Lewis acid-catalyzed reactions of N-allylanilines with diazo compounds involving aza-Claisen rearrangement

Article abstract of DOI:10.1016/j.mencom.2015.11.013

N-Allyl-N-methylanilines react with methyl diazoacetate or diazoacetone in the presence of Y, Sc or Sm triflates to give the corresponding methyl N-(2-allylaryl)-N-methylglycinates or 2-allyl-N-methyl-N-(2-oxopropyl)aniline. The formation of these compoun

Full text of DOI:10.1016/j.mencom.2015.11.013

Mendeleev
Communications
Mendeleev Commun., 2015, 25, 438–439
Lewis acid-catalyzed reactions of N-allylanilines with
diazo compounds involving aza-Claisen rearrangement
Alexander G. Badamshin,a,b Leonid V. Spirikhin, Rinat F. Salikov,
a
c
Vladimir A. Dokichev and Yury V. Tomilov*c
a,b
a
Ufa Institute of Chemistry, Russian Academy of Sciences, 450054 Ufa, Russian Federation.
Fax: +7 347 235 6066; e-mail: dokichev@anrb.ru
Ufa State Aviation Technical University, 450000 Ufa, Russian Federation
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. Fax: +7 499 135 6390; e-mail: tom@ioc.ac.ru
b
c
DOI: 10.1016/j.mencom.2015.11.013
N-Allyl-N-methylanilines react with methyl diazoacetate or diazoacetone in the presence of Y, Sc or Sm triflates to give the corre-
sponding methyl N-(2-allylaryl)-N-methylglycinates or 2-allyl-N-methyl-N-(2-oxopropyl)aniline. The formation of these compounds
involves the aza-Claisen rearrangement.
Me
Catalytic reactions of diazo compounds with unsaturated com­
N
pounds are widely used in the synthesis of practically important
+
N2CHC(O)R2
polyfunctional products.1 The direction of occurring reactions
–5
(cyclopropanation, 1,3­dipolar cycloaddition, insertion) is con­
R1
1
2
siderably affected both by the structure of the olefins and diazo
compounds and by the catalyst nature. Forexample, diazomethane
reacts with allylamines in the presence of (PhCN) PdCl to afford
1a R = H
b R = OMe
c R = F
2a R = OMe
1
2
1
1
2b R = Me
1
2
2
Me
2
cyclopropanes, whereas the reaction of ethyl diazoacetate with
allylamines in the presence of Fe, Co, Ni, Rh or Ru based catalysts
occurs as a [2,3]­sigmatropic rearrangement of the resulting
N
C(O)R2
M(OTf)3
6 6
C H , 80 °C
R1
N­ylides to homoallylic derivatives, viz., esters of unsaturated
N,N­dialkylamino acids.3
,6–8
It was recently found that rare­
3a R = H, R = OMe
1
2
1
2
M = Y, Sc, Sm
3b R = R = OMe
earth metal triflates have an activating effect on 1,3­dipolar cyclo­
addition of diazo esters to electron­deficient dipolarophiles to
give the corresponding 1­ or 2­pyrazolines.9
1
2
3
4
c R = F, R = OMe
1
2
R = H, R = Me
In this work we studied the catalytic reaction of N­allyl­
N­methylanilines 1a–c with methyl diazoacetate 2a or diazo­
acetone 2b in the presence of Lewis acids, namely, yttrium,
samarium and scandium triflates.† In fact, N­allylaniline 1a
reacts with diazo compounds 2a or 2b in the presence ofY(OTf)3
to produce methyl N­(2­allylphenyl)­N­methylglycinate 3a or
Scheme 1
corresponding 2­allylanilines 3b and 3c in 63 and 50% yields,
†
respectively (see Scheme 1).
The structures of the compounds obtained were confirmed by
H and C NMR spectra using 2D correlation techniques. The
1
13
2
­allyl­N­methyl­N­(2­oxopropyl)aniline 4 in 66 and 56% yields,
HMBC spectrum proved to be most informative for determination
respectively (Scheme 1). This process is also favoured by other
Lewis acids such as Sc(OTf) and Sm(OTf) , but the yield of
Methyl N-(2-allylphenyl)-N-methylglycinate 3a: yield 66%, yellow oil.
3
3
–1
IR (CHCl , n/cm ): 2977, 2893, 1753, 1637, 1598, 1492, 1435, 1200,
rearranged product 3a is somewhat lower: 45 and 38%, respec­
tively, with nearly complete conversion of the starting substrates
3
1
1
122, 1019, 997, 915. H NMR, d: 2.83 (s, 3H, NMe), 3.49 (br.d, 2H,
CH , J 6.43 Hz), 3.67 (s, 2H, NCH ), 3.70 (s, 3H, OMe), 5.05–5.08 and
3
2
2
1
a and 2a.
5
(
5
(
.09–5.10 (both m, 2×1H, =CH ), 5.95–6.04 (m, 1H, =CH), 7.01–7.05
2
N­Allylaniline derivatives 1b,c react with methyl diazoacetate
13
m, 1H, Ar), 7.14–7.22 (m, 3H, Ar). C NMR, d: 35.2 (CH ), 42.1 (NMe),
2
in a similar way and, if 20 mol% Y(OTf) is used, give the
3
8.5 (NCH ), 51.5 (OMe), 115.9 (=CH ), 121.1, 123.7, 126.85, 130.51,
2 2
4CH, Ar), 134.6 (C ), 137.9 (=CH), 150.8 (C ), 171.1 (COO). Found (%):
2
1
†
1H and 13C NMR spectra were recorded on a Bruker AVANCE II 300
C, 71.10; H, 7.76, N, 6.43. Calc. for C H NO (%): C, 71.21; H, 7.81,
13
17
2
spectrometer (300 and 75 MHz, respectively) in CDCl containing 0.05%
N, 6.39.
Methyl N-(2-allyl-4-methoxyphenyl)-N-methylglycinate 3b: yield 63%,
3
1
13
Me Si as the internal standard.Assignments of H and C signals were made
4
–1
with the aid of 1D DEPT­135 and 2D COSY, NOESY, HSQC and HMBC
yellow oil. IR (CHCl , n/cm ): 2999, 2971, 2837, 1753, 1500, 1200.
3
14
1
3
spectra. N­Allyl­N­methylaniline was obtained using a reported procedure.
H NMR, d: 2.79 (s, 3H, NMe), 3.49 (br.d, 2H, CH , J 6.5 Hz), 3.65 (s,
2
General procedure for the synthesis of compounds 3a–c and 4. A solu­
tion of methyl diazoacetate or diazoacetone (0.7 mmol) in benzene (2 ml)
was slowly added to a stirred solution of N­allylaniline 1a–c (0.7 mmol)
and 0.14 mmol of the catalyst (Y, Sc or Sm triflates) in benzene (2 ml) at
2H, NCH ), 3.69 (s, 3H, OMe), 3.76 (s, 3H, OMe), 5.06 (t, 1H, from
2
3
=CH , J 1.5 Hz), 5.08–5.13 (m, 1H, from =CH ), 5.88–6.08 (m, 1H,
2
2
5
3
4
3 4
=CH), 6.72 (dd, 1H, H , J 8.5 Hz, J 3.0 Hz), 6.75 (d, 1H, H , J 3.0 Hz),
7.14 (d, 1H, H , J 8.5 Hz). C NMR, d: 35.2 (CH ), 42.9 (NMe), 51.6
6
3
13
2
5
3
8
0°C. The reaction mixture was refluxed for 2–3 h, then dichloromethane
(CO Me), 55.5 (OMe), 58.7 (NCH ), 111.9 (C ), 115.7 (C ), 116.0 (=CH ),
2
2
2
6
2
1
4
(
5 ml) was added and the mixture was filtered through a small pad of
122.8 (C ), 137.0 (C ), 137.7 (=CH), 144.0 (C ), 156.3 (C ), 171.5 (COO).
MS, m/z (%): 249 (34) [M] , 190 (100) [M–CO Me] , 174 (31). HRMS,
m/z: 250.1433 (calc. for C H NO , m/z: 250.1438 [M+H] ).
+
+
silica gel. After removal of solvents in vacuo 2­allylanilines 3a–c and 4
2
+
were isolated by column chromatography on SiO (hexane–AcOEt, 50:1).
2
14 19
3
©
2015 Mendeleev Communications. Published by ELSEVIER B.V.
–
438 –
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.

