targets and common structural components in numerous biologi-
cally active natural products and pharmaceuticals.3 The strain
energy of cyclopropenes may also be exploited in a host of
cycloaddition and rearrangement reactions, providing numerous
other molecules of interest.1
During our recent investigations into the development of
stereoselective carbometalation-ring-opening reactions of bis-
activated cyclopropenes to produce multisubstituted alkenes,2d
the reaction of cyclopropene 1a with commercially available
Grignard reagent 2 was conducted (eq 1). Instead of furnishing
products derived from addition of the nucleophilic alkyl
functionality of 2, the major product isolated in this reaction
was the alkenyl bromide 3a. We attributed this initially
surprising result to reaction of cyclopropene 1a with magnesium
bromide produced from the Schlenk equilibrium4 of the Grignard
reagent. This hypothesis was supported by reaction of 1a with
MgBr2 itself, which also produced 3a, but in 96% yield (eq 2).
Stereoselective Formation of Alkenyl Halides via
Magnesium Halide Promoted Ring Opening of
Bis-Activated Cyclopropenes
Yi Wang and Hon Wai Lam*
School of Chemistry, UniVersity of Edinburgh,
The King’s Buildings, West Mains Road,
Edinburgh, EH9 3JJ, United Kingdom
ReceiVed NoVember 5, 2008
In the presence of stoichiometric magnesium halides, a range
of bis-activated cyclopropenes undergo highly stereoselective
ring-opening reactions to produce multisubstituted alkenyl
halides. More highly functionalized compounds may be
obtained by trapping of the magnesium enolate intermediates
in situ.
This process is closely related to the results of Ma and co-
workers, who described a series of alkali metal halide induced
cyclopropene ring-opening-alkylation reactions that required
an alkali metal carbonate additive for highest yields (representa-
tive example shown in eq 3).5a However, their process differs
from ours in that simple protonolysis of the initial ring-opened
species was not described in their work.5a The majority of
examples described by Ma were conducted using a bis-activated
cyclopropene that was unsubstituted at the alkene, although four
results using trisubstituted cyclopropenes were reported (as in
eq 3).5a
Cyclopropenes, the smallest unsaturated carbocycles, are an
important class of building blocks for organic synthesis.1 The
high strain energy stored within the three-membered ring of
cyclopropenes may be harnessed in the design of novel chemical
transformations that are often unavailable to simple alkenes.1,2
For example, cyclopropenes are highly susceptible to a broad
range of addition reactions across the double bond1b to provide
functionalized cyclopropanes, which themselves are important
(1) For reviews, see: (a) Binger, P.; Bu¨ch, H. M. Top. Curr. Chem. 1987,
135, 77–151. (b) Baird, M. S. Cyclopropenes: Transformations (Houben-Weyl);
Thieme: Stuttgart, Germany, 1997; Vol. E17d/2, pp 2781-2790. (c) Nakamura,
M.; Isabe, H.; Nakamura, E. Chem. ReV. 2003, 103, 1295–1326. (d) Fox, J. M.;
Yan, N. Curr. Org. Chem. 2005, 9, 719–732. (e) Rubin, M.; Rubina, M.;
Gevorgyan, V. Synthesis 2006, 1221–1245. (f) Rubin, M.; Rubina, M.;
Gevorgyan, V. Chem. ReV. 2007, 107, 3117–3179. (g) Marek, I.; Simaan, S.;
Masarwa, A. Angew. Chem., Int. Ed. 2007, 46, 7364–7376.
(2) For recent, selected examples of investigations into the reactivity of
cyclopropenes, see: (a) Fisher, L. A.; Fox, J. M. J. Org. Chem. 2008, 73, 8474–
8478. (b) Sherill, W. M.; Rubin, M. J. Am. Chem. Soc. 2008, 130, 13804–13809.
(c) Fordyce, E. A. F.; Luebbers, T.; Lam, H. W. Org. Lett. 2008, 10, 3993–
3996. (d) Wang, Y.; Fordyce, E. A. F.; Chen, F. Y.; Lam, H. W. Angew. Chem.,
Int. Ed. 2008, 47, 7350–7353. (e) Pallerla, M. K.; Yap, G. P. A.; Fox, J. M. J.
Org. Chem. 2008, 73, 6137–6141. (f) Alnasleh, B. K.; Sherrill, W. M.; Rubin,
M. Org. Lett. 2008, 10, 3231–3234. (g) Yan, N.; Liu, X.; Fox, J. M. J. Org.
Chem. 2008, 73, 563–568. (h) Fordyce, E. A. F.; Wang, Y.; Luebbers, T.; Lam,
H. W. Chem. Commun. 2008, 1124–1126. (i) Rubina, M.; Woodward, E. W.;
Rubin, M. Org. Lett. 2007, 9, 5501–5504. (j) Masarwa, A.; Stanger, A.; Marek,
I. Angew. Chem., Int. Ed. 2007, 46, 8039–8042. (k) Trofimov, A.; Rubina, M.;
Rubin, M.; Gevorgyan, V. J. Org. Chem. 2007, 72, 8910–8920. (l) Chuprakov,
S.; Malyshev, D. A.; Trofimov, A.; Gevorgyan, V. J. Am. Chem. Soc. 2007,
129, 14868–14869. (m) Hirashita, T.; Shiraki, F.; Onishi, K.; Ogura, M.; Araki,
S. Org. Biomol. Chem. 2007, 5, 2154–2158. (n) Giudici, R. E.; Hoveyda, A. H.
J. Am. Chem. Soc. 2007, 129, 3824–3825.
To establish whether the serendipitous result of eq 2 could
be translated into a general and efficient process, a range of
bis-activated cyclopropenes 1a-1g were reacted with stoichio-
metric quantities of magnesium halides, and these results are
presented in Table 1. Using MgBr2, cyclopropenes 1a-1e
containing alkyl or aryl functionality on the alkene efficiently
underwent the ring-opening reaction to provide alkenyl bromides
(3) (a) Liu, H. W.; Walsh, C. T. Biochemistry of the Cyclopropyl Group In
The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.; Wiley: Chichester,
UK, 1987; pp 959-1025. (b) Salaun, J. Top. Curr. Chem. 2000, 207, 1–67.
(4) Schlenk, W.; Schlenk, W., Jr. Chem. Ber. 1929, 62, 920–924.
10.1021/jo802475x CCC: $40.75
Published on Web 12/30/2008
2009 American Chemical Society
J. Org. Chem. 2009, 74, 1353–1355 1353