1
determined by H NMR spectroscopy). cycloisomerisation of 13
Notes and references
was less diastereo-selective (4 : 3, determined by 1H NMR
spectroscopy). The non-hindered dimethyl ether 15 is efficiently
cyclo-isomerised to give 16a. The unsymmetrrical 1,6-diene 17 was
rapidly cyclo-isomerised to provide fused exo-