Blue light-promoted N–H insertion of amides, isatins, sulfonamides and imides into aryldiazoacetates: Synthesis of unnatural α-aryl amino acid derivatives

Article abstract of DOI:10.1016/j.tet.2020.131316

A photochemical protocol using blue light allows the N–H insertion of amides, isatins, sulfonamides and imides into aryldiazoacetates to afford the corresponding α-amino esters. This method is experimentally simple, inexpensive and tolerates numerous functional groups, thus allowing the straightforward preparation of a variety of α-aryl amino acid derivatives in good yields.

Full text of DOI:10.1016/j.tet.2020.131316

Journal Pre-proof
Blue light-promoted N–H insertion of amides, isatins, sulfonamides and imides into
aryldiazoacetates: Synthesis of unnatural α-aryl amino acid derivatives
Celso Y. Okada, Jr., Caio Y. dos Santos, Igor D. Jurberg
PII:
S0040-4020(20)30471-3
https://doi.org/10.1016/j.tet.2020.131316
TET 131316
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 7 February 2020
Revised Date: 25 May 2020
Accepted Date: 28 May 2020
Please cite this article as: Okada Jr. CY, dos Santos CY, Jurberg ID, Blue light-promoted N–H insertion
of amides, isatins, sulfonamides and imides into aryldiazoacetates: Synthesis of unnatural α-aryl amino
acid derivatives, Tetrahedron (2020), doi: https://doi.org/10.1016/j.tet.2020.131316.
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Blue light-promoted N-H insertion of amides,
isatins, sulfonamides and imides into
aryldiazoacetates: synthesis of unnatural α-
aryl amino acid derivatives
Leave this area blank for abstract info.
Celso Y. Okada Jr, Caio Y. dos Santos, Igor D. Jurberg*
Institute of Chemistry, State University of Campinas, 13083-862, SP, Brazil

1
Tetrahedron
journal homepage: www.elsevier.com
Blue light-promoted N-H insertion of amides, isatins, sulfonamides and imides into
aryldiazoacetates: synthesis of unnatural α-aryl amino acid derivatives
Celso Y. Okada Jr.,a Caio Y. dos Santosa and Igor D. Jurberga,
a Institute of Chemistry, State University of Campinas, Campinas, 13083-862, SP, Brazil
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A photochemical protocol using blue light allows the N-H insertion of amides, isatins,
sulfonamides and imides into aryldiazoacetates to afford the corresponding α-amino esters. This
method is experimentally simple, inexpensive and tolerates numerous functional groups, thus
allowing the straightforward preparation of a variety of α-aryl amino acid derivatives in good
yields.
Available online
2009 Elsevier Ltd. All rights reserved
.
This article is dedicated in respect and admiration to
Prof. Nuno Maulide, recipient of the 2020
Tetrahedron Young Investigator Award
Keywords:
Photochemistry
Visible light
Carbenes
N-H insertion
Amides
———
Corresponding author. Tel.: +55-19-3521-3065; e-mail: ijurberg@unicamp.br

2
Tetrahedron
1. Introduction
Examples
of
visible
light-mediated
photochemical
transformations involving aryldiazoacetates include the O-H
insertion of carboxylic acids, N-H insertion of amines, C-H
insertion of alkanes and arenes, cyclopropanation of styrene and
aromatic rings,13a,13b,13c synthesis of trisubstituted alkenes,13d
cyclopropenation of alkynes,13e,13f rearrangements involving
sulfur ylides,13e,13g,13h,13i ring-expansion reactions,13j N-H
insertions of carbazoles,13k,13l pyrazoles and 1,2,3-triazoles,13l Si-
H insertions13m and couplings with boronic acids.13n
Inspired by this new reactivity, we questioned whether
amides, isatins, sulfonamides and imides (which can be broadly
represented as 8) could be employed in such a photochemical
protocol, in order to produce the corresponding α-aryl amino acid
derivatives (which can be also broadly represented as 9, Scheme
1b).
1.1. Unnatural a-Amino acids
Unnatural α-amino acid derivatives are important, because
they can be used to significantly expand the chemistry of
peptides beyond the 20 canonical monomers. Each of these units
can be associated to specific features and unique roles in protein
structure and function.1 By introducing new units to proteins'
alphabet; new structures, and therefore, new functions can be
harvested. Examples of modifications that can be made include
but are not limited to the installation of metal ion chelators,
photocaged and photocross-linking moieties, new reactive
functional groups, probes (in different contexts) and
fluorophores.2
Several protocols have been described over the years for the
preparation of a variety of unnatural α-amino acids 1. A selection
of some remarkable strategies include: i) α-alkylation of glycine
surrogates 2 employing either chiral auxiliaries, templates3 or
phase transfer catalysts (PTC);4 ii) modification of the side chain
of α-amino acids 3 using various strategies,5 including halogen-
metal exchange6 and cross-coupling reactions;5b,7 iii) α-
nitrogenation of esters 4, which historically have relied on the
use of chiral auxiliaries or templates;8 iv) Strecker-based
strategies starting from aldehydes 5;9 and v) enzymatic reductive
amination
2.1 Blue Light-Promoted N-H Insertion of Amides
We started investigating the blue light-promoted N-H
insertion of 2-pyrrolidinone 10a into aryldiazoacetate 7a, aiming
at the preparation of the corresponding product 11a. At the
outset, we varied the stoichiometry of each reacting partner,
while keeping the amount of the other reagent constant (Table 1,
Entries 1-10). The change in ratios 1:y (y = 1, 2, 3, 4, 5, 10) of
7a:10a shows an accompanying increase in the yield of 11a up to
50% for the use of 5 equiv. of 10a (Table 1, Entry 5). In this
series, this represents an optimal result, as further increase of 10a
to 10 equiv. does not improve the yield of 11a, which remains as
50% (Table 1, Entry 6). On the other hand, when changing the
ratio x:1 (x = 2, 3, 4, 5) of 7a:10a, it is possible to observe also
the accompanying increase of the yield of 11a up to 54%, which
corresponds to the use of 5 equiv of 7a (Table 1, Entry 10). This
yield is slightly higher than the one obtained with the opposite
stoichiometry (Table 1, Entry 5).
However, because the aryldiazoacetate component 7a is more
valuable than the amide 10a, we decided to further explore the
optimization of this reaction using 7a as the limiting reagent,
while adding a catalytic amount of base. The rationale behind this
approach is that the use of a base could potentially improve
proton transfer events involved in the formation of 11a.13l,16
Indeed, upon examination of a number of bases for this
transformation (see the SI for more details), DBU (20 mol%) has
shown to be the optimal choice. The reaction of a 1:1 mixture of
7a:10a in the presence of DBU (20 mol%) affords 11a in 33%
yield (Table 1, Entry 11). However, the reaction of a 1:5 mixture
of 7a:10a in the presence of DBU (20 mol%) significantly
improves the yield of 11a to 79% (Table 1, Entry 12). Of note,
when this same transformation is carried out in the dark, no
conversion is observed (Table 1, Entry 13).
Scheme 1. a) Most common general strategies for the synthesis of unnatural
α-amino acids. b) Photochemical strategy explored in this work.
of α-keto esters 6, employing transaminases10 or
dehydrogenases11 (Scheme 1a).
In contrast to these previous methods, we became interested in
investigating the photochemically promoted N-H insertion of
NH-EWG motifs of amine derivatives 8 into aryldiazoacetates 7,
in order to produce the corresponding unnatural α-aryl amino
acid derivatives 9 (Scheme 1b).
With the optimal reaction conditions in hand, we investigated
the scope of this photochemical N-H insertion. Cyclic amides
Table 1. Optimization for the N-H insertion of amides.
2. Results and Discussion
Recently, numerous visible light-mediated transformations
using aryldiazoacetates 7 have been disclosed.12,13,14 These
reactions were initially proposed to be based on the ability of
aryldiazoacetates 7 to undergo photolysis under blue light
irradiation to afford carbene intermediates, which could be
trapped by a variety of reagents. Although this reactivity is
certainly operating under such conditions, it has been recently
suggested that a competing mechanism based on a photoinduced
proton transfer (PPT) event may become the major reaction
pathway for some O-H insertions of alcohols;15 and possibly
could be also occurring in other X-H insertion reactions.
entry
x
1
1
1
1
1
y
1
2
3
4
5
base (z mol%) yielda 11a (%)
1
2
3
4
5
-
-
-
-
-
24
33
43
47
50

3
6
7
1
2
3
4
5
1
1
1
10
1
-
50
40
46
50
54
33
79
0b
typically modest, in the range of 30-58%, but an exception was
noted when the electron-donating group OMe was present at the
aryldiazoacetate partner 7b; which was able to produce a 78%
yield for the corresponding N-H insertion compound 13d. Of
note, when the reaction is performed in the absence of DBU (20
mol%), one always observes lower yields. Again, the higher
yields obtained when using a catalytic amount of base is
presumably a consequence of more efficient proton transfer
events contributing to the overall increase in yields.13l,16 Finally,
when each of these reactions is performed in the dark, no reaction
is produced. In this case, one observes only unreacted starting
substrates 7 and 12 (Scheme 3).
-
8
1
-
9
1
-
10
11
12
13
1
-
1
DBU (20)
DBU (20)
DBU (20)
5
5
aYields based on 1H NMR analysis of the crude reaction mixture using 1,3,5-
trimethoxybenzene as internal standard. bReaction in the dark.
2-pyrrolidinone 10a, 2-piperidinone 10b, 2-azepanone 10c can be
used in this protocol to afford the corresponding compounds 11a,
11b, and 11c in good isolated yields, 70%, 55% and 63%,
respectively (Scheme 2). Acetamides 10d and 10e produce
slightly
Scheme 3. Scope of the N-H insertion of isatins into aryldiazoacetates.
aPerformed without base, yield estimation based on 1H NMR of the crude
reaction mixture using 1,3,5-trimethoxybenzene as internal standard.
bPerformed without base, yield estimation based on 1H NMR of the crude
reaction mixture using naphthalene as internal standard cReaction in the dark.
2.3 Blue Light-Promoted N-H Insertion of Sulfonamides.
Investigations involving sulfonamides started with the
optimization of reaction conditions employing aryldiazoacetate
7a and sulfonamide 14a to afford N-H inserted compound 15a
(Table 2). Optimal conditions were established using 4 equiv. of
14a, in DCM, at room temperature, in the absence of any base
(Table 2, Entry 4). When the same reaction is performed in the
dark, it does not work in any extension (Table 2, Entry 6). This
demonstrates the need for the blue light irradiation. Concerning
i
the use of bases, interrogation on the use of Pr2NEt (Table 2,
Entry 7), 2,6-lutidine (Table 2, Entry 8), K3PO4 (Table 2, Entry
9) or DBU (Table 2, Entry 10), among others, (see SI for
additional details) did not reveal any better results.
At this stage, we moved on to investigate the scope of the N-H
inserted products 15 that could be obtained when using this
method. Initial evaluation involving different sulfonamides 14
Scheme 2. Scope of the N-H insertion of amides into aryldiazoacetates.
aPerformed without base, yield estimation based on 1H NMR of the crude
b
reaction mixture using naphthalene as internal standard. Performed without
1
base, yield estimation based on H NMR of the crude reaction mixture using
1,3,5-trimethoxybenzene as internal standard. cReaction in the dark.
lower yields for the corresponding N-H inserted products, 11d
and 11e, in 45% and 42% yields, respectively (Scheme 2).
Primary amides pentanamide 10f and benzamide 10g afford the
corresponding N-H inserted compounds 11f and 11g in modest
yields, 32% and 34%, respectively. Interrogation on the scope of
the aryldiazoacetate partner 7 reveals similar performance for
different aryl moieties. N-H inserted compounds 11h-11m can be
prepared in respectable yields, 60-66% (Scheme 2).
Table 2. Optimization for the N-H insertion of sulfonamides.
entry
x
1
2
3
4
base (20 mol%)
yielda 15a (%)
1
2
3
4
-
-
-
-
26
40
45
54
2.2 Blue Light-Promoted N-H Insertion of Isatins
In the sequence, we became interested in evaluating the use of
isatins 12, which could undergo N-H insertions under the same
previously established optimal conditions to afford compounds
13a-13h (see also SI for additional details). Yields obtained were

