Visible-light-induced Beckmann rearrangement by organic photoredox catalysis

Article abstract of DOI:10.1021/acs.orglett.0c02168

A facile and general strategy for efficient direct conversion of oximes to amides using an inexpensive organic photocatalyst and visible light is described. This radical Beckmann rearrangement can be performed under mild conditions. Various alkyl aryl ketoximes and diaryl ketoximes can be effectively converted into the corresponding amides in excellent yields.

Full text of DOI:10.1021/acs.orglett.0c02168

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Letter
Visible-Light-Induced Beckmann Rearrangement by Organic
Photoredox Catalysis
Li Tang, Zhi-Lv Wang, Hai-Lan Wan, Yan-Hong He,* and Zhi Guan*
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sı Supporting Information
ABSTRACT: A facile and general strategy for efficient direct conversion of oximes to amides using an inexpensive organic
photocatalyst and visible light is described. This radical Beckmann rearrangement can be performed under mild conditions. Various
alkyl aryl ketoximes and diaryl ketoximes can be effectively converted into the corresponding amides in excellent yields.
mides are one of the most important structural motifs in
necessary to develop more mild methods for this useful
reaction.
A
organic chemistry and are widely found in natural and
1
synthetic compounds. An efficient method for synthesizing
The first photochemical Beckmann rearrangement was
1
9
amides from oximes is known as the Beckmann rearrange-
observed by De Mayo and co-workers in 1963. In 2010,
Roth discussed the light-driven Beckmann rearrangement in a
2
ment. Conventional acid-catalyzed Beckmann rearrangement
20
begins with the protonation of the hydroxyl group to form a
better leaving group. The substituent at the trans position of
the leaving group then migrates to the nitrogen, resulting in a
carbocation and releasing one molecule of water. The water
then attacks the carbocation and eventually forms the amide
review (Scheme 1, a). These photochemical Beckmann
Scheme 1. Photochemistry of Beckmann Rearrangement
3
product. In order to achieve this conversion, an excess of
strong acids, dehydrating media, and elevated temperatures are
4
typically required. Unfortunately, these harsh conditions are
often incompatible with sensitive functional groups and cause
corrosion of equipment in the industry. Based on this
consideration, improvements upon the original procedures of
Beckmann rearrangement have primarily concentrated on
modified conditions to minimize side reactions.
In the past two decades, some efforts have been made to
catalyze Beckmann rearrangement using various reagents, such
5
as cyanuric chloride, bis(2-oxo-3-oxazolidinyl)phosphinic
6
chloride (BOP-Cl)/ZnCl , p-toluenesulfonyl chloride
2
7
8
9
(
TsCl)/ZnCl2, bromodimethylsulfonium/ZnCl2, HgCl2,
triphosphazene, 1,3,5-triazo-2,4,6-triphosphorine 2,2,4,4,6,6-
1
0
11
12
chloride (TAPC), cyclopropenium, propylphosphonic,
1
3
14
Received: July 10, 2020
I /PPh ,
(
FeCl /AgSbF ,
dichloroimidazolidinedione
2
3
3
6
1
5
16
17
DCID), N-methyl-imidazolium, 1 Ca(NTf ) /nBu NPF ,
2
2
4
6
8
and boronic acid/perfluoropinacol. However, most of these
methods still involve toxic, corrosive, or irritating agents, some
of which require high temperature conditions. Given the
importance of the Beckmann rearrangement reaction, it is still
©
XXXX American Chemical Society
https://dx.doi.org/10.1021/acs.orglett.0c02168
A
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Letter
rearrangements were all conducted under ultraviolet (UV)
light, which is not suitable for compounds that are sensitive to
photodegradation under UV irradiation. In addition, the yields
of the amides obtained by these methods are low. Visible light
is more readily available than UV and has advantages in the
synthesis of compounds that are unstable under UV
irradiation. Because of these characteristics, visible-light has
were used instead of HFIP, no desired product was detected
(Table 1, entries 3 and 4). These results indicated that HFIP is
essential for this photoredox-catalyzed Beckmann rearrange-
ment, which may be due to its strong hydrogen-bonding
24
ability. We then tried mixed solvents of acetonitrile or
CH Cl with HFIP (Table 1, entries 5 and 6) and found that
2
2
product 2a could be obtained with 83% yield in CH Cl /HFIP
2
2
21
wider applicability than UV in organic synthesis. In organic
photoredox catalysis, organic dyes can convert visible light into
chemical energy by single electron transfer with substrates
(1:1) (Table 1, entry 6). This result suggested that HFIP along
with nonpolar solvents can achieve higher yields. Encouraged
by this result, a mixed solvent of dichloroethane (DCE)/HFIP
(1:1) was tested, which gave a good yield of 89% (Table 1,
entry 7). Next, some photocatalysts were screened (Table 1,
entries 7−11). Both 9-mesityl-3,6-ditert-butyl-10-phenylacridi-
nium tetrafluoroborate (PC-2) and 10-methyl-9-phenylacridi-
nium perchlorate (PC-3) gave product in excellent yields
(Table 1, entries 8 and 9). Since PC-3 is much cheaper than
PC-2, PC-3 was chosen as the photocatalyst for the visible-
light induced Beckmann rearrangement. In addition, the
reaction proceeded well under argon (Table 1, entry 12),
proving that the reaction is redox-neutral. As expected, no
desired product was detected in the absence of photocatalyst
22
under very mild conditions, thereby activating substrates.
