Protonation and transformations of α-diazo-β-dicarbonyl compounds in superacids: generation of the strongest carbon-centered cationic electrophiles at the protonation of diazomalonates in Friedel–Crafts reactions

Article abstract of DOI:10.1016/j.tet.2016.06.051

Protonation of diazodiketones N₂C(COR)₂in Br?nsted superacids (TfOH, FSO₃H, TfOH–SbF₅) gives rise to stable and non-reactive O,O-diprotonated at carbonyl oxygens species N₂C(C(=OH⁺)R)₂, which were studied by means of¹H and¹³C NMR. Diazomalonates N₂C(CO₂Alk)₂, contrary to diazodiketones, react with TfOH or HF, releasing nitrogen and producing triflates of oxymalonates TfOCH(CO₂Alk)₂or fluoromalonates FCH(CO₂Alk)₂, respectively. Diazoketoesters N₂C(COR)(CO₂Alk) react in the same way only with TfOH, but not with HF. The reactions of diazomalonates with arenes ArH (benzene, toluene, xylenes) in TfOH solution yield corresponding Friedel–Crafts reaction products ArCH(CO₂Alk)₂. According to performed DFT calculations, trication⁺CH(C(=OH⁺)OMe)₂, a possible intermediate, which is derived from protonation of dimethyl diazomalonate, should be the strongest cationic carbon-centered electrophile known up to date.

Full text of DOI:10.1016/j.tet.2016.06.051

Tetrahedron 72 (2016) 4835e4844
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Protonation and transformations of a-diazo-b-dicarbonyl
compounds in superacids: generation of the strongest
carbon-centered cationic electrophiles at the protonation of
diazomalonates in FriedeleCrafts reactions
,
b
Eugeniy T. Satumov a, Jury J. Medvedev a, Denis I. Nilov a, Maria A. Sandzhieva a
,
,b,
Irina A. Boyarskaya a, Valerij A. Nikolaev a, Aleksander V. Vasilyev a
*
a Department of Organic Chemistry, Institute of Chemistry, Saint Petersburg State University, Universitetskaya nab., 7/9, Saint Petersburg 199034, Russia
b Department of Chemistry, Saint Petersburg State Forest Technical University, Institutsky per. 5, Saint Petersburg 194021, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 April 2016
Received in revised form 6 June 2016
Accepted 20 June 2016
Available online 27 June 2016
Protonation of diazodiketones N2C(COR)2 in Brønsted superacids (TfOH, FSO3H, TfOHeSbF5) gives rise to
stable and non-reactive O,O-diprotonated at carbonyl oxygens species N2C(C(]OHþ)R)2, which were
studied by means of 1H and 13C NMR. Diazomalonates N2C(CO2Alk)2, contrary to diazodiketones, react
with TfOH or HF, releasing nitrogen and producing triflates of oxymalonates TfOCH(CO2Alk)2 or fluo-
romalonates FCH(CO2Alk)2, respectively. Diazoketoesters N2C(COR)(CO2Alk) react in the same way only
with TfOH, but not with HF. The reactions of diazomalonates with arenes ArH (benzene, toluene, xylenes)
in TfOH solution yield corresponding FriedeleCrafts reaction products ArCH(CO2Alk)2. According to
performed DFT calculations, trication þCH(C(]OHþ)OMe)2, a possible intermediate, which is derived
from protonation of dimethyl diazomalonate, should be the strongest cationic carbon-centered elec-
trophile known up to date.
Keywords:
Diazocompounds
Superacids
Triflates
Fluoroorganic compounds
FriedeleCrafts reactions
Ó 2016 Elsevier Ltd. All rights reserved.
1. Introduction
was to investigate the protonation and subsequent trans-
formations of diazodicarbonyl compounds in Brønsted superacids,
Diazocarbonyl compounds play an important role in organic
synthesis. In general, reactions of these compounds are catalyzed
by transition metal compounds and proceed via the formation of
metalecarbene complexes as key intermediates leading to various
functionalized derivatives of carbo- and heterocycles.1 Apart from
that, many reactions of diazocarbonyl compounds are promoted by
Brønsted acids (see reviews 2aec). The transformation of diazo-
compounds in Brønsted superacids still remains a poorly studied
area of chemistry (see recent research papers 2d,e). At the same
time, strong ability of protonation and extremely low nucleophi-
licity of superacids play a crucial role in the generation and stabi-
lization of cationic species. The application of superacids in the
chemistry of diazocompounds could provide new possibilities for
organic synthesis.
including FriedeleCrafts reactions with arenes. Three types of
diazodicarbonyl compounds, diazodiketones 1aee, diazo-
ketoesters 1f,g, and diazomalonates 1h,i, were used in this study
(Fig. 1).
2. Results and discussion
2.1. NMR study of protonation of diazocompounds 1aei in
Brønsted superacids. Reactions of diazocompounds 1fei with
TfOH and HF
First, the stability of diazocompounds 1aei was investigated in
various Brønsted superacids. It was found that diazoketoesters 1f,g
and diazomalonates 1h,i reacted with CF3SO3H (TfOH) (Hammet
acidity function H0 ꢀ14 [see Ref. 4]) or FSO3H (H0 ꢀ15) at room
temperature releasing nitrogen (vide infra). Despite this fact,
diazodiketones 1aee were stable not only in solutions of these
acids, but even in much more stronger conjugate BrønstedeLewis
superacid TfOHeSbF5 (H0 wꢀ19) at room temperature. No evolu-
tion of nitrogen was observed with diazodiketones 1aee and they
This research is an expansion of our recent works on activation
of organic compounds in superacids.3 The main goal of the project
* Corresponding author. Tel./fax: þ7 812 670 93 90; e-mail address: aleksvasil@
mail.ru (A.V. Vasilyev).
http://dx.doi.org/10.1016/j.tet.2016.06.051
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

4836
E.T. Satumov et al. / Tetrahedron 72 (2016) 4835e4844
O
O
O
O
O
O
O
Ph
Ph
Me
Ph
Me
Me
Me
Me
N2
N2
N2
N2
N2
Cl
Me
O
O
O
O
1e
1a
1c
1d
1b
O
O
O
O
O
Ph
Me
MeO
MeO
EtO
EtO
N2
N2
N2
N2
EtO
1g
MeO
1f
O
O
1h
1i
Fig. 1. Diazocompounds 1aei used in this study.
were quantitatively recovered after quenching of their superacid
solutions with water.
