Ed. 2020, 59, 6525-6528. (d) C.
Brenninger, A. Pöthig, T. Bach, Angew. Chem. Int. Ed. 2017, 56, 4337-
4341. (e) S. Poplata, A. Bauer, G. Storch, T. Bach, Chem. Eur. J. 2019,
25, 8135-8148. (f) L. M. Mohr, A. Bauer, C. Jandl, T. Bach, Org. Biomol.
Chem., 2019, 17, 7192-7203. (g) D. Sarkar, N. Bera, S. Ghosh, Eur. J.
Org. Chem. 2020, 1310-1326. (h) M. M. Maturi, T. Bach, Angew. Chem.
Int. Ed. 2014, 53, 7661-7664. i) Rigotti, R. Mas-Ballesté, J. Alemán, ACS
Catal. 2020, 10, 5335–5346. j) T. Neveselý, C. G. Daniliuc, R. Gilmour,
Org. Lett. 2019, 21, 9724–9728.
Keywords: energy transfer • cycloaddition • photocatalysis •
dienes
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6
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10.1002/chem.202003641
Chemistry - A European Journal
FULL PAPER
Entry for the Table of Contents
R2
R2
R3
*
Ph
R1
R1
EnT
X
Ph
X
X
O
O
O
29 examples
27-99% yield
R3
A highly efficient and straightforward photocatalytic strategy for the preparation of tetrahydrocyclobuta[c]quinolin-3(1H)-ones is reported.
The reaction presents a high functional group tolerance and diastereoselectivity. Mechanistic evidence supports an energy-transfer
(EnT) pathway. The synthetic utility of these molecules was further demonstrated by derivatizations in different positions of the
heterocyclic scaffold.
Institute and/or researcher Twitter usernames: @de_zezao, @mwpaixao, @MatsuoBianca, @ChemistryKoenig
This article is protected by copyright. All rights reserved.