Porphyrins as Photoredox Catalysts in Csp2-H Arylations: Batch and Continuous Flow Approaches

Article abstract of DOI:10.1021/acs.joc.8b02355

We have investigated both batch and continuous flow photoarylations of enol-acetates to yield different α-arylated aldehyde and ketone building blocks by using diazonium salts as the aryl-radical source. Different porphyrins were used as SET photocatalysts, and photophysical as well as electrochemical studies were performed to rationalize the photoredox properties and suggest mechanistic insights. Notably, the most electron-deficient porphyrin (meso-tetra(pentafluorophenyl)porphyrin) shows the best photoactivity as an electron donor in the triplet excited state, which was rationalized by the redox potentials of excited states and the turnover of the porphyrins in the photocatalytic cycle. A two-step continuous protocol and multigram-scale reactions are also presented revealing a robust, cost-competitive, and easy methodology, highlighting the significant potential of porphyrins as SET photocatalysts.

Full text of DOI:10.1021/acs.joc.8b02355

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Article
Porphyrins as Photoredox Catalysts in Csp2-H
Arylations: Batch and Continuous Flow Approaches
Aline A. N. de Souza, Nathalia S Silva, Andressa Vidal Müller,
Andre S Polo, Timothy J Brocksom, and Kleber Thiago de Oliveira
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02355 • Publication Date (Web): 20 Nov 2018
Downloaded from http://pubs.acs.org on November 20, 2018
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Porphyrins as Photoredox Catalysts in Csp2-H Arylations:
Batch and Continuous Flow Approaches
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Aline A. N. de Souza,1 Nathalia S. Silva,1 Andressa V. Müller,2 André S. Polo,2
Timothy J. Brocksom1,2 and Kleber T. de Oliveira1*
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1.
Departamento de Química, Universidade Federal de São Carlos, São
Carlos, SP, 13565-905, Brazil.
2. Centro de Ciências Naturais e Humanas, Universidade Federal do ABC,
Santo André, SP, 09210-580, Brazil.
*E-mail: kleber.oliveira@ufscar.br, ktoquimico@gmail.com
Graphical Abstract
CONTINUOUS FLOW
PHOTOCATALYSIS
Ar
R2
OAc
R1
N2BF4
R2
NH
N
Ar
Ar
R1
N
HN
Ar
O
R
R
R
BATCH
PHOTOCATALYSIS
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ABSTRACT
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We have investigated both batch and continuous flow photoarylations of enol-
acetates to yield different -arylated aldehyde and ketone building blocks by
using diazonium salts as the aryl-radical source. Different porphyrins were used
as SET photocatalysts, and photophysical as well as electrochemical studies
were performed to rationalize the photoredox properties and suggest
mechanistic insights. Notably, the most electron-deficient porphyrin (meso-
tetra(pentafluorophenyl)porphyrin) shows the best photoactivity as an electron-
donor in the triplet excited-state, which was rationalized by the redox potentials
of excited states and the turnover of the porphyrins in the photocatalytic cycle.
Scope, a two-step continuous protocol and multigram-scale reactions are also
presented revealing a robust, cost-competitive and easy methodology,
highlighting the significant potential of porphyrins as SET photocatalysts.
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INTRODUCTION
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Although photochemical reactions have been known for a long time,1,2
only in the last century have significant chemical transformations been widely
performed using visible light to promote catalysis.3,4,5,6,7,8 Among various C-H
(sp2) functionalizations, arylation reactions have gained importance in
methodology studies due to their application in active pharmaceutical ingredient
(API) and natural product syntheses.9,10,11,12 Metal complexes based on Ru(II)
and Ir(III) have been used to perform these photoarylations, especially by single
electron transfer (SET), thus generating aryl-radicals from aryl-
diazonium/iodonium salts and other activated aromatic systems.13,14
Ruthenium(II) and Iridium(III) compounds usually have triplet excited states with
high reduction potentials (0.7–2.0 V) and long lifetimes (over 1000 ns), which
make them very useful for many organic SET photocatalyzed reactions.
However, Ru and Ir based complexes are expensive and with no prospect for
sustainable use in scaled up applications. An alternative to these transition
metal-photocatalysts is the use of organic dyes, whose photocatalytic properties
can match or even surpass the efficiency of metal-complexes, with
advantageous low cost, availability and easier residual clean-up of the products,
opening up many possibilities in chemical synthesis.9,15
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Given this background, porphyrins are useful tetra-pyrrolic organic dyes
with great potential to replace many metal-complexes, working as oxidizing or
reducing agents and presenting similar lifetimes of the triplet state when
compared to some metallo-complexes.15,16 Metal-free porphyrins have been
only recently explored as SET photoredox catalysts, probably due to the relative
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difficulty to access their excited state redox potentials, the relative old-fashioned
and inefficient synthetic routes to obtain these compounds,17 and their
conditional use as ligands of transition metals for catalysis; 18 however, many of
these issues have been currently solved,19 making porphyrin derivatives very
promising and cost-competitive photocatalysts.15,16,20 Regarding the use of
porphyrins as SET catalysts, Kanai and coworkers21 have reported an electron
rich porphyrin derivative in coumarin arylation, though they did not investigate if
the reactions are just thermal or also photocatalyzed by ambient light. Two
recent and seminal applications of porphyrins as SET photocatalysts were
published by Gryko and coworkers reporting in the first tetraphenylporphyrin
(TPP) as photoredox catalyst in reactions of aldehydes with diazo compounds16
and in the second different porphyrins in photoarylations of heteroarenes.22
However, in this second publication they did not clearly explain the high SET
photoactivity of the meso-tetra(pentafluorophenyl)porphyrin (TPFPP), which
worked as an excellent photo-reducer despite containing twenty fluorine atoms
attached to the aryl groups surrounding the porphyrin core. In addition, this last
methodology was only applied on a very low scale (0.25 mmol), with a reduced
scope and utilizing batch conditions. Normally, methodologies on radical
photoarylation are performed by using arenediazonium salts23 on very low
scales, since these salts are considered to present safety and experimental
concerns due to their low stabilities.24 An alternative to avoid this safety concern
is the use of reactors operating under continuous flow conditions,25,26,27,28,29
which allows safe and precise reaction control, scale up, automation and
sustainability. In addition, the in-situ generation of these compounds has been
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used in multigram and end-to-end approaches in flow,30 with no need for
stocking diazonium salts.
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In this present study, we have considered all these concerns, and
evaluated two different porphyrins as photoredox catalysts in Csp2-H
photoarylations of enol-acetates in both batch and continuous flow conditions.