4
Tetrahedron
5
6
5
4
4
4
4
4
-
-
54
0b
insertion compounds 17d-i in a narrow range of modest, yet
synthetically useful yields, 37-54% (Scheme 5).
iPr2NEt
2,6-lutidine
K3PO4
DBU
46
54
47
0c
Ar
CO2R1
O
7
H
DCM, rt
Ar
CO2R1
O
N
O
+
O
N
N2
R2 R2
8
General
Procedure D
R2 R2
7 (1 equiv.)
16 (5 equiv.)
17
9
MeO
10
Ph
CO2Me
O
CO2Me
O
Ph
CO2Me
N
N
aYields based on 1H NMR analysis of the crude reaction mixture using 1,3,5-
trimethoxybenzene as internal standard. bReaction in the dark. Starting
materials are fully recovered. cDegradation is observed.
Ph
CO2Me
O
O
O
N
O
N
O
O
CF3 CF3
17c
48% (0%)a
17a
52% (0%)a
17b
47% (0%)a
17d
46% (0%)a
allowed the preparation of the corresponding α-aryl amino acid
derivatives 15a-15h in synthetically useful yields, 40-65%,
demonstrating that primary and secondary sulfonamides carrying
aromatic and alkyl chains are well tolerated (Scheme 4).
Investigation of aryldiazoacetates 7 revealed that electron-
donating substitutents produce the corresponding compounds
15i-15o in good yields, while electron-withdrawing groups seem
to be less tolerated, as it was revealed by the frustrated attempts
aiming at the preparation of 15p and 15q. (Scheme 4).
Br
Cl
F
F
MeO
MeO
CO2Me
CO2Me
O
CO2Me
CO2Me
N
N
N
N
O
O
O
O
O
O
O
17e
17f
48% (0%)a
17g
45% (0%)a
17h
40% (0%)a
37% (0%)a
Br
O
O
O
N
O
17i
54% (0%)a
Scheme 5. Scope of the N-H insertion of imides into aryldiazoacetates.
aPerformed in the dark.
2.5 Mechanistic Investigations
In light of previous findings from our group and others, we
questioned whether if the mechanism for the N-H insertions
reported herein could be differentiated between a carbene-
mediated reaction13 or a photoinduced proton transfer process.15
Competition experiments reacting aryldiazoacetate 7a with 2-
pyrrolidinone 10a, isatin 12a, methanesulfonamide 14a or
phthalimide 16a were carried out in the presence of styrene 18
aiming to evaluate these mechanistic alternatives (Table 3).
Reactions of 1:1:1 and 1:5:5 mixtures of 7a:10a:18 in the
absence of DBU produce mixtures with yields 15%:16% and
30%:28% for 11a:19, respectively (Table 3, Entries 1 and 2). The
same mixtures react in the presence of DBU (20 mol%) to
produce analogous mixtures with yields 24%:35% and 40%:38%
for 11a:19, respectively (Table 3, Entries 3 and 4). Reactions of
1:1:1 and 1:5:5 mixtures of 7a:12a:18 in the absence of DBU
produce mixtures with yields 8%:6% and 20%:10% for 13a:19,
respectively (Table 3, Entries 5 and 6). The same mixtures react
in the presence of DBU (20 mol%) to produce analogous
mixtures with yields 33%:5% and 44%:10% for 13a:19,
respectively (Table 3, Entries 7 and 8). The reaction of 1:1:1 and
1:4:4 mixtures of
Scheme 4. Scope of the N-H insertion of sulfonamides into aryldiazoacetates.
aPerformed in the dark.
Table 3. Intermolecular competition experiments.
2.4 Blue Light-Promoted N-H Insertion of Imides.
Additional investigations on the scope of the photochemical
N-H insertion strategy involving imides has revealed the optimal
amount of 5 equiv. of the imide partner 16, in DCM, at room
temperature, in the absence of any base (see SI for details).
Under these conditions, phthalimide 16a, succinimide 16b and
bistrifluoroacetamide 16c can be inserted into aryldiazoacetate 7a
in 52%, 47% and 48% yields, respectively (Scheme 5). In
addition, a variety of substituents on the aryl moiety of
aryldiazoacetates 7 are tolerated in similar extensions when
reacting with phthalimide 16a to produce the corresponding N-H
entry
8, x
y
1
5
1
9, yield (%)a 19, yield (%)a
1
2
10a, 1
10a, 5
10a, 1
11a, 15
11a, 30
11a, 24
16
28
35
3c

5
4c
5
10a, 5
12a, 1
12a, 5
12a, 1
12a, 5
14a, 1
14a, 4
16a, 1
16a, 5
5
1
5
1
5
1
4
1
5
11a, 40
13a, 8
38
6
10
5
10
7
20
5b
9b
1
2b
3
10a
10a
12a
12a
14a
16a
11m, 25
11m, 40
13h, 27
13h, 39
15o, 29
17i, 25
12
20
8
10
5
6
13a, 20
13a, 33
13a, 44
15a, 34
15a, 45
17a, 40b
17a, 53b
7c
8c
9
4b
5
6
3
10
11
12
aEstimation based on 1H NMR of the crude reaction mixture using
naphthalene as internal standard. bUsing DBU (20 mol%).
aEstimation based on 1H NMR of the crude reaction mixture using
b
1
naphthalene as internal standard. Estimation based on H NMR of the crude
reaction mixture using 1,3,5-trimethoxybenzene as internal standard. Using
c
DBU (20 mol%).
7a:14a:18 produce mixtures with yields of 34%:7% and
45%:20% of 15a:19, respectively (Table 3, Entries 9 and 10).
Finally, reactions of 1:1:1 and 1:5:5 mixtures of 7a:16a:18 afford
mixtures with yields 40%:5% and 53%:9% for 17a:19,
respectively (Table 3, Entries 11 and 12).
Scheme 6. Proposed mechanistic scenario.
The formation of cyclopropane 19 suggests the involvement
of a carbene intermediate derived from aryldiazoacetate 7a,
which reacts with styrene 18. The formation of N-H-inserted
compounds 11a, 13a, 15a and 17a in different extensions might
be potentially derived from a photoinduced proton transfer
mechanism and/ or from a carbene intermediate. In order to
further investigate this reactivity conundrum, we turned our
attention to the use of allyl 2-(4-bromophenyl)-2-diazoacetate 7g
in order to evaluate the potential competition between
intramolecular cyclopropanation reactions and intermolecular N-
H insertions, using 1:1 mixtures of reagents (Table 4). When
probing these mechanistic scenarios using 2-pyrrolidinone 10a,
we observe the formation of cyclopropane 20 in the absence or
presence of DBU (20 mol%), in 12% or 20% yields, respectively;
while the N-H insertion product 11m is obtained in the absence
or presence of DBU (20 mol%) in 25% or 40%, respectively
(Table 4, Entries 1 and 2). When arildiazoacetate 7g reacts with
isatin 12a, a similar product distribution is also observed:
cyclopropane 20 is obtained in 8% or 10% yields, in the absence
or presence of DBU (20 mol%), respectively; while 13h is
obtained in 27% or 39% in the absence or presence of DBU (20
Our interpretation is that less acidic N-H bonds of amides 10
(e.g. pKa 2-pyrrolidinone 10a in DMSO = 24.2)17 and isatins 12
(e.g. pKa isatin 12a in DMSO ≤ 18.2)18 will afford less acidic
ammonium moieties in ylide intermediates 22. In agreement with
this view, in the case of more acidic N-H bonds of sulfonamides
14 (e.g. pKa methanesulfonamide 14a in DMSO = 17.5)19 and
imides 16 (e.g. pKa succinimide 16b in DMSO = 14.6),20 no base
is needed and a photoinduced proton transfer is more likely to
occur (Scheme 6). Indeed, in these latter cases, the yields for the
conversions of aryldiazoacetates 7 to the final compounds 9 are
not improved in the presence of DBU or other bases (see the SI
for more details).
3. Conclusions
In summary, we have been able to demonstrate that numerous
amines carrying electron-withdrawing groups (amides, isatins,
sulfonamides and imides) can undergo N-H insertions into
aryldiazoacetates under blue light irradiation. The protocols
established here are inexpensive and straightforward; and allow
the preparation of numerous non-natural α-aryl amino acid
derivatives in synthetically useful yields. Some of these protocols
incorporated the addition of DBU as an aminocatalyst, which
showed the ability to improve the efficiency of the overall
transformation. This effect is tentatively attributed to more
efficient proton transfer events, with the base acting as a proton
shuttle between reaction intermediates. More acidic NH-EWG-
containing substrates 8 seem to involve a photoinduced proton
transfer-mediated mechanism as the major pathway, while less
acidic derivatives have their mechanisms apparently display a
more important contribution of a carbene intermediate, thus
possibly proceeding via a combination of both pathways,
photolysis and PPT.
mol%), respectively (Table 4, Entries
3 and 4). When
arildiazoacetate 7g reacts with methanesulfonamide 14a or
phthalimide 16a, then cyclopropane 20 is produced only in trace
amounts for both cases, while the corresponding N-H insertion
products 15o, or 17i, are observed in 29% or 25% yields,
respectively (Table 4, Entries 5 and 6).
These observations suggest that a carbene intermediate is
involved in a larger extension for the reactions involving 2-
pyrrolidinone 10a and isatin 12a, while a proton transfer
mechanism is more likely to be more pronounced in reactions
with methanesulfonamide 14a and phthalimide 16a (Scheme 6).
Considering the photochemical reactions involving amides 10
and isatins 12, the positive impact in yields observed when using
a catalytic amount of DBU can be possibly attributed to its
assistance in proton transfer events to convert the putative ylide
intermediate 22 to the final compound 916 (Scheme 6).
4. Experimental Section
All aryldiazoacetates used in this work are known compounds
(methyl 2-diazo-2-phenylacetate14b 7a, methyl 2-diazo-2-(4-
methoxyphenyl)acetate13l
7b,
methyl
2-diazo-2-(3-
methoxyphenyl)acetate13l 7c, methyl 2-(4-chlorophenyl)-2-
diazoacetate13l 7d, methyl 2-(4-bromophenyl)-2-diazoacetate13l
7e, methyl 2-diazo-2-(3,4-difluorophenyl)acetate13l 7f, methyl 2-
allyl 2-(4-bromophenyl)-2-diazoacetate13l 7g, diazo-2-(3,4-
Table 4. Intermolecular N-H insertion versus intramolecular
cyclopropanation reactions competition experiments.
dimethoxyphenyl)acetate13n
7h,
methyl
2-diazo-2-(2-
methoxyphenyl)acetate21 7i, and were prepared according to the
literature.
entry
8
9, yield(%)a 20, yield(%)a