Based on this extreme stability and non-reactivity of 1aee in
superacids, we undertook a study on their protonation in TfOH and
FSO3H using NMR. Table 1 contains the data on 13C NMR spectra of
diazodiketones 1aee in CDCl3 and their protonated forms in TfOH
at room temperature (see spectral figures in Supplementary data).
Principally, compounds 1aee in TfOH solutions may form pro-
tonated (specifically solvated) species on the carbonyl oxygen
atoms and/or on the nitrogen atom of diazo group. However, taking
Table 1
Selected 13C NMR data of starting diazodiketones 1aee (CDCl3) and their protonated forms (TfOH)
Diazodiketones
13C NMR data (500 MHz, room temperature)
Signal of C]O
Signal of C]N
Starting diazodiketone Protonated form
Chemical shift
Starting diazodiketone Protonated form
Chemical shift difference
dTfOH dCDCl
in CDCl3, dCDCl , ppm
in TfOH, dTfOH, ppm difference
in CDCl3, dCDCl , ppm
in TfOH, dTfOH, ppm DdC
¼
ꢀ
3
3
3
DdC
¼
dTfOH
ꢀ
dCDCl
3
O
Me
N2
189.0
186.0
199.4
196.4
10.4
82.6
95.2
12.6
Me
O
1a
O
Ph
N2
10.4
12.2
83.9
83.5
87.7
90.5
3.8
7.0
Ph
O
1b
O
Me
190.6
[C]O(Me)]
184.9
202.8
[C]O(Me)]
195.3
N2
[C]O(Me)]
10.4
[C]O(Ph)]
Ph
[C]O(Ph)]
[C]O(Ph)]
O
1c
O
Me
189.9
[C]O(Me)]
183.5
203.4
[C]O(Me)]
193.90
13.5
[C]O(Me)]
10.5
83.3
90.5
7.2
N2
Cl
[C]O(Ar)]
[C]O(Ar)]
[C]O(Ar)]
O
1d
O
Me
N2
190.7
202.0
11.3
83.1
89.3
6.2
Me
[C]O(Me)]
184.6
[C]O(Me)]
194.5
[C]O(Me)]
9.9
O
[C]O(Ar)]
[C]O(Ar)]
[C]O(Ar)]
1e

E.T. Satumov et al. / Tetrahedron 72 (2016) 4835e4844
4837
into account the higher basicity of the carbonyl oxygen
carbonyl oxygens may give several signals, as well. Due to exchange
with superacidic media, the signals of these protons are broadened
and so their integration is not quantitative. Also the signals of ar-
omatic protons were broad and unresolved due to high viscosity of
FSO3H at ꢀ80 ꢁC.
þ
ðpKBH ¼ ꢀ2:85 to ꢀ 5:55Þ, one would expect that the pre-
dominant protonated forms of diazodiketones 1aee are O,O-
diprotonated structures Aaee. Further protonation of diazo group
is unlikely. This is in agreement with the literature data on pro-
tonation of diazomonocarbonyl compounds, which produce in
superacids only O-protonated cations.1a,5
When reactions of compounds 1fei were carried out in neat
TfOH, the evolution of nitrogen was observed. Diazomalonates 1h,i
reacted with TfOH at room temperature very fast leading easily to
the formation of the corresponding triflates of oxymalonates 2c,d
in quantitative yields (Scheme 2). The same type of extrusion of
nitrogen by the triflate group occured with diazoketoesters 1f,g.
Nevertheless, in this case formation of triflates 2a,b took place
harder and required increasing of reaction time up to 4 h (Scheme
2). It should be noted that these types of dicarbonyl triflates 2 are
rare.8
In the 1H NMR spectra of protonated forms of 1aee the signals of
protons bonded to carbonyl oxygen were not registered due to the
fast proton exchange in superacid TfOH at room temperature (see
spectral figures in Supplementary data). Also, for compounds 1aee
all signals of protons of aryl and alkyl groups in TfOH were down-
field shifted relative to the same signals in CDCl3. The difference
of the chemical shifts of carbonyl groups in 13C NMR spectra in TfOH
and CDCl3 solutions was around 9.9e13.5 ppm (see Table 1). This
kind of down-field shift of these carbon signals indicates a sub-
stantial degree of protonation of carbonyl groups in TfOH. When
compared to the carbon spectra in CDCl3, the signals of carbon
atoms of diazo group were down-field shifted for 3.8e12.6 ppm
(see Table 1). This may point out to an induced shift due to the
protonation of carbonyls. Protonation of carbon atom of diazo
group in 1aee was not observed by 1H and 13C NMR, since no new
signals corresponding to CeH fragment were registered in the
spectra.
Therefore, qualitative observation shows that diazodiketones
1aee are very stable and completely non-reactive in superacids
(vide supra), while diazoketoesters 1f,g react harder than diazo-
malonates 1h,i. This range of the reactivity reflects a difference in
an electron withdrawing character of the protonated keto and ester
groups. According to the found range of basicity of these groups in
the superacids PhC]O>MeC]O>CO2Et,3a similar range should be
assumed for the acceptor properties of the protonated groups
PhC(]OHþ)>MeC(]OHþ)>C(]OHþ)OEt. It means that pro-
tonated keto and ester groups in the species Afei (Scheme 3),
which are derived from diazoketoesters 1f,g and diazomalonates
1h,i, are weaker acceptors relative to O-protonated keto groups in
diazodiketones 1aee. Consequently, in superacids further pro-
tonation of carbon or nitrogen atoms of diazo group in the com-
pounds 1gei (but not in 1aee) may occur leading to the formation
of the species Bfei or Dfei, respectively (Scheme 3). It is very
likely that both of these species may eliminate nitrogen giving rise
to intermediate species Cfei or react with triflate ion producing
triflates 2 (Scheme 2).
Three new signals of protons, which are attached to carbonyl
oxygens, were observed in the region of 14e15.5 ppm in 1H NMR
spectrum of protonated form of diazodiketone 1e in FSO3H at low
temperature ꢀ80 ꢁC (Fig. 2). Proton exchange with superacidic
medium is suppressed at ꢀ80 ꢁC as compared to room temperature.
The most probably that protonation of two carbonyl groups of 1e
leads to a dication, the structure of which may be presented as the
mesomeric forms I, II, and III or as a general form Ae (Scheme 1).
Moreover, at this low temperature dication Ae may exist as E,Z-
conformers (Scheme 1) with hindered rotation around C(O)eC(N2)
bonds, analogous to E,Z-conformers of the initial diazodicarbonyl
compounds.6,7 An observation of several signals of non-equivalent
methyl group of acetyl moiety in 1H NMR (Fig. 2) may be an addi-
tional evidence for the existence of E,Z-conformers of Ae. Apart
from that, in these conformers the protons, which are bonded to
The fluorination of diazomalonates 1h,i with neat HF gave rise
to fluoromalonates 3a,b, respectively (Scheme 4). Ketoesters 1f,g
did not react with HF, due to its reduced acidity as compared to
TfOH. Diazomalonates 1h,i did not lead to formation of corre-
sponding compounds 3a,b in less acidic system HFepyridine,
CH2Cl2
Me(Ar)
FSO3H
OH
Me
+
N2
Me
2Harom.
OH
2Harom.
Ae
COMe
protons bonded to
carbonyl oxygens
1
Fig. 2. H NMR spectrum of protonated form Ae of diazodiketone 1e in FSO3H at 80 ꢁC (500 MHz, CH2Cl2 was added as internal standard).

4838
E.T. Satumov et al. / Tetrahedron 72 (2016) 4835e4844
OH+
Me
+
N2
Ar
O H
O
O
O H
N2
O H
OH
II
Me
Ar
H+
Me
Ar
Me
Ar
+
N2
N2
O H
O H
Ae
I
1e
Me
Ar
+
N2
Ar =
Me
O H
III
Me
Ar
OH
OH
Me
OH
N2
HO
HO
Me
Ar
HO
Ar
Me
HO
+
+
N2
+
+
N2
N2
OH
E-,Z-Ae
Ar
Z-,E-Ae
E-,E-Ae
Z-,Z-Ae
Scheme 1. Possible structures of protonated forms of diazodiketone 1e.
O
O
O
which was previously used for fluorination of diazomonocarbonyl
derivatives.9 This synthesis of fluoromalonates 3a,b is one of
a number of ways to diazocompounds using various fluorine
sources.10
Me
Me
TfOH, r.t., 4 h
- N2
OTf
N2
MeO
MeO
O
2a (17 %)
1f
O
O
RO
RO
RO
RO
HF, 0 oC, 5 h
- N2
O
O
N2
F
Ph
Ph
EtO
TfOH, r.t., 3 h
- N2
N2
OTf
O
O
EtO
1h (R = Me)
1i (R = Et)
3a (R = Me, 82 %)
3b (R = Et, 84 %)
O
O
1g
2b (56 %)
Scheme 4. Formation of fluoromalonates 3a,b from diazomalonates 1h,i in neat HF.
O
O
RO
RO
RO
RO
TfOH, r.t., 0.5 h
- N2
2.2. Reactions of diazocompounds 1fei with arenes in TfOH
N2
OTf
The main results on reactions of dimethyl diazomalonate 1h
with benzene under the action of TfOH are presented in Table 2.
Diazoester 1h produces FriedeleCrafts alkylation product 4a along
with triflate 2c in TfOH (entries 1e3). Other Brønsted acids FSO3H
(H0¼ꢀ15, 40 equiv, ꢀ35 ꢁC, 1 h), and Tf2NH (30 equiv, 80 ꢁC, 1 h) or
O
O
1h (R = Me)
1i (R = Et)
2c (R = Me, 95 %)
2d (R = Et, 90 %)
Scheme 2. Formation of triflates 2aed from diazodicarbonyl compounds 1fei in TfOH
(yield of 2a was low (17%) due to incomplete conversion of starting compound 1f).
O
O
OH
OH
OH
OH
OH
R'
R'
R'
R'
2 H+
H+
H
H
N2
N2
N2
OH
- N2
RO
RO
RO
RO
Af-i
Cf-i
1f-i
Bf-i
H+
- N2
OH
R'
N2
H
RO
OH
Df-i
Scheme 3. The assumed mechanism of protonation of diazoketoesters 1f,g and diazomalonates 1h,i in superacids.

E.T. Satumov et al. / Tetrahedron 72 (2016) 4835e4844
4839
Table 2
Reactions of dimethyl diazomalonate 1h with benzene in TfOH
MeO2C
N2
MeO2C
1h
MeO2C
MeO2C
MeO2C
MeO2C
H+
Ph
OTf
2c
4a
Entry
Reaction conditions
Acida
Reaction products
Yield, %
Temperature, ꢁC
Time, h
Total yield of 4a and 2c, %
Ratio of 4a/2c
4a
2c
1
2
3
4
TfOH (H0¼ꢀ14) (40 equiv)
TfOH (H0¼ꢀ14) (40 equiv)
TfOH (H0¼ꢀ14) (40 equiv)
TfOHeSbF5 (H0¼ꢀ19) (40 equiv)
rt
rt
60
rt
0.5
24
0.25
0.25
34
33
80
db
50
19
5
84
52
85
d
1:1.5
1.8:1
16:1
d
Traces
a
Hammet acidity function values H0 are from Ref. 4.
Complete conversion of 2a with formation of unidentified compounds.
b
methyltriflate MeOTf (30 equiv, 80 ꢁC, 1 h) did not yield 4a. In these
cases quantitative recovery of unreacted starting compound 1h
took place. Apart from that, reactions of 1h under the action of
FSO3H (40 equiv, rt, 1 h), TfOHeSbF5 (H0¼ꢀ19, 40 equiv, rt, 0.25 h),
H2SO4 (100 equiv, rt, 1 h), or AlCl3 (5 equiv, rt, 1 h, CH2Cl2 as co-
solvent) resulted in the formation of complex mixtures of un-
identified compounds. So, TfOH seems to be the best media to
conduct FriedeleCrafts reactions of diazomalonates with arenes.
The formation of both dimethyl phenylmalonate 4a and triflate
2c, which were formed in concurrent reactions, evidenced on the
high reactivity of intermediate cationic species (see Scheme 3),
which were derived from 1h in the superacid TfOH. A higher re-
action temperature 60 ꢁC allowed to increase the yield of 4a (entry
3), indicating that activation barrier is higher for FriedeleCrafts
process, than for triflate formation.
The same trends were observed for reaction of diazomalonate 1i
with benzene, resulting in the formation of malonate 5a and triflate
2d (Scheme 5). Contrary to compounds 1h,i, diazoketoesters 1f,g
did not give the products of benzene (and other arenes) alkylation,
forming only corresponding triflates 2a,b (see Scheme 2). It could
be explained by a higher electrophilicity and reactivity (and result,
lower selectivity) of intermediate cationic species, generated from
1f,g, as compared to the same species from 1h,i. The reason for this
is likely due to the stronger electron withdrawing properties of
protonated keto group in 1f,g, relative to protonated ester group in
1h,i (vide supra).
formed. The same reactivity was observed with anisol and veratrol,
apparently due to a proto-solvation of methoxy groups in super-
acids,4 that make these arenes slightly deactivated for electrophilic
substitution.
Both the formation of triflates 2c,d and low regioselectivity in
reactions with arenes evidence on the extremely high reactivity of
intermediate cations, which were derived from 1h,i in TfOH. Thus,
reaction with toluene affords ortho-, meta- and para-isomers 4bed
(entries 1 and 2, Table 3) and 5bed (entry 1, Table 4) in approxi-
mately equal amounts. The same situation is observed with re-
actions with o-xylene (entries 3 and 4, Table 3; entry 2, Table 4),
and m-xylene (entries 5 and 6, Table 3; entry 3, Table 4). Further-
more, the migration of methyl group in aromatic ring is observed
under the formation of compounds 4h (entries 5 and 6, Table 3), 4g
(entries 7 and8, Table 3), 5h (entry 3, Table 4), 5g (entry 4, Table
4) that is akin to the behavior of polymethylated arenes in super-
acidic media.4 Increasing the reaction temperature up to 60 ꢁC do
not lead to substantial increase of amount of FriedeleCrafts re-
action products 4 (compare pairs of experiments at rt and 60 ꢁC in
Table 4).
2.3. DFT calculations of cationic species derived from pro-
tonation of diazomalonate 1h
Based on the obtained data on transformations of diazo-
malonates 1h,i in TfOH (Scheme 2) or HF (Scheme 4), and their re-
EtO2C
TfOH
EtO2C
EtO2C
N2
Ph
OTf
0.5 h
EtO2C
EtO2C
EtO2C
5a
2d
1i
r. t.
60 oC
74 %
82 %
15 %
4 %
Scheme 5. Reaction of diazomalonate 1i with benzene in neat TfOH (40 equiv) at various temperatures for 0.5 h.
The results of reactions of diazomalonates 1h,i with donating
actions with arenes in TfOH (Tables 2e4, Scheme 5), one may
assume the formation of several intermediate cationic species B, C, D
(see Scheme 3), which are able to take part in the considered re-
actions in superacids. To estimate electronic and electrophilic
properties of such species the DFT study of cations Bh, Dh, Ch, de-
rived from diazomalonate 1h, was undertaken (Table 5). For this
purpose charge distribution, contribution of atomic orbital into
arenes (toluene, isomeric xylenes) in TfOH are presented in Tables 3
and 4. These reactions produced mixtures of FriedeleCrafts alkyl-
ation products 4bej, 5bej and triflates 2c,d. The structures of
dialkyl arylmalonates 4bej, 5bej were determined by means of 1H
NMR and GCeMS, along with comparison with literature spectral
data for these compounds (see Experimental part).
Reactions of 1h,i with electron deficient arenes, chlorobenzene,
bromobenzene, 1,2-dichlorobenzenes, did not lead to Friedele-
Crafts products at all. In these cases triflates 2c,d were solely
LUMO, and global electrophilicity indices u
11 were calculated. As it is
evident from the obtained data, among three species, Bh, Dh, Ch, the
trication Ch has the highest value of electrophilicity 24.0 eV that

4840
E.T. Satumov et al. / Tetrahedron 72 (2016) 4835e4844
Table 3
Reactions of dimethyl diazomalonate 1h with arenes in neat TfOH (40 equiv) for 0.5 h at various temperatures
R
R
MeO2C
MeO2C
MeO2C
MeO2C
MeO2C
MeO2C
TfOH
0.5 h
N2
OTf
2c
4b-j
1h
Entry
Arene, R
Reaction temperature, ꢁC
Reaction products
Dimethyl arylmalonate 4
Yield of 2c, %
Total yield of 4 and 2c, %
Ratio of 4/2c
No.
R
Yield, %
1
2
Me
Me
rt
4b
4c
4d
4b
4c
4d
4e
4f
4e
4f
4g
4h
4i
4g
4h
4i
4j
4g
4j
2-Me
3-Me
4-Me
2-Me
3-Me
4-Me
2,3-Me2
3,4-Me2
2,3-Me2
3,4-Me2
2,4-Me2
3,5-Me2
2,6-Me2
2,4-Me2
3,5-Me2
2,6-Me2
2,5-Me2
2,4-Me2
2,5-Me2
2,4-Me2
9
9
56
17
84
(4bþ4cþ4d)/2c
1:2
10
17
16
17
10
15
7
5
15
5
5
10
4
3
25
5
60
67
(4bþ4cþ4d)/2c
3:1
3
4
5
1,2-Me2
1,2-Me2
1,3-Me2
rt
48
25
57
73
37
82
(4eþ4f)/2c
1:2
60
rt
(4eþ4f)/2c
1:2
(4gþ4hþ4i)/2c
1:2
6
1,3-Me2
60
47
64
(4gþ4hþ4i)/2c
1:2.8
7
8
1,4-Me2
1,4-Me2
rt
60
19
90
49
(4jþ4g)/2c
1:2
60
24
6
(4jþ4g)/2c
4g
1.5:1
Table 4
Reactions of diethyl diazomalonate 1i with arenes in neat TfOH (40 equiv) at room temperature for 0.5 h
R
R
EtO2C
EtO2C
EtO2C
EtO2C
EtO2C
EtO2C
TfOH
N2
OTf
2d
r.t., 0.5 h
5b-j
1i
Entry
1
Arene, R
Me
Reaction products
Diethyl arylmalonate 5
Yield of 2d, %
Total yield of 5 and 2d, %
Ratio of 5/2d
No.
R
Yield, %
5b
5c
5d
5e
5f
5g
5h
5i
2-Me
3-Me
4-Me
2,3-Me2
3,4-Me2
2,4-Me2
3,5-Me2
2,6-Me2
2,5-Me2
2,4-Me2
13
31
70
(5bþ5cþ5d)/2d
26 (5cþ5d)
1.2:1
2
3
1,2-Me2
1,3-Me2
18
27
24
8
8
30
5
30
35
75
75
(5eþ5f)/2d
1.5:1
(5gþ5hþ5i)/2d
1.1:1
4
1,4-Me2
5j
5g
35
70
(5jþ5g)/2d
1:1
allows it to be considered as a ‘superelectrophile’.12 Apart from that,
Ch bears the biggest positive charge on the carbon Ca, and possesses
the highest contribution of this carbon into its LUMO, as compared
to cations Bh and Dh that shows a coincidence of charge and orbital
control in the reactivity of the atom Ca in Ch.
In our opinion, the participation of the N-protonated cation Dh
in these reactions is unlikely, because in order to achieve target
products the proton migration should occur to the carbon of diazo
group that may considerably increase activation barrier for trans-
formations of Dh. More probable is formation of species Bh and Ch,
which can both operate as reactive intermediates: the former reacts
in SN2 way, the latter in SN1 one. Of course, it is difficult to distin-
guish between these two, Bh and Ch, in the studied processes. But,
taking into account extremely high reactivity of trication Ch,
namely this species may be the most probable reactive in-
termediate generated while protonation of diazomalonates in
superacid.
Additionally we compared electrophilic properties of various
carbo-centered cations, H3Cþ, F3Cþ, H3C(O])Cþ, PhH2Cþ, which
have been postulated as intermediate species in miscellaneous
FriedeleCrafts reactions. As a result, trication Ch is characterized by
the highest electrophilic properties relative to all other species

E.T. Satumov et al. / Tetrahedron 72 (2016) 4835e4844
4841
Table 5
Selected electronic characteristics (DFT calculations) of starting diazomalonate 1h, cations Bh, Dh, Ch, derived from protonation of 1h (see Scheme 3), and characteristics of
other carbon-centered cationic electrophiles
c
c
c
Species
EHOMO, eV
ELUMO, eV
u,
a eV
q(Ca),b
e
q(N1),b
e
q(N2),b
e
k(Ca)LUMO
,
%
k(N1)LUMO
,
%
k(N2)LUMO
, %
O
MeO C
C
N N
a
ꢀ7.44
ꢀ2.45
2.45
5.45
ꢀ0.21
0.13
0.11
18.6
15.5
16.1
1
2
MeO C
O
1h
OH
MeO C
H
C
N N
a
ꢀ12.25
ꢀ11.59
ꢀ12.47
ꢀ5.42
ꢀ6.45
ꢀ9.87
ꢀ0.20
0.16
0.25
d
0.48
0.12
d
0.1
11.7
55.0
36.5
31.5
d
46.2
26.3
d
MeO C
OH
1
2
Bh
OH
C
MeO
MeO
C
N
NH
a
7.92
0.06
1
2
C
OH
Dh
OH
MeO C
C
H
a
24.0
0.38
MeO C
OH
Ch
CH3
ꢀ15.23
ꢀ15.76
ꢀ13.51
ꢀ6.96
ꢀ5.13
ꢀ3.23
7.45
5.13
3.41
0.38
1.45
1.00
d
d
d
d
d
d
99.4
65.2
57.8
d
d
d
d
d
d
a
CF3
a
H3C C O
a
ꢀ8.57
ꢀ4.85
6.05
0.04
d
d
45.0
d
d
H2C
a
a
Global electrophilicity index
Natural charges.
Contribution of atomic orbital into the molecular orbital.
u
¼(EHOMOþELUMO)2/8(ELUMOꢀEHOMO).
b
c
from Table 5. This trication may be considered as the strongest
carbon-centered electrophile.
4. Experimental part
4.1. General
3. Conclusions
The NMR spectra of solutions of compounds in CDCl3 were
recorded on a Bruker-400 spectrometer at 25 ꢁC (at 400, 101, and
Protonation and transformations of diazodicarbonyl compounds
in Brønsted superacids (TfOH, FSO3H, TfOHeSbF5) have been
studied for the first time. Diazodiketones in these superacids give
rise to the stable and non-reactive O,O-diprotonated on carbonyl
oxygens cations. Diazomalonates react with TfOH and HF, releasing
nitrogen, with the formation of triflates of oxymalonates or fluo-
romalonates, respectively. Diazoketoesters have intermediate re-
376 MHz for 1H, 13C, and 19F NMR spectra, respectively). The residual
1
proton-solvent peak of CDCl3 (
carbon signal of CDCl3
signal of CFCl3 (
0.0 ppm) for 19F NMR spectra were used as refer-
d
7.26 ppm) for H NMR spectra, the
(d
77.0 ppm) for 13C NMR spectra, and the
d
ences. NMR experiments in the superacids TfOH at 25 ꢁC or in FSO3H
at ꢀ80 ꢁC were performed on a Bruker AM-500 spectrometer (at 500,
and 125 MHz for 1H, and 13C NMR spectra, respectively). NMR spectra
in superacids were referenced to the signal of CH2Cl2 added as in-
activity
between
diazodiketones
and
diazomalonates.