Mendeleev Commun., 2015, 25, 438–439
of the position of the allyl substituent. In fact, methylene protons
Me
N
of the allyl substituent in compound 3a displayed cross­peaks
not only with the signals of the vinyl C atoms but also with two
quaternary and one methine C atoms of the benzene ring.
Note that in the absence of a diazo compound, no migration
of the allyl group in compound 1a occurs in the presence of
BrCH2CO2Me
6 °C
5
CO2Me
8
(67%)
N
LA
O
Me
N
Y(OTf) at 80°C, even upon longer heating (6 h). Indeed, unlike
3
N
Lewis
acid
C(O)R
the Claisen rearrangement of vinyl and aryl allyl ethers, rearrange­
ment of their nitrogen analogues requires much more drastic
conditions, namely, heating to 230–270°C or use of Lewis acids
Me
[3,3]
– N2
1
+ 2
N
C6H6,
80 °C
R
10–12
3 or 4
(
mainly BF ·OEt ) at 120–170°C.
3 2
In order to estimate the effect of temperature on the reaction
7
of methyl diazoacetate with allylaniline 1a, we performed their
Me
CHC(O)R
Me
thermolysis in xylene under reflux in the absence of any initiators.
N
[2,3]
N
CO2Me
3
,6–8
Like in case of catalysts based on transition metals,
2
methyl
xylene,
140°C
N2
‡
­(N­methyl­N­phenylamino)pent­4­enoate 5 – a product of [2,3]­
–
sigmatropic rearrangement of N­ylide 6 (R = OMe) generated
upon thermal carbene decomposition of the diazo compound
6
5 (58%)
(Scheme 2) – proved to be the main reaction product.
Scheme 2
Thus, the reaction of methyl diazoacetate with allylaniline in
the presence of Y, Sc and Sm triflates differs from their reaction
proceeding at elevated temperature (140°C) or in the presence
of catalysts based on transition metal compounds, which is
undoubtedly due to differences in the nature of the intermediates.
In the latter two cases, the process occurs as a [2,3]­sigmatropic
rearrangement of N­ylides 6 that are formed due to attack of
the amino group by the carbene, whereas the same reaction in
the presence of rare earth metal triflates occurs as an aromatic
aza­Claisen rearrangement of ionic intermediate 7. In other words,
elimination of a nitrogen molecule from the diazo compound in
the presence of different initiators probably occurs at different
stages of the process.
However, even under these rather mild conditions, the resulting
quaternary salt was unstable and underwent deallylation to give
compound 8. In general, this process is known for some N­allyl­
§
anilines. In particular, it proceeds rather efficiently in the presence
1
3
of palladium and TsOH.
In conclusion, we have found that decomposition of diazo
compounds in the presence of N­allylanilines and rare­earth metal
triflates occurs through a [3,3]­sigmatropic rearrangement of the
intermediate ylide with migration of the allyl substituent to an
ortho position of the aromatic ring, whereas thermal decomposi­
tion, similarly to decomposition with transition metal complexes,
occurs through a [2,3]­sigmatropic rearrangement with migration
of the allyl moiety to the ylide centre.
To estimate whether it is possible to perform the aza­Claisen
rearrangement in a series of quaternized aniline salts by analogy
with intermediate 7, we studied the reaction of N­allylaniline 1a
with methyl bromoacetate in acetone under reflux conditions.
This work was supported by the Russian Science Foundation
(grant no. 14­33­00022).
References
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–1
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13
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3
2
(
1
CH ), 42.6 (NMe), 51.7 (OMe), 58.3 (NCH ), 113.3 (d, C , J 22.0 Hz),
2 2 C,F
5
2
6
3
16.5 (=CH ), 116.7 (d, C , J 22.2 Hz), 123.1 (d, C , J 8.5 Hz),
2 C,F C,F
37.0 (=CH), 137.6 (d, C , 3J
2
1
4
1
7.3 Hz), 146.6 (C ), 159.6 (d, C ,
C,F
19
1
JC,F 242.4 Hz), 171.3 (COO). F NMR, d: –119.2 (dd, J 12.2 and
.7 Hz). MS, m/z (%): 237 (19) [M] , 178 (100) [M–CO Me] , 162 (28).
HRMS, m/z: 238.1244 (calc. for C H FNO , m/z: 238.1238 [M+H] ).
H,F
+
+
8
2
8
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+
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3
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2-Allyl-N-methyl-N-(2-oxopropyl)aniline 4: yield 56%, yellow oil.
9
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Nauk, Ser. Khim., 2010, 963).
1
3
H NMR, d: 2.08 (s, 3H, Me), 2.64 (s, 3H, NMe), 3.44 (d, 2H, CH2,
J 6.2 Hz), 3.62 (s, 2H, NCH ), 4.95–5.08 (m, 2H, =CH ), 5.87–6.01 (m,
2
2
13
1
2
1
H, =CH), 6.93–7.06 (m, 1H, Ar), 7.07–7.27 (m, 3H, Ar). C NMR, d:
1
0 (a) U. Nubbemeyer, The Claisen Rearrangement: Methods and Appli-
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7.3 (Me), 34.9 (CH ), 43.1 (NMe), 67.3 (NCH ), 115.9 (=CH ), 120.6,
2
2
2
2
1
23.9, 127.6, 130.6 (CH, Ar), 134.5 (C ), 137.7 (=CH), 151.1 (C ), 207.4
(
b) U. Nubbemeyer, Top. Curr. Chem., 2005, 244, 149; (c) P. Sharma,
(
C=O). Found (%): C, 76.70; H, 8.48, N, 6.80. Calc. for C H NO (%):
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13 17
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‡
Methyl 2-(N-methyl-N-phenylamino)pent-4-enoate 5. A solution of
compounds 1a (4 mmol, 0.59 g) and 2a (8 mmol, 0.80 g) in xylene (4 ml)
was refluxed for 2 h, then the solvent was removed in vacuo and the
residue was separated by chromatography on SiO to yield product 5 (58%),
2
15
whose spectral data are completely consistent with described earlier.
§
15 L. G. Shakhbazyan, A. V. Babakhanyan, D. V. Grigoryan and S. T.
Methyl N-methyl-N-phenylglycinate 8. A solution of 1a (6 mmol, 0.88 g)
and methyl bromoacetate (8 mmol, 1.55 g) in acetone (10 ml) was refluxed
for 24 h. The reaction mixture was cooled, the solvent was removed in vacuo
Kocharyan, Russ. J. Gen. Chem., 2003, 73, 1608 (Zh. Obshch. Khim.,
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1
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2
yield compound 8 (67%) as a yellow oil. Spectral data of 8 are completely
consistent with reported previously.16
Received: 24th April 2015; Com. 15/4610
439 –
–