centers of the starting pyrazoline. To our knowledge, this is
one of the few examples of extrusion of nitrogen from
pyrazolines under thermal conditions giving rise to optically
pure cyclopropanes with complete control of the stereose-
lectivity.
of the pyrazoline ring, supporting an electron-withdrawing
group able to stabilize the negative charge.18
Due to the potential interest of the availability of a
cyclopropane moiety in organic structures, as a consequence
of its presence in building blocks of naturally occurring
compounds19 or to its effectiveness in restricting the con-
formational mobility of biologically active compounds,20 we
embarked on the task of transforming our previously
synthesized enantiopure sulfonyl cyanocyclopropanes (6 and
7) into other cyclopropane derivatives.21
Reductive desulfonylation of compounds 7a (R ) n-Bu)
and 7b (R ) t-Bu) proved to be a difficult task in the
synthesis of other sulfinyl cyclopropanes.3 In our case, we
used different systems to get the hydrogenolysis of the C-S
bond such as Li+Naft-,22 [Al(Hg)],23 [Na(Hg)],24 Ni(Raney),
Li/EtNH2,25 but the results obtained were not satisfactory in
any case. Finally, it was accomplished by treatment of 7a
and 7b with magnesium in methanol following previously
reported procedures,20a,26 which were slightly modified.27
After 1-3 days at room temperature, we obtained the
expected compounds (Scheme 3) in ca. 80% yield of the
crude reaction (chemically pure by NMR). Distillation of
the crude mixture afforded 8a and 8b in 60 and 56% yields,
respectively.28 The four-step procedure described herein for
preparing enantiomerically pure cyclopropanes containing
two chiral centers (one of them quaternary) from sulfinyl
Whereas a diradical mechanistic pathway has been pro-
posed by several groups13 to explain the highly stereoselec-
tive evolution of pyrazolines under photolytic conditions, the
course of the thermal decomposition of pyrazolines into
cyclopropanes still remains controversial. Indeed, the hitherto
reported stereochemical results from thermal decomposition
of 1-pyrazolines are quite divergent and strongly dependent
on the nature of the substituents at the ring. Ionic14 or
diradical15 mechanisms have been postulated to explain the
most usual pyrolytic processes proceeding without stereo-
selectivity, although there is a report that assumes a diradical
mechanism to explain some stereoselective transformations.16
Many years ago,17 a concerted mechanism was invoked
to account for the retention of configuration observed in some
cyclopropanes resulting from extrusion of nitrogen of pyra-
zolines. Bearing in mind the electron-withdrawing groups
existing at the pyrazoline rings reported herein, our stereo-
chemical results are consistent with the concerted thermal
decomposition proposed by McGreer17a,b of a series of 4-
and 5-alkyl-substituted 3-methyl-3-methoxycarbonyl-∆1-
pyrazolines, which afford cyclopropanes by extrusion of
nitrogen through a polar transition state, where the degree
of bond breaking of the C(3)-N bond is advanced over the
bond breaking of the C(5)-N bond (Figure 2). The common
(18) Stereoselective formation of alkylidenecyclopropanes by thermal
nitrogen extrusion from alkylidenepyrazolines has been recently published
(Hamaguchi, M.; Nakaishi, M.; Nagai, T.; Tamura, H. J. Org. Chem. 2003,
68, 9711). The mechanistic model proposed in that paper by the authors is
not significantly different from that proposed by McGreer in refs 16a and
16b. Alkylidenepyrazolines described therein also contain electron-
withdrawing groups (apparently very important in the course of the reaction)
and quaternary centers.
(19) See, for example, Hirohara, H.; Mitsuda, S.; Audo, E.; Komaki, R.
In Biocatalysts in Organic Synthesis; Tramper, J., Van der Plas, H. C., Linko,
P., Eds.; Elsevier: Amsterdam, 1985; p 119. See also Johnson, C. R.;
Barbachyn, M. J. Am. Chem. Soc. 1982, 104, 4290. Greuter, H.; Dingwall,
J.; Martin, P.; Bellus, D. HelV. Chim. Acta 1981, 64, 2812. Kim, G.; Chu-
Moyer, M. Y.; Danishefsky, S. J.; Schulte, G. K. J. Am. Chem. Soc. 1993,
115, 30. Salau¨n, J. Top. Curr. Chem. 2000, 207, 1. Pietruszka, J. Chem.
ReV. 2003, 103, 1051. Wessjohann, L. A.; Brandt, W.; Thiemann, T. Chem.