Diazomalonates in TfOH behave with arenes as alkylating agent in
FriedeleCrafts reactions. According to DFT calculations, in-
termediate tricationic species, which are derived from diazo-
malonates in superacids, are the strongest carbon-centered
electrophiles.
ternal standard: d d 53.84 ppm for
5.32 ppm for 1H NMR spectra, and
13C NMR spectra. HRMS was carried out at instruments Bruker maXis
HRMS-ESI-QTOF. The preparative reactions were monitored by thin-
layer chromatography carried out on silica gel plates (Alugram SIL G/

4842
E.T. Satumov et al. / Tetrahedron 72 (2016) 4835e4844
UV-254), using UV light for detection. Preparative column chroma-
tography was performed on silica gel 60 Merck.
reaction mixture at 0 ꢁC. The reaction mixture was stirred at 0 ꢁC for
5 h. Then, reaction mixture was poured into ice-water (100 mL).
The obtained mixture was neutralized with solid NaHCO3, and
extracted with dichloromethane (3ꢂ25 mL). The combined organic
layers were washed with water (25 mL), dried over Na2SO4, and
concentrated under reduced pressure. Crude material was purified
by column chromatography (silica gel; hexane/EtOAc; linear gra-
dient: 0e2% EtOAc).
DFT calculations. All computations were carried out at the DFT/
HF hybrid level of theory using Becke’s three-parameter hybrid
exchange functional in combination with the gradient-corrected
correlation functional of Lee, Yang, and Parr (B3LYP) by using
GAUSSIAN 2003 program packages.13 The geometry optimization
was performed using the 6-311þG(2d,2p) basis set (standard 6-311
basis set added with polarization (d,p) and diffuse functions). Op-
timizations were performed on all degrees of freedom and solvent-
phase optimized structures were verified as true minima with no
imaginary frequencies. The Hessian matrix was calculated analyt-
ically for the optimized structures in order to prove the location of
correct minima and to estimate the thermodynamic parameters.
Solvent-phase calculations used the Polarizable Continuum Model
(PCM) with water as a solvent.
4.3.1. Dimethyl 2-fluoromalonate 3a.15 Yield 82% as a colorless oil;
dH (400 MHz, CDCl3) 5.33 (1H, d, J 48 Hz, CH), 3.89 (6H, s, 2Me); dC
(101 MHz, CDCl3) 164.2 (d, J 24.2 Hz), 85.1 (d, J 198 Hz), 53.3; dF
(376 MHz, CDCl3) ꢀ195.24 (d, J 48 Hz); HRMS (ESI): MNaþ, found
201.0534, [C7H11FO4Na]þ requires 201.0539.
4.3.2. Diethyl 2-fluoromalonate 3b.16 Yield 84% as a colorless oil; dH
(400 MHz, CDCl3) 5.28 (1H, d, J 48.2 Hz, CH), 4.34 (4H, qd, J 7.2,
2.7 Hz, 2CH2),1.34 (6 H, t, J 7.2 Hz, 2Me); dC (101 MHz, CDCl3) d 163.9
Synthesis and properties of starting diazodicarbonyl com-
pounds 1aei are given in works.1c,14
(d, J 24.2 Hz), 85.3 (d, J 197 Hz), 62.7, 13.9; dF (376 MHz, CDCl3)
ꢀ195.09 (d, J¼48.2 Hz); HRMS (ESI): MNaþ, found 173.0221,
[C5H7FO4Na]þ requires 173.0226.
4.2. General procedure for reaction of diazocompounds 1fei
in TfOH. Characterization of compounds 2aed
Diazo compound (1.5 mmol) was added dropwise to a stirred
portion of TfOH (3 mL) at room temperature. The reaction mixture
was stirred for 0.5 h (for 1h,i), 3 h (for 1g) or 4 h (for 1f), then
poured into water (100 mL) and extracted with dichloromethane
(3ꢂ30 mL). The combined organic layers were consequently
washed with water (2ꢂ30 mL), saturated aqueous solution of
NaHCO3 (1ꢂ30 mL), water (2ꢂ30 mL), and dried over Na2SO4.
Solvent was removed under reduced pressure. Crude material was
purified by flash chromatography (silica gel; eluent: hexane/ace-
tone; linear gradient: 0e5% of acetone) to afford compounds 2aed.
4.4. General procedure for reaction of diazomalonates 1h,i
with arenes in TfOH. Characterization of compounds 4aej,
5aej
Mixture of TfOH (2 mL) and arene (0.5 mL for benzene; 1 mmol
for other arenes) was stirred at room temperature or 60 ꢁC (see
Tables 2e4, Scheme 5), and diazo compound (0.6 mmol) was added
dropwise The reaction mixture was stirred for 30 min, then poured
into water (50 mL), and extracted with dichloromethane
(3ꢂ30 mL). The combined organic layers were consequently
washed with water (2ꢂ30 mL), saturated aqueous solution of
NaHCO3 (30 mL), water (2ꢂ30 mL), and dried over Na2SO4. Solvent
was removed under reduced pressure. Crude material was purified
by flash chromatography (silica gel; eluent: hexane/EtOAc; linear
gradient: 0e20% of EtOAc). Yields of the obtained compounds 4aej,
5aej are given in Tables 2e4, and Scheme 5.
4.2.1. Methyl
3-oxo-2-(trifluoromethylsulfonyloxy)butanoate
2a. Yield 17% as a yellowish oil; dH (400 MHz, CDCl3) 5.48 (1H, s, CH),
3.88 (3H, s, MeO), 2.37 (3H, s, Me); dC (101 MHz, CDCl3) 193.3, 162.3,
118.4 (q, J 320 Hz), 84.1, 54.0, 26.5; dF (376 MHz, CDCl3) ꢀ74.50; HRMS
(ESI): MHþ, found 264.9994, [C6H8F3O6S]þ requires 264.9988.