Yadav reported a Beckmann rearrangement executed by the
Vilsmeier−Haack reagent, which is produced in situ by visible-
light-driven reaction of carbon tetrabromide with N,N-
23
dimethylformamide (DMF) (Scheme 1, b). This indirect
photocatalytic reaction requires an excessive amount of highly
toxic and irritating carbon tetrabromide. Herein, we report a
direct photoredox-catalyzed radical Beckmann rearrangement
using a commercially available inexpensive organic dye, 10-
+
methyl-9-phenylacridinium (Ph-Acr-Me ) perchlorate, as a
photocatalyst (Scheme 1, c). By this reaction, various oximes
can be efficiently converted into amides by visible-light
irradiation under ambient and neutral conditions.
(
Table 1, entry 13) or light source (Table 1, entry 14).
With the optimized conditions (Table 1, entry 9) in hand,
We began our studies by irradiating the solution of
acetophenone oxime 1a and 2.0 mol % 9-mesityl-10-
methylacridinium perchlorate (PC-1) in 1,1,1,3,3,3-hexa-
fluoro-2-propanol (HFIP) by using 9 W blue light-emitting
diodes (LEDs). The product N-phenylacetamide 2a was
afforded in 76% isolated yield after 5 h (Table 1, entry 1).
Replacing HFIP with CF CH OH only provided the product
the substrate scope was evaluated for the visible-light induced
Beckmann rearrangement (Scheme 2). The methyl substituted
acetophenone oximes were treated under standard conditions
to give corresponding amides 2b−2d. The o-methyl-
substituted acetophenone oxime gave a much lower yield
than the m- and p-methyl-substituted acetophenone oximes,
3
2
a
in 19% yield (Table 1, entry 2). When other commonly used
solvents, such as acetonitrile and dichloromethane (CH Cl ),
Scheme 2. Scope of Oximes
2
2
a
Table 1. Reaction Optimization
b
entry
photocatalyst
solvent
yield (%)
1
2
3
4
5
6
7
8
9
PC-1
PC-1
PC-1
PC-1
PC-1
PC-1
PC-1
PC-2
PC-3
PC-4
PC-5
PC-3
HFIP
CF CH OH
76
19
nd
nd
27
83
89
91
91
40
80
91
nd
nd
3
2
CH CN
3
CH Cl
2
2
CH CN/HFIP = 1:1
3
CH Cl /HFIP = 1:1
2
2
DCE/HFIP = 1:1
DCE/HFIP = 1:1
DCE/HFIP = 1:1
DCE/HFIP = 1:1
DCE/HFIP = 1:1
DCE/HFIP = 1:1
DCE/HFIP = 1:1
DCE/HFIP = 1:1
10
11
12
13
14
c
d
e
PC-3
a
a
Reaction conditions: 1a (0.5 mmol) and photocatalyst (2 mol %) in
solvent (5.0 mL) was irradiated with 9 W blue LEDs at rt for 5 h.
Reaction conditions: 1 (0.5 mmol) and PC-3 (2 mol %) in DCE/
HFIP = 1:1 (5.0 mL) were irradiated with 9 W blue LEDs at rt for 5
h; isolated yields are provided; 24 h. Oximes were prepared as a
mixture of isomers.
b
c
d
e
b
c
Isolated yield. Under argon. Without photocatalyst; Without
light; nd for not detected.
B
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pubs.acs.org/OrgLett
Letter
possibly due to steric hindrance. Then acetophenone oximes
dark experiments (Figure S4) showed that the visible light-
induced Beckmann rearrangement may involve a chain
reaction. Quantum yield measurements (the quantum yield
of 2a is 20.4) further confirmed that the photoredox Beckman
reaction involves a chain propagation. It has been reported that
certain Beckmann rearrangements proceed through the self-
with various substituents at the p-position were tested (2d−
2
p). In general, the oximes with electron-rich groups showed
better reaction efficiency (2d−2h and 2o) than those with
electron-withdrawing groups (2i and 2j), indicating that this
visible-light-induced Beckmann rearrangement is affected by
the electronic effect. There are some exceptions for electron-
rich monosubstituted acetophenone oximes which gave amides
9
,13,17
propagating pathway of nitrilium.
It is necessary to verify
whether the chain reaction pathway is a free-radical chain
propagation or a nitrilium self-propagation cycle. Therefore,
some experiments were designed to study the chain reaction
(Scheme 4). It was found that after a certain period of
2
n in low yields due to the opacity of the reaction mixture,
which affects the absorption of light by the photocatalyst. Next,
the disubstituted acetophenone oximes were treated under
standard conditions to give corresponding amides 2q−2u in
good to excellent yields. 2-Acetonaphthone oxime was
converted to amide 2v in a very good yield, while 1-
acetonaphthone oxime gave amide 2w in a low yield, possibly
due to steric effects. Heteroaromatic oximes could also be
converted to the corresponding amides (2x and 2y). In
addition to acetophenone oxime, other alkyl phenyl ketoximes
could also give the corresponding amides 2aa and 2ab in
excellent yields. The pentenyl phenyl ketoxime was compatible
with this rearrangement process to afford the amide 2ac.
Benzyl phenyl ketoximes also worked well to provide
corresponding amides (2ad and 2ae) in good yields.
Benzanilide 2af could be obtained in good yield by irradiating
Scheme 4. Investigation of Chain Reaction
benzophenone oxime. Finally, some E/Z mixtures of ketoximes
1
[
E/Z ratios were determined by HNMR, see Supporting
Information (SI)] were tested. When cyclopropyl phenyl
ketoxime 1ag (E/Z = 1.91:1.00) was treated under the
standard conditions, only 2ag was obtained as the sole amide
product. However, oximes 1ah (E/Z = 1.70:1.00) and 1ai (E/
Z = 1.56:1.00) each gave two kinds of amides, and the ratio of
the two amides was irrelevant to the E/Z ratio of the
corresponding oxime from which they were produced. The
three examples above showed that this photomediated
Beckmann rearrangement is inconsistent with the general
case of trans-migration (the substituent at the trans position of
the hydroxyl in the oxime migrates to the nitrogen).
Next, a gram-scale experiment of 1a was performed under
the standard conditions, which gave acetanilide 2a in an
excellent isolated yield (Scheme 3). This further demonstrated
that the visible-light-induced Beckmann rearrangement has
great potential in practical applications.
irradiation under standard conditions the reaction can
continue without light (Scheme 4, b), which further confirmed
that the photoinduced Beckmann rearrangement does involve
a chain reaction. However, after the addition of the radical
scavenger TEMPO (Scheme 4, c), this chain reaction was
terminated, indicating that this chain reaction is a radical chain
reaction rather than a nitrilium self-propagation.
Previous reports showed that the radical Beckmann
25
rearrangement may be through the oxaziridine intermediate.
In order to further understand the visible-light-induced
1
8
Beckmann rearrangement, O-labeling experiments were
1
8
executed (Scheme 5). When 5.0 equiv of H2 O was added
Scheme 5. 18O-Labeling Experiments
Scheme 3. Gram-Scale Reaction
UV−vis experiments showed that 1a cannot absorb visible
light, while PC-3 has obvious absorption in the wavelength
range (420−490 nm) of the 9 W blue LEDs used (Table S1
and Figure S1). These results proved that PC-3 is essential for
this reaction. Fluorescence quenching experiments revealed
that, whether or not HFIP is present, 1a can significantly
quench the fluorescence of PC-3 (Figures S2 and S3),
indicating that the reaction is initiated by the excited state of
the photocatalyst. At the same time, it also proved that HFIP is
only used as a solvent with strong hydrogenbonding ability
rather than directly quenching the photocatalyst. The light/
to the standard reaction system, the amide 2a was obtained
1
8
only in a low yield of 34%, but a small portion of O from
water was successfully introduced into the product (Scheme 5,
a). This result indicated that water is involved in the reaction
and acts as a source of oxygen for the product amide, but
excess water is detrimental to the reaction. Considering the
1
8
18
amount of H2 O used, the amount of O incorporated in the
C
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Letter
product was less than expected. We speculate that this may be
because the solvent was not absolutely dry so that the water in
the solvent participated in the reaction; the water derived from
the hydroxyl group of the oxime participated in the next round
to give 2-I which undergoes tautomerization to form amide
product 2. In this process, water from intermediate 7 can
attack intermediate 3 as a nucleophile.
In summary, we have successfully developed a novel organic
photoredox-catalyzed Beckmann rearrangement as a powerful
method for the synthesis of amides from oximes. A novel
mechanism involving a radical-chain reaction has been
proposed for this photoinduced Beckmann rearrangement.
18
reaction (this was confirmed by the following O-labeling
experiments). Then, 18O-labeled acetophenone oxime 1a was
18
treated under standard conditions to give O-labeled amide
a, but the proportion of 18O-labeled amide 2a in the product
2
18
was slightly reduced compared to the O-labeled oxime 1a in
the substrate (Scheme 5, b). Finally, when an equimolar
mixture of O-labeled acetophenone oxime 1a (M/M + 2 =
ASSOCIATED CONTENT
sı Supporting Information
■
1
8
*
5
1
2.4:100.0) and butyrophenone oxime 1ab (M/M + 2 =
00.0:0.7) was irradiated under standard conditions, amide 2a
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c02168.
(M/M + 2 = 100.0:47.0) in 90% yield and amide 2ab (M/M +
2
= 100.0:27.6) in 85% yield were obtained (Scheme 5, c). The
Experimental procedures, mechanism studies, character-
ization of new compounds and spectral data (PDF)
results indicated that the visible-light-induced Beckmann
rearrangement undergoes the leaving of the hydroxyl group
to form water, which can serve as the oxygen source of the
product amide, and that the rearrangement did not occur
through oxaziridine intermediate.
AUTHOR INFORMATION
Corresponding Authors
■
On the basis of the above experiments, a plausible
mechanism for visible-light-induced Beckmann rearrangement
was proposed (Scheme 6). Initial oxidation of ketoxime 1 by
Yan-Hong He − Key Laboratory of Applied Chemistry of
Chongqing Municipality, School of Chemistry and Chemical
Engineering, Southwest University, Chongqing 400715, China;
orcid.org/0000-0002-6405-285X; Email: heyh@
swu.edu.cn
Zhi Guan − Key Laboratory of Applied Chemistry of Chongqing
Municipality, School of Chemistry and Chemical Engineering,
Southwest University, Chongqing 400715, China; orcid.org/
Scheme 6. Plausible Mechanism
0
000-0002-0369-6141; Email: guanzhi@swu.edu.cn
Authors
Li Tang − Key Laboratory of Applied Chemistry of Chongqing
Municipality, School of Chemistry and Chemical Engineering,
Southwest University, Chongqing 400715, China
Zhi-Lv Wang − Key Laboratory of Applied Chemistry of
Chongqing Municipality, School of Chemistry and Chemical
Engineering, Southwest University, Chongqing 400715, China
Hai-Lan Wan − Key Laboratory of Applied Chemistry of
Chongqing Municipality, School of Chemistry and Chemical
Engineering, Southwest University, Chongqing 400715, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c02168
Notes
the visible-light-excited photoredox catalyst PC-3 generates the
iminoxyl radical 3. The nucleophilic attack of water on
intermediate 3 forms intermediate 4, and then deprotonation
of intermediate 4 gives N-centered radical intermediate 5.
Intermediate 5 undergoes radical 1,2-rearrangement to form
the C-centered radical intermediate 6. It is worth noting that
both R and R may migrate, and groups with higher steric
hindrance appear to be more likely to migrate. This can explain
the generation of products 2ag−2ai (Scheme 2) that did not
conform to the classical trans-migration. We speculate that the
radical 1,2-rearrangement of intermediate 5 to form
intermediate 6 is beneficial for decreasing steric crowding at
the quaternary carbon center. Since the lone pair in the 2p
orbital of N and O stabilizes the α-carbon radical, 6 is a more
stable intermediate. Intermediate 6 can be converted to
intermediate 7 by oxidizing the radical anion of the photoredox
catalyst to complete a photocatalytic cycle or by oxidizing
substrate 1 to imino radical 3 for radical chain reaction.
Intermediate 7 gains a proton and loses one molecule of water
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was financially supported by the National Natural
Science Foundation of China (Nos. 21672174 and 21977084)
and the Natural Science Foundation of Chongqing (No.
cstc2019jcyj-msxmX0297).
1
2
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