1844
A. Kamimura et al. / Tetrahedron Letters 54 (2013) 1842–1844
OH
N
Acknowledgment
Zn powder (20 eq.)
no reaction
We are grateful to a financial aid from Yamaguchi University
based on the YU Strategic Program for Fostering Research Activities
(2010–2011).
(recovery of 3b, 96%)
1N HCl
MeOH, r.t.
Pr
MeO2C CO2Me
3b
Supplementary data
Scheme 3.
Supplementary data (1H and 13C NMR) associated with this arti-
recovery of starting material 1a in 19%, while no formation of 2b
was observed in the reaction performed at pH 6.1 (entries 3 and
4). The yields of 3b were about 18–27% throughout these entries
(entries 1–4). Prolonged reaction time never improved yield of
2b, but the yield of 3b decreased (entry 5).
The present double cleavage of cyclopropane was assumed to
pass through the following reaction mechanism (Scheme 2).
Zinc powder under acidic conditions reduced the nitro group
of 1 to give nitrosocyclopropane A, which may accept one elec-
tron from excess amounts of zinc powder to generate radical B.
References and notes
1. Brackmann, F.; de Meijere, A. Chem. Rev. 2007, 107, 4493.
2. Wurz, R. P.; Charette, A. B. Org. Lett. 2005, 7, 2313.
3. Vanier, S. F.; Larouche, G.; Wurz, R. P.; Charette, A. B. Org. Lett. 2010, 12, 672.
4. (a) Wurz, R. P.; Charette, A. B. Org. Lett. 2003, 5, 2327; (b) Moreau, B.; Charette, A.
B. J. Am. Chem. Soc. 2005, 127, 18014; (c) Moreau, B.; Alberico, D.; Lindsay, V. N.
G.; Charette, A. B. Tetrahedron 2012, 68, 3487.
5. (a) Kamimura, A.; Kadowaki, A.; Yoshida, T.; Takeuchi, R.; Uno, H. Chem. Eur. J.
2009, 15, 10330; (b) Kamimura, A.; Takeuchi, R.; Ikeda, K.; Moriyama, T.;
Sumimoto, M. J. Org. Chem. 2012, 77, 2236.
6. Ono, N. The nitro group in organic synthesis; Wiley-VCH: New York, 2001.
7. (a) Wurz, R. P.; Charette, A. B. J. Org. Chem. 2004, 69, 1262; (b) Lindsay, V. N. G.;
Nicolas, C.; Charette, A. B. J. Am. Chem. Soc. 2011, 133, 8972.
8. (a) Kaim, L. E.; Gacon, A. Tetrahedron Lett. 1997, 38, 3391; (b) Olah, G. A.; Narang,
S. C.; Field, L. D.; Fung, A. P. J. Org. Chem. 1983, 48, 2766; (c) Denis, J. N.; Krief, A. J.
Chem. Soc., Chem. Commun. 1980, 544; (d) Wehril, P. A.; Schaer, B. J. Org. Chem.
1977, 42, 3956; (e) Olah, G. A.; Vankar, Y. D.; Gupta, B. G. B. Synthesis 1979, 36;
(f) Urpí, F.; Vilarrasa, J. Tetrahedron Lett. 1990, 31, 7497; (g) Tsay, S. C.; Gani, P.;
Hwu, J. R. J. Chem. Soc., Perkin Trans. 1 1991, 1493; (h) Chang, R. K.; Kim, K.
Tetrahedron Lett. 1996, 37, 7791.
9. Typical experimental procedure: Preparation of dimethyl 2-allyl-2-(1-
cyanobutyl)malonate (2b): Zinc powder (1.4610 g, 22.3 mmol) was washed
with 1 M HCl (5 mL), water (5 mL), and EtOH (2 Â 10 mL) in this order and dried
in vacuo. Dimethyl 1-nitro-2-propylbicyclo[3.1.0]hexane-3,3-dicarboxylate (1b,
306.8 mg, 1.08 mmol) was dissolved in MeOH (20 mL) and 1 M HCl (10 mL) was
added. Pretreated Zn powder was added to the reaction solution at room
temperature over 10 min and the resulting mixture was stirred for 2 h at room
temperature. Aqueous NaHCO3 (10 mL) was added to the reaction mixture. The
reaction mixture was filtered over celite and the filtrate was concentrated to
about half of its volume in vacuo to remove MeOH. The resulting aqueous
solution was extracted with EtOAc (3 Â 30 mL). The organic phase was dried
over MgSO4. Crude product 2b, obtained by filtration and concentration, was
purified by flash chromatography (silica gel/hexane–EtOAc 10:1 v/v) to give 2b
in 62% yield (184.2 mg, 0.727 mmol). Colorless oil, 1H NMR (500 MHz, CDCl3) d
5.65 (dq, J = 9.9, 7.4 Hz, 1H), 5.20 (d, J = 17.0 Hz, 1H), 5.16 (d, J = 10.1 Hz, 1H),
3.77 (s, 6H), 3.13 (dd, J = 11.3, 3.3 Hz, 1H), 2.82 (dd, J = 14.5, 7.4 Hz, 1H), 2.76 (dd,
J = 14.5, 7.5 Hz, 1H), 1.70–1.36 (m, 4H), 0.93 (t, J = 7.1 Hz, 3H); 13C NMR
(126 MHz, CDCl3) d 169.0, 168.9, 131.0, 120.8, 119.4, 59.0, 53.1, 53.0, 37.7, 35.2,
30.2, 21.0, 13.4; IR (neat) 2243 cmÀ1; HRMS (ESI M+H) m/z 254.1389. Calcd for
Intermediate
B underwent cleavage of cyclopropane to give
oxime radical C. When the reaction was carried out under less
acidic conditions such as in aqueous NH4Cl, the second electron
transfer took place to give anion D that underwent immediate
protonation to give oxime 3. On the other hand, the reaction un-
der strong acidic conditions, the oxime was protonated to gener-
ate
E and the second electron transfer induced E1cb-type
elimination from F to give acyclic nitrile 2. The reaction path-
ways depended on the acidity of the reaction conditions; under
strongly acidic conditions using aqueous HCl, the reaction pro-
gressed through E to 2 exclusively. Although oxime radical C
was assumed as the key reaction intermediate, oxime 3 was no
longer a reaction intermediate once it was formed. Indeed, treat-
ment of 3b under aqueous HCl conditions in the presence of zinc
powder failed the conversion to 2b but resulted in the recovery
of 3b in 96% (Scheme 3).
In conclusion we have found a novel conversion of bicyclic
nitrocyclopropanes into vinyl nitriles in good yields. This reaction
contains double carbon–carbon bonds’ cleavages. During the
reduction, generation of radicals that induce carbon–carbon bond
cleavage is assumed and this is potentially useful to generate re-
mote radicals from the reaction center. Further exploration on this
reaction is now underway in our laboratory.
C
13H20NO4 254.1392.