4.2.2. Ethyl
3-oxo-3-phenyl-2-(trifluoromethylsulfonyloxy)prop-
4.4.1. Dimethyl 2-phenylmalonate 4a.17 Colorless oil; dH (400 MHz,
CDCl3)3.75(s, 6H),4.66(s,1H), 7.34e7.42 (m, 5H); dC (101MHz, CDCl3)
168.7, 132.7, 129.4, 128.8, 128.4, 57.7, 52.3; GCeMS (EI): 208 [Mþ].
anoate 2b. Yield 56% as a yellowish oil; dH (400 MHz, CDCl3) 7.99 (2H,
d, J 7.5 Hz, 2Harom.), 7.68 (1H, t, J 7.5 Hz,1Harom.), 7.54 (2H, t, J 7.5 Hz,
2Harom.), 6.19 (1H, s, CH), 4.31 (2H, q, J 7.1 Hz, CH2), 1.24 (3H, t, J
7.1 Hz, Me); dC (101 MHz, CDCl3) 185.7,162.5,135.0,132.9,129.4,129.1,
118.4 (q, J 320 Hz), 81.8, 63.8,13.7; dF (376 MHz, CDCl3) ꢀ74.27; HRMS
(ESI): MNaþ, found 363.0124, [C12H11F3O6SNa]þ requires 363.0126.
4.4.2. Dimethyl 2-(2-methylphenyl)malonate 4b.18 Colorless oil; dH
(400 MHz, CDCl3) 7.37e7.40 (1H, m, 1Harom.), 7.16e7.29 (3H, m,
3Harom.), 4.91 (1H, s, CH), 3.76 (6H, s, 2MeO), 2.34 (3H, s, Me);
GCeMS (EI): 222 [Mþ].
4.2.3. Dimethyl 2-(trifluoromethylsulfonyloxy)malonate 2c. Yield
95% as a yellowish oil; dH (400 MHz, CDCl3) 5.52 (1H, s, CH),
3.91(6H, s, 2MeO); dC (101 MHz, CDCl3) 162.2, 118.5 (q, J 320 Hz),
78.1, 54.3; dF (376 MHz, CDCl3) ꢀ74.26; HRMS (ESI): MNaþ, found
302.9755, [C6H7F3O7SNa]þ 302.9757.
4.4.3. Dimethyl 2-(3-methylphenyl)malonate 4c.19 Colorless oil; dH
(400 MHz, CDCl3) 7.16e7.29 (4H, m, 4Harom.), 4.61 (1H, s, CH), 3.75
(6H, s, 2MeO), 2.36 (3H, s, Me); GCeMS (EI): 222 [Mþ].
4.4.4. Dimethyl 2-(4-methylphenyl)malonate 4d.20 Colorless oil; dH
(400 MHz, CDCl3) 7.16e7.29 (4H, m, 4Harom.), 4.61 (1H, s, CH), 3.75
(6H, s, 2MeO), 2.34 (3H, s, Me); GCeMS (EI): 222 [Mþ].
4.2.4. Dimethyl 2-(trifluoromethylsulfonyloxy)malonate 2d. Yield
90% as a yellowish oil; dH (400 MHz, CDCl3) 5.47 (1H, s, CH), 4.36
(4H, dq, J 7.1, 3.6 Hz, 2CH2), 1.34 (6H, t, J 7.1 Hz, 2Me); dC (101 MHz,
CDCl3) 161.7, 118.5 (q, J 320 Hz), 78.4, 63.9, 14.0; dF (376 MHz, CDCl3)
ꢀ74.30; HRMS (ESI): MNaþ, found 331.0068, [C8H11F3O7SNa]þ re-
quires 331.0070.
4.4.5. Dimethyl 2-(2,3-dimethylphenyl)malonate 4e.21 Colorless oil;
dH (400 MHz, CDCl3) 7.13e7.99 (3H, m, 3Harom.), 4.97 (1H, s, CH), 3.76
(6H,s,2MeO), 2.31(3H, s,Me), 2.23(3H, s,Me);GCeMS(EI):236[Mþ].
4.3. General procedure for reaction of diazomalonates 1h,i
with HF. Characterization of compounds 3a,b
4.4.6. Dimethyl 2-(3,4-dimethylphenyl)malonate 4f.21 Colorless oil;
dH (400 MHz, CDCl3) 7.13e7.19 (3H, m, 3Harom.), 4.59 (1H, s, CH), 3.75
(6H, s,2MeO), 2.26(3H, s,Me), 2.25(3H, s,Me);GCeMS(EI):236[Mþ].
Anhydrous liquid hydrogen fluoride (5 mL, 0.25 mmol) was
placed into polypropylene flask at 0 ꢁC under nitrogen atmosphere.
Diazomalonate (0.5 mmol) was added dropwise into the stirred
4.4.7. Dimethyl 2-(2,4-dimethylphenyl)malonate 4g.21 Colorless oil;
dH (400 MHz, CDCl3) 7.25e7.28 (1H, m, 1Harom.), 6.99e7.06 (2H, m,

E.T. Satumov et al. / Tetrahedron 72 (2016) 4835e4844
4843
2Harom.), 4.87 (1H, s, 1Harom.), 3.75 (6H, s, 2MeO), 2.30 (6H, s,
Me), 2.29 (3H, s, Me), 1.25e1.29 (6H, m, 2Me); GCeMS (EI): 264
2Me); GCeMS (EI): 236 [Mþ].
[Mþ].
4.4.8. Dimethyl 2-(2,6-dimethylphenyl)malonate 4h.21 Colorless oil;
dH (400 MHz, CDCl3) 7.00e7.05 (3H, m, 3Harom.), 5.07 (1H, s, CH),
3.76 (6H, s, 2MeO), 2.31 (6H, s, 2Me); GCeMS (EI): 236 [Mþ].
Acknowledgements
This work was supported by Saint Petersburg State University
(grants no. 12.50.1187.2014, and no. 12.38.195.2014). Spectral
studies were performed at Center for Magnetic Resonance and
Center for Chemical Analysis and Materials Research of Saint
Petersburg State University.
4.4.9. Dimethyl 2-(3,5-dimethylphenyl)malonate 4i.22 Colorless oil;
dH (400 MHz, CDCl3) 7.00e7.05 (3H, m, 3Harom.), 4.58 (1H, s, CH),
3.76 (6H, s, 2MeO), 2.35 (6H, s, 2Me); GCeMS (EI): 236 [Mþ].
