J. Am. Chem. Soc. 2001, 123, 8139-8140
Acyloxymethylzinc Reagents: Preparation,
8139
Reactivity, and Solid-State Structure of This Novel
Class of Cyclopropanating Reagents
Andre´ B. Charette,* Andre´ Beauchemin, and
Se´bastien Francoeur
1
De´partement de Chimie, UniVersite´ de Montre´al
Que´bec, Canada H3C 3J7
diethylzinc affords a reactive carbenoid. Furthermore, H NMR
analysis indicated that the zinc-iodine exchange had occurred
as Et-I was formed quantitatively, thus affording the carbenoid
of the general structure B. More conveniently, the desired
alkylzinc reagent can be prepared in the presence of the alkene,
using photoinduced zinc-iodine exchange.12,13 The reactivity of
this carbenoid was examined mainly by its reaction with a variety
of unfunctionalized olefins (Table 1),14 since these substrates are
generally poorly reactive under the existing Simmons-Smith
protocols.15
ReceiVed April 11, 2001
Cyclopropanes are the focus of much interest as they are found
in many natural and unnatural products possessing interesting
biological activities.1 They are also useful synthetic intermediates2
and can serve as mechanistic probes in many organic reactions.3
Surprisingly, however, the number of approaches to access
cyclopropanes from alkenes is limited to methodologies developed
a few decades ago. These include free carbenes,4 transition metal-
catalyzed diazo decomposition,5 Simmons-Smith reaction,6 and
Michael initiated ring closure.7 The development of a reagent that
would overcome the inherent limitations of these classical
approaches would be of great value. Indeed, the use of a large
excess of reagent (>5 equiv) is often required and so far only
the Simmons-Smith reaction is capable of an efficient enanti-
oselective methylene transfer, in cases where allylic alcohols are
used as substrates.6 In this perspective, we were interested in the
development of a new concept of metal carbenoids that could
show increased reactivity and/or provide new avenues to perform
enantioselective cyclopropanation reactions. Herein, we report
conceptually different carbenoids, the acyloxymethylzinc car-
benoids, which are reactive and promising cyclopropanating
reagents. Furthermore, these reagents are the first examples of
zinc carbenoids that can cyclopropanate alkenes without involving
the breaking of a carbon-halogen bond in the methylene transfer
process.8
As illustrated in Table 1, this reagent cyclopropanates ef-
ficiently a variety of unfunctionalized alkenes (entries 1-4).
Interestingly, trans-stilbene, which is often unreactive under most
Simmons-Smith protocols, gives the desired product in modest
yield (entry 5).16 As expected, the cyclopropanation of function-
alized substrates proved also efficient (entry 6). While the reaction
conditions are not optimized,17 the data presented in Table 1
unambiguously demonstrate the synthetic potential of zincmethy-
lesters as efficient cyclopropanating reagents. Although this type
of reagent is precedented, the parent zincmethylbenzoate com-
pounds have been shown to be poorly reactive as either electro-
philes18 or nucleophiles.19
The structure of a member of this class of carbenoids was
confirmed by X-ray crystallography. The bis(benzoyloxymethyl)-
zinc analogue 2 was prepared using both the reported18 and
photoinduced12 routes (eq 1). An ORTEP drawing of 2 is shown
in Figure 1 and selected bond lengths and angles are presented
in Table 2.20
Drawing on the experimental evidence for Lewis acid catalysis
in the Simmons-Smith reaction9 and Nakamura’s reported five-
membered, cyclic transition state model A,10 we reasoned that a
carbenoid with internal Lewis acid activation could be an efficient
methylene transfer reagent. We therefore became interested in
the versatile carbenoid template B since this family of reagents
is the methylene transfer equivalent of peracids in epoxidation
reactions (C).
In contrast with other carbenoid complexes in which the zinc
center displays a tetrahedral geometry,21 the zinc center in 2
resides in a distorted square-bipyramidal environment. The Zn-C
With this model in mind, the R1 group should be electron
withdrawing to increase the electrophilicity of the carbenoid,
which is expected to be enhanced through intramolecular coor-
dination to the zinc atom (Scheme 1, B). Gratifyingly, it was found
that a 1:1 mixture of iodomethyl perfluoropentanoate 111 and
(11) This iodide was selected for its physical properties. As described in
the Experimental Section, it can be purified by distillation, without being
hydrophilic and/or volatile enough to jeopardize product isolation.
