Scheme 1. CM of Symmetrical Disubstituted Olefins
The high activity of these catalyst systems now allows
R-olefins as well as 1,2-disubstiuted olefin starting materials
for CM of R,â-unsaturated carbonyl olefins,7 vinylphospho-
nates,8 and vinylsulfones.9 In addition, we also reported the
cross-metathesis of terminal olefin with 1,1-disubstiuted
olefins.10 Unfortunately, these reactions exhibited low olefin
stereoselectivity and required moderately high catalyst load-
ings and reaction temperatures. In addition, only methyl
groups as the second geminal substituent were reported in
our initial work. We anticipated that the use of identical
substituents on the geminal carbon would expand the
substrate scope, without being complicated by the issue of
poor stereoselectivity. In this Letter, we report the convenient
CM of symmetrical 1,1-disubstituted olefins with a variety
of CM partners, including an isoprenoid synthetic route by
the homologation of R-olefins with isobutylene or 2-methyl-
2-butene.11
(entry 1). Also, the reactions tolerate substrates that could
Table 1. Cross-Metathesis with Isobutylene Using 3
Our initial work began with the cross-metathesis of
isobutylene with terminal olefins (Table 1).12 These reactions
offer a convenient alternative to the use of Ph3PdC(CH3)2
and the corresponding aldehyde to form prenyl functionality.
Prenyl groups are a ubiquitous structural element in many
natural products13 and are also frequently employed in ene
chemistry. For example, the reaction works well with simple
ring close as demonstrated in the homoallylic hepatadiene
case (entry 2). Senecioic acid derivations are also readily
available from the CM reaction with the corresponding
acrylate ester (entry 3). In addition, a protected secondary
allylic alcohol is well tolerated and provides the CM product
in quantitative yield (entry 5). With these results in hand,
we investigated other symmetrically substituted olefins and
found that both methylenecyclohexane and 2-methylene-1,3-
dibenzoate work well as CM partners with 5-hexenyl acetate
(Scheme 1). Since the 1,1-disubstituted olefin does not
dimerize, it can be fully recovered and used in subsequent
CM reactions.
Interestingly, we did observe a background dimerization
of a small amount of isobutylene to tetramethylethylene, but
this did not affect the CM efficiency. The CM efficiency is
surprising since the catalyst loadings are very low relative
to the amount of bulk olefin in the reaction, with an effective
catalyst loading of 0.0001 mol %. The inability of the 1,1-
disubstituted olefin to readily homodimerize allows it to serve
(6) (a) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999,
1, 953. (b) Sanford, M. S.; Love, J. A.; Grubbs, R. H. J. Am. Chem. Soc.
2001, 123, 6543.
(7) (a) Chatterjee, A. K.; Morgan, J. P.; Scholl, M.; Grubbs, R. H. J.
Am. Chem. Soc. 2000, 122, 3783. (b) Choi, T.-L.; Chatterjee, A. K.; Grubbs,
R. H. Angew. Chem., Int. Ed. 2000, 39, 1277. (c) Choi, T.-L.; Lee, C. W.;
Chatterjee, A. K.; Grubbs, R. H. J. Am. Chem. Soc. 2001, 123, 10417.
(8) Chatterjee, A. K.; Choi, T.-L.; Grubbs, R. H. Synlett 2001, 1034.
(9) Grela, K.; Bieniek, M. Tetrahedron Lett. 2001, 42, 6425.
(10) Chatterjee, A. K.; Grubbs, R. H. Org. Lett. 1999, 1, 1751.
(11) Some of these olefins have been demonstrated in other CM systems
from this group, see: ref 7c and Goldberg, S. D.; Grubbs, R. H. Angew.
Chem., Int. Ed. 2002, 41, 807.
(12) Typical isobutylene CM procedure: To an oven dried, 100 mL
Fischer-Porter bottle with Teflon stir bar, ruthenium metathesis catalyst
(15.0 mg, 0.018 mmol, 1.0 mol %) was added. The bottle was capped with
a rubber septum and flushed with dry nitrogen and cooled to -78 °C (or
temperature sufficient to freeze substrate). Substrate (1.0 mmol) was injected
into the bottle. Once the substrate was frozen, a pressure regulator was
attached to the bottle. The bottle was evacuated and backfilled with dry
nitrogen 3 times. Subsequently, isobutylene (5-10 mL, 50-100 equiv) was
condensed into the bottle. The bottle was backfilled to ∼2 psi with nitrogen,
sealed, and allowed to slowly warm to room temperature, at which time it
was transferred to an oil bath at 40 °C. After stirring for 12-18 h, the
bottle was removed from the oil bath and allowed to cool to room
temperature. The isobutylene was slowly vented off at room temperature
until the pressure apparatus could be safely disassembled. The remaining
mixture was taken up in organic solvent for subsequent silica gel
chromatography and/or spectrographic characterization.
(13) The following paper provides an excellent application of the methods
described in this Letter in an allyl to prenyl conversion, see: Spessard, S.
J.; Stoltz, B. M. Org. Lett. 2002, 4, 1943.
1940
Org. Lett., Vol. 4, No. 11, 2002