4.4.10. Dimethyl 2-(3,5-dimethylphenyl)malonate 4j.21,23 Colorless
oil; dH (400 MHz, CDCl3) 7.19 (1H, m, 1Harom.), 7.03e7.09 (2H, m,
2Harom.), 4.88 (1H, s,1Harom.), 3.77 (6H, s, 2MeO), 2.32 (3H, s, Me),
2.29 (3H, s, Me); GCeMS (EI): 236 [Mþ].
Supplementary data
These data includes copies of 1H, 13C and 19F NMR spectra of the
obtained compounds and details of DFT calculations. Supplemen-
tary data related to this article can be found at http://dx.doi.org/
10.1016/j.tet.2016.06.051.
4.4.11. Diethyl 2-phenylmalonate 5a.17 Colorless oil; dH (400 MHz,
CDCl3) 7.34e7.42 (5H, m, 5Harom.), 4.61 (1H, s, CH), 4.17e4.26 (4H,
m, 2CH2), 1.26 (6H, t, J 7.1 Hz, 2Me); dC (101 MHz, CDCl3) 168.3,
132.9, 129.4, 128.7, 128.3, 61.9, 58.1, 14.1; GCeMS (EI): 236 [Mþ].
References and notes
1. See books and reviews on chemistry of diazocompounds: (a) Regitz, M.; Maas,
G. Diazo Compounds. Properties and Synthesis; Acad.: New York, NY, 1986; (b)
Ford, A.; Miel, H.; Ring, A.; Slattery, C. N.; Maguire, A. R.; McKervey, M. A. Chem.
Rev. 2015, 115, 9981e10080; (c) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern
Catalytic Methods for Organic Synthesis with Diazo Compounds: From Cyclopro-
panes to Ylides; John Wiley: New York, NY, 1998; (d) Medvedev, J. J.; Nikolaev, V.
A. Russ. Chem. Rev. 2015, 84, 737e757; (e) Galkina, O. S.; Rodina, L. L. Russ. Chem.
Rev. 2016, 85, 537e555; (f) Liu, Z.; Wang, J. J. Org. Chem. 2013, 78, 10024e10030;
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Chem. 2012, 16, 224e251; (i) Lloyd, M. G.; D’Acunto, M.; Taylor, R. J. K.; Uns-
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4.4.12. Diethyl 2-(2-methylphenyl)malonate 5b.24 Colorless oil; dH
(400 MHz, CDCl3) 7.39e7.41 (1H, m, 1Harom.), 7.13e7.29 (3H, m,
3Harom.), 4.87 (1H, s, CH), 4.20e4.24 (4H, m, 2CH2), 2.36 (3H, s,
Me), 1.24e1.29 (6H, m, 2Me); GCeMS (EI): 250 [Mþ].
4.4.13. Diethyl 2-(3-methylphenyl)malonate 5c.24,25 Colorless oil; dH
(400 MHz, CDCl3) 7.13e7.29 (4H, m, 4Harom.), 4.57 (1H, s, CH),
4.20e4.24 (4H, m, 2CH2), 2.34 (3H, s, Me), 1.24e1.29 (6H, m, 2Me),
GCeMS (EI): 250 [Mþ].
4.4.14. Diethyl 2-(4-methylphenyl)malonate 5d.24 Colorless oil; dH
(400 MHz, CDCl3) 7.13e7.23 (4H, m, 4Harom.), 4.57 (1H, s,1Harom.),
4.20e4.24 (4H, m, 2CH2), 2.34 (3H, s, Me), 1.24e1.29 (6H, m, 2Me);
GCeMS (EI): 250 [Mþ].
4.4.15. Diethyl 2-(2,3-dimethylphenyl)malonate 5e.26 Colorless oil;
dH (400 MHz, CDCl3) 7.10e7.24 (3H, m, 3Harom.), 4.93 (1H, s, CH),
4.16e4.26 (4H, m, 2CH2), 2.30 (3H, s, Me), 2.23 (3H, s, Me),
1.25e1.29 (6H, m, 2Me); GCeMS (EI): 264 [Mþ].
4.4.16. Diethyl 2-(3,4-dimethylphenyl)malonate 5f.26 Colorless oil;
dH (400 MHz, CDCl3) 7.10e7.24 (3H, m, 3Harom.), 4.54 (1H, s, CH),
4.16e4.26 (4H, m, 2CH2), 2.26 (3H, s, Me), 2.25 (3H, s, Me),
1.25e1.29 (6H, m, 2Me); GCeMS (EI): 264 [Mþ].
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4.4.17. Diethyl 2-(2,4-dimethylphenyl)malonate 5g.26 Colorless oil;
dH (400 MHz, CDCl3) 7.27e7.29 (1H, m, 1Harom.), 7.00e7.19 (2H, m,
2Harom.), 4.83 (1H, s, CH), 4.19e4.25 (4H, m, 2CH2), 2.30 (6H, s,
2Me), 1.25e1.28 (6H, m, 2Me); GCeMS (EI): 264 [Mþ].
4.4.18. Diethyl 2-(3,5-dimethylphenyl)malonate 5h.17 Colorless oil;
dH (400 MHz, CDCl3) 7.00e7.19 (3H, m, 3Harom.), 4.53 (1H, s, CH),
4.19e4.25 (4H, m, 2CH2), 2.30 (6H, s, 2Me), 1.25e1.28 (6H, m, 2Me);
GCeMS (EI): 264 [Mþ].
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4.4.19. Diethyl 2-(2,6-dimethylphenyl)malonate 5i.24 Colorless oil;
dH (400 MHz, CDCl3) 7.00e7.19 (3H, m, 3Harom.), 5.03 (1H, s, CH),
4.19e4.25 (4H, m, 2CH2), 2.30 (6H, s, 2Me), 1.25e1.28 (6H, m, 2Me);
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dH (400 MHz, CDCl3) 7.19 (1H, s, 1Harom.), 7.01e7.10 (2H, m,
2Harom.), 4.83 (1H, s, CH), 4.20e4.25 (4H, m, 2CH2), 2.31 (3H, s,

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