(12) The zinc-iodine exchange reaction is slow and it is inhibited by the
presence of alkenes. For a similar observation, see: (a) Miyano, S.; Hashimoto,
H. Bull. Chem. Soc. Jpn. 1973, 46, 1895. The use of a UV-vis source is
required to achieve quantitative formation of the carbenoid, see: (b) Charette,
A. B.; Beauchemin, A.; Marcoux, J.-F. J. Am. Chem. Soc. 1998, 120, 5114.
(13) The photolysis is performed using a GE 275W sunlamp or a 300W
OSRAM Ultra-Vitalux lamp.
(14) In contrast to diiodomethane, irradiation of iodide 1 in the absence of
Et2Zn does not lead to cyclopropane formation, see: Kropp, P. J. Acc. Chem.
Res. 1984, 17, 131 and references therein.
(15) For superior reagents to cyclopropanate unfunctionalized alkenes,
see: (a) Denmark, S. E.; Edwards, J. P. J. Org. Chem. 1991, 56, 6974. (b)
Yang, Z. Q.; Lorenz, J. C.; Shi, Y. Tetrahedron Lett. 1998, 39, 8621. (c)
Charette, A. B.; Francoeur, S.; Martel, J.; Wilb, N. Angew. Chem., Int. Ed.
2000, 112, 4539.
(1) Salau¨n, J. Curr. Med. Chem. 1995, 2, 511.
(2) (a) Small Ring Compounds in Organic Synthsis VI; de Meijere, A.,
Ed.; Springer: Berlin, Germany, 2000; Vol. 207. (b) Houblen-Weyl, Methods
of Organic Chemistry; Thieme: Stuttgart, 1997; Vol. E 17c.
(3) Nonhehel, D. C. Chem. Soc. ReV. 1993, 22, 347.
(4) Doering, W. v. E.; Hoffman, A. K. J. Am. Chem. Soc. 1954, 76, 6162.
(5) (a) Doyle, M. P. Chem. ReV. 1986, 86, 919. (b) Lydon, K. M.;
McKervey, M. A. In ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N.,
Pfaltz, A., Yamamoto, H., Eds.; Springer-Verlag: Berlin, Germany, 1999;
Vol. II, p 539. (c) Pfaltz, A. In ComprehensiVe Asymmetric Catalysis; Jacobsen,
E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer-Verlag: Berlin, Germany,
1999; Vol II, p 513.
(6) Charette, A. B.; Beauchemin, A. Org. React. (N.Y.) 2001, 58, in press.
(7) Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1962, 84, 867.
(8) Motherwell reported a superb route to zinc carbenoids using Zn/Hg,
carbonyl compounds (or their equivalents), and TMSCl. However, the proposed
intermediate for these reactions is the chloro-alkylzinc reagent, see: Moth-
erwell, W. B.; O’Mahony, D. J. R.; Popkin, M. E. Tetrahedron Lett. 1998,
39, 5285 and cited references.
(9) Charette, A. B.; Brochu, C. J. Am. Chem. Soc. 1995, 117, 11367.
(10) Nakamura, E.; Hirai, A.; Nakamura, M. J. Am. Chem. Soc. 1998, 120,
5844.
(16) Zn/Cu, CH2I2 (6 equiv), Et2O: 24%, see: (a) Brown, R. S.; Traylor,
T. G. J. Am. Chem. Soc. 1973, 95, 8025. EtZnI/CH2I2 (3 equiv), Et2O: 48%,
see: (b) Sawada, S.; Inouye, Y. Bull. Chem. Soc. Jpn. 1969, 42, 2669. Et2-
Zn/TFA/CH2I2 (4 equiv), CH2Cl2: 70%, see ref 15b.
(17) A significant amount of the carbenoid decomposition is due to
homologation to form n-C4F9CO2Zn(n-Pr), as in the case of EtZnCH2I:
Charette, A. B.; Marcoux, J.-F. J. Am. Chem. Soc. 1996, 118, 4539.
(18) Wittig, G.; Jautelat, M. Liebigs Ann. Chem. 1967, 702, 24.
(19) Knochel, P.; Chou, T.-S.; Chen, H. G.; Yeh, M. C. P.; Rozema, M. J.
J. Org. Chem. 1989, 54, 5202.
10.1021/ja0109287 CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/27/2001