A R T I C L E S
Bull and Charette
synthesis of numerous complex structures and natural products,15
employing diastereo- and enantioselective methods.1,16,17 Fur-
thermore, the Simmons-Smith reaction and the carbenoid
reagents have been the subject of several theoretical investiga-
tions.18
Despite the extensive studies that the Simmons-Smith
cyclopropanation has attracted, an intramolecular version of the
reaction, involving an alkyl diiodide containing a pendant alkene,
has not previously been reported.19 Moreover, to date there are
only limited examples of the use of alkyl-substituted carbenoids
to form trisubstituted cyclopropanes in an intermolecular
manner.20,21 We previously reported such an intermolecular
reaction between allylic alcohols and substituted alkyl diiodides
to generate trisubstituted cyclopropanes with excellent yields
and stereocontrol (eq 1).20e We envisaged developing an
intramolecular Simmons-Smith cyclopropanation reaction, to
access bicyclic structures not easily available by other methods
and to examine the reactivity of the substituted zinc-carbenoids
(eq 2).
Figure 1. Intramolecular cyclopropanation methods for the formation of
[n.1.0] bicycles.
our studies into an intramolecular Simmons-Smith (IMSS)
cyclopropanation.
The Simmons-Smith cyclopropanation remains one of the
most powerful methods to form cyclopropanes stereospecifi-
cally.9 Since the original reports in the late 1950s,10 the reaction
has been subject to several important modifications.11-14 These
include the use of diethyl zinc to generate the required carbenoid
as reported by Furukawa,12 which provided simpler reaction
procedures and allowed the use of noncoordinating solvents.
The structures of carbenoids formed from CH2I2 are well-
understood, following NMR studies and crystal structures of
the carbenoid complexed with diethers and bipyridines.13
Additionally, more reactive zinc carbenoid species are now
available.14 Variants of this reaction have been exploited in the
Here we describe our studies into the feasibility and develop-
ment of an intramolecular Simmons-Smith cyclopropanation,
which resulted in the successful synthesis of [3.1.0] and [4.1.0]
bicycloalkanes. Salient features also include the synthesis of
(15) For reviews see: (a) Pietruszka, J. Chem. ReV. 2003, 103, 1051–1070.
(b) Donaldson, W. A. Tetrahedron 2001, 57, 8589–8627.
(16) For examples see: (a) Arai, I.; Mori, A.; Yamamoto, H. J. Am. Chem.
Soc. 1985, 107, 8254–8256. (b) Mash, E. A.; Nelson, K. A. J. Am.
Chem. Soc. 1985, 107, 8256–8258. (c) Imai, T.; Mineta, H.; Nishida,
S. J. Org. Chem. 1990, 55, 4986–4988. (d) Charette, A. B.; Coˆte´, B.;
Marcoux, J.-F. J. Am. Chem. Soc. 1991, 113, 8166–8167. (e) Charette,
A. B.; Lebel, H. J. Org. Chem. 1995, 60, 2966–2967. (f) Evans, D. A.;
Burch, J. D. Org. Lett. 2001, 3, 503–505. (g) Aggarwal, V. K.; Fang,
G. Y.; Meek, G. Org. Lett. 2003, 5, 4417–4420, Also see reference
34.
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2004, 126, 8664–8665. (b) Hodgson, D. M.; Chung, Y. K.; Nuzzo, I.;
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(19) For an example of the use of an R-carbonyl diiodide and AIBN/HSnBu3
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´
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