LETTER
Cyclopropanation Mediated by Lithium Iodide
2979
Table 4 Reactions of 1a with Various Electron-Deficient Alkenesa
O
Me
O
OH
OH
N
N
1d or 1f
NC
CN
R1
R2
R3
or
+
CH2Bz2
89%
CO2Et
LiI
100 °C, 2 d
EtO2C
+
R1
1a +
Br
91% (from both 1d and 1f)
CO2Et
R3
DMF, r.t.
O
Me
CN
R2
2c–h
4
3
81%
R1
R2
R3
Time Yield (%)
(h)
Equation 6
Entry 2
3b
4
On the basis of the above observations, we have a tenta-
tive scenario that the reaction starts with liberation of a
bromonium ion from dibromides 1, which is presumably
trapped by iodide ion to prevent a recombination leading
to 1. The resulting bromomalononitrile anion undergoes a
Michael addition to 2 affording cyclopropanes 3 via in-
tramolecular cyclization.
1
2
3
4
5
6c
7
2c
Ph
Ph
Ph
Ph
Ph
Ph
Et
CN
Ac
Ac
CO2Et
Ac
1
1
3
3
1
1
3
3ac 90 (47:53)
0
2d
2e
2f
0
79
41
49
83
CO2Et
trace
trace
trace
CO2Et Ac
The different behavior of dibromides 1a and 1b was
marked by a cyclic voltammetric study, which revealed
that the redox potentials of 1a and 1b in DMF vs. Ag/Ag+
were shown at –0.62 V and –1.39 V, respectively, reflect-
ing the yields of cyclopropanes.
2g
2g
2h
CO2Et CO2Et
CO2Et CO2Et
3ag 24 (45:55) 63
3ah 48 (50:50)
CN
CN
0
a Conditions: 1a (0.50 mmol), 2 (0.60 mmol), DMF (1 mL), r.t.
b Values in parentheses refer to the diastereomeric ratio.
c Alkene (3 equiv) and LiI (2 equiv) were used.
In summary, the cyclopropanation of electron-deficient
alkenes were achieved by using a combination of active
methylene dibromides and LiI under mild conditions.7
philic brominating agents (Equation 5),6 which release a
bromonium ion, likewise NBS. The presence of phenolic
OH is necessary to promote this bromination; anisole was Typical Reaction Procedure (Entry 5, Table 1)
To a mixture of 1b (77 mg, 0.50 mmol) and LiI (67 mg, 0.50 mmol)
inert for the bromination. Both the two bromine atoms in
1c are capable of taking part in the transformation. (3) We
tested the reaction of dibromides 1d and 1f with phenol (2
equiv) at 100 °C for 2 days according to the conditions in
the literature6 affording dibenzoylmethane (89%) and bar-
bituric acid (81%), respectively, along with p-bromophe-
nol (91%) in both the cases (Equation 6). Dibromides 1d
and 1f were protonated by the phenolic proton, which may
play a critical role to prevent a reverse reaction regenerat-
ing the dibromides.
in DMF (1 mL), 2b (70 mL, 0.60 mmol) was added, and the mixture
was stirred for 1 h. The product was extracted with Et2O, washed
with H2O and brine, and dried over Na2SO4. The solvent was re-
moved under reduced pressure, and the product was purified by
chromatography on SiO2 (elution with hexane–EtOAc = 2:1, then
EtOAc) affording 3bb (124 mg, 94%, dr = 51:49).
Ethyl 1,2,2-Tricyano-3-phenylcyclopropanecarboxylate4a (3bb)
1H NMR (200 MHz, CDCl3): d = 1.21 (t, J = 7.2 Hz, 3 Ha), 1.47 (t,
J = 7.2 Hz, 3 Hb), 3.98 (s, 1 Ha), 4.04 (s, 1 Hb), 4.25 (q, J = 7.2 Hz,
2 Ha), 4.52 (q, J = 7.2 Hz, 2 Hb), 7.29–7.46 (m, 5 Ha), 7.50 (s, 5 Hb).
H
Diethyl 2,2-Dicyano-3-phenylcyclopropane-1,1-dicarboxylate
(3cb)
CN
CN
Ph
aq EtOH
84%
BrCH(CN)2
+
2b
1H NMR (200 MHz, CDCl3): d = 1.19 (t, J = 7.2 Hz, 3 H, CH3),
1.39 (t, J = 7.2 Hz, 3 H, CH3), 3.95 (s, 1 H, CH), 4.23 (q, J = 7.2 Hz,
2 H, CH2), 4.32 (q, J = 7.0 Hz, 2 H, CH2), 7.35–7.40 (m, 5 H, Ph).
NC
CN
Equation 3 (from ref. 3b)
1,1-Dicyano-2,2-dibenzoyl-3-phenylcyclopropane (3db)
1H NMR (200 MHz, CDCl3): d = 4.38 (s, 1 H), 7.20–7.64 (m, 7 H),
7.68–7.77 (m, 2 H), 7.98–8.08 (m, 2 H). 13C NMR (50 MHz,
CDCl3): d = 16.5, 41.2, 56.0, 110.0, 112.3, 127.5, 128.4, 128.7,
128.9, 129.1, 129.1, 129.4, 129.5, 133.7, 134.7, 135.1, 187.7, 188.0
(one aromatic carbon is overlapping).
H
CN
CN
Ph
Br2
CH2(CN)2
+
2b
NaOEt, EtOH
93%
NC
CN
Equation 4 (from ref. 4a)
1,1-Cyano-6,6-dimethyl-2-phenylspiro[2.5]octane-4,8-dione
(3eb)
OH
OH
1H NMR (200 MHz, CDCl3): d = 1.21 (s, 6 H, 2 × CH3), 2.60–2.83
1c or BrCH(CO2Et)2
(m, 4H), 4.12 (s, 1 H), 7.10–7.20 (m, 2 H), 7.30–7.40 (m, 3 H). 13
NMR (50 MHz, CDCl3): d = 22.1, 28.5, 29.0, 30.2, 44.3, 49.4, 53.2,
54.4, 109.5, 111.0, 127.1, 128.4, 128.8, 128.9, 195.9, 198.0.
C
Br
82%
(from both bromides)
Equation 5 (from ref. 5)
Synlett 2008, No. 19, 2977–2980 © Thieme Stuttgart · New York