Spirally twisted imidazolium iminyl ylide structures from 1,2-rearrangements in reactions of imidazolium dicyanomethanide 1,3-dipoles with maleic anhydride: new perspectives on the Boekelheide-Fedoruk ring expansions

Article abstract of DOI:10.1016/j.tetlet.2006.06.089

The reactions of 1-substituted-imidazolium-3-dicyanomethanides with maleic anhydride gave new ylide products from a Michael reaction and 1,2-rearrangements. These experiments, combined with theoretical calculations, provide an interesting new perspective

Full text of DOI:10.1016/j.tetlet.2006.06.089

Tetrahedron Letters 47 (2006) 6107–6111
Spirally twisted imidazolium iminyl ylide structures from
1,2-rearrangements in reactions of imidazolium
dicyanomethanide 1,3-dipoles with maleic anhydride:
new perspectives on the Boekelheide–Fedoruk ring expansions
Richard N. Butler,a,* Helena A. Gavin,a Eamon M. Moloney,a Patick McArdle,a
Desmond Cunninghama and Luke A. Burkeb
aChemistry Department, National University of Ireland, Galway, Ireland
bChemistry Department, Rutgers University, Camden, NJ 08102, USA
Received 12 April 2006; revised 7 June 2006; accepted 15 June 2006
Available online 10 July 2006
Abstract—The reactions of 1-substituted-imidazolium-3-dicyanomethanides with maleic anhydride gave new ylide products from a
Michael reaction and 1,2-rearrangements. These experiments, combined with theoretical calculations, provide an interesting new
perspective on the Boekelheide–Fedoruk ring expansions.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
interesting ring-expansion of the cycloadducts 4, was
first reported by Boekelheide and Fedoruk (Scheme
1).1 Our interest in azinium dicyanomethanides2
attracted us to this rearrangement which we feel
merits revisiting. Earlier it was thought that such
The reaction of 1-substituted imidazolium dicyano-
methanides 1 with dimethyl acetylenedicarboxylate
(DMAD), which gives imidazo[2,3-a]pyridines 5 by an
H
N
N
CN
C
CN
6
5
5
3
C
4
CN
R'
4N
+
CN
6
R'
3
N
N
H
2
7
7
Y
2
8a
1N
R
7a
N
R
1N
8
CO2Me
MeO2C
R'
CO2Me
R
4
5 R= Me; R'= CO2Me
6 R= Me; R'= H
7 R=CH2Ph; R'=CO2Me
8 R=CH2Ph; R'=H
1 R= Me; Y= CH
2 R= CH2Ph; Y= CH
3 R= Ph; Y= N
N
H
N
DMAD
C
CN
from 3
CN
CO2Me
H
N
N
Δ
N
N
N
CO2Me
CO2Me
N
CO2Me
Ph
Ph
10
9
Scheme 1.
*
Corresponding author. Tel.: +353 91 492478; fax: +353 91 525700; e-mail: r.debuitleir@nuigalway.ie
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.06.089

6108
R. N. Butler et al. / Tetrahedron Letters 47 (2006) 6107–6111
111.6
NC CN
58.6
7.58H
123.4
9.14H
135.1
N
6.59
162.1
NH
NH
NH
8.01H
111.7
149.6
O
115.2
118.3
117.7
CN
109.6
59.7
149.5
152.2
7.30 (s) H
3
CN
CN
83.2
4+
7
8
6
N
N
N
N
H
83.3
139.0
3.66
127.5
2
119.7
7.01H
7.53
OMe
H
3.84
53.5
53.6
138.5
148.4
8H.84
5
142.3
143.2 OMe
120.7
123.4
N
H5.12
O
-
86.1
N
N 141.9
1N
144.1
H8.05
N
9
7.42
86.3
161.9
165.2
90.0
163.2
11
3.80Me
159.0
O
3.83Me
m, 2H 149.0
10
92.1
OMe
O
O
39.2
35.8
113.6
129.6
3.86, 53.3
136.3
165.0
O
OMe
2.96, 51.1
O
OMe4.03
7.29 (m, 2H)
O
7.55,
m, 3H
51.6
165.8
124.5
129.8
6.93 (m, 3H)
129.9
121.3
9 (CD3CN, 0 oC)
10 (CD3CN)
6 (CDCl3)
12 (DMSO-d6)
for C-7, pulse delay 5 s, >9000 scans
Figure 1. Proton and carbon-13 NMR signals (JEOL GXFT-400), assignments supported by DEPT, NOEDS and calculated8 shifts.
ring-expansion rearrangements occurred in the 6,5-fused
ring cycloadducts of azinium-N-dicyanomethanides3 but
this proved not to be the case.4 The proposed mechanism
of the ring expansion 4!5 involved anion formation
by loss of the bridgehead H(7a) proton, cleavage of
the N(4)–C(5) bond and attack by the N-(4) anion on
the nitrile carbon, that is, a conjugated E1cb type pro-
cess followed by a 6-exo-dig ring closure. Herein, from
new results using maleic anhydride (MA) as the dipol-
arophile, we show that, (i) the bridgehead H-(7a) proton
is not necessary for the rearrangement and, (ii) the ring-
expansion is not a necessary part of the rearrangement.
To date the only cycloadduct intermediate isolated5
in these ring expansion reactions has been the unstable
species 9 from Huisgen cycloaddition of the 1,2,4-tri-
13 NMR) and exceptional shielding of the enamine b-
carbon (C-8, 80–90 ppm) due to the resonance forms.
When we used N-phenylmaleimide (NPM) the initial
cycloadduct 13, underwent in situ oxidation and rear-
ranged to the ring-expanded product 14 (77%) (Scheme
2). An X-ray structure7 of the orange plate-like crystals of
14 (mp >300 ꢁC, from MeCN) showed a flat molecule with
the 5-imino proton syn coplanar with the 6-cyano
˚
group at a distance of 2.809 A from the triple bond
(Fig. 2). With maleic anhydride (MA) as the dipolaro-
N(5)
C(11)
N(2)
azolium substrate
3
with DMAD. Thiazolium
N-dicyanomethanides react with alkenes to give stable
C(4)
C(3)
C(2)
O(1)
saturated cycloadducts,6 such as 13 (S instead of NMe).
C(1)
N(1)
N(3)
C(8)
C(9)
2. Results
C(5)
C(6)
C(17)
C(12)
C(16)
We have prepared compounds 5–10, including the new
examples 6–8 and confirmed their structures by proton
and carbon-13 NMR spectra (Fig. 1). The structures
of compounds 5–8 and 10 have a characteristic structural
signature, an embedded enediamine unit (atoms C-8, C-
8a, N-1, N-4) which causes exceptional deshielding of
the enamine a-carbon (C-8a, 140–150 ppm in carbon-
C(7)
O(2)
C(15)
N(4)
C(10)
C(13)
C(14)
Figure 2. X-ray crystal structure of 14.
N4
H
CN
C
C3 CN
N
H
-
+
CN
1.794 Å
H
O
+
+
CN
-
N
N
2
O
N
1
b
H
O
N
R
N
N
R
O
O
O
R
a
O
MA
O
O
11
12 R= Me
2.719 Å
15 R=CH2Ph
1
H
N
NC CN
N
H
NPM
O
C
N
N
H
H
''O''
in situ
N
Ph
N
N
O
Me
O
Me
N
O
Ph
13
14
Scheme 2.

R. N. Butler et al. / Tetrahedron Letters 47 (2006) 6107–6111
Table 1. Calculated reaction energies (DER), activation energies (Ea) and distances8
CN
6109
C
+
CN
N
O
a
N
R
b
Y
O
Entry
Cycloaddition reaction
DER (kJmolꢀ1
Cycloadducts
˚
Transition states
˚
)
Ea (kJmolꢀ1
a (A)
˚
˚
b (A)
Y
)
a (A)
b (A)
1
2
3
4
5
6
7
8
O
O
O
O
NH
NH
NH
NH
NPh
NPh
NPh
NPh
endo
exo
ꢀ5.94
ꢀ5.95
0.01
1.600
1.603
—
1.633
1.604
—
44.6
57.38
ꢀ12.78
0.01
52.77
54.90
ꢀ2.13
0.44
49.43
56.89
ꢀ7.46
0.06
1.794
2.050
—
2.719
2.132
—
Ediff
exo/endo
endo
exo
1.00
—
—
—
—
ꢀ18.12
ꢀ25.53
6.41
12.02
ꢀ17.81
ꢀ23.00
5.19
1.596
1.597
—
1.618
1.592
—
1.914
2.194
—
2.430
2.046
—
Ediff
exo/endo
endo
exo
—
—
—
—
9
1.598
1.595
—
1.620
1.592
—
2.122
2.193
—
2.100
2.056
—
10
11
12
Ediff
exo/endo
7.48
—
—
—
—
˚
phile, the reaction changed to a potentially two step
cycloaddition but the second step failed to complete.
The products were the ylides 12 and 15 in which the
1,2-rearrangement has still occurred (Scheme 2,
Fig. 1). The NMR spectra of these products clearly
showed the simple intact imidazolium unit, the imine
unit bonded to the imidazole N-3 and the altered maleic
anhydride unit (Fig. 1). This rearrangement may be a
1,2-sigmatropic process, but it could also parallel the
Stevens rearrangement which involves short lived caged
diradicals.
where only one bond is formed, a, 1.794 A versus b,
˚
2.719 A (Table 1, entry 1 and Scheme 2). The normal
1,3-dipolar cycloaddition where both new bonds a and
b are well formed (Table 1, entry 2) for maleic anhydride
has Ea 12.78 kJ higher and involved an exo-approach.
Hence, the experimental and theoretical results are in
good agreement. Effectively, with maleic anhydride the
reaction has changed to a Michael reaction but the
Boekelheide–Fedoruk type rearrangement has still
occurred.9 A possible, but now unlikely sigmatropic ring
expansion mechanism is shown by the arrows in 9
(Scheme 1). The NMR data for compound 9 (Fig. 1)
were measured at 0 ꢁC in CD3CN. The temperature
was then raised to that of the probe (19 1 ꢁC) and pro-
ton spectra were measured at 30 min intervals, with C-13
spectra being accumulated between the intervals, over
16 h. The signals for 9 declined while those of 10 grew.
In addition an intermediate, showing four simple singlet
signals (which appeared at dH 8.55, 7.53, 3.72 OMe,
3.39 OMe, with 8.55 drifting upfield) was seen to devel-
op, reaching a maximum at ca. 6 h, and then decline and
disappear as the spectra fully changed to 10. This inter-
mediate was also seen to develop and decline in the C-13
NMR spectra but due to the large number of close and
overlapping signals, assignments were tenuous. The C-
13 signals which we believe to be associated with the
proton signals are shown in structure 16 (Scheme 3).
The products 12 and 15 were initially stable at ambient
temperature but on standing, they decomposed to imid-
azole-containing gums. Theoretical calculations8 of the
transition state for their formation suggest that the
structures are twisted so that the maleic anhydride unit
spirals under the imidazolium ring. Calculated8 transi-
tion states for the reactions of compound 1 with maleic
anhydride, maleimide and N-phenylmaleimide (NPM)
are shown in Table 1. For NPM the reaction is a normal
Huisgen cycloaddition with both new bonds a and b
almost equally developed in the transition state (a,
˚
˚
2.122 A; b, 2.100 A) and a favoured endo stereochemis-
try (Table 1, entries 9 and 10). With maleic anhydride
the results are quite different. The activation energy Ea
is significantly lower for the favoured endo approach
.
.
.
.
N
.
.
.N
CN
C
N
.
H
7.53H
137.5
H
..
CO2Me3.72
CN
CN
+
+
N
N
N
52.3
H
H
N
N
N
.
9
.
10
-
N
CO2Me3.39
N
CO2Me
N
CO2Me
-
H8.55
52.1
Ph
138.0
CO2Me
Ph
Ph
CO2Me
18
17
16
Scheme 3.

6110
R. N. Butler et al. / Tetrahedron Letters 47 (2006) 6107–6111
To a solution of tetracyanoethylene oxide (TCNEO)
(1.74 g, 12.1 mmol) in ethyl acetate (15 ml) at 0 ꢁC, 1-
methylimidazole (0.96 ml, 12.1 mmol), neat or in EtOAc
(3.0 ml), was added dropwise with stirring. When the
addition was complete, a pale brown solid separated from
the solution. The product 1 (1.15 g, 65%), mp 143–144 ꢁC
(from ethanol using Norit) was filtered off and washed with
cold ethyl acetate. The filtrate rapidly turned dark brown.