Thus we describe an efficient, safe and cost competitive methodology using
very low loadings of porphyrin derivatives, shorter reaction times, scalability and
scope, when compared to [Ru(bpy)3]Cl2 or organic dyes such as Eosin Y and
Rose Bengal (Scheme 1).31
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König and co-workers, JOC 2012.
Batch
R2
a) [Ru(byp)3]Cl2 (1mol%), 2h, 80% yield
b) Eosin Y (10mol%), 2h, 50% yield
c) Bengal Rose (5mol%), 2h, 32% yield
R1
Photocatalyst
R
O
O
N2BF4
O
+
R
R2
R1
This work
Porphyrins as photocat at (0.5 mol%)
R2
aryldiazonium activated
salts olefin
25 min, and up to 86% yield
R1
Photocatalyst
R
studies in batch and continuous flow
with scope, safety, scalability (up to
3 g scale) and shorter reaction times
O
Flow
Scheme 1. Visible light mediated photoarylations.
RESULTS AND DISCUSSION
The proof of concept that porphyrin derivatives work as SET
photocatalysts in photoarylations of enol-acetates was performed in batch with
the diazonium salt 1a and the enol-acetate 2a using the meso-
tetraphenylporphyrin (TPP) (Scheme 2, Table 1).
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N2BF4
O
Porphyrin
Solvent
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O
+
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9
O2N
LEDs
Batch
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NO2
3a
2a
1a
Scheme 2. Reaction model in batch conditions.
Table 1: Reactions with TPP in batch at 25 oC.
entrya
TPP (mol%)
time (h)
LEDs (28 W)b
White
White
White
Blue
yield 3a (%)c
1
2
5
2
2
2
2
2
4
2
2
2
2
2
44
45
3
1
42
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5
53/57d
55
5
5
Blue
6
2
Blue
55
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1
Blue
54
8
0.5
0
Blue
55
9
Blue
32e
16e
10
0
Dark
a 1 mmol of 1a and 15 mmol of 2a in 6 mL of CH2Cl2:DMF (3.5:2.5) mixture (total volume 8 mL)
b homemade batch reactor – see supporting information
c isolated yields
d Double checked reaction
e Experiments were performed in the presence of DMF/CH2Cl2 mixture, with or without light (see
ref 32, p. 775 for details on the background reaction).
As shown in Table 1 (entries 1–3) the α-aryl-ketone 3a was obtained in
42–45% yield, independent of the TPP charge (1–5 mol%) using white LEDs.
However, using blue LEDs (entries 4–8, Table 1) 3a was isolated in 53–55%
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yield independent of the charge of TPP (0.5–5 mol%). Surprisingly, reaction
without TPP under blue LEDS (entry 9, Table 1), or no TPP and no light yielded
3a in 32 and 16% yield, respectively. These are background reaction conditions
and the occurrence of the product 3a is explained by the different manners in
which aryl radicals are slowly generated in the presence of DMF and thermal
conditions.32 According to the literature, aryl radicals can be generated from
arenediazonium salts through many different approaches using metals (Cu(I),
Fe(II), etc), anion induced dediazotization, photoinduced electron transfer and
solvent induced dediazotization.32 Our background results from entries 9 and 10
(Table 1) can be explained by these last two cases (Scheme 3). However, these
are only competitive reactions for radical generation, and we have found a
significant increase in the yields in the presence of TPP also indicating the
occurrence of SET photocatalysis, as previously evidenced by Gryko’s group in
the arylation of heteroaromatics.22
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O
N
O
N
N
N
N
H
+
N
R
R
H
expontaneous
or
h
h
O
N2
+
+
R
H
N
Scheme 3: Proposal based on the literature32 for the background reaction.
After testing the TPP SET photoactivity we then decided to test the
meso-tetrakis(pentafluorophenyl)porphyrin (TPFPP) as photocatalyst. Improved
yields were obtained in all entries (Table 2) using TPFPP, and the best result
was found by using blue LEDs, TPFPP at 0.5 mol% and 0 oC (entry 5, Table 2)
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obtaining compound 3a in 74% yield. The evident effect of the temperature was
demonstrated in this last experiment, also highlighting the better photocatalytic
SET effect of TPFPP. As is well-known, triplet life-times of porphyrins are
increased at lower temperatures improving the efficiency of these
photocatalysts.33 A control experiment (entry 6, Table 2) was performed using
the same conditions of entry 5, however, without TPFPP showing that the
product 3a can be obtained in 40% yield. This result corroborates with the
photo-induced radical generation and arylation, but definitely does not equal the
SET photocatalytic effect of TPFPP (74% yield, entry 5, Table 2).
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Table 2: Reactions with TPFPP in batch.
entrya,b TPFPP (mol%) LEDs (28 W) Temperature (oC) yield 3a (%)c
1
2
3
4
5
6
2
1
Blue
Blue
Blue
White
Blue
Blue
25
25
25
25
0
69
69
0.5
0.5
0.5
0
68
64
74/74d,e
40d
0
a 1 mmol of 1a and 15 mmol of 2a in 6 mL of CH2Cl2:DMF (3.5:2.5) mixture (total volume 8 mL)
b all the reactions were performed in 2h.
c isolated yields
d reaction performed inside a temperature-controlled freezer
e double checked reaction
Subsequently, the solvent effect was also investigated since
photocatalyzed reactions are very solvent-dependent. As presented in Table 3,
different mixtures were tested always considering the modulation of the polarity
and the reagent solubilities. The mixture CH2Cl2:CH3NO2:DMF (3.5:2.0:0.5)
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o
(entry 1, Table 3), using TPFPP at 0.5 mol%, 0 C and using white LEDs gave
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3a in 71% yield. Nevertheless, using these same conditions, but with blue LEDs
(entry 2, Table 3), compound 3a was obtained in 79–80% yield in a double-
checked experiment, thus indicating the higher efficiency of blue light for
exciting TPFPP. Regarding this result, we have shown how the blue LEDs
emission spectra fits better with the absorption band of this porphyrin (see the
supporting information). In addition, an experiment (entry 3, Table 3) clearly
showed the SET photocatalytic effect of TPFPP, since under dark conditions
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o
and at 0 C (background) only traces of compound 3a were found. This result
also corroborates with the previously presented background reactions (entries
o
9–10, Table 1), since the temperature effect (0 C) is decisive to inhibit the
chemical aryl-radical formation, while only the photocatalytic effect is present.
Table 3: Reactions with TPFPP in batch at 0 oC.
entrya,b
solvent (ratio)
CH2Cl2:CH3NO2:DMF (3.5:2.0:0.5)
CH2Cl2:CH3NO2:DMF (3.5:2.0:0.5)
CH2Cl2:CH3NO2:DMF (3.5:2.0:0.5)
DMF e
LEDs (28 W) yield 3a (%)c
1
2
3
4
5
6
white
blue
71
79/80d
1
no light
blue
69
CH3NO2:DMF (2.5:3.5)
CH3NO2:DMF (5:1)
blue
76
Blue
82/81d
a 1 mmol of 1a and 15 mmol of 2a in 6 mL of solvent/mixture using TPFPP (0.5 mol%) (total
volume 8 mL)
b all the reactions were performed in 2h at 0oC.
c isolated yields
d double checked reaction
e reactions in pure CH2Cl2 or CH3NO2 were not considered due to the low solubility of 1a.
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The use of only DMF as solvent (entry 4, Table 3) allowed the isolation of
compound 3a in 69% yield, and the mixtures of nitromethane and DMF (entries
5 and 6, Table 3) gave 3a in 76 and 82% yield, respectively, demonstrating
CH3NO2:DMF 5:1 as the best solvent mixture (double-checked experiment).
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After finding some optimized conditions and the best solvent mixture
(CH3NO2:DMF 5:1), the temperature effect was checked again, as well as the
reaction time and lower excesses of enol acetate 2a (Table 4).
Table 4: Reactions with TPFPP in batch with CH3NO2:DMF (5:1).
entrya
ratio 1a:2a
(mmol)
1:15
TPFPP
(mol%)
0.5
LEDs (28
W)
temperature
reaction
yield 3a
(%)b
82
(oC)
0
time (h)
1
2
3
5
6
Blue
2
2
8
2
2
1:15
0.5
Blue
25
25
0
72
1:15
0.5
no light
Blue
28
1:5
0.5
57
1:1
0.5
Blue
0
44
a in 6 mL of CH3NO2:DMF (5:1)
b isolated yields
Entry 1 (Table 4) presents the same result as entry 6 (Table 3) and was
repeated only for easy comparison with different parameters from Table 4. The
o
temperature effect (0 C, 82% yield) is relevant as demonstrated by entry 2
o
(Table 4) in which an experiment at 25 C gave 3a in 72% yield. The 8h
experiment in the dark (entry 3, Table 4) gave 3a in 28% yield, in agreement
with the thermal solvent induced de-diazotization.
Smaller excesses of 2a were also evaluated giving 3a in 57% yield by
when using 5 eqv (entry 5, Table 4) and 44% yield when using 1 eqv (entry 6,
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Table 4). For these last results we have detected the presence of aryl-dimers by
CG-MS indicating that the use of 2a in large excess is crucial.
After optimizing the photoarylations of 2a with the diazonium salt 1a in
batch, we adapted this protocol to continuous flow conditions using a home-
made PFA tubing photo-reactor (Scheme 4) (see the supporting information for
construction details).
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N2BF4
O
Conditions
Table 4
O
+
O
O2N
Photo-Flow
NO2
1a
2a
3a
fan
Continuous Photo-Flow Setup
BPR
250 psi
PUMP
R
reaction mixture at 0oC,
protected from light
O
Products
Blue LEDs
(28W)
coiled with PFA tube (1/8 inch, 20 mL)
over a jacketed glass reactor (0oC)
Scheme 4. Continuous photo-flow setup.
Therefore, we decided to start with the optimized conditions from Table 3
(entry 6). All the tested total flow rates (0.1–1.0 mL.min-1) (Table 5) furnished
the compound 3a in the range 73–92%, but with very different throughputs
(g/day). Considering that the idea is to apply the continuous protocol for
different aryldiazonium salts we adopted entry 5 (Table 5) with 0.4 mL.min-1
total flow as the optimized condition (88% yield, 11.4 g/day and residence time
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= 50 min). It is important to highlight that all the optimizations in flow were
developed using the same amounts of substrates and solvent mixture (1 mmol
of 1a and 15 mmol of 2a in 6 mL of CH3NO2:DMF (5:1) - 8 mL total volume) for
comparison with batch conditions. For batch experiments we used a glass tube,
and for continuous flow conditions the reaction mixture was directly pumped
using at the end the proper solvent mixture to push all the reaction through the
photo-flow reactor.
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Table 5: Reactions under continuous flow conditions.
entrya,b flow (mL.min-1) residence time (min) yield 3a (%)c throughput (g/day)
1
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3
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7
8
1.0
0.8
0.6
0.5
0.4
0.3
0.2
0.1
20
25
73
86
23.5
22.2
33
92
17.8
40
84/85d
88
13.5/13.7
11.4
50
67
84
8.0
100
200
83
5.4
84
2.7
a mixture of 1 mmol of 1a and 15 mmol of 2a in 6 mL of CH3NO2:DMF (5:1), TPFPP (0.5 mol%)
(total volume 8 mL)
b Homemade 20 mL PFA continuous photoreactor, blue LEDs (28W) with PFA tubes cooled to 0
oC – check the supporting information for details.
c isolated yields
d
double checked experiment
Subsequently, the scope of different aryldiazonium salts was studied
under continuous flow, thus obtaining compounds 3b–n (Scheme 5). The three
substrates containing NO2 groups (3b–c) were obtained in 70–88% yields,
confirming the efficiency of the protocol and the reactivities of nitro-aryl-radicals.
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The group containing fluorine atoms (3e–g) was obtained in moderate yields
(34–54%), and the other electron-withdrawing substituted diazonium salts 1h–j
led to the corresponding arylated products in 57–76% yields. The non-
substituted arylated product 3d and others substituted with electron-donating
groups (3k–n) were obtained in 33–48% yields. For comparison, batch
experiments (50 min) with the diazonium salts 1f and 1k gave 3f and 3k in 13
and 30% yield, respectively, confirming that our continuous protocol is more
efficient. There was no formation of the products 3o and 3p, probably due to the
higher reactivity of their radicals, with evidence of radical dimerization (as
detected by GC-MS).
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O
Conditions
entry 4, Table 4
N2BF4
O
R
R
+
O
7
8
9
Photo-Flow
1 a-p
3a-p
2a
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NO2
O2N
O
O
O
O
O
O
O2N
3a
3c
(70%)
(88%)
3b
3d
(30%)
(74%)
F
F
O
O
O
Cl
F
3e
3g
(54%)
(47%)
3f
3h
(76%)
(34%)
CF3
F3C
O
MeO
O
O
Et
3l
(48%)
3j
3k
(43%)
(67%)
3i
(57%)
OMe
O
MeO
O
O
O
N
O
O
3p
(0%)
3o
(0%)
3m
3n
(40%)
(33%)
Scheme 5. Scope with different aryl-diazonium salts.
After exploring the scope of aryldiazonium salts, we investigated different
enol acetates (2b–g) with 1a as radical source using our optimized photo-flow
continuous conditions (Scheme 6). The aldehyde 4b was obtained in 45% yield,
the arylated ketones 4c–4g in yields from 26–77%.
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R
O
Conditions
entry 4, Table 4
R1
N2BF4
O
+
O
R
O2N
R1
O2N
Photo-Flow
1 a
4b-h
2 b-g
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O
H
O
O
O2N
O2N
O2N
4c
(77%)
O
4b
(45%)
4d
(40%)
O
O2N
O
O2N
O2N
4f
(31%)
4e
(26%)
4g
(50%)
Scheme 6. Scope with different enol-acetates.
Two-step Protocol for Photoarylations
Aiming at exploring a two-step protocol for photoarylations with TPFPP
we constructed a setup for in-situ aryl diazonium salt generation (Scheme 7,
Table 6).
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O
5
6
7
O
N2CO2CF3
NH2
NaNO2
TFA
2a
O
8
9
O2N
Flow
Photo-Flow
NO2
NO2
5
3a
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Two-step Continuous Photo-Flow Setup
0.2 mL.min-1
4 mL
PUMP 1
BPR
Solvent
mixture
250 psi
2a
5
enol-acetate (
)
p-nitroaniline ( )
TPFPP, TFA
DMF at 0 oC
O
and
O2N
3a
Blue LEDs
(28W)
0.2 mL.min-1
4 mL
PUMP 2
Solvent
mixture
NaNO2/DMF, 0oC
coiled with PFA tube (1/8 inch, 20 mL)
over a jacketed glass reactor (0 oC)
Scheme 7. End-to end protocol for photoarylations.
Table 6: Two-step protocol under continuous flow conditions.
Entry NaNO2 (mmol) acid (mmol) overall Yield 3 (%)b throughput (g/day)
1a
2a
3a
4a
5
2
2
1
2
2
2
TFA (1.3)
TFA (0.65)
TFA (0.65)
PTSA (0.5)
HBF4 (1.3)
HBF4 (1.3)
28
49
4.5
7.9
36
5.8
-
-
53
6.8
6c
43/45d
8.3/8.7
a PUMP 1 at 0.2 mL.min-1: mixture of 4 (1 mmol), 2 (15 mmol), TFA, TPFPP (0.5 mol%) and
DMF (1.3 mL). PUMP 2 at 0.2 mL.min-1: NaNO2 and DMF (3.5 mL) (overall flow at 0.4 mL.min-1)
b isolated yields
c PUMP 1 at 0.3 mL.min-1: mixture of 4 (1 mmol), 2a (15 mmol), TPFPP (0.5 mol%) and DMF
(1.3 mL). PUMP 2 at 0.3 mL.min-1: NaNO2 and DMF (3.5 mL) (overall flow at 0.6 mL.min-1)
d double checked experiment
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The use of 2 equiv of NaNO2 and TFA (1.3 equiv) for the diazotization of
4 (entry 1, Table 6) furnished the corresponding product 3a in 28% overall yield;
however, using 0.65 equiv of TFA a significant increase was observed obtaining
3a in 49% yield. Lower amounts of NaNO2 (1 equiv, entry 3, Table 6) gave 3a,
but in 36% overall yield. PTSA does not work in this two-step protocol probably
due to deactivation by protonation of TPFPP. The experiment with HBF4 (entry
5, Table 6) gave compound 3a in 53% yield and a throughput of 6.8 g/day. With
a 0.6 mL.min-1 overall flow, but maintaining the other reaction conditions,
compound 3a was obtained in 43–45% yield in double checked experiments
(8.3–8.7 g/day). In addition, we tested the process intensification of this two-
step protocol, carrying out a long-running experiment for 8h in a continuous
steady state mode, obtaining compound 3a in 48% yield (3.03 g, 16.9 mmol).
This last result was obtained using the same reaction conditions of entry 6
(Table 6), and shows an easy process intensification of the protocol with the
same efficiency of the standard protocol.
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In summary, we have found that the two-step protocol is efficient
considering that the overall 45% yield means almost 70% for each step.
Photophysical and Electrochemical Measurements and Mechanistic
Insights
We then evaluated the photophysical and excited state electrochemical
aspects of this protocol to rationalize the SET process of porphyrins in
photoarylations. The results obtained with TPFPP were better than the
photocatalyzed experiments with TPP, and no clear explanation is reported in
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the literature. Therefore, why does a very electron deficient SET photocatalyst
(TPFPP, with 20 fluorine atoms) work better than the corresponding neutral
porphyrin (TPP)? It is important to highlight that a similar effect was previously
observed by Gryko and co-workers22 in photoarylations of heterocycles, but no
clear rationalization was provided.
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First, we measured the photophysical and electrochemical properties of
TPP, TPFPP and 1a in order the estimate the thermodynamics of the SET
processes (for the electrochemical and photoelectrochemical measurements
and details, see the supporting information).


The Eox*[TPP+ /TPP*] and Eox*[TPFPP+ /TPFPP*] and Ered of 1a were
15,34
determined according to literature protocols.
As shown in Scheme 8 the
triplet Eox* determined for TPP is -0.35V against +0.13V for TPFPP. However,
considering the Ered of 1a (+0.58V), both photocatalysts can efficiently reduce
1a and yield the corresponding aryl radical, with GSET -21.4 and -10.4 kcal.mol-
1, respectively. If only the Gibbs energy of the radical generation (GSET) is
considered, no explanation for the better efficiency of TPFPP can be found.
However, considering all the photocatalytic cycle we found a significantly more

favored turnover of TPFPP+ to TPFPP, since its steady state oxidation potential
(+1.77V) is 0.52V higher than for TPP (1.25V), thus justifying the improved
photocatalytic efficiency of TPFPP. Summing up, both TPP and TPFPP can
efficiently generate aryl radicals from aryldiazonium salts, but TPFPP is the best
since its turnover is more efficient.
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Eox*[TPP /TPP*] = -0.35 V
Eox*[TPFPP /TPFPP*] = +0.13 V
5
6
7
8
Ered = 0.58 V
N2BF4
Ered = 0.58 V
Visible Light
1TPP*
Visible Light
1TPFPP*
N2BF4
3TPP*
TPP
3TPFPP*
TPFPP
Most
Favored
Porphyrin
Turnover
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NO2
R
R
NO2
Turnover
G
SET= -21.4 kcal.mol-1

G
SET= -10.4 kcal.mol-1

TPP
N2
TPFPP
N2
R
R
E (TPP /TPP) = +1.25 V
E (TPFPP /TPFPP) = +1.77 V
BF4
+
BF4
+
NO2
NO2
Scheme 8. Proposed photocatalytic cycle with experimental photo and
electrochemical measurements.
The mechanistic proposal (Scheme 9) is very similar to the previously
described by Köning31 which used different photocatalysts. Essentially, the
photocatalytic cycle starts with the blue light exciting of TPFPP from the steady
state (PS) to the singlet state (1PS*) with a free decay to the triplet sate (3PS*),
which presents an adequate Eox* and longer lifetime as well. As demonstrated
by our photo-electrochemical measurements (Scheme 8) in the triplet state,
TPFPP is able to reduce the diazonium salt 1a, thus generating the aryl radicals
A which are trapped by 2a to yield B. The intermediate B can be promptly
oxidized giving the cation C and, subsequently, 3a. Aiming to add more support
to our mechanistic proposal we performed an experiment in the presence of
1eqv of TEMPO and detected the coupled product 6 by GC-MS (supporting
Information).
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O2N
O
6
7
8
3a
9
residual
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water
Visible Light
N2BF4
1PS*
OAc
N2BF4
3PS*
PS
C
NO2
1a
NO2
1a
PS
N2
OAc
N2
+
B
BF4
+
OAc
NO2
A
NO2
2a
A
O
N
PS = porphyrin
O2N
6
Scheme 9. Mechanistic Proposal
CONCLUSIONS
A protocol for the synthesis of -aryl-ketones/aldehyde by photoarylation with
diazonium salts is described using two different porphyrins (TPP and TPFPP)
as SET photocatalysts. Batch and continuous flow optimized conditions are
presented with significant yields (up to 92%), including a multigram scale
experiment (3.03 g) performed under continuous flow conditions. The scope
containing different diazonium salts and different enol-acetates is demonstrated,
with a two-step protocol for the continuous photoarylations. Finally,
photophysical and electrochemical studies provides a plausible rationalization
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for the better TPFPP efficiency as photocatalyst, and radical trapping
5
6
experiments gave us some mechanistic insights on the photocatalytic cycle.
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EXPERIMENTAL SECTION
Generalities: The starting materials were purchased from Sigma-Aldrich and
used without any purification, and the solvents were used after distillation. Thin-
layer chromatography (TLC) in silica gel 60 with F254 (0.25 mm) was used to
identify product formation, and the purification of products was carried out by
1
column chromatography (silica gel, pore size 60 Å, 230 – 400 mesh). H NMR
and 13C NMR spectra were acquired with a Bruker Avance 400 spectrometer,
operating at 400.15 and 100.62 MHz, respectively, using CDCl3, acetone-d6 or
dimethylsufoxide-d6 as solvents and tetramethylsilane as internal reference.
Chemical shifts are reported in δ (ppm) relative to tetramethylsilane and the
coupling constants (J) in Hertz (Hz). The multiplicities were assigned as: singlet
(s), doublet (d), triplet (t), quadruplet (q), double doublet (dd), double triplet (dt),
triple doublet (td) and multiplet (m). The continuous flow reactors are home-
made and a KNAUER HPLC pump (AZURA P 4.1S) used for pumping the
solutions. A Chiller RTE 101 (NESLAB) with a water / ethylene glycol mixture,
operating at 0 °C was used in the jacketed reactions, and a back-pressure
regulator (250 psi) connected at the end of the systems. The irradiation was
conducted with 28W blue and white LEDs.
Experimental Procedures
Aryldiazonium tetrafluoroborate salts were prepared according to the
literature.23
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4-nitrobenzenediazonium tetrafluoroborate (1a).31 Obtained as a light-yellow
5
6
1
solid in 86% yield (8.6 mmol, 2.04 g). H NMR (400 MHz, DMSO-d6): H 8.72
7
8
9
(d, J = 9.0 Hz, 2H), 8.94 (d, J = 9.0 Hz, 2H). 13C {1H} NMR (100 MHz, DMSO-
d6): C 121.8, 126.0, 134.4, 153.2.
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2-nitrobenzenediazonium tetrafluoroborate (1b).31 Obtained as a white solid
1
in 87% yield (8.7 mmol, 2.06 g). H NMR (400 MHz, DMSO-d6): H 8.41 (t, J =
8.0 Hz, 1H), 8.53 (t, J = 8.0 Hz, 1H), 8.79 (d, J = 8.0 Hz, 1H), 9.11 (d, J = 8.0
13
Hz, 1H). C {1H} NMR (100 MHz, DMSO-d6): C 111.1, 128.0, 136.5, 142.2,
144.5.
3-nitrobenzenediazonium tetrafluoroborate (1c).31 Obtained as a white solid
1
in 43% yield (4.3 mmol,1.02 g). H NMR (400 MHz, DMSO-d6): H 8.24 (t, J =
13
8.3 Hz, 1H), 8.98 – 9.04 (m, 2H), 9.62 (t, J = 2.0 Hz, 1H). C {1H} NMR (100
MHz, DMSO-d6): C 118.2, 128.1, 132.7, 135.0, 137.9, 147.6.
Benzenediazonium tetrafluoroborate (1d).23a Obtained as a white solid in
70% yield (7.0 mmol, 1.34 g). 1H NMR (400 MHz, DMSO-d6): H 7.98 (t, J = 8.0
13
Hz, 2H), 8.26 (t, J = 8.0 Hz, 2H), 8.66 (t, J = 8.0 Hz, 1H). C {1H} NMR (100
MHz, DMSO-d6): C 116.0, 131.2, 132.6, 140.8.
4-fluorobenzenediazonium tetrafluoroborate (1e).23a Obtained as a white
1
solid in 79% yield (7.9 mmol,1.66 g). H NMR (400 MHz, DMSO-d6): H 7.85 –
7.91 (m, 2H), 8.91 – 8.96 (m, 2H). 13C {1H} NMR (100 MHz, DMSO-d6): C
112.2, 120.6 (d, J = 25.6 Hz), 138.0 (d, J = 12.8 Hz), 170.5 (d, J = 268.8 Hz).
2-fluorobenzenediazonium tetrafluoroborate (1f).35 Obtained as a white solid
1
in 80% yield (8.0 mmol,1.68 g). H NMR (400 MHz, DMSO-d6): H 7.82 (t, J =
8.0 Hz, 1H), 8.01 (t, J = 8.0 Hz, 1H), 8.35 – 8.41 (m, 1H), 8.71 – 8.7 (m, 1H).
13C {1H} NMR (100 MHz, DMSO-d6): C 105.5 (d, J = 12.80 Hz), 118.6 (d, J =
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15.0 Hz), 127.4 (d, J = 2.2 Hz), 133.4 (d, J = 3.7 Hz), 144.6 (d, J = 9.0 Hz),
160.2 (d, J = 273.3 Hz).
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8
9
3-fluorobenzenediazonium tetrafluoroborate (1g).36 Obtained as a white
solid in 82% yield (8.2 mmol,1.72 g). 1H NMR (400 MHz, (CD3)2CO-d6): H 8.15
– 8.20 (m, 1H), 8.22 – 8.27 (m, 1H), 8.70 – 8.73 (m, 1H), 8.75 – 8.78 (m, 1H).
13C {1H} NMR (100 MHz, (CD3)2CO-d6): C 117.8 (d, J = 12.0 Hz); 120.5 (d, J =
30.1 Hz), 130.6 (d, J = 21.0 Hz), 130.8 (d, J = 3.7 Hz), 134.8 (d, J = 9.0 Hz),
162.2 (d, J = 253.7 Hz).
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4-chlorobenzenediazonium tetrafluoroborate (1h).23a Obtained as a white
solid in 75% yield (7.5 mmol,1.70 g).1H NMR (400 MHz, (CD3)2CO-d6): H 8.14
– (d, J = 9.0 Hz, 2H), 8.84 (d, J = 9.0 Hz, 2H). 13C {1H} NMR (100 MHz,
(CD3)2CO-d6): C 115.0, 132.9, 135.4, 149.0.
2-trifluoromethylbenzenediazonium tetrafluoroborate (1i).31 Obtained as a
white solid in 86% yield (8.6 mmol, 2.23 g).1H NMR (400 MHz, (CD3)2CO-d6):
H 8.46 (t, J = 8.0 Hz, 1H), 8.55 (d, J = 8.0 Hz, 1H), 8.68 (t, J = 8.0 Hz, 1H), 9.21
(d, J = 8.0 Hz, 1H). 13C {1H} NMR (100 MHz, (CD3)2CO-d6): C 113.8, 122.0 (d,
J = 274.0 Hz), 130.7 (d, J = 36.1 Hz), 131.6 (d, J = 3.0 Hz); 136.5, 137.2; 143.4.
3-trifluoromethylbenzenediazonium tetrafluoroborate (1j).23a Obtained as a
1
white solid in 83% yield (8.3 mmol, 2.16 g). H NMR (400 MHz, DMSO-d6): H
8.24 (t, J = 8.0 Hz, 1H), 8.68 (d, J = 8.0 Hz, 1H), 8.97 (d, J = 8.0 Hz, 1H), 9.22
(s, 1H). 13C {1H} NMR (100 MHz, DMSO-d6): C 118.3, 122.0 (d, J = 273.3 Hz),
130.1 (d, J = 3.7 Hz), 130.1 (d, J = 34.6 Hz), 132.7, 136.5, 137.2 (d, J = 3.0 Hz).
4-ethylbenzenediazonium tetrafluoroborate (1k).37 Obtained as a white solid
in 78% yield (7.8 mmol,1.71 g).1H NMR (400 MHz, DMSO-d6): H 1.25 (t, J =
7.0 Hz, 3H), 2.83 – 2.90 (m, 2H), 7.85 (d, J = 8.0 Hz, 2H), 8.58 (d, J = 8.0 Hz,
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2H). C {1H} NMR (100 MHz, DMSO-d6): C 14.4, 29.0, 112.1, 130.7 132.8,
5
6
159.3.
7
8
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4-methoxybenzenediazonium tetrafluoroborate (1l).31 Obtained as a grey
solid in 85% yield (8.5 mmol,1.88 g). 1H NMR (400 MHz, DMSO-d6): H 4.04 (s,
3H), 7.48 (d, J = 9.4 Hz, 2H), 8.60 (d, J = 9.4 Hz, 2H). 13C {1H} NMR (100 MHz,
DMSO-d6): C 57.4, 103.2, 117.2, 136.0, 168.8.
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2-methoxybenzenediazonium tetrafluoroborate (1m).38 Obtained as a light
orange solid in 74% yield (7.4 mmol,1.64 g).1H NMR (400 MHz, DMSO-d6): H
4.19 (s, 3H), 7.43 – 7.57 (m, 1H), 7.68 (d, J = 8.4 Hz, 1H), 8.21 – 8.25 (m, 1H),
8.51 (dd, J = 8.4 and 1.6 Hz, 1H). 13C {1H} NMR (100 MHz, DMSO-d6): C 58.6,
102.2, 114.8, 122.8, 132.3, 143.7, 162.0.
3-methoxybenzenediazonium tetrafluoroborate (1n).23a Obtained as a white
solid in 78% yield (7.8 mmol,1.73 g). 1H NMR (400 MHz, (CD3)2CO-d6): H 4.02
(s, 3H), 7.90 – 7.93 (m, 1H), 7.98 (m, 1H), 8.37 (t, J = 2.3 Hz, 1H), 8.44 – 8.47
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(m, 1H). C {1H} NMR (100 MHz, (CD3)2CO-d6): C 57.3, 116.3, 117.0, 126.6,
130.0, 133.4, 161.5.
4-(dimethylamino)benzenediazonium tetrafluoroborate (1o).39 Obtained as
a white solid in 70% yield (7.0 mmol,1.64 g). 1H NMR (400 MHz, DMSO-d6): H
3.26 (s, 6H), 7.06 (d, J = 9.8 Hz, 2H), 8.21 (d, J = 9.8 Hz, 2H). 13C {1H} NMR
(100 MHz, DMSO-d6): C 40.4, 88.9, 113.8, 134.0, 156.1.
3,4-(Methylenedioxy) benzenediazonium tetrafluoroborate (1p).38 Obtained
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as a solid in 45% yield (4.5 mmol,1.06 g). H NMR (400 MHz, DMSO-d6): H
6.45 (s, 2H), 7.48 (d, J = 8.7 Hz, 1H), 8.04 (d, J = 2.1 Hz, 1H), 8.04 (dd, J = 8.7
and 2.1 Hz, 1H). 13C {1H} NMR (100 MHz, DMSO-d6): C 104.4, 105.5, 109.4,
110.6, 134.1, 148.4, 158.8.
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General procedure for the preparation of non-commercial enol-acetates.40
To a flask containing PTSA (0.5 g), a mixture of the ketones (1.0 equiv.,160
mmol), and isopropenyl acetate (1.8 equiv, 288 mmol) was added and
subsequently heated at 100 °C. After 24 hours, the reaction mixture was diluted
in ethyl acetate (30 mL) and washed with water (3 x 50 mL) and saturated
NaHCO3 solution (50 mL). The organic layer was separated and dried with
Na2SO4, filtered and concentrated under reduced pressure. AII products were
purified by column chromatography using toluene/ethyl acetate (9.8:0.2) as
eluent.
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1-phenylvinyl acetate (2c).40 Obtained in 50% yield (23.5 g, 144.9 mmol). H
NMR (400 MHz, (CD3)2CO-d6): H 2.28 (s, 3H), 5.03 (d, J = 2.3 Hz, 1H), 5.61
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(d, J = 2.3 Hz, 1H), 7.61 – 7.41 (m, 2H), 7.58 – 7.58 (m, 2H). C {1H} NMR
(100 MHz, (CD3)2CO-d6): C 20.9, 102.5, 125.7, 129.4, 129.7, 135.4, 154.0,
169.3.
1-cycloheptenyl acetate (2d).41 Obtained in 60% yield (26.6 g, 172.6 mmol).
1H NMR (400 MHz, CDCl3): H 1.58 – 1.72 (m, 6H), 2.07 – 2.10 (m, 5H), 2.29 –
2.32 (m, 2H), 5.45 (t, J = 6.45 Hz, 1H). 13C {1H} NMR (100 MHz, CDCl3): C
20.9, 25.2, 25.2, 26.9, 30.9, 33.0, 117.9, 153.1, 169.7.
1-cyclohexenyl acetate (2e).40 Obtained in 80% yield (32.3 g, 230.4 mmol). 1H
NMR (400 MHz, CDCl3): H 1.58 – 1.61 (m, 2H), 1.72 – 1.75 (m, 2H), 2.09 –
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2.13 (m, 7H), 5.34 – 5.36 (m, 1H). C {1H} NMR (100 MHz, CDCl3): C 21.0,
21.6, 22.5, 23.5, 26.7, 113.9, 148.3, 169.4.
1-cyclopentenyl acetate (2f).42 Obtained in 65% yield (23.6 g, 187.2 mmol).1H
NMR (400 MHz, DMSO-d6): H 1.84 – 1.88 (m, 2H), 2.09 (s, 3H), 2.26 – 2.28
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(m, 2H), 2.35 – 2.37(m, 2H), 5.34 – 5.37 (m, 1H). 13C {1H} NMR (100 MHz,
DMSO-d6): C 20.9, 20.9, 28.4, 30.9, 112.7, 151.1, 168.4.
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2-pentenyl acetate (2g).40 Obtained in 72% yield (26.5 g, 206.7 mmol). Mixture
E/Z. 1H NMR (400 MHz, DMSO-d6): H 0.91–0.96 (m, 3H), 1.39 – 1.41 (m, 2H),
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1.57–1.59 (m, 1H), 2.06–2.23 (m, 5H), 5.01– 5.07 (m, 1H). C {1H} NMR (100
MHz, DMSO-d6): C 10.6, 11.2, 11.3, 11.4, 20.6, 20.8, 21.8, 26.4, 109.2, 111.2,
150.4, 150.5, 168.3, 169.4.
General procedure for enol-acetate photoarylation in batch.
TPFPP (4.87 mg, 0.5 mol%, 0.005 mmol) and DMF (1 mL) were added to a
screwcap glass tube (15 mL). Nitromethane (5.0 mL), enol acetate (15 equiv,
1.65 mL) and 4-nitrobenzenediazonium tetrafluoroborate (1 equiv, 236.0 mg)
were added and the tube closed with a rubber septum, fully protected from light
and degassed for five minutes under argon and with ultrasound. The reaction
mixture was stirred for 2 hours at 0 °C (freezer) with irradiation by the blue
LEDs. The workup was performed with water (20 mL) and extracted with
toluene (3 x 30 mL). The organic layer was dried over Na2SO4, filtered and
concentered under reduced pressure. The reaction was purified by column
chromatography using hexane:ethyl acetate (9:1) as eluent.
General procedure for enol-acetate photoarylation under continuous flow
conditions. TPFPP (4.87 mg, 0.5 mol%, 0.005 mmol) and DMF (1 mL) were
added to a glass tube (15 mL). Nitromethane (5.0 mL), enol acetate (15 equiv,
1.65 mL) and 4-nitrobenzenediazonium tetrafluoroborate (1 equiv, 236.0 mg)
were added and the tube closed with a rubber septum, fully protected from light
and degassed for five minutes under argon and with ultrasound. The reaction
mixture was transferred to a PFA loop (9.0 mL), cooled at 0 °C and pumped
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(0.4 mL.min-1) through the blue LED reactor (20 mL total volume), also
maintained at 0oC using a cooled jacketed glass reactor. The solvent mixture
5:1 nitromethane/dimethylformamide was used for pumping the reaction
mixture. All products were purified on silica gel using a hexane/ethyl acetate
solvent gradient (from 9.5:0.5 to 9.0:1.0).
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1-(4-nitrophenyl)propan-2-one (3a).31 Obtained as a yellow oil in 88% yield
(0.88 mmol, 156 mg) 1H NMR (400 MHz, CDCl3): H 2.25 (s, 3H), 3.87 ( s, 2H),
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7.37 (d, J = 9.0 Hz, 2H), 8.19 (d, J = 9.0 Hz, 2H). C {1H} NMR (100 MHz,
CDCl3): C 29.8, 49.8, 123.6, 130.5, 141.7, 146.9, 204.3.
1-(2-nitrophenyl)propan-2-one (3b).31 Obtained as a yellow oil in 74% yield
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(0.74 mmol, 132.5 mg). H NMR (400 MHz, CDCl3): H 2.30 (s, 3H), 4.12 ( s,
2H), 7.27 (dd, J = 8.0 and 1.0 Hz,1H), 7.44 (td, J = 8.0 and 1.3 Hz, 1H), 7.58
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(td, J = 8.0 and 1.0 Hz, 1H), 8.09 (dd, J = 8.0 and 1.3 Hz, 1H). C {1H} NMR
(100 MHz, CDCl3): C 30.0, 48.6, 125.2, 128.4, 130.4, 133.6, 133.7, 148.6,
203.7.
1-(3-nitrophenyl)propan-2-one (3c).31 Obtained as a yellow oil in 70% yield
(0.70 mmol, 125 mg). 1H NMR (400 MHz, CDCl3): H 2.26 (s, 3H), 3.88 (s, 2H),
7.50 – 7.55 (m, 2H), 8.06 (s, 1H), 8.12 – 8.15 (m, 1H). 13C {1H} NMR (100 MHz,
CDCl3): C 29.9, 49.6, 122.1, 124.5, 129.5, 135.9, 136.0, 148.3, 204.5.
1-phenylpropan-2-one (3d).43 Obtained as a yellow oil in 30% yield (0.30
mmol, 40.2 mg). 1H NMR (400 MHz, CDCl3): H 2.07 (s, 3H), 3.61 (s, 2H), 7.14
– 7.12 (m, 2H), 7.17 – 7.21 (m, 1H), 7.24 – 7.28 (m, 2H). 13C {1H} NMR (100
MHz, CDCl3): C 29.3, 51.0, 127.1, 128.8, 129.4, 134.2, 206.4.
1-(4-fluorophenyl)propan-2-one (3e).44 Obtained as a yellow oil in 47% yield
(0.47 mmol, 71.4 mg). 1H NMR (400 MHz, CDCl3): H 2.08 (s, 3H), 3.60 (s, 2H),
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6.94 (t, J = 8.3 Hz, 2H), 7.06 – 7.10 (m, 2H). 13C {1H} NMR (100 MHz, CDCl3):
C 29.3, 49.9, 115.6 (d, J = 21.8 Hz), 129.9 (d, J = 2.3 Hz), 131.0 (d, J = 8.0
Hz), 161.8 (d, J = 245.4 Hz), 206.0.
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1-(2-fluorophenyl)propan-2-one (3f).45 Obtained as a yellow oil in 43% yield
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(0.43 mmol, 65.4 mg). H NMR (400 MHz, CDCl3): H 2.13 (d, J = 0.3 Hz, 3H),
3.67 ( s, 2H), 6.97 – 7.00 ( m, 1H), 7.03 (td, J = 7.5 and 2.0 Hz, 1H), 7.10 (td, J
= 7.5 and 2.0 Hz, 1H), 7.16 – 7.22 (m, 1H). 13C {1H} NMR (100 MHz, CDCl3): C
29.4, 43.9, 115.4 (d, J = 21.8 Hz), 121.6 (d, J = 16.6 Hz), 124.2 (d, J = 3.0 Hz),
129.0 (d, J = 8.3 Hz), 131.6 (d, J = 4.5 Hz), 161.0 (d, J = 245.4 Hz), 205.0.
1-(3-fluorophenyl)propan-2-one (3g).46 Obtained as a yellow oil in 54% yield
(0.54 mmol, 82.1 mg). 1H NMR (400 MHz, CDCl3): H 2.09 (s, 3H), 3.62 (s, 2H),
6.82 – 6.90 (m, 2H), 7.21 (m, Hz, 1H). 13C {1H} NMR (100 MHz, CDCl3): C
29.41, 50.39, 113.95 (d, J = 20.3 Hz), 116.40 (d, J = 21.8 Hz), 125.15 (d, J =
3.0 Hz), 130.2 (d, J = 8.3 Hz), 136.5 (d, J = 7.0 Hz), 163.0 (d, J = 246.2 Hz),
205.5.
1-(4-chlorophenyl)propan-2-one (3h).31 Obtained as a yellow oil in 76% yield
(0.76 mmol, 128 mg). 1H NMR (400 MHz, CDCl3): H 2.16 (s, 3H), 3.67 (s, 2H),
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7.12(d, J= 8.2 Hz, 2H), 7.29 (d, J= 8.2 Hz, 2H). C {1H} NMR (100 MHz,
CDCl3): C 29.4, 50.0, 128.8, 130.8, 132.6, 133.0, 205.7.
1-(2-(trifluoromethyl)phenyl)propan-2-one (3i).31 Obtained as a yellow oil in
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57% yield (0.57 mmol, 115 mg). H NMR (400 MHz, CDCl3): H 2.21 (s, 3H),
3.92 (s, 2H), 7.28 (d, J = 7.8 Hz, 1H), 7.39 (t, J = 7.8 Hz, 1H), 7.53 (t, J = 7.8
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Hz, 1H), 7.67 (d, J = 7.8 Hz, 1H). C {1H} NMR (100 MHz, CDCl3): C 29.6,
47.4, 124.5 (d, J = 273.3 Hz), 126.2 (d, J = 5.3 Hz), 127.3, 131.9, 132.7, 132.8,
204.7.
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1-(3-(trifluoromethyl)phenyl)propan-2-one (3j).44 Obtained as a yellow oil in
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67% yield (0.67 mmol, 135 mg). H NMR (400 MHz, CDCl3): H 2.20 (s, 3H),
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3.78 (s, 2H), 7.38 (m, 1H), 7.45 (m, 2 H), 7.53 (m, 1H). 13C {1H} NMR (100
MHz, CDCl3): C 29.6, 50.2, 123.9 (d, J = 20.3 Hz), 124.3 (d, J = 21.8 Hz), 126.2
(d, J = 3.0 Hz), 129.1, 130.9 (d, J = 7.0 Hz), 133.0, 135.0 (d, J = 246.2 Hz);
205.2.
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1-(4-ethylphenyl)propan-2-one (3k).47 Obtained as a yellow oil in 43% yield
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(0.43 mmol, 69.7 mg). H NMR (400 MHz, CDCl3): H 1.22 (t, J = 7.7 Hz, 3H),
2.13 (s, 3H), 2.63 (q, J = 7.7 Hz, 2H), 3.65 ( s, 2H), 7.11(d, J = 8.2 Hz, 2H), 7.16
(d, J = 8.2 Hz, 2H). 13C {1H} NMR (100 MHz, CDCl3): C 15.6, 28.5, 29.2, 50.7,
128.3, 129.4, 131.4, 143.0, 206.8.
1-(4-methoxyphenyl)propan-2-one (3l).31 Obtained as a yellow oil in 48%
yield (0.48 mmol, 78.7 mg). 1H NMR (400 MHz, CDCl3): H 2.06 (s, 3H), 3.56 (s,
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2H), 3.72 (s, 3H), 6.80 (d, J = 9.0 Hz, 2H), 7.04 (d, J = 9.0 Hz, 2H). C {1H}
NMR (100 MHz, CDCl3): C 29.1, 50.1, 55.3, 114.2, 126.3, 130.4, 158.7, 206.9.
1-(2-methoxyphenyl)propan-2-one (3m).48 Obtained as a yellow oil in 40%
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yield (0.40 mmol, 65.6 mg). H NMR (400 MHz, CDCl3): H 2.05 (s, 3H), 3.58 (
s, 2H), 3.72 ( s, 2H), 6.79 (d, J = 8.0 Hz, 1H), 6.84 (td, J = 8.0 and 1.2 Hz, 1H),
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7.04 (dd, J = 8.0 and 1.2 Hz, 1H), 7.17 (td, J = 8.0 and 1.2 Hz, 1H). C {1H}
NMR (100 MHz, CDCl3): C 29.3, 45.6, 55.3, 110.5, 120.7, 123.6, 128.6, 131.1,
157.4, 207.1.
1-(3-methoxyphenyl)propan-2-one (3n).44 Obtained as a yellow oil in 33%
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yield (0.33 mmol, 54.1 mg). H NMR (400 MHz, CDCl3): H 2.08 (s, 3H), 3.59 (
s, 2H), 3.73 (s, 3H), 6.67 – 6.68 (m, 1H), 6.71–6.76 ( m, 2H), 7.16–7.20 (m, 1H).
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