ReV. 2003, 103, 1625.
Figure 2. Proposed transition states for the concerted nitrogen
extrusion under thermal conditions.
(20) (a) Kazuta, Y.; Matsuda, A.; Shuto, S. J. Org. Chem. 2002, 67,
1669. (b) D´ıaz, M.; Ortun˜o, R. M. Tetrahedron: Asymmetry 1996, 7, 3465.
(21) The low stability of the benzyl derivatives 2c and 3c - they
decomposed upon standing at room temperature for several hours - justified
that their use in further transformations was discarded.
(22) (a) Ager, D. J. J. Chem. Soc., Chem. Commun. 1984, 486. (b) Ager,
D. J. J. Org. Chem. 1984, 49, 168.
feature of compounds 4 and 5 with those studied by
McGreer17a,b is the existence of a quaternary carbon at C-3
(12) Double Pulsed Field Gradient Echo-DPFGS (Bruker DRX-500).
(13) (a) Muray, E.; Illa, O.; Castillo, J. A.; Alvarez-Larena, A.;
Bourdelande, J. L.; Branchadell, V.; Ortun˜o, R. M. J. Org. Chem. 2003,
68, 4906 and references therein. (b) Karatsu, T.; Itoh, H.; Kikunaga, T.;
Ebashi, Y.; Hotta, H.; Kitamura, A. J. Org. Chem. 1995, 60, 8270. (c) White,
D. H.; Condit, P. B.; Bergman, R. G. J. Am. Chem. Soc. 1972, 94, 1348.
(14) (a) Tabushi, I.; Takagi, K.; Okano, M.; Oda, R. Tetrahedron 1967,
23, 2621. (b) Van Auken, T. V.; Rinehart, K. L., Jr. J. Am. Chem. Soc.
1962, 84, 3736.
(15) (a) Padwa, A.; Meske, M.; Rodr´ıguez, A. Heterocycles 1995, 40,
191. (b) Reedich, D. E.; Sheridan, R. S. J. Am. Chem. Soc. 1988, 110,
3697. (c) Crawford, R. J.; Erickson, G. L. J. Am. Chem. Soc. 1967, 89,
3907. (d) Crawford, R. J.; Ali, L. H. J. Am. Chem. Soc. 1967, 89, 3908.
(16) Nakano, Y.; Hamaguchi, M.; Nagai, T. J. Org. Chem. 1989, 54,
1135.
(23) De Lucchi, O.; Lucchini, V.; Marchioro, C.; Valle, G.; Modena, G.
J. Org. Chem. 1986, 51, 1457.
(24) Trost, B. M.; Seoane, P.; Mignani, S.; Acemoglu, M. J. Am. Chem.
Soc. 1989, 111, 7487.
(25) Solladie`, G.; Demailly, G.; Greck, C. J. Org. Chem. 1985, 50, 1552.
(26) Benedetti, F.; Berti, F.; Risaliti, A. Tetrahedron Lett. 1993, 34, 6443.
Brown, A. C.; Carpino, L. A. J. Org. Chem. 1985, 50, 1749.
(27) Reported procedure did not yield the expected cyclopropanes.
Therefore, it was modified as follows: To a flask containing 15 mL of
anhydrous methanol were added Mg turnings (10 equiv), and the mixture
was heated (55 °C) under argon. A solution of sulfonyl cyclopropane (1
equiv) in 3 mL of anhydrous methanol was cannulated under positive argon
pressure, and the resulting mixture was vigorously stirred at room
temperature. Two additional portions of Mg (2 × 10 equiv) were added at
regular intervals (every 2 h). Upon completion, the reaction was quenched
by dilution with CH2Cl2 (10 mL) and further addition of Na2SO4‚10H2O
(200 mg). The mixture was stirred overnight, filtered through a Celite pad,
and concentrated under reduced pressure.
(17) (a) McGreer, D. E.; Chiu, W. K.; Vinge, M. G.; Wong, K. C. K.
Can. J. Chem. 1965, 43, 1407. (b) McGreer, D. E.; Masters, I. M. E.; Liu,
M. T. H. J. Chem. Soc., Perkin Trans. 2 1975, 1791. (c) Deleux, J. P.;
Leroy, G.; Weiler, J. Tetrahedron 1973, 29, 1135. (d) Eberhard, P.; Huisgen,
R. J. Am. Chem. Soc. 1972, 94, 1345.
(28) All the tested chromatographic attempts to purify compounds 8a
and 8b were unsuccessful.
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