Attempts to isolate more product or starting material from
the filtrate by removing the solvent under reduced pressure
led to a brown sticky residue due to decomposition of
TCNEO. Compound 1: Anal. Calcd for C7H6N4: C, 57.55;
H, 4.1; N, 38.35. Found: C, 57.45; H, 3.95; N, 38.2. IR
(Nujol mull): 2180 cmꢀ1 and 2134 cmꢀ1 (CN); dH NMR
(400 MHz, DMSO-d6): 3.88 (s, 3H, CH3), 7.70 (dd, J,
1.4 Hz, 2H, H-4 and H-5), 9.15 (s, 1H, H-2); dC NMR
(100 MHz, DMSO-d6): 35.8 (CH3), 60.3 (Cꢀ), 123.2 (two
CN), 123.5 (C-5), 124.4 (C-4), 137.5 (C-2); (for Cꢀ pulse
delay, 3s, 17,000 scans).
We tentatively suggest that the intermediate may be the
ylide 16 resulting from cleavage of the C(7)–C(7a) bond
of 9. In parallel to the formation of 12 and 15, this may
undergo 1,2-rearrangement to the ylide diradical 17
which ring closes (RORC) and aromatises to 10 (Scheme
3).
3. Conclusion
The mechanism of the thermal ring expansions of the
unstable Huisgen cycloadducts formed in the reactions
of azolium-N-dicyanomethanide 1,3-dipoles with alkyne
dipolarophiles has been reassessed. The most likely
mechanism is heterolysis of the C7–C7a bond generating
a ylide intermediate, possessing resonance-stabilised
termini, which undergoes 1,2-rearrangement followed
by ring closure.
1-Benzyl-imidazolium-3-dicyanomethanide 2 was similarly
prepared (73%), mp 177–179 ꢁC (from ethanol), Anal.
Calcd for C13H10N4: C, 70.25; H, 4.55; N, 25.21; Found: C,
69.85; H, 4.55; N, 24.78.; IR (cmꢀ1) 2160, 2180 (J, 1.4 Hz,
CN); dH NMR (400 MHz, DMSO-d6): 5.32 (s, 2H, benzyl
CH2), 7.59–7.42 (m, 5H, Ph), 7.66 (s, 1H, H-5), 7.75 (s, 1H,
H-4), 9.36 (s, 1H, H-2); dC NMR (100 MHz, DMSO-d6):
52.1 (benzyl CH2), 122.6 (C-5), 123.0 (two CN), 124.7 (C-
4), 128.3 (C-30), 128.7 (C-40), 129.0 (C-20), 134.9 (C-10),
136.4 (C-2).
Acknowledgements
E.M.M. acknowledges support from the Irish
Research Council for Science, Engineering and
Technology. L.A.B. acknowledges the National Science
Foundation for a computer equipment grant (MRI
9871088).
Synthesis of 1-methyl-5-imino-6-cyano-8-methoxycarbonyl-
imidazo-[1,2-a] pyridine 6.
References and notes
A solution of 1 (0.28 g, 1.92 mmol) in acetonitrile (10 ml)
was treated with methyl propiolate (0.17 ml, 1.92 mmol),
stirred at 0–5 ꢁC (ice-bath) for 72 h and the solvent
removed under reduced pressure to give a crude dark
brown solid (0.42 g, 95%); fractional crystallisation from
EtOH gave 6 as a pale yellow solid mp 155–157 ꢁC (51%)
and a dark red gum. Anal. Calcd for C11H10N4O2: C, 57.4;
1. Boekelheide, V.; Fedoruk, N. A. J. Am. Chem. Soc. 1968,
90, 3830–3834.
2. Butler, R. N.; Coyne, A. G.; Burke, L. A. J. Chem. Soc.,
Perkin Trans. 2 2001, 1781–1784; Butler, R. N.; Coyne, A.
G.; McArdle, P.; Cunningham, D.; Burke, L. A. J. Chem.
Soc., Perkin Trans. 1 2001, 1391–1397.
H, 4.4; N, 24.3; Found: C, 57.4; H, 4.5; N, 24.7. IR (cmꢀ1
)
3107 (NH), 2204 (CN), 1723 (C@O), 1613 (C@N); dH, dC
NMR Figure 1. Compounds 7, mp 131–133 ꢁC and 8, mp
190–191 ꢁC were similarly prepared. (Due to contamination
by a dark-red gum, compound 7 was better prepared by the
method described for 9 below).
3. Linn, W. J.; Webster, O. W.; Benson, R. E. J. Am. Chem.
Soc. 1965, 87, 3651–3656.
4. Basketter, N.; Plunkett, A. O. Chem. Commun. 1971, 1578.
´
5. Dıez-Barra, E.; Pardo, C.; Elguero, J.; Arriau, J. J. Chem.
Soc., Perkin Trans. II 1983, 1317–1320.
Imidazolium ylides 12 and 15.
6. Tsuge, O.; Shimize, V.; Shimoharada, H.; Kanemasa, S.
Heterocycles 1982, 19, 2259–2262.
A solution of 1 (0.5 g, 3.42 mmol) in acetonitrile (10 ml)
was treated with a solution of maleic anhydride (0.33 g,
3.42 mmol) in acetonitrile, and the mixture stirred at room
temperature for 3 h. The solution was then evaporated
under reduced pressure at a temperature below 35 ꢁC.
Addition of ether to the residue gave a brown solid,
compound 12 (0.62 g, 72%), mp 180–181 ꢁC (from aceto-
nitrile). Anal. Calcd for C11H8N4O3: C, 54.1; H, 3.3; N,
22.95. Found: C, 54.35; H, 3.6; N, 22.7%. IR (cmꢀ1) 3330
(N–H), 2175 (CN), 1792, 1734 (C@O); dH, dC NMR Figure
1. Evaporation of the ethereal filtrate led only to isolation
of an oily residue. Compound 15 was prepared similarly but
under N2 with the stirring continued for 27 h. Compound
15, a sticky brown solid, (0.33 g, 86%). dH NMR (400 MHz,
CD3CN): 5.24 (s, 1H, H-9), 5.31 (s, 2H, benzyl CH2), 7.27–
7.39 (m, 7H, H-2, H-3 and Ph), 8.52 (s, 1H, H-5), 9.8–11.62
(br, 1H, moisture sensitive NH); dC NMR (100 MHz,
CD3CN) 52.4 (benzyl CH2), 62.2 (C-7), 92.2 (C-9), 118.8
(CN), 119.5 (C-8), 121.5 (C-2), 121.8 (C-3), 128.5 (C-20),
134.2 (C-10), 129.1 (C-40), 129.3 (C-30), 135.4 (C-5), 150.0 (C-6),
165.4, 166.1 (C@O); (for C-7 pulse delay 4 s, 12,800 scans).
Synthesis of compounds 9 and 10 (cf Ref. 5).
7. Crystal structure determination for structure 14. Crystal
data, C17H11N5O2, M = 317.31, monoclinic, a = 7.134(2),
˚
b = 24.240(2),
c = 8.589(2) A,
b = 93.23(5)ꢁ,
V =
3
3
˚
1482.9(6) A , space group P21/a, Z = 4, Dc 1.421 Mg/m ,
l = 0.099 mmꢀ1, F(000) = 656, unique reflections = 2789
[R(int) = 0.0155], observed I > 2rI = 1838, data/restraints/
parameters = 2789/219. The final R1 = 0.0734 and
wR2 = 0.1232 (all data). Crystallographic data (excluding
structure factors) for the structures in this paper have been
deposited with the Cambridge Crystallographic Data Cen-
tre as supplementary publication number CCDC 601383.
Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2
1EZ, UK [fax: +44 (0)1223336033 or e-mail: deposit@
ccdc.cam.ac.uk].
8. Theoretical calculations: All geometry optimisations used
the B3LYP/6-31G(d) theoretical method and analytical
frequencies to characterise minima, as found in Gauss-
ian03. The computer output can be obtained at http://
camchem.rutgers.edu/~burke as well as calculated NMR
chemical shifts.
A solution of 3 (0.37 g, 1.77 mmol) in DMF (20 ml), cooled
to 0 ꢁC, was treated with DMAD (0.218 ml, 1.77 mmol),
9. Typical examples: Synthesis of 1-methyl-imidazolium-3-
dicyanomethanide 1.

R. N. Butler et al. / Tetrahedron Letters 47 (2006) 6107–6111
6111
and allowed to stand at 0 ꢁC for 4.5 h, then filtered and the
filtrate added to ice-cold water. The resulting brown
product 9 (0.44 g, 71%) was collected on a jacketed sintered
glass funnel at ꢀ5 ꢁC, washed with EtOH (10 · 1 ml, 0 ꢁC)
and Et2O (3 · 1 ml, 0 ꢁC) dH, dC NMR at 0 ꢁC see Figure 1.
When a solution of 9 (0.2 g, 0.5 mmol) in CH3CN (15 ml)
was stirred at 50 ꢁC for 2 h and ambient temperature for
50 h, and then evaporated under reduced pressure, 10 was
obtained in 80% yield, mp 167 ꢁC, lit.,5 mp 172–174 ꢁC; dH
NMR, dC NMR see Figure 1.