6
Tetrahedron
General Procedure A: Blue light-promoted N-H insertion of
171.6, 136.6, 129.0, 128.5, 127.2, 56.3, 52.8, 36.1, 27.5, 22.3,
amides 10 into aryldiazoacetates 7
13.7. M.P.: 42 - 44 oC. IR (ATR, cm-1): 2957, 2933, 2872, 1743,
1648, 1499, 1212, 1173. HRMS (ESI+): Calcd. for
[C14H19NO3+H]+: 250.1438, found: 250.1440.
Under air, at room temperature, a 4-mL vial is charged with
aryldiazoacetate 7 (0.1 mmol, 1 equiv.), amide 10 (0.5 mmol, 5
equiv.) and DCM (3 mL, 0.033 M in respect to aryldiazoacetate
7). Then, DBU (3 µL, 20 mol%) is added. The reaction mixture is
stirred at room temperature under blue light irradiation for 12 h
(using two LED lamps, 15 W each, displaced at approximate
distances of 5 cm each from the reaction vessel). Then, the
reaction mixture is concentrated under reduced pressure and
purified by flash column chromatography to afford the
corresponding N-H inserted amides 11 in the stated yields.
methyl 2-benzamido-2-phenylacetate (11g):23
White solid, 9 mg, 34%. Rf = 0.29 (8:2 Hex:AcOEt). H NMR
(250 MHz, CDCl3), δ (ppm): 7.84 – 7.81 (m, 2H), 7.52 – 7.36
(m, 8H), 7.15 (d, J = 6.5 Hz, 1H), 5.79 (d, J = 6.7 Hz, 1H), 3.77
(s, 3H). 13C NMR (62.5 MHz, CDCl3), 1C could not be
unambiguously assigned, δ (ppm): 171.5, 166.5, 136.5, 133.6,
131.9, 129.0, 128.6, 127.3, 127.1, 56.8, 52.9.
1
methyl 2-(2-oxopyrrolidin-1-yl)-2-phenylacetate (11a):
methyl
(11h):
2-(4-methoxyphenyl)-2-(2-oxopyrrolidin-1-yl)acetate
Colorless oil, 16 mg, 70%. Rf = 0.38 (8:2 Hex:AcOEt). 1H NMR
(250 MHz, CDCl3) δ (ppm): 7.53 – 7.49 (m, 2H), 7.41 – 7.35
(m, 3H), 6.02 (s, 1H), 3.76 – 3.65 (m, 5H), 2.67 – 2.53 (m, 2H),
2.13 – 2.02 (m, 2H). 13C NMR (62.5 MHz, CDCl3) δ (ppm):
172.1, 170.1, 134.7, 129.1, 128.7, 127.5, 77.6, 55.1, 52.5, 30.8,
23.2. IR (ATR, cm-1): 2942, 1734, 1683, 1185, 1063. HRMS
(ESI+): Calcd. for [C13H15NO3+H]+: 234.1125, found: 234.1120.
1
White solid, 16 mg, 61%. Rf = 0.27 (8:2 Hex:AcOEt). H NMR
(250 MHz, CDCl3) δ (ppm): 7.42 (d, J = 8.2 Hz, 2H), 6.90 (d, J
= 8.2 Hz, 2H), 5.93 (s, 1H), 3.80 (s, 3H), 3.75 – 3.64 (m, 5H),
2.64 – 2.51 (m, 2H), 2.09 – 2.00 (m, 2H). 13C NMR (62.5 MHz,
CDCl3) δ (ppm): 172.0, 170.4, 160.2, 129.0, 126.8, 114.1, 77.1,
55.3, 55.2, 52.4, 30.8, 23.2. M.P.: 89 - 91 C. IR (ATR, cm-1):
o
2980, 2891, 1744, 1653, 1602, 1520, 1439, 1378, 1216,
1185,1043, 1013. HRMS (ESI+): Calcd. for [C14H17NO4+H]+:
264.1230, found: 264.1237.
methyl 2-(2-oxopiperidin-1-yl)-2-phenylacetate (11b):
Colorless oil, 14 mg, 55%. Rf = 0.33 (8:2 Hex:AcOEt). 1H NMR
(250 MHz, CDCl3) δ (ppm): 7.52 – 7.49 (m, 2H), 7.39 – 7.34
(m, 3H), 5.93 (s, 1H), 3.69 (s, 3H), 3.46 (t, J = 5.7 Hz, 2H), 2.34
– 2.20 (m, 2H), 1.78 – 1.71 (m, 2H), 1.59 – 1.53 (m, 2H). 13C
NMR (62.5 MHz, CDCl3) δ (ppm): 170.9, 161.3, 135.3, 128.7,
128.6, 127.5, 74.2, 52.1, 46.7, 25.6, 22.3, 20.1. IR (ATR, cm-1):
2945, 2859, 1744, 1683, 1602, 1378, 1205, 1084. HRMS
(ESI+): Calcd. for [C14H17NO3+H]+: 248.1281, found: 248.1287.
methyl
2-(3-methoxyphenyl)-2-(2-oxopyrrolidin-1-yl)acetate
(11i):
Colorless oil, 16 mg, 61%. Rf = 0.25 (8:2 Hex:AcOEt). 1H NMR
(250 MHz, CDCl3) δ (ppm): 7.30 (d, J = 7.8 Hz, 1H), 7.10 –
7.05 (m, 2H), 6.90 (dd, J = 8.0 Hz, J = 2.0 Hz, 1H), 5.97 (s, 1H),
3.82 (s, 3H), 3.77 – 3.65 (m, 5H), 2.66 – 2.53 (m, 2H), 2.12 –
2.01 (m, 2H). 13C NMR (62.5 MHz, CDCl3) δ (ppm): 172.0,
170.1, 159.8, 136.1, 129.7, 119.8, 114.8, 112.8, 77.4, 55.3, 55.2,
52.5, 30.8, 23.3. IR (ATR, cm-1): 2962, 2860, 1754, 1642, 1227,
1043. HRMS (ESI+): Calcd. for [C14H17NO4+H]+: 264.1230,
found: 264.1235.
methyl 2-(2-oxoazepan-1-yl)-2-phenylacetate (11c):
Colorless oil, 16 mg, 63%. Rf = 0.40 (8:2 Hex:AcOEt). 1H NMR
(250 MHz, CDCl3) δ (ppm): 7.54 – 7.50 (m, 2H), 7.41-7.33 (m,
3H), 5.82 (s, 1H), 3.69 (s, 3H), 3.41 (t, J = 5.0 Hz, 2H), 2.53 (t, J
= 5.0 Hz, 2H), 1.79 – 1.73 (m, 2H), 1.62 – 1.50 (m, 4H). 13C
NMR (62.5 MHz, CDCl3) δ (ppm): 170.8, 167.6, 135.1, 128.7,
128.5, 127.5, 74.8, 52.0, 48.6, 31.7, 31.2, 27.6, 23.1. IR (ATR,
cm-1): 3374, 2952, 2849, 1683, 1439, 1196, 1003. HRMS
(ESI+): Calcd. for [C15H19NO3+H]+: 262.1438, found: 262.1448.
methyl 2-(4-chlorophenyl)-2-(2-oxopyrrolidin-1-yl)acetate (11j):
1
White solid, 18 mg, 66%. Rf = 0.28 (8:2 Hex:AcOEt). H NMR
(250 MHz, CDCl3) δ (ppm): 7.45 (d, J = 8.0 Hz, 2H), 7.34 (d, J
= 8.0 Hz, 2H), 5.97 (s, 1H), 3.72 – 3.64 (m, 5H), 2.62 – 2.52 (m,
2H), 2.10 – 2.05 (m, 2H). 13C NMR (62.5 MHz, CDCl3) δ
(ppm): 171.8, 169.8, 135.0, 133.3, 128.9, 128.8, 77.2, 55.2, 52.6,
methyl 2-(N-benzylacetamido)-2-phenylacetate (11d):22
colorless oil: 13 mg, 45%. Rf = 0.42 (7:3 Hex:AcOEt). 1H NMR
(250 MHz, CDCl3) δ (ppm): 7.24 – 7.17 (m, 8H), 6.98 – 6.95
(m, 2H), 6.01 (s, 1H), 4.65 (d, J = 17.5 Hz, 1H), 4.43 (d, J = 17.5
Hz, 1H), 3.74 (s, 3H), 2.11 (s, 3H). 13C NMR (62.5 MHz,
CDCl3) δ (ppm): 172.5, 171.1, 137.3, 134.0, 129.8, 128.7, 128.6,
128.4, 127.0, 126.0, 62.0, 52.4, 50.1, 22.3.
o
30.8, 23.3. M.P.: 99 - 101 C. IR (ATR, cm-1): 2952, 2882,
1754, 1673, 1480, 1378, 1257, 1033. HRMS (ESI+): Calcd. for
[C13H14ClNO3+H]+: 268.0735, found: 268.0746.
methyl 2-(4-bromophenyl)-2-(2-oxopyrrolidin-1-yl)acetate (11k):
1
White solid, 20 mg, 65%. Rf = 0.28 (8:2 Hex:AcOEt). H NMR
(250 MHz, CDCl3) δ (ppm): 7.51 (d, J = 8.2 Hz, 2H), 7.38 (d, J
= 8.2 Hz, 2H), 5.96 (s, 1H), 3.77 – 3.64 (m, 5H), 2.72 – 2.45 (m,
2H), 2.13 – 2.02 (m, 2H). 13C NMR (62.5 MHz, CDCl3) δ
(ppm): 171.8, 169.7, 133.8, 131.9, 129.1, 123.2, 76.7, 55.2, 52.6,
30.8, 23.3. M.P.: 63 - 65 oC. IR (ATR, cm-1): 2972, 2871, 1744,
1642, 1205, 1165, 1054. HRMS (ESI+): Calcd. for
[C13H14BrNO3+H]+: 312.0230, found: 312.0233.
methyl 2-(N-(4-formylphenyl)acetamido)-2-phenylacetate (11e):
Colorless oil: 13 mg, 42%. Rf = 0.44 (1:1 Hex:AcOEt). 1H NMR
(250 MHz, CDCl3) δ (ppm): 9.93 (s, 1H), 7.70 (d, J = 8.7 Hz,
2H), 7.23 – 7.14 (m, 5H), 6.99 – 6.96 (m, 2H), 6.28 (s, 1H), 3.78
(s, 3H), 1.87 (s, 3H). 13C NMR (62.5 MHz, CDCl3) δ (ppm):
191.1, 171.1, 170.4, 145.3, 135.5, 133.2, 131.4, 130.1, 130.0,
128.7, 128.6, 63.4, 52.6, 23.2. IR (ATR, cm-1): 2952, 1754,
1662, 1612, 1369, 1297, 1205, 1175, 1084, 1003. HRMS
(ESI+): Calcd. for [C18H17NO4+H]+: 312.1230, found: 312.1229.
methyl
2-(3,4-difluorophenyl)-2-(2-oxopyrrolidin-1-yl)acetate
(11l):
1
White solid, 17 mg, 62%. Rf = 0.33 (8:2 Hex:AcOEt). H NMR
(250 MHz, CDCl3) δ (ppm): 7.39 – 7.31 (m, 1H), 7.24 – 7.14
(m, 2H), 5.95 (s, 1H), 3.73 – 3.64 (m, 5H), 2.66 – 2.53 (m, 2H),
2.10 – 2.03 (m, 2H). 13C NMR (62.5 MHz, CDCl3) δ (ppm):
171.7, 169.5, 150.7 (dd, J = 123.9Hz, J = 5.8Hz), 150.3 (dd, J =
122.8Hz, J = 5.2 Hz), 131.6 (dd, J = 2.6Hz, J = 2.3Hz), 123.6
(dd, J = 3.2 Hz, J = 1.8 Hz), 117.4 (d, J = 8.7Hz), 116.5 (d, J =
methyl 2-pentanamido-2-phenylacetate (11f):
White solid, 8 mg, 32%. Rf = 0.24 (9:1 Hex:AcOEt). H NMR
(250 MHz, CDCl3) δ (ppm): 7.35 (app s, 5H), 6.39 (d, J = 7.0
Hz, 1H), 5.60 (d, J = 7.0 Hz, 1H), 3.73 (s, 3H), 2.25 (t, J = 7.2
Hz, 2H), 1.65 – 1.58 (m, 2H), 1.38 – 1.32 (m, 2H), 0.90 (t, J =
7.2 Hz, 3H). 13C NMR (62.5 MHz, CDCl3) δ (ppm): 172.4,
1

7
9.2Hz), 76.2, 55.2, 52.7, 30.7, 23.3. 19F NMR (235 MHz,
CDCl3) δ (ppm): -136.6 (d, J = 10.6 Hz), -137.0 (d, J = 10.6
Hz). M.P.: 53 - 55 oC. IR (ATR, cm-1): 3023, 2972, 2881, 1764,
1662, 1511, 1450, 1297, 1196, 1043. HRMS (ESI+): Calcd. for
[C13H13F2NO3+H]+: 270.0936, found: 270.0944.
7.27 (m, 3H), 7.07 (t, J = 7.6 Hz, 1H), 6.92 – 6.88 (m, 2H), 6.68
(d, J = 8.0 Hz, 1H), 6.32 (s, 1H), 3.86 (s, 3H), 3.80 (s, 3H). 13C
NMR (62.5 MHz, CDCl3) δ (ppm): 182.5, 168.8, 159.9, 158.2,
149.8, 138.0, 129.4, 125.3, 123.9, 123.8, 118.0, 114.5, 113.3,
56.8, 55.3, 53.0. IR (ATR, cm-1): 2940, 1734, 1611,1516, 1272,
1253, 1179, 1032. HRMS (ESI+): Calcd. for [C18H15NO5+H]+:
326.1023, found: 326.1024.
allyl 2-(4-bromophenyl)-2-(2-oxopyrrolidin-1-yl)acetate (11m)
Colorless oil, 20 mg, 60%. Rf = 0.42 (8:2 Hex:AcOEt). 1H NMR
(250 MHz, CDCl3) δ (ppm): 7.51 (d, J = 8.5 Hz, 2H), 7.39 (d, J
= 8.5 Hz, 2H), 5.99 (s, 1H), 5.89-5.74 (m, 1H), 5.24-5.15 (m,
2H), 4.69-4.60 (m, 2H), 3.66 (t, J = 7.3 Hz, 2H), 2.72-2.45 (m,
2H), 2.15-1.99 (m, 2H). 13C NMR (62.5 MHz, CDCl3) δ (ppm):
171.7, 168.9, 133.8, 131.9, 131.4, 129.1, 123.2, 118.4, 76.8, 65.9,
55.1, 30.8, 23.3. IR (ATR, cm-1): 3219, 2951, 1735, 1685, 1654,
1637, 1617, 1592, 1559, 1486, 1437, 1363, 1208, 1171. HRMS
(ESI+): Calcd. for [C15H16BrNO3 + H]+: 338.0386, found:
338.0384.
methyl
2-(4-chlorophenyl)-2-(2,3-dioxoindolin-1-yl)acetate
(13e):
1
Yellow oil, 14 mg, 42%. Rf = 0.27 (8:2 Hex:AcOEt). H NMR
(250 MHz, CDCl3) δ (ppm): 7.64 (dd, J = 1.0, J = 7.6 Hz, 1H),
7.46 – 7.30 (m, 5H), 7.11 (t, J = 7.6 Hz, 1H), 6.64 (d, J = 8.0 Hz,
1H), 6.30 (s, 1H), 3.86 (s, 3H). 13C NMR (62.5 MHz, CDCl3) δ
(ppm): 182.0, 168.0, 158.0, 149.3, 138.1, 135.0, 130.7, 129.4,
129.3, 125.5, 124.1, 118.0, 112.8, 56.5, 53.2. IR (ATR, cm-1):
2950, 1734, 1611, 1471, 1495, 1354, 1179, 1095. HRMS
(ESI+): Calcd. for [C17H12ClNO4+H]+: 330.0528, found:
330.0538.
General Procedure B: Blue light-promoted N-H insertion of
isatins 12 into aryldiazoacetates 7.
Under air, at room temperature, a 4-mL vial is charged with
aryldiazoacetate 7 (0.1 mmol, 1 equiv.), isatin 12 (0.5 mmol, 5
equiv.), DBU (3 µL, 20 mol%) and DCM (3 mL, 0.03 M in
respect to aryldiazoacetate 7). The reaction mixture is stirred at
room temperature under blue light irradiation for 12 h (using two
LED lamps, 15 W each, displaced at approximate distances of 5
cm each from the reaction vessel). Then, the reaction mixture is
concentrated under reduced pressure and purified by flash
column chromatography to afford the corresponding N-H
inserted isatins 13 in the stated yields.
methyl 2-(4-bromophenyl)-2-(2,3-dioxoindolin-1-yl)acetate (13f).
Yellow oil, 19 mg, 52%. Rf = 0.63 (1:1 Hex:AcOEt). H NMR
1
(250 MHz, CDCl3) δ (ppm): 7.64 (dd, J = 1.0 Hz, J = 8.0 Hz,
1H), 7.53 (d, J = 8.0Hz, 2H), 7.43 (dt, J = 1.0 Hz, J = 8.0 Hz,
1H), 7.26 (d, J = 8.0 Hz, 2H), 7.11 (t, J = 8.0 Hz, 1H), 6.64 (d, J
= 8.0 Hz, 1H), 6.28 (s, 1H), 3.86 (s, 3H). 13C NMR (62.5 MHz,
CDCl3) δ (ppm): 182.0, 168.0, 158.1, 149.4, 138.1, 132.3, 131.2,
129.7, 125.6, 124.2, 123.2, 118.0, 112.9, 56.6, 53.2. IR (ATR,
cm-1): 2945, 1739, 1613, 1471, 1357, 1303, 1181, 1013. HRMS
(ESI+): Calcd. for [C17H12BrNO4+H]+: 374.0022, found:
374.0038.
methyl 2-(2,3-dioxoindolin-1-yl)-2-phenylacetate (13a):
Yellow oil, 14 mg, 47%. Rf = 0.28 (8:2 Hex:AcOEt). H NMR
1
methyl 2-(3,4-difluorophenyl)-2-(2,3-dioxoindolin-1-yl)acetate
(250 MHz, CDCl3) δ (ppm): 7.62 (d, J = 7.4 Hz, 1H), 7.42 –
7.32 (m, 6H), 7.07 (t, J = 7.4 Hz, 1H), 6.66 (d, J = 8.0 Hz, 1H),
6.39 (s, 1H), 3.87 (s, 3H). 13C NMR (62.5 MHz, CDCl3) δ
(ppm): 182.3, 168.5, 158.2, 149.7, 138.0, 132.1, 129.1, 129.0,
128.0, 125.3, 123.9, 118.0, 113.3, 57.2, 53.0. IR (ATR, cm-1):
2940, 1730, 1609, 1469, 1357, 1220, 1179. HRMS (ESI+):
Calcd. for [C17H13NO4+H]+: 296.0917, found: 296.0919.
(13g):
1
Yellow oil, 10 mg, 30%. Rf = 0.53 (8:2 Hex:Acetone). H NMR
(250 MHz, CDCl3) δ (ppm): 7.66 (dd, J = 1.0 Hz, J = 7.5 Hz,
1H), 7.47 (dt, J = 1.5 Hz, J = 8.0 Hz, 1H), 7.31-7.24 (m, 1H),
7.21-7.11 (m, 3H), 6.65 (d, J = 8.0 Hz, 1H), 6.24 (s, 1H), 3.86 (s,
3H). 13C NMR (62.5 MHz, CDCl3) δ (ppm): 181.8, 167.7,
158.0, 150.5 (dd, J = 6.1 Hz, J = 124.9 Hz), 150.4 (dd, J = 124.4
Hz, J = 6.4 Hz), 149.1, 138.2, 129.1 (dd, J = 2.4 Hz, J = 2.1 Hz),
125.7, 124.3, 124.3 (dd, J = 3.2 Hz, J = 1.9 Hz), 118.0, 118.0 (d,
J = 8.6 Hz), 117.5 (d, J = 9.4 Hz), 112.5, 56.1, 53.4. 19F (235
MHz, CDCl3) δ (ppm): -135.2 (d, J = 21.2 Hz), -136.3 (d, J =
21.2Hz). IR (ATR, cm-1): 2970, 1741, 1613, 15221, 1473, 1283,
1186. HRMS (ESI+): Calcd. for [C17H11F2NO4+H]+: 332.0729,
found: 332.0733.
methyl 2-(5-chloro-2,3-dioxoindolin-1-yl)-2-phenylacetate (13b):
1
Yellow oil, 16 mg, 50%. Rf = 0.30 (8:2 Hex:AcOEt). H NMR
(250 MHz, CDCl3) δ (ppm): 7.58 (d, J = 2.1 Hz, 1H), 7.41 –
7.30 (m, 6H), 6.59 (d, J = 8.5 Hz, 1H), 6.41 (s, 1H), 3.89 (s, 3H).
13C NMR (62.5 MHz, CDCl3) δ (ppm): 181.4, 168.4, 157.7,
147.9, 137.3, 131.7, 129.8, 129.2 (2x), 127.8, 125.1, 118.8,
114.8, 57.2, 53.1. IR (ATR, cm-1): 2920, 2815, 1739, 1607,
1441, 1357, 1216, 1127, 1013. HRMS (ESI+): Calcd. for
[C17H12ClNO4+H]+: 330.0528, found: 330.0532.
allyl 2-(4-bromophenyl)-2-(2,3-dioxoindolin-1-yl)acetate (13h)
Yellow oil, 23 mg, 58%. Rf = 0.25 (8:2 Hex:AcOEt). H NMR
1
(250 MHz, CDCl3) δ (ppm): 7.64 (dd, J = 1.2 Hz, J = 7.5 Hz,
1H), 7.52 (d, J = 8.3 Hz, 2H), 7.43 (dt, J = 1.2 Hz, J = 8.0 Hz,
1H), 7.27 (d, J = 8.3Hz, 2H), 7.11 (t, J = 7.5 Hz, 1H), 6.65 (d, J =
8.0 Hz, 1H), 6.31 (s, 1H), 5.90-5.84 (m, 1H), 5.34-5.25 (m, 2H),
4.75 (d, J = 6.0 Hz, 2H). 13C NMR (62.5 MHz, CDCl3) δ
(ppm): 182.0, 167.2, 158.1, 149.3, 138.0, 132.2, 131.2, 130.7,
129.7, 125.5, 124.1, 123.2, 120.0, 118.0, 113.0, 67.0, 56.6. IR
(ATR, cm-1): 2931, 1727, 1609, 1591, 1490, 1466, 1410, 1355,
1301, 1273, 1215, 1178. HRMS (ESI+): Calcd. for
[C19H14BrNO4 + H]+: 400.0179, found: 400.0180.
methyl
(13c):
2-(5,6-dichloro-2,3-dioxoindolin-1-yl)-2-phenylacetate
1
Yellow oil, 10 mg, 30%. Rf = 0.27 (8:2 Hex:AcOEt). H NMR
(250 MHz, CDCl3) δ (ppm): 7.60 (d, J = 2.8 Hz, 1H), 7.53 –
7.48 (m, 3H), 7.38 – 7.35 (m, 3H), 6.65 (s, 1H), 3.82 (s, 3H). 13
C
NMR (62.5 MHz, CDCl3) δ (ppm): 180.5, 168.0, 157.9, 144.5,
139.6, 133.8, 130.5, 128.6, 127.9, 124.5, 124.0, 121.3, 118.4,
58.3, 53.4. IR (ATR, cm-1): 2940, 1745, 1613, 1458, 1389, 1283,
1156, 1013. HRMS (ESI+): Calcd. for [C17H11Cl2NO4+H]+:
364.0138, found: 364.0144.
General Procedure C: Blue light-promoted N-H insertion of
sulfonamides 14 into aryldiazoacetates 7.
methyl
2-(2,3-dioxoindolin-1-yl)-2-(4-methoxyphenyl)acetate
(13d):
Under air, at room temperature, a 4-mL vial is charged with
aryldiazoacetate 7 (0.1 mmol, 1 equiv.), sulfonamide 14 (0.4
mmol, 4 equiv.) and DCM (3 mL, 0.033 M in respect to
1
Yellow oil, 25 mg, 78%. Rf = 0.33 (8:2 Hex:AcOEt). H NMR
(250 MHz, CDCl3) δ (ppm): 7.61 (d, J = 7.6 Hz, 1H), 7.43 –

8
Tetrahedron
1
aryldiazoacetate 7). The reaction mixture is stirred at room
Colorless oil, 19 mg, 58%. Rf = 0.24 (7:3 Hex:DCM). H NMR
(250 MHz, CDCl3) δ (ppm): 7.29 – 7.22 (m, 5H), 7.13 – 7.10
(m, 3H), 7.01 – 6.97 (m, 2H), 5.82 (s, 1H), 4.62 (d, J = 16.0 Hz,
1H), 4.31 (d, J = 16.0 Hz, 1H), 3.80 (s, 3H), 2.81 (s, 3H). 13C
NMR (62.5 MHz, CDCl3) δ (ppm): 171.2, 136.8, 133.7, 129.5,
128.9, 128.8, 128.2, 128.0, 127.2, 63.9, 52.5, 49.4, 40.9. IR
(ATR, cm-1): 3022, 2955, 1754, 1450, 1338, 1205, 1135, 1073.
HRMS (ESI+): Calcd. for [C17H19SNO4+H]+: 334.1108, found:
334.1118.
temperature under blue light irradiation for 12 h (using two LED
lamps, 15 W each, displaced at approximate distances of 5 cm
each from the reaction vessel). Then, the reaction mixture is
concentrated under reduced pressure and purified by flash
column chromatography to afford the corresponding N-H
inserted sulfonamides 15 in the stated yields.
methyl 2-(methylsulfonamido)-2-phenylacetate24 (15a):
Colorless oil, 16 mg, 65%. Rf = 0.38 (1:1 Hex:AcOEt). 1H NMR
(250 MHz, CDCl3) δ (ppm): 7.38 (app s, 5H), 5.70 (d, J = 6.8
Hz, 1H), 5.22 (d, J = 6.8 Hz, 1H), 3.73 (s, 3H), 2.73 (s, 3H). 13C
NMR (62.5 MHz, CDCl3) δ (ppm): 170.8, 135.7, 129.2, 129.0,
127.4, 59.5, 53.2, 42.1.
methyl
(15h):
2-(N-phenethylmethylsulfonamido)-2-phenylacetate
1
Colorless oil, 19 mg, 40%. Rf = 0.53 (7:3 Hex:DCM). H NMR
(250 MHz, CDCl3) δ (ppm): 7.48 – 7.37 (m, 6H), 7.19 – 7.15
(m, 2H), 6.82 (dd, J = 7.8 Hz, J = 1.8 Hz, 2H), 5.87 (s, 1H), 3.80
(s, 3H), 3.54 – 3.40 (m, 1H), 3.35 – 3.23 (m, 1H), 2.95 (s, 3H),
2.80 – 2.68 (m, 1H), 1.85 – 1.75 (m, 1H). 13C NMR (62.5 MHz,
CDCl3) δ (ppm): 171.2, 138.5, 134.4, 129.5, 129.2, 129.1, 128.7,
128.4, 126.3, 63.5, 52.5, 48.1, 38.9, 37.2. IR (ATR, cm-1): 3035,
2942, 1734, 1440, 1328, 1205, 1145, 688. HRMS (ESI+): Calcd.
for [C18H21SNO4+H]+: 348.1264, found: 348.1279.
methyl 2-((4-methylphenyl)sulfonamido)-2-phenylacetate25 (15b):
White solid, 20 mg, 61%. Rf = 0.34 (8:2 Hex:AcOEt). H NMR
(250 MHz, CDCl3) δ (ppm): 7.64 (d, J = 9.0 Hz, 2H), 7.28 –
7.20 (m, 7H), 5.80 (d, J = 7.8 Hz, 1H), 5.08 (d, J = 7.8 Hz, 1H),
3.58 (s, 3H), 2.40 (s, 3H). 13C NMR (62.5 MHz, CDCl3) δ
(ppm): 170.5, 143.5, 136.9, 135.2, 129.4, 128.7, 128.5, 127.1
(2x), 59.3, 52.9, 21.4.
1
methyl 2-(4-methoxyphenyl)-2-(methylsulfonamido)acetate (15i):
1
methyl 2-phenyl-2-(phenylsulfonamido)acetate (15c):
White solid, 18 mg, 58%. Rf = 0.36 (8:2 Hex:AcOEt). H NMR
White solid, 19 mg, 70%. Rf = 0.27 (6:4 Hex:AcOEt). H NMR
1
(250 MHz, CDCl3) δ (ppm): 7.29 (d, J = 8.8 Hz, 2H), 6.90 (d, J
= 8.8 Hz, 2H), 5.54 (d, J = 6.3 Hz, 1H), 5.16 (d, J = 6.3 Hz, 1H),
3.80 (s, 3H), 3.73 (s, 3H), 2.72 (s, 3H). 13C NMR (62.5 MHz,
CDCl3) δ (ppm): 171.0, 160.1, 128.7, 127.6, 114.5, 58.9, 55.3,
53.1, 42.2. M.P.: 89 - 91 oC. IR (ATR, cm-1): 3269, 2968, 1744,
1520, 1450, 1338, 1235, 1145, 1074. HRMS (ESI+): Calcd. for
[C11H15SNO5+H]+: 274.0744, found: 274.0747.
(250 MHz, CDCl3) δ (ppm): 7.77 – 7.73 (m, 2H), 7.53 – 7.28
(m, 3H), 7.27 – 7.21 (m, 5H), 5.76 (d, J = 7.7 Hz, 1H), 5.11 (d, J
= 7.7 Hz, 1H), 3.59 (s, 3H). 13C NMR (62.5 MHz, CDCl3) δ
(ppm): 170.4, 139.9, 135.0, 132.7, 128.9, 128.8, 128.7, 127.1
o
(x2), 59.3, 53.0. M.P.: 106 - 108 C. IR (ATR, cm-1): 3274,
2969, 1744, 1581, 1439, 1348, 1216, 1165, 1084. HRMS
(ESI+): Calcd. for [C15H15SNO4+H]+: 306.0795, found:
306.0805.
methyl 2-(3-methoxyphenyl)-2-(methylsulfonamido)acetate (15j):
Colorless oil, 15 mg, 55%. Rf = 0.30 (6:4 Hex:AcOEt). 1H NMR
(250 MHz, CDCl3) δ (ppm): 7.30 (t, J = 7.0 Hz, 1H), 6.96 –
6.88 (m, 3H), 5.60 (d, J = 7.0 Hz, 1H), 5.18 (d, J = 7.0 Hz, 1H),
3.81 (s, 3H), 3.74 (s, 3H), 2.75 (s, 3H). 13C NMR (62.5 MHz,
CDCl3) δ (ppm): 170.7, 160.1, 137.1, 130.3, 119.6, 114.5, 113.1,
59.4, 55.4, 53.3, 42.2. IR (ATR, cm-1): 3274, 2969, 1744, 1520,
1450, 1338, 1235, 1145, 1074. HRMS (ESI+): Calcd. for
[C11H15SNO5+H]+: 274.0744, found: 274.0745.
methyl 2-((4-bromophenyl)sulfonamido)-2-phenylacetate (15d):
White solid, 18 mg, 50%. Rf = 0.36 (8:2 Hex:AcOEt). H NMR
1
(250 MHz, CDCl3) δ (ppm): 7.58 – 7.50 (m, 4H), 7.31 – 7.18
(m, 5H), 5.80 (d, J = 7.2 Hz, 1H), 5.11 (d, J = 7.2 Hz, 1H), 3.64
(s, 3H). 13C NMR (62.5 MHz, CDCl3) δ (ppm): 170.4, 139.1,
134.8, 132.1, 128.9, 128.8, 128.6, 127.6, 127.2, 59.4, 53.2. MP:
79 - 81 oC. IR (ATR, cm-1): 3313, 2942, 1734, 1572, 1450, 1348,
1216,
1165,
1074.
HRMS
(ESI+):
Calcd.
for
[C15H14SBrNO4+H]+: 383.9900, found: 383.9910.
methyl
(15k):
2-(3,4-dimethoxyphenyl)-2-(methylsulfonamido)acetate
Colorless oil, 16 mg, 52%. Rf = 0.33 (4:6 Hex:AcOEt). 1H NMR
(250 MHz, CDCl3) δ (ppm): 6.95 – 6.84 (m, 3H), 5.48 (d, J =
6.1 Hz, 1H), 5.15 (d, J = 6.1 Hz, 1H), 3.89 (s, 3H), 3.88 (s, 3H),
3.75 (s, 3H), 2.73 (s, 3H). 13C NMR (62.5 MHz, CDCl3) δ
(ppm): 170.9, 149.7, 149.5, 128.0, 120.1, 111.4, 110.2, 59.3,
56.1, 56.0, 53.3, 42.2. IR (ATR, cm-1): 3300, 2942, 1744, 1520,
1450, 1328, 1245, 1145, 1115, 1024. HRMS (ESI+): Calcd. for
[C12H17SNO6+H]+: 304.0849, found: 304.0858.
methyl 2-phenyl-2-(N-phenylmethylsulfonamido)acetate (15e):
1
Colorless oil, 15 mg, 46%. Rf = 0.27 (7:3 Hex:DCM). H NMR
(250 MHz, CDCl3) δ (ppm): 7.25 – 7.13 (m, 8H), 7.00 – 6.96
(m, 2H), 6.21 (s, 1H), 3.80 (s, 3H), 3.12 (s, 3H). 13C NMR (62.5
MHz, CDCl3) δ (ppm): 171.9, 135.9, 133.4, 132.4, 129.9, 128.8
(2x), 128.6, 128.4, 66.0, 52.7, 39.9. IR (ATR, cm-1): 3047, 2969,
1754, 1490, 1338, 1227, 1135, 1063. HRMS (ESI+): Calcd. for
[C16H17SNO4+H]+: 320.0951, found: 320.0949.
methyl 2-(4-bromophenyl)-2-(methylsulfonamido)acetate (15l):
Colorless oil, 14 mg, 43%. Rf = 0.5 (6:4 Hex:AcOEt). H NMR
methyl
phenylacetate (15f):
2-(N-(naphthalen-2-yl)methylsulfonamido)-2-
1
1
(250 MHz, CDCl3) δ (ppm): 7.53 (d, J = 8.4 Hz, 2H), 7.27 (d, J
= 8.4 Hz, 2H), 5.68 (d, J = 6.3 Hz, 1H), 5.19 (d, J = 6.3 Hz, 1H),
3.74 (s, 3H), 2.77 (s, 3H). 13C NMR (62.5 MHz, CDCl3) δ
(ppm): 170.3, 134.8, 132.3, 129.1, 123.2, 58.8, 53.4, 42.2. IR
(ATR, cm-1): 3247, 2982, 1744, 1470, 1399,1318, 1155, 1084.
HRMS (ESI+): Calcd. for [C10H12SBrNO4+H]+: 321.9743,
found: 321.9745.
Brown oil, 17 mg, 40%. Rf = 0.33 (3:7 Hex:DCM). H NMR
(250 MHz, CDCl3) δ (ppm): 7.88 (s, 1H), 7.75 – 7.72 (m, 2H),
7.59 (d, J = 8.6 Hz, 1H), 7.46 – 7.44 (m, 2H), 7.18 – 7.00 (m,
6H), 6.30 (s, 1H), 3.82 (s, 3H), 3.16 (s, 3H). 13C NMR (62.5
MHz, CDCl3) δ (ppm): 172.0, 133.4 (2x), 133.1, 132.8, 131.5,
129.9, 129.7, 128.6, 128.5, 128.4, 128.2, 127.5, 126.9, 126.2,
66.1, 52.7, 40.0. IR (ATR, cm-1): 3049, 2929, 1744, 1612, 1450,
1348, 1207, 1155, 1073. HRMS (ESI+): Calcd. for
[C20H19SNO4+H]+: 370.1108, found: 370.1119.
methyl 2-(4-chlorophenyl)-2-(methylsulfonamido)acetate (15m):
1
White solid, 12 mg, 42%. Rf = 0.36 (6:4 Hex:AcOEt). H NMR
(250 MHz, CDCl3) δ (ppm): 7.38 (d, J = 8.6 Hz, 2H), 7.33 (d, J
methyl 2-(N-benzylmethylsulfonamido)-2-phenylacetate (15g):

9
= 8.6 Hz, 2H), 5.60 (d, J = 6.2 Hz, 1H), 5.20 (d, J = 6.2 Hz, 1H),
3.75 (s, 3H), 2.77 (s, 3H). 13C NMR (62.5 MHz, CDCl3) δ
(ppm): 170.4, 135.1, 134.3, 129.4, 128.8, 58.8, 53.4, 42.2. M.P.:
(ESI+): Calcd. for [C13H9F6NO4+H]+: 358.0509, found:
358.0501.
o
107 - 109 C. IR (ATR, cm-1): 3270, 2929, 1754, 1662, 1500,
methyl 2-(4-bromophenyl)-2-(2-oxopyrrolidin-1-yl)acetate (17d):
Colorless oil, 15 mg, 46%. Rf = 0.4 (3:7 Hex:DCM). H NMR
1
1420, 1328, 1165, 1076. HRMS (ESI+): Calcd. for
[C10H12SClNO4+H]+: 278.0248, found: 278.0252.
(250 MHz, CDCl3) δ (ppm): 7.86 – 7.83 (m, 2H), 7.73 – 7.70
(m, 2H), 7.48 (d, J = 7.6 Hz, 2H), 6.87 (d, J = 7.6 Hz, 2H), 5.97
(s, 1H), 3.80 (s, 3H), 3.79 (s, 3H). 13C NMR (62.5 MHz, CDCl3)
δ (ppm): 168.8, 167.1, 159.7, 134.2, 131.9, 131.1, 126.6, 123.6,
113.9, 55.3 (2x), 53.0. IR (ATR, cm-1): 2920, 1737, 1704, 1613,
1516, 1389, 1248, 1102. HRMS (ESI+): Calcd. for
[C18H15NO5+H]+: 326.1023, found: 326.1035.
methyl 2-(2-methoxyphenyl)-2-(methylsulfonamido)acetate (15n)
Colorless oil, 19 mg, 70%. Rf = 0.42 (6:4 Hex:AcOEt). 1H NMR
(250 MHz, CDCl3) δ (ppm): 7.38-7.27 (m, 2H), 7.00-6.89 (m,
2H), 5.64 (d, J = 8.4 Hz, 1H), 5.27 (d, J = 8.4 Hz, 1H), 3.83 (s,
3H), 3.71 (s, 3H), 2.82 (s, 3H). 13C NMR (62.5 MHz, CDCl3) δ
(ppm): 171.1, 156.7, 130.4, 130.1, 124.8, 121.1, 111.2, 57.0,
55.6, 53.0, 41.9. IR (ATR, cm-1): 3280, 2964, 1739, 1526, 1359,
1159, 1068. HRMS (ESI+): Calcd. for [C11H15NO5S+H]+:
274.0744, found: 274.0749.
methyl
2-(3,4-dimethoxyphenyl)-2-(1,3-dioxoisoindolin-2-
yl)acetate (17e):
1
White solid, 14 mg, 40%. Rf = 0.5 (3:7 Hex:DCM). H NMR
(250 MHz, CDCl3) δ (ppm): 7.88 – 7.84 (m, 2H), 7.78 – 7.71
(m, 2H), 7.15-7.09 (m, 2H), 6.83 (d, J = 7.5 Hz, 1H), 5.95 (s,
1H), 3.89 (s, 3H), 3.86 (s, 3H), 3.81 (s, 3H). 13C NMR (62.5
MHz, CDCl3) δ (ppm): 168.7, 167.2, 149.3, 148.8, 134.3, 134.2,
131.8, 127.0, 123.6, 122.5, 112.9, 110.8, 56.0, 55.7, 53.1. M.P.:
allyl 2-(4-bromophenyl)-2-(methylsulfonamido)acetate (15o)
1
Colorless oil, 17 mg, 49%. Rf = 0.5 (6:4 Hex:AcOEt). H NMR
(250 MHz, CDCl3) δ (ppm): 7.53 (d, J = 8.3 Hz, 2H), 7.27 (d, J
= 8.3 Hz, 2H), 5.82-5.73 (m, 1H), 5.54 (d, J = 6.3 Hz, 1H), 5.24-
5.16 (m, 3H), 4.71-4.56 (m, 2H), 2.77 (s, 3H). 13C NMR (62.5
MHz, CDCl3) δ (ppm): 169.5, 134.8, 132.4, 130.7, 129.1, 123.3,
119.5, 67.0, 58.9, 42.3. IR (ATR, cm-1): 1745, 1711, 1488, 1467,
1379, 1290, 1211, 1183, 1100, 1072. HRMS (ESI+): Calcd. for
[C12H14BrNO4S+H]+: 347.9900, found: 347.9901.
159 - 161 C. IR (ATR, cm-1): 2918, 1752, 1719, 1521, 1385,
o
1257, 1147. HRMS (ESI+): Calcd. for [C19H17NO6+H]+:
356.1129, found: 356.1140.
methyl
2-(4-chlorophenyl)-2-(1,3-dioxoisoindolin-2-yl)acetate
(17f):
1
General Procedure D: Blue light-promoted N-H insertion of
imides 16 into aryldiazoacetates 7.
Colorless oil, 16 mg, 48%. Rf = 0.33 (3:7 Hex:DCM). H NMR
(250 MHz, CDCl3) δ (ppm): 7.88 – 7.84 (m, 2H), 7.75 – 7.72
(m, 2H), 7.49 (d, J = 8.5 Hz, 2H), 7.33 (d, J = 8.5 Hz, 2H), 5.97
(s, 1H), 3.81 (s, 3H). 13C NMR (62.5 MHz, CDCl3) δ (ppm):
168.2, 167.0, 134.7, 134.4, 132.9, 131.7, 131.2, 128.8, 123.7,
55.1, 53.2. IR (ATR, cm-1): 2912, 1750, 1711, 1600, 1493, 1382,
Under air, at room temperature, a 4-mL vial is charged with
aryldiazoacetate 7 (0.1 mmol, 1 equiv.), imide 16 (0.5 mmol, 5
equiv.) and DCM (3 mL, 0.033 M in respect to aryldiazoacetate
7). The reaction mixture is stirred at room temperature under blue
light irradiation for 16 h (using two LED lamps, 15 W each,
displaced at approximate distances of 5 cm each from the
reaction vessel). Then, the reaction mixture is concentrated under
reduced pressure and purified by flash column chromatography
to afford the corresponding N-H inserted imides 17 in the stated
yields.
1218,
1091,
1020.
HRMS
(ESI+):
Calcd.
for
[C17H12ClNO4+H]+: 330.0528, found: 330.0538.
methyl
2-(4-bromophenyl)-2-(1,3-dioxoisoindolin-2-yl)acetate
(17g):
1
Colorless oil, 17 mg, 45%. Rf = 0.33 (3:7 Hex:DCM). H NMR
(250 MHz, CDCl3) δ (ppm): 7.88 – 7.84 (m, 2H), 7.76 – 7.72
(m, 2H), 7.49 (d, J = 8.0 Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 5.96
(s, 1H), 3.81 (s, 3H). 13C NMR (62.5 MHz, CDCl3) δ (ppm):
168.1, 167.0, 134.4, 133.4, 131.8, 131.7, 131.5, 123.7, 123.0,
55.1, 53.2. IR (ATR, cm-1): 2911, 1750, 1715, 1600, 1384, 1184.
HRMS (ESI+): Calcd. for [C17H12BrNO4+H]+: 374.0022, found:
374.0025.
methyl 2-(1,3-dioxoisoindolin-2-yl)-2-phenylacetate26 (17a):
1
White solid, 15 mg, 52%. Rf = 0.25 (3:7 Hex:DCM). H NMR
(250 MHz, CDCl3) δ (ppm): 7.87 – 7.84 (m, 2H), 7.74 – 7.70
(m, 2H), 7.57 – 7.53 (m, 2H), 7.37 – 7.34 (m, 3H), 6.02 (s, 1H),
3.81 (s, 3H). 13C NMR (62.5 MHz, CDCl3) δ (ppm): 168.5,
167.1, 134.4, 134.2, 131.8, 129.7, 128.6 (x2), 123.6, 55.8, 53.0.
methyl 2-(2,5-dioxopyrrolidin-1-yl)-2-phenylacetate (17b):
Colorless oil, 12 mg, 47%. Rf = 0.24 (3:7 Hex:DCM). H NMR
methyl 2-(3,4-difluorophenyl)-2-(1,3-dioxoisoindolin-2-yl)acetate
1
(17h):
1
(250 MHz, CDCl3) δ (ppm): 7.51 – 7.47 (m, 2H), 7.36 – 7.33
(m, 3H), 5.84 (s, 1H), 3.79 (s, 3H), 2.74 (s, 4H). 13C NMR (62.5
MHz, CDCl3) δ (ppm): 175.8, 168.0, 133.9, 130.0, 128.8, 128.5,
56.4, 53.1, 28.2. IR (ATR, cm-1): 2915, 1702, 1610, 1387, 1240,
1175, 1089, 1005. HRMS (ESI+): Calcd. for [C13H13NO4+H]+:
248.0917, found: 248.0911.
Colorless oil, 12 mg, 37%. Rf = 0.33 (DCM). H NMR (250
MHz, CDCl3) δ (ppm): 7.89 – 7.86 (m, 2H), 7.77 – 7.73 (m,
2H), 7.48 – 7.40 (m, 1H), 7.29 – 7.24 (m, 1H), 7.15 – 7.08 (m,
1H), 5.94 (s, 1H), 3.81 (s, 3H). 13C NMR (62.5 MHz, CDCl3) δ
(ppm): 167.8, 166.9, 150.5 (dd, J = 124.4 Hz, J = 5.6 Hz), 150.0
(dd, J = 123.8 Hz, J = 6.3Hz), 134.4, 131.6, 131.3 (dd, J = 2.7Hz,
J =2.5 Hz), 126.1 (dd, J = 3.1 Hz, J = 1.9Hz), 123.8, 119.1 (d, J
= 9.4Hz), 117.3 (d, J = 8.8 Hz), 54.6, 53.3. 19F NMR (235 MHz,
CDCl3) δ (ppm): -136.5 (d, J = 10.6Hz), -137.2 (d, J = 10.6Hz).
IR (ATR, cm-1): 2930, 1764, 1714, 1632, 1531, 1389, 1277,
1115. HRMS (ESI+): Calcd. for [C17H11F2NO4+H]+: 332.0729,
found: 332.0736.
methyl
2-phenyl-2-(2,2,2-trifluoro-N-(2,2,2-
trifluoroacetyl)acetamido)acetate (17c): Yellow solid, 17 mg,
48%. Rf = 0.29 (8:2 Hex:AcOEt). 1H NMR (250 MHz, CDCl3) δ
(ppm): 7.43 – 7.41 (m, 2H), 7.38 – 7.33 (m, 3H), 5.18 (s, 1H),
3.76 (s, 3H). 13C NMR (62.5 MHz, CDCl3), 1C could not be
unambiguously assigned, δ (ppm): 174.1, 158.6 (q, J = 17.5Hz),
138.1, 128.6, 128.5, 126.6, 72.9, 53.0. 19F NMR (235 MHz, d6-
DMSO) δ (ppm): -73.7. MP: 40 - 42 oC. IR (ATR, cm-1): 3442,
1739, 1693, 1456, 1436, 1188, 1162, 1097, 1069. HRMS
allyl
2-(4-bromophenyl)-2-(1,3-dioxoisoindolin-2-yl)acetate
(17i)
Colorless oil, 22 mg, 54%. Rf = 0.45 (3:7 Hex:AcOEt). 1H NMR
(250 MHz, CDCl3) δ (ppm): 7.88-7.83 (m, 2H), 7.77-7.72 (m,

10
Tetrahedron
Biomol Chem. 2019, 17, 432-448. b) Candeias, N. R.; Afonso, C.
A. M.; Curr. Org. Chem. 2009, 13, 763-787. c) Galkina, O. S.;
Rodina, L. L.; Russ. Chem. Rev. 2016, 85, 537-555.
2H), 7.49 (d, J = 8.8 Hz, 2H), 7.43 (d, J = 8.8 Hz, 2H), 5.98
(s, 1H), 5.95-5.80 (m, 1H), 5.25-5.20 (m, 2H), 4.79-4.65 (m, 2H).
13C NMR (62.5 MHz, CDCl3), 1C cannot be unambiguously
assigned, δ (ppm): 167.3, 167.0, 134.4, 133.4, 131.7, 131.5,
131.2, 123.7, 122.9, 119.1, 66.9, 55.2. IR (ATR, cm-1): 3275,
1735, 1488, 1437, 1410, 1323, 1248, 1205, 1149. HRMS
(ESI+): Calcd. for [C19H14BrNO4 + H]+: 400.0179, found:
400.0179.
13 a) Jurberg, I. D.; Davies, H. M. L.; Chem. Sci. 2018, 5112-5118.
b) Guo, Y.; Nguyen, T. V.; Koenigs, R. M.; Org. Lett. 2019, 21,
8814-8818. c) Zhang, X.; Du, C.; Zhang, H.; Li, X.-C.; Wang, Y.-
L.; Niu, J. L.; Song, M.-P.; Synthesis 2019, 51, 889-898. d) Xiao,
T.; Mei, M.; He, Y.; Zhou, L.; Chem. Commun. 2018, 54, 8865-
8868. e) Hommelsheim, R.; Guo, Y.; Yang, Z.; Empel, C.;
Koenigs, R. M.; Angew. Chem. Int. Ed. 2019, 58, 1203-1207. f)
He, F.; Koenigs, R. M.; Chem. Commun. 2019, 55, 4881-4884. g)
Yang, Z.; Guo, Y.; Koenigs, R. M.; Chem. Eur. J. 2019, 25, 6703-
6706. h) Yang, J.; Wang, J.; Huang, H.; Qin, G.; Jiang, Y.; Xiao,
T.; Org. Lett. 2019, 21, 2654-2657. i) Orłowska, K.; Rybicka-
Jasińska, K.; Krajewski, P.; Gryko, D.; Org. Lett. 2020, 22, 1018-
1021. j) Jana, S.; Yang, Z.; Pei, C.; Xu, X.; Koenigs, R. M.; Chem.
Sci. 2019, 10, 10129-10134. k) Empel, C.; Patureau, F. W.;
Koenigs, R. M.; J. Org. Chem. 2019, 84, 11316-11322. l)
Stivanin, M. L.; Fernandes, A. A. G.; da Silva, A. F.; Okada Jr., C.
Y.; Jurberg, I. D. Adv. Synth. Catal. 2020, 362, 1106-1111. m) He,
F.; Li, F.; Koenigs, R. M.; J. Org. Chem. 2020, 85, 1240-1246. n)
da Silva, A. F.; Afonso, M. A. S.; Cormanich, R. A.; Jurberg, I. D.
Chem. Eur. J. 2020, 26, 5648-5653.
Acknowledgments
The authors gratefully acknowledge CNPq for a PhD
Fellowship to C. Y. O. Jr and Fapesp for a Research Grant to I.
D. J. (2017/24017-0).
References and notes
1. Lau, J. L.; Dunn, M. K. Bioorg. Med. Chem. 2018, 26, 2700-2707.
2. For a selection of reviews, see: a) Young, T. S.; Schultz, P. G. J.
Biol. Chem. 2010, 285, 11039-11044. b) Maluch, I.; Czarna, J.;
Drag, M.; Chem. Asian J. 2019, 14, 4103-4113. c) Lang, K.; Chin,
J. W.; Chem. Rev. 2014, 114, 4764-4806. d) Hodgson, D. R. W.;
Sanderson, J. M. Chem. Soc. Rev. 2004, 33, 422-430.
14 For other previous contributions from our group to the chemistry
of aryldiazoacetates, see: a) Jurberg, I. D.; Davies, H. M. L.; Org.
Lett. 2017, 19, 5158-5161. b) Thurow, S.; Fernandes, A. A. G.;
Quevedo-Acosta, Y.; de Oliveira, M. F.; de Oliveira, M. G.;
Jurberg, I. D.; Org. Lett. 2019, 21, 6909-6913.
3. For a selection of references, see: a) Schöllkopf, U.; Busse, U.;
Lonsky, R.; Hinrichs, R. Liebigs Ann. Chem. 1986, 2150-2163. b)
Ager, D. J.; Prakash, I.; Schaad, D. R.; Chem. Rev. 1996, 96, 835-
876. c) Seebach, D.; Juaristi, E.; Miller, D. D.; Schickli, C.;
Weber, T. Helv. Chim. Acta 1987, 70, 237-261.
15 S. Jana; Z. Yang; F. Li; C. Empel; J. Ho; R. M. Koenigs; Angew.
Chem. Int. Ed. 2020, 59, 5562-5566.
16 a) Saito, H.; Morita, D.; Uchiyama, T.; Miyake, M.; Miyairi, S.;
Tetrahedron Lett. 2012, 53, 6662-6664. b) Xu, B.; Zhu, S.-F.; Xie,
X.-L.; Shen, J.-J.; Zhou, Q.-L.; Angew. Chem. Int. Ed. 2011, 50,
11483-11486. c) Ren, Y.-Y.; Zhu, S.-F.; Zhou, Q.-L.; Org.
Biomol. Chem. 2018, 16, 3087-3094.
17 Bordwell, F. G.; Fried, H. E.; J. Org. Chem. 1991, 56, 4218-4223.
18 To the best of our knowledge, the pKa of isatin in DMSO has not
been previously reported. One can infer to be somehow similar or
lower than 18.2, which corresponds to the pKa (DMSO) of 2-
oxindole. See ref. 17.
19 Bordwell, F. G.; Algrim, D.; J. Org. Chem. 1976, 41, 2507-2508.
20 Bordwell, F. G.; Acc. Chem. Res. 1988, 21, 456-463.
21 Chan, W.-W.; Y.; S.-H.; Zhou, Z.; Chan, A. S. C.; Yu, W.-Y.;
Org. Lett. 2010, 12, 604-607.
22 Spectroscopic data are in good agreement with reported literature.
See: Mita, T.; Chen, J.; Sato, Y. Org. Lett., 2014, 16, 2200–2203.
23 Spectroscopic data are in good agreement with reported literature.
See: Kang, J.; Chen, L.; Cui, H.; Zhang, Li; Su, C.-Y. Chinese J.
Chem. 2017, 35, 964 – 968.
24 Spectroscopic data are in good agreement with reported literature.
See: Kawahara, S.; Nakano, A.; Esumi, T.; Iwabuchi, Y.;
Hatakeyama, S.; Org. Lett. 2003, 5, 3103-3105.
25 Spectroscopic data are in good agreement with reported literature.
See: Mita, T.; Higuchi, Y.; Sato, Y. Chem. Eur. J. 2013, 19, 1123 -
1128.
26 Spectroscopic data are in good agreement with reported literature.
See: Sánchez-Antonio, O.; González-Olvera, R.; Aguilera-Cruz,
A.; Reyes-Ramírez, A.; Juaristi, E. Tetrahedron 2019, 75, 130594.
4
For reviews, see: a) O'Donnell, M. J.; Acc. Chem. Res. 2004, 37,
506-517. b) Lygo, B.; Andrews, B. I. Acc. Chem. Res. 2004, 37,
518-525. For a selection of references, see: c) O'Donnell, M. J.;
Wu, S.; Huffman, J. C.; Tetrahedron 1994, 50, 4507-4518. d)
Corey, E. J.; Xu, F.; Noe, M. C.; J. Am. Chem. Soc. 1997, 119,
12414-12415. e) Ooi, T.; Kameda, M.; Maruoka, K.; J. Am. Chem.
Soc. 1999, 121, 6519-6520. f) Ooi, T.; Takeuchi, M.; Kameda, M.;
Maruoka, K.; J. Am. Chem. Soc. 2000, 122, 5228-5229.
See for instance: a) Koskinen, A. M. P.; Hassila, H.; Myllymäki,
V. T.; Rissanen, K.; Tetrahedron Lett. 1995, 36, 5619-5622. b)
Dunn, M. J.; Jackson, R. F. W.; Tetrahedron 1997, 53, 13905-
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D.; Tetrahedron: Asymmetry 1995, 6, 2819-2828.
5
6
7
Kenworthy, M. N.; Kilburn, J. P.; Taylor, R. J. K.; Org. Lett.
2004, 6, 19-22.
a) Sabat, M.; Johnson, C. R.; Org. Lett. 2000, 2, 1089-1092. b)
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Kenworthy, M. N.; Taylor, R. J. K. Tetrahedron 2004, 45, 2467-
2471.
8
See for instance: a) Cox, G. G.; Harwood, L. M.; Tetrahedron:
Asymmetry, 1994, 5, 1669-1672. b) Evans, D. A; Britton, T. C.;
Dorow, R. L.; Dellaria, J. F.; J. Am. Chem. Soc. 1986, 108, 6395-
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Supplementary Material
1
Supplementary material contains H and 13C NMR spectra of all
9
See for instance: a) Gröger, H. Chem. Rev. 2003, 103, 2795-2827.
b) Yet, L. Angew. Chem. Int. Ed. 2001, 40, 875-877.
N-H inserted compounds reported in this work.
10 See for instance: a) Stewart, J. D.; Curr. Opin. Chem. Biol. 2001,
5, 120-129. b) Schulz, A.; Taggeselle, P.; Tripier, D.; Bartsch, K.;
Appl. Environ. Microbiol. 1990, 56, 1-6. c) Li, T.; Kootstra, A. B.;
Fotheringham, I. G.; Org. Process Res. Dev. 2002, 6, 533-538. d)
Galkin, A.; Kulakova, L.; Yamamoto, H.; Tanizawa, K.; Tanaka,
H.; Esaki, N.; Soda, K. J. Ferment. Bioeng. 1997, 83, 299-300.
11 See for instance: a) Brunhuber, N. M. W.; Blanchard, J. S.; Crit.
Rev. Biochem. Mol. Biol. 1994, 29, 415-467. b) Brunhuber, N. M.
W.; Thoden, J. B.; Blanchard, J. S.; Vanhooke, J. L.; Biochemistry
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Kottenhahn, M.; Schwarm, M.; Kula, M.-R.; J. Biotechnol. 1997,
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12 For reviews on photochemical reactions using diazo compounds,
see: a) Ciszewski, Ł. W.; Rybicka-Jasińska, K.; Gryko, D.; Org.

Declaration of interests
☒ The authors declare that they have no known competing financial interests or personal relationships
that could have appeared to influence the work reported in this paper.
☐The authors declare the following financial interests/personal relationships which may be considered
as potential competing interests: