Controlling Photooxygenation with a Bifunctional Quinine-BODIPY Catalyst: towards Asymmetric Hydroxylation of β-Dicarbonyl Compounds

Article abstract of DOI:10.1002/ejoc.201900984

We report herein a new catalytic strategy towards asymmetric photooxygenation of β-dicarbonyl compounds. Our method is based on the synthesis of a bifunctional photosensitizer composed of a quinine organocatalyst grafted to an iodo-BODIPY framework capable of generating singlet oxygen. The quinine moiety serves both to interact with the substrate for promoting photooxygenation and to deactivate singlet oxygen in the absence of substrate. The bifunctional photosensitizer prepared was subsequently applied in the asymmetric oxygenation of a series of β-dicarbonyl compounds under green light irradiation. Control experiments and kinetic analyses were carried out to shed the light on the mechanism.

Full text of DOI:10.1002/ejoc.201900984

DOI: 10.1002/ejoc.201900984
Full Paper
Photooxygenation
Controlling Photooxygenation with a Bifunctional Quinine-
BODIPY Catalyst: towards Asymmetric Hydroxylation of
ꢀ
-Dicarbonyl Compounds
[a]
[a]
[b]
[a]
Jérôme Fischer, Lucas Mele, Hélène Serier-Brault, Pierrick Nun, and
Vincent Coeffard*[
a]
Abstract: We report herein a new catalytic strategy towards promoting photooxygenation and to deactivate singlet oxygen
asymmetric photooxygenation of ꢀ-dicarbonyl compounds. Our in the absence of substrate. The bifunctional photosensitizer
method is based on the synthesis of a bifunctional photosensi- prepared was subsequently applied in the asymmetric oxygen-
tizer composed of a quinine organocatalyst grafted to an iodo- ation of a series of ꢀ-dicarbonyl compounds under green light
BODIPY framework capable of generating singlet oxygen. The irradiation. Control experiments and kinetic analyses were car-
quinine moiety serves both to interact with the substrate for ried out to shed the light on the mechanism.
Introduction
Light-driven catalysis is a thriving field of research owing to the
solute stereochemistry in the addition of singlet oxygen still
remains a challenging task. Pioneering works in introducing chi-
rality involved cyclodextrin-porphyrins catalytic systems.
[
12]
[
1]
synthetic potential of this strategy in organic chemistry. In
efforts to design new catalytic systems, the combination of
photochemistry and asymmetric catalysis has been emerging
as a relevant and efficient strategy by which chirality can be
introduced into molecular architectures. Within this context,
the induction of chemical processes under light illumination is
triggered either by photoinduced electron transfer or energy
transfer. While asymmetric visible light-induced electron trans-
fer has been applied in a range of synthetic transformations in
the past decade, the concept of asymmetric energy transfer
Very low levels of enantioselection were obtained for these sys-
tems in photooxygenation of alkenes. Following on from these
studies, most of the reported strategies lie in the combination
of a chiral catalyst for substrate activation and a photosensitizer
aiming at generating singlet oxygen under light. For example,
the combination of enamine catalysis and photosensitization
was studied for the asymmetric oxygenation of aldehydes and
[
2]
[
13]
ketones at the α-position. Diverse aminocatalysts were inves-
tigated leading to the corresponding products with variable re-
sults in terms of enantiomeric excesses. In addition, the syn-
thetic appeal of this strategy suffers from the low stability of
enamine intermediates and/or aminocatalysts towards singlet
oxygen. In 2012, the group of Meng described enantioselective
[
3]
photocatalysis has received less attention. The recent works
in this field have mainly focused on enantioselective [2+2]
photocycloadditions and asymmetric photooxygenation reac-
[
4]
1
tions via singlet oxygen generation. Singlet oxygen ( O ) is
2
[
14]
photooxygenations by phase-transfer catalysis.
The authors
the first excited state of molecular oxygen which can be gener-
ated under light irradiation by triplet-triplet energy transfer be-
tween an excited photosensitizer and ground state triplet oxy-
focused their work on the hydroxylation of a series of indanone-
[
15]
and tetralone-derived ꢀ-keto esters and ꢀ-keto amides.
sides organocatalytic strategies, the group of Xiao reported in
017 the preparation of bifunctional photocatalysts for enantio-
selective aerobic oxidation of ꢀ-keto esters, mainly derived from
Be-
[
5]
gen. The high electrophilicity of singlet oxygen makes this
oxidant very reactive towards a multitude of substrates. For in-
stance, photooxygenation is a leading method for heteroatom
2
[
16]
indanone.
In-situ complexation of the bisoxazoline ligand
[
6]
oxidation, [4+2] and [2+2] cycloaddition to form endoperox-
with Ni(acac) enabled the formation of the desired oxygenated
[
7]
[8]
2
ides, ene reaction and dearomatization of electron rich aro-
products in high yields and excellent enantioselections. In light
of the previous works, an important impediment to developing
asymmetric photooxygenation lies in possible background race-
[
9]
[10]
matic compounds such as phenols and furans.
glet oxygen has found numerous applications in the construc-
tion of densely functionalized architectures, control over ab-
While sin-
[
11]
[
17]
mic processes lowering the enantioselectivity levels.
This is
particularly the case for substrates which do not require any
activation such as alkenes involved in ene-hydroxylation or di-
ene systems for the formation of endoperoxides through [4+2]
cycloaddition. In order to tackle the challenge of asymmetric
photooxygenation, we planned to design novel catalytic sys-
tems for which the chiral moiety would play a dual role (Fig-
ure 1). Thus, it would direct the enantioselective photooxy-
[
a] Université de Nantes,
CEISAM UMR CNRS 6230,
4
4000, Nantes, France
E-mail: vincent.coeffard@univ-nantes.fr
[
b] Institut des Matériaux Jean Rouxel, Université de Nantes,
CNRS, 2 rue de la Houssinière, BP 32229, 44322 Nantes, France
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201900984.
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Figure 1. Asymmetric photooxygenation strategies.
genation (ON mode) and would deactivate singlet oxygen into toluene has no influence on the results (entries 4–6). Slightly
triplet state when the substrate does not interact with the chiral lower enantioselections were observed by decreasing the
system (OFF mode). Within the broader field of science, the amount of 2 or by increasing the reaction concentrations (en-
design of photosensitizers able to deliver singlet oxygen in a tries 7 & 8). The use of TPP did not improve the results (entry
controlled way is a tremendous research field with applications 9). Therefore, the best conditions involve 5 mol-% of quinine
both in organic synthesis and in photodynamic therapy.[18] To and chloroform as the solvent (entry 3). Based on these results,
put this strategy into practice, we turned our attention to the we then screened a series of Cinchona-derived catalysts in order
Cinchona alkaloids which are privileged structures in asymmet- to study the structural influence on the reaction outcome
ric catalysis. In addition, the group of Zanocco have demon- (Scheme 1).
strated that Cinchona alkaloids, cinchonidine, cinchonine,
quinine and quinidine, are physical quenchers of singlet oxygen
Table 1. Photooxygenation of 1 catalyzed by 2 and quinine.[a]
through a charge transfer mechanism between the quinuclidine
[
19]
nitrogen and singlet oxygen.
Inspiring studies by the group
of Melchiorre have shown that quinine could promote an asym-
metric conjugate addition of methyl-2-oxo-1-indanecarboxylate
1
to maleimides in chloroform with high enantiomeric ex-
[
20]
cesses.
In light of these works, we conjectured that quinine
would play both the role of singlet oxygen quencher and or-
ganocatalytic promoter.
Results and Discussion
Entry[a]
Conditions
Yield [%]
ee[b]
First, we elected to use 1,3-dicarbonyl compound 1 as a model
substrate and quinine as a chiral catalyst (Table 1). To assess
whether photooxygenation of 1 could be achieved without
quinine, we chose iodo-BODIPY 2 as a photosensitizer owing to
its ability to efficiently promote photooxidative transforma-
tion. After the photooxygenation step, a triphenylphosphine
reducing protocol was carried out to transform the hydroperox-
ide function into the alcohol 3 which was isolated in 50 % yield
[c]
1
2
3
4
5
6
7
8
9
No Quinine, CHCl
Q (2 mol-%), CHCl
Q (5 mol-%), CHCl
3
50
33
83
73
67
32
69
89
61
n.d.
n.d.
38
25
25
12
34
33
36
3
3
Q (10 mol-%), CHCl
Q (10 mol-%), Toluene
Q (20 mol-%), CHCl
3
3
[
21]
[d]
Q (5 mol-%), CHCl3
[
[
e]
f]
Q (5 mol-%), CHCl
Q (5 mol-%), CHCl
3
3
(
entry 1). Therefore, this result shows that no activation is re-
[a] Reaction conditions unless otherwise noted: 1 (0.21 mmol), 2 (2 mol-
), O , Green LEDs, solvent (4.2 mL), r.t., 45 min. n.d.: not determined. [b]
Enantiomeric excesses were determined by chiral HPLC. [c] PPh (0.21 mmol)
was added at the end of the reaction. [d] 1 mol-% of 2. [e] 2.1 mL of CHCl
f] 2 mol-% of TPP (tetraphenylporphyrin) was used instead of 2.
%
2
quired for the photooxygenation of 1 underlining the challeng-
ing task to conduct an asymmetric version of this reaction. The
reactions with 2 and 5 mol-% of quinine (Q) were then investi-
gated and the best results were obtained with 5 mol-% of
3
3
.
[
quinine (entries 2 & 3). In this example, careful analysis of the
Commercially available cinchonidine gave similar levels of
1
crude by H NMR showed that alcohol 3 was formed without yields and enantioselectivities as the quinine catalyst. A lower
any traces of the corresponding hydroperoxide product. There- level of enantiomeric excess for 3 was obtained with quinidine
fore, the reductive work-up with triphenylphosphine was not while the opposite enantiomer was obtained as the major prod-
carried out when using quinine. Increasing the catalytic loading uct in the cinchonine-catalyzed photooxygenation. Quinine
of quinine led to a slight decrease of enantioselectivities and gave the best results both in terms of yield and enantioselec-
switching from chloroform to another aprotic solvent such as tivity and this prompted us to investigate the functionalization
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Scheme 1. Cinchona-derived catalyst screening.
of the quinine moiety for the photooxygenation. Substitution and 62 %, respectively albeit with low enantioselectivities. From
of the alcohol by a benzyl group (structure 4) had a negative the catalyst screening, the best reaction conditions involve the
impact on the enantioselection. Photooxygenation of 1 cata- use of 5 mol-% of quinine with 2 mol-% of iodo-BODIPY 2.
lyzed by 4 afforded the product in 51 % yield and 4 % ee. This In efforts to improve the enantioselectivities, we surmised that
result shows the importance of the free hydroxyl function in connecting the photosensitizer 2 to the quinine could lower
transferring the chiral information. Very low yields and enantio- the background racemic photooxygenation by bringing in close
selectivities were observed for the photooxygenation of 1 in proximity the source of singlet oxygen and the quencher. The
the presence of the catalyst 5. In order to increase the steric synthetic route towards bifunctional photocatalyst 11 is de-
hindrance around the hydroxyl group, the derivative 6 was pre- scribed in Scheme 2.
pared and was tested in the photooxygenation but no improve-
The synthesis started by alkylation of 4-hydroxybenzalde-
ment was observed compared to quinine. The anthraquinone- hyde with 1-azido 3-iodopropane in the presence of potassium
bridged catalyst, (DHQ) AQN, and the pyrimidine-based carbonate affording the aldehyde 7 in 53 % yield. Starting from
2
(
DHQ) Pyr were also examined providing compound 2 in 76 % 7 and 2,4-dimethylpyrrole, the classical three-step sequence
2
Scheme 2. Synthesis of the bifunctional photocatalyst 11.
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produced BODIPY 8 in 38 % overall yield. Double iodination in was isolated in 73 % yield and 36 % ee. Compound 19 was
the presence of N-iodosuccinimide in dichloromethane led to obtained in a very low yield while the products 20 and 21 could
the BODIPY 9 which underwent a copper-catalyzed Huisgen not be obtained under green LED irradiation in the presence of
1,3-dipolar cycloaddition with 10,11-didehydroquinine 10. Un- 5 mol-% of 11 and the starting materials were recovered. Some
der these conditions, the bifunctional photocatalyst 11 was iso- mechanistic insights were considered by means of control ex-
lated in 69 % yield. The catalytic activity of 11 was then probed periments and kinetic analyses. We first investigated the ability
by performing the photooxygenation of 1 (Scheme 3).
of singlet oxygen quenching of the catalyst 11 by performing
1
the photooxygenation of anthracene which is a O chemical
2
trap (Figure 2).
Scheme 3. Photooxygenation catalysed by 11.
Irradiation from green LED in the presence of 5 mol-% of 11
at room temperature enabled the formation of 3 with slightly
better enantiomeric excesses than reaction with 2 mol-% of 2
in conjunction with 5 mol-% of quinine. A better yield was ob-
tained by running the reaction at 0 °C while lowering the reac-
tion temperature did not improve the enantiomeric excess. We
next evaluated the substrate scope (Scheme 4).
Figure 2. Photooxygenation kinetic profiles.
Irradiation for 45 min in the presence of 5 mol-% of 11 led
1
to 90 % H NMR yield of anthracene-9,10-endoperoxide while
an increase of the kinetic activity was observed with iodo-BOD-
IPY 2. Therefore, the quinine moiety would act as a singlet oxy-
gen quencher in the photooxygenation of anthracene. The acti-
Scheme 4. Substrate screening.
We first evaluated different alkyl-2-oxo-1-indanecarboxylates vation role of quinine in the photooxygenation of ꢀ-dicarbonyl
under the optimized reaction conditions. Alcohols 12 and 13 compounds was investigated by monitoring the oxidation of 1.
were obtained in good yields and similar levels of enantioselec- A fast photooxygenation process was observed by running the
tion. Surprisingly, the product 14 was produced in 58 % yield reaction with 5 mol-% of 11. The kinetic was much slower when
but in racemic form. Switching from alkyl 2-oxo-1-indanecarb- the iodo-BODIPY 2 was used highlighting the crucial role of
oxylate to alkyl 1-oxo-2-indanecarboxylate substrates had a quinine in activating the substrate 1 towards singlet oxygen. It
negative impact on the enantioselectivities. Alcohols 15, 16 and is worthwhile noting that the hydroperoxide product 3′ was
1
7 were obtained in moderate-to-excellent yields but with very obtained with iodo-BODIPY 2 and therefore, this is an interme-
low enantiomeric excesses. Nevertheless, the compound 18 diate in the photooxygenation reaction.
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Control experiments have also been carried out to get a bet- General procedure for the photooxygenation: To a Schlenk flask
was added ꢀ-dicarbonyl compounds (0.21 mmol) and photosensi-
ter understanding of the reaction mechanism (Scheme 5). First,
photooxygenation of 1 was carried out in the presence of tri-
phenylphosphine in order to in-situ reduce the hydroperoxide
intermediate 3′. The results suggest that addition of singlet oxy-
gen to 1 demonstrates low enantioselection. Secondly, the
hydroperoxide 3′ was prepared in-situ and quinine (5 mol-%)
was added to the reaction mixture followed by the ethyl-
tizer 2 or 11 was added in CHCl (4.2 mL). The reaction medium
3
was gently bubbled with dioxygen throughout the reaction time
and the homogeneous solution was irradiated with two green LEDs
(1 W, 75 Lm, 535 nm typical wavelength). The distance from the
light source to the irradiation Schlenk vessel was 2 cm without the
use of any filters. The reaction was stirred for the appropriate reac-
tion time at which point the solvent was removed under reduced
derived substrate. This outcome suggests that the enantioselec- pressure. The crude was purified by chromatography on silica gel
tion would originate from the reaction of the hydroperoxide to give the desired product.
intermediate 3′ with the substrate.[
22]
Methyl 1-hydroxy-2-oxo-2,3-dihydro-1H-indene-1-carboxylate
3
: The compound 3 was prepared according to the general proce-
dure starting from methyl 2-oxoindane 1-carboxylate (0.21 mmol,
0 mg) and 11 (10.5 μmol, 10.5 mg, 5 mol-%). The reaction mixture
4
was stirred for 1 h. Purification by column chromatography, eluting
with 6:4 petroleum ether/diethyl ether, gave compound 3 as a solid
(
34.7 mg, 80 %). M.p. 138–140 °C; δH (300 MHz, CDCl ) 7.45–7.32
3
(4H, m), 4.31 (1H, s), 3.86 (1H, d, J = 22.0 Hz), 3.72 (3H, s), 3.62 (1H,
d, J = 22.0 Hz); δ (75 MHz, CDCl ) 209.7, 170.7, 138.8, 137.4, 130.2,
C
3
–
1
1
(
28.3, 125.2, 124.4, 81.6, 53.8, 41.4. IR (ATR)/cm 3398 (υ, O-H), 1767
υ, C=O), 1739 (υ, C=O); HRMS (ESI) Calcd for C H O Na [M+Na] :
+
11 10 4
229.0477 found: 229.0470.
Ethyl
1-hydroxy-2-oxo-2,3-dihydro-1H-indene-1-carboxylate
Scheme 5. Control experiments.
1
2: The compound 12 was prepared according to the general pro-
cedure starting from ethyl 2-oxoindane 1-carboxylate (0.21 mmol,
2.9 mg) and 11 (10.5 μmol, 10.5 mg, 5 mol-%). The reaction mix-
4
ture was stirred for 45 min. Purification by column chromatography,
eluting with 7:3 petroleum ether/diethyl ether, gave compound 12
Conclusions
as an oil (29.1 mg, 63 %). δH (300 MHz, CDCl ) 7.44–7.32 (4H, m),
3
In summary, we prepared a new bifunctional photosensitizer
composed of a iodo-BODIPY architecture connected to a quin-
ine moiety which plays a dual role. In the absence of substrate,
singlet oxygen would be physically quenched in order to pre-
vent racemic background photooxygenation while interaction
4
7
.31 (1H, s), 4.24 (1H, dq, J = 10.7, 7.2 Hz), 4.13 (1H, dq, J = 10.7,
.2 Hz), 3.84 (1H, d, J = 21.8 Hz), 3.62 (1H, d, J = 21.8 Hz), 1.15 (3H,
t, J = 7.2 Hz); δC (75 MHz, CDCl ) 209.8, 170.2, 139.1, 137.4, 130.1,
3
–1
1
28.2, 125.2, 124.3, 81.6, 63.1, 41.4, 13.8. IR (ATR)/cm 3385
(
υ, O-H), 1766 (υ, C=O), 1737 (υ, C=O); HRMS (ESI) Calcd for
+
of the substrate with the aminocatalyst would trigger the pho- C H O Na [M+Na] : 243.0633 found: 243.0622.
12 12 4
tooxygenation. To this aim, the bifunctional photosensitizer has
been applied to the photooxygenation of a focus selection of
Isopropyl 1-hydroxy-2-oxo-2,3-dihydro-1H-indene-1-carboxyl-
ate 13: The compound 13 was prepared according to the general
procedure starting from isopropyl 2-oxoindane 1-carboxylate
ꢀ-dicarbonyl compounds and the oxygenated products have
been isolated with enantiomeric excesses of up to 40 %. Kinetic
analyses and control experiments were carried out in order to
get a better understanding of the mechanism.
(0.21 mmol, 45.8 mg) and 11 (10.5 μmol, 10.5 mg, 5 mol-%). The
reaction mixture was stirred for 4 h. Purification by column chroma-
tography, eluting with 7:3 petroleum ether/diethyl ether, gave com-
pound 13 as an oil (32.6 mg, 66 %). δH (300 MHz, CDCl ) 7.43–7.30
3
(4H, m), 5.02 (1H, sept, J = 6.3 Hz), 4.34 (1H, s), 3.81 (1H, d, J =
Experimental Section
21.8 Hz), 3.60 (1H, d, J = 21.8 Hz), 1.17 (3H, d, J = 6.3 Hz), 1.06 (3H,
d, J = 6.3 Hz); δ (75 MHz, CDCl ) 209.9, 169.8, 139.2, 137.4, 129.9,
C
3
General remarks: 1H NMR and C spectra were recorded on a
13
–1
128.2, 125.1, 124.1, 81.7, 71.3, 41.5, 21.3 (2C). IR (ATR)/cm 3422 (υ,
1
13
BRUKER AC300 (300 MHz for H and 75 MHz for C) at room tem-
O-H), 1768 (υ, C=O), 1729 (υ, C=O). HRMS (ESI) Calcd for C H O Na
13 14 4
perature on samples dissolved in CDCl . Chemical shifts (δ) are
given in parts per million and coupling constants are given as abso-
lute values expressed in Hertz. High-resolution mass spectrometry
+
3
[
M+Na] : 257.0790 found: 257.0784.
Tertbutyl 1-hydroxy-2-oxo-2,3-dihydro-1H-indene-1-carboxyl-
(HRMS) analyses were recorded on a XEVO G2-XS QTOF (Waters).
ate 14: The compound 14 was prepared according to the general
Infrared spectra were recorded with a Bruker Tensor 27 FT ATR spec- procedure starting from tertbutyl 2-oxoindane 1-carboxylate
trometer. Melting points were determined on a Stuart melting point (0.21 mmol, 48.8 mg) and 11 (10.5 μmol, 10.5 mg, 5 mol-%). The
SMP3 apparatus. Thin-layer chromatography (TLC) was carried out
reaction mixture was stirred for 4 h. Purification by column chroma-
on aluminium sheets precoated with silica gel 60 F254 (Merck).
tography, eluting with 7:3 petroleum ether/diethyl ether, gave com-
Column chromatography separations were performed using Merck pound 14 as a solid (30.2 mg, 58 %). M.p. 93–95 °C; δH (300 MHz,
Kieselgel 60 (0.040–0.060 mm). Chloroform was dried immediately
CDCl ) 7.42–7.30 (4H, m), 4.29 (1H, bs), 3.78 (1H, d, J = 21.7 Hz), 3.58
3
before use by distillation from standard drying agents. The iodo-
(1H, d, J = 21.7 Hz), 1.34 (9H, s); δC (75 MHz, CDCl ) 210.4, 169.4,
3
[21]
[23]
BODIPY photosensitizer 2,
O-benzylquinine 4,
9-amino-9-de-
139.8, 137.4, 129.9, 128.2, 125.2, 124.0, 84.7, 82.0, 41.7, 27.7 (3C). IR
[23]
[24]
–1
oxyepiquinine 5,
2-phenylquinine 6,
and 10,11-didehydro- (ATR)/cm 3408 (υ, O-H), 1764 (υ, C=O), 1735 (υ, C=O). HRMS (ESI)
quinine 10[ were prepared according to literature procedures.
25]
Calcd for C H O Na [M+Na] : 271.0946 found: 271.0938.
+
1
4 16 4
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Methyl 2-hydroxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylate
5: The compound 15 was prepared according to the general pro-
4-(3-Azidopropoxy) benzaldehyde 7: 4-hydroxybenzaldehyde
(11.4 mmol, 1.39 g, 1.20 equiv.), azido-3-iodopropane (9.48 mmol,
1
cedure starting from methyl 1-oxoindane 2-carboxylate (0.21 mmol, 2.00 g, 1.00 equiv.) and potassium carbonate (56.88 mmol, 7.86 g,
0 mg) and 11 (10.5 μmol, 10.5 mg, 5 mol-%). The reaction mixture 6.00 equiv.) were dissolved in acetone (40 mL) under argon and
was stirred for 3 h. Purification by column chromatography, eluting heated to reflux during 16 h. The reaction mixture was then filtered,
4
with 7:3 petroleum ether/diethyl ether, gave compound 15 as a
concentrated in vacuo, diluted in dichloromethane (30 mL). The
solution was then washed with water (3 × 20 mL), dried with
Na SO , filtered and concentrated in vacuo. Purification by column
solid (16.1 mg, 37 %). δH (300 MHz, CDCl ) 7.80 (1H, dd, J = 7.7,
3
0
7
.7 Hz), 7.67 (1H, td, J = 7.3, 1.4 Hz), 7.49 (1H, dt, J = 7.7, 1.4 Hz),
.43 (1H, td, J = 7.3, 0.7 Hz), 4.02 (1H, s), 3.73 (3H, s), 3.73 (1H, d, chromatography, eluting with 75:25 petroleum ether/ethyl acetate,
2
4
J = 17.3 Hz), 3.25 (1H, d, J = 17.3 Hz). The analytical data are in
gave 4-(3-azidopropoxy) benzaldehyde 7 as a light yellow liquid
complete agreement with the previously published data.[
26]
(1.04 g, 53 %). δH (300 MHz, CDCl ) 9.89 (1H, s), 7.87–7.82 (2H, m),
3
7
2
.03–6.98 (2H, m), 4.13 (2H, t, J = 6.0 Hz), 3.53 (2H, t, J = 6.5 Hz),
.13–2.04 (2H, m); The analytical data are in complete agreement
Ethyl
6: The compound 16 was prepared according to the general pro-
cedure starting from ethyl 1-oxoindane 2-carboxylate (0.21 mmol,
2.9 mg) and 11 (10.5 μmol, 10.5 mg, 5 mol-%). The reaction mix-
2-hydroxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylate
1
with the previously published data. Further analysis matched with
the literature.
[
27]
4
ture was stirred for 3 h. Purification by column chromatography,
eluting with 7:3 petroleum ether/diethyl ether, gave compound 16
4,4-Difluoro-8-(4-(3-azidopropoxy))phenyl-1,3,5,7-tetramethyl-
4-bora-3a,4a-diaza-s-indacene 8: Compound (4.87 mmol,
7
as a solid (27.2 mg, 59 %). δH (300 MHz, CDCl ) 7.79 (1H, dd, J = 1.00 g, 1.00 equiv.), 2,4-dimethylpyrrole (9.75 mmol, 926 mg,
3
7
7
.7, 0.8 Hz), 7.66 (1H, td, J = 7.4, 0.8 Hz), 7.49 (1H, dt, J = 7.7, 0.8 Hz),
.42 (1H, td, J = 7.4, 0.8 Hz), 4.16 (1H, dd, J = 7.1, 2.3 Hz), 4.12 (1H,
2.00 equiv.) and trifluoroacetic acid (0.1 mL) in diethyl ether
(235 mL) were stirred under Argon at room temperature during
16 h. 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (4.87 mmol,
1.105 g, 1.00 equiv.) in dichloromethane (32 mL) was then added
and allowed to stir for 1 h at room temperature. The reaction mix-
ture was cooled to 0 °C, triethylamine (19.5 mL) then boron trifluor-
ide ethyl etherate (19.5 mL) were added and allowed to stir for 1 h
at 0 °C. The organic layer was then washed with water (4 × 200 mL),
dried with Na SO and concentrated in vacuo. Purification by col-
dd, J = 7.1, 2.3 Hz), 4.02 (1H, s), 3.72 (1H, d, J = 17.3 Hz), 3.24 (1H,
d, J = 17.3 Hz), 1.17 (3H, t, J = 7.1 Hz). The analytical data are in
complete agreement with the previously published data.[26]
Isopropyl 2-hydroxy-1-oxo-2,3-dihydro-1H-indene-2-carboxyl-
ate 17: The compound 17 was prepared according to the general
procedure starting from isopropyl 1-oxoindane 2-carboxylate
(0.21 mmol, 45.8 mg) and 11 (10.5 μmol, 10.5 mg, 5 mol-%). The
2
4
umn chromatography, eluting with 1:1 dichloromethane/petroleum
ether, gave compound 8 as an orange solid (786 mg, 38 %). δH
reaction mixture was stirred for 4 h. Purification by column chroma-
tography, eluting with 7:3 petroleum ether/diethyl ether, gave com-
(
300 MHz, CDCl ) 7.19–7.14 (2H, m), 7.02–6.98 (2H, m), 5.96 (2H, s),
pound 17 as a solid (42.3 mg, 86 %). δH (300 MHz, CDCl ) 7.77 (1H,
3
3
4.09 (2H, t, J = 6.0 Hz), 3.55 (2H, t, J = 6.6 Hz), 2.54 (6H, s), 2.09 (2H,
dd, J = 7.7, 0.8 Hz), 7.64 (1H, td, J = 7.3, 0.8 Hz), 7.47 (1H, dt, J =
app. quint., J = 6.3 Hz), 1.42 (6H, s). The analytical data are in com-
7
4
.7, 0.8 Hz), 7.40 (1H, td, J = 7.3, 0.8 Hz), 5.05 (1H, sept, J = 6.3 Hz),
.07 (1H, s), 3.68 (1H, d, J = 17.3 Hz), 3.22 (1H, d, J = 17.3 Hz), 1.17
[
28]
plete agreement with the previously published data.
(
3H, d, J = 6.3 Hz), 1.10 (3H, d, J = 6.3 Hz). The analytical data are
4
,4-Difluoro-8-(4-(3-azidopropoxy))phenyl-2,6-diodo-1,3,5,7-
[
26]
in complete agreement with the previously published data.
tetramethyl-4-bora-3a,4a-diaza-s-indacene 9: Compound 8
Methyl
1-hydroxy-2-oxo-1,2-dihydroacenaphthylene-1-carb-
(0.945 mmol, 400 mg, 1.00 equiv.) was dissolved in dichloromethane
oxylate 18: The compound 18 was prepared according to the gen- (38 mL) in a round-bottom flask under argon. N-Iodosuccinimide
eral procedure starting from methyl 2-oxo-1,2-dihydroacenaphthyl- (3.78 mmol, 851 mg, 4 equiv.) was added and the reaction mixture
ene-1-carboxylate (0.21 mmol, 47.5 mg) and 11 (10.5 μmol,
0.5 mg, 5 mol-%). The reaction mixture was stirred for 1 h. Purifica-
was stirred at room temperature for 1 h. The product was concen-
trated in vacuo. Purification by column chromatography, eluting
1
tion by column chromatography, eluting with 7:3 petroleum ether/ with 7:3 petroleum ether/dichloromethane, gave compound 9 as a
diethyl ether, gave compound 18 as a solid (37.1 mg, 73 %). M.p.
red solid (340 mg, 53 %). δ (300 MHz, CDCl ) 7.14 (2H, d, J =
63–165 °C; δH (300 MHz, CDCl ) 8.17 (1H, d, J = 8.1 Hz), 8.04 (1H,
8.8 Hz), 7.03 (2H, d, J = 8.8 Hz), 4.13 (2H, t, J = 6.0 Hz), 3.57 (2H, t,
J = 6.0 Hz), 2.64 (6H, s), 2.12 (2H, quint, J = 6.0 Hz), 1.44 (6H, s); δ
(75 MHz, CDCl ) 159.8, 156.7 (2C), 145.5 (2C), 141.6, 131.8 (2C), 129.3
H
3
1
3
d, J = 7.0 Hz), 7.97 (1H, d, J = 8.3 Hz), 7.78 (1H, dd, J = 8.1, 7.0 Hz),
C
7
3
1
.79 (1H, dd, J = 8.3, 7.0 Hz), 7.71 (1H, d, J = 7.0 Hz), 4.50 (1H, bs),
3
.66 (3H, s); δC (75 MHz, CDCl ) 199.0, 171.3, 143.4, 136.3, 132.3, (2C), 127.1, 115.5 (2C), 85.7 (2C), 64.8, 48.3, 28.9, 17.3 (2C), 16.1
3
–
31.2, 131.0, 128.9, 128.6, 126.5, 123.2, 120.8, 81.3, 53.8. IR (ATR)/ (2C). HRMS (ESI) Calcd for C22
H
21
N
5
OF
I
2
B [M – H] : 672.9933 found:
2
–1
cm 3447 (υ, O-H), 1718 (υ, C=O). HRMS (ESI) Calcd for C H O Na
972.9918.
14 10 4
+
[M+Na] : 265.0477 found: 265.0469.
Photosensitizer 11: In a Schlenk tube were added compound 9
(0.296 mmol, 200 mg, 1.00 equiv.), 10 (0.444 mmol, 143 mg,
1.50 equiv.) in
(0.119 mmol, 23.5 mg, 0.40 equiv.) and then copper sulfate pentahy-
drate (0.030 mmol, 7.4 mg, 0.10 equiv.) were added and stirred at
room temperature for 16 h. The solution was then concentrated in
vacuo and dissolved in dichloromethane (40 mL). The organic layer
was washed with a low concentration NaCl solution (3 × 20 mL)
and dried with Na SO . The product was evaporated in vacuo. Puri-
Methyl 1-hydroxy-2-oxo-1,2,3,4-tetrahydronaphthalene-1-carb-
oxylate 19: The compound 18 was prepared according to the
general procedure starting from methyl 2-oxo-1,2,3,4-tetrahydro-
naphthalene-1-carboxylate (0.21 mmol, 46.2 mg, 1.00 equiv.) and
a 1:3 H2O:THF mixture. Sodium ascorbate
1
1 (10.5 μmol, 10.5 mg, 5 mol-%) in CHCl (4.2 mL). The reaction
3
mixture was stirred for 4 h. Purification by column chromatography,
eluting with 7:3 petroleum ether/diethyl ether, gave compound 19
as a solid (8.5 mg, 18 %). M.p. 95–98 °C; δH (300 MHz, CDCl ) 7.64
3
2
4
(1H, m), 7.33 (2H, m), 7.22 (1H, m), 4.56 (1H, s), 3.72 (3H, s), 3.35
fication by column chromatography, eluting with a 9:1 to 7:3 ethyl
(
1H, m), 3.07 (2H, m), 2.68 (1H, m); δ (75 MHz, CDCl ) 206.9, 169.9,
acetate/methanol gradient, gave photosensitizer 11 as a red solid
C
3
1
36.1, 134.7, 129.0, 128.1, 127.6, 126.6, 79.8, 53.5, 34.6, 27.6. IR (ATR)/
(204 mg, 69 %). M.p. 178–181 °C; δH (300 MHz, CDCl ) 8.68 (1H, d,
3
–1
cm 3424 (υ, O-H), 1741 (υ, C=O), 1709 (υ, C=O). HRMS (ESI) Calcd J = 4.5 Hz), 7.86 (1H, d, J = 9.2 Hz), 7.55 (1H, d, J = 4.5 Hz), 7.21 (s,
for C H O Na [M+Na] : 243.0633 found: 243.0629.
+
1H), 7.19 (1H, dd, J = 9.2, 2.6 Hz), 7.12–7.10 (3H, m), 6.91 (2H, d, J =
6357 © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
12 12 4
Eur. J. Org. Chem. 2019, 6352–6358
www.eurjoc.org

Full Paper
8
4
3
2
1
1
1
5
.7 Hz), 6.01 (1H, br. S), 4.46 (2H, t, J = 6.9 Hz), 4.17–4.03 (1H, m),
.00–3.97 (1H, m), 3.89–3.78 (m, 1H), 3.82 (3H, s), 3.71–3.63 (1H, m),
.59–3.42 (2H, m), 3.28–3.20 (1H, m), 3.06–2.95 (1H, m), 2.64 (6H, s),
.34–2.25 (2H, m), 2.20–2.05 (2H, m), 1.97–1.78 (2H, m), 1.40 (6H, s),
.30–1.18 (2H, m); δ (75 MHz, CDCl ) 159.5, 158.2, 156.9 (2C), 148.7,
[7] M. R. Iesce, F. Cermola, in Handbook of Organic Photochemistry and
Photobiology, 3rd ed., (Eds.: A. Griesbeck, M. Oelgemöller, F. Ghetti), CRC
Press: Boca Raton, FL, 2012, p. 727–764.
[
8] For selected reviews about Schenck-ene reactions: a) P. Bayer, R. Pérez-
Ruiz, A. Jacobi von Wangelin, ChemPhotoChem 2018, 2, 559–570; b) M. N.
Alberti, M. Orfanopoulos, Chem. Eur. J. 2010, 16, 9414–9421; c) M. N.
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9179.
C
3
47.5, 145.7, 145.3, 144.2, 141.3, 131.8 (2C), 131.6, 129.4 (2C), 127.5,
26.1, 125.8, 122.1, 121.1, 118.8, 115.4 (2C), 100.7, 85.8 (2C), 64.4,
9.8, 56.3, 55.0, 47.2, 43.8, 32.5, 29.9, 28.0, 25.8, 20.2, 17.3 (2C), 16.2
2C). IR (ATR)/cm– 3232 (υ, O-H), 2930 (υ, C-H), 1526 (υ, C-H), 1175
1
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(
υ, C-O), 993 (υ, C=C), 525 (υ, C-I); HRMS (ESI) Calcd for
–
C H N O F I B [M – H] : 995.1614 found: 995.1578.
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Acknowledgments
This work was supported by The Région Pays de la Loire
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NANO2 project) which financed a PhD grant for JF. We also
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Keywords: Asymmetric catalysis · Energy transfer ·
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Received: July 9, 2019
Eur. J. Org. Chem. 2019, 6352–6358
www.eurjoc.org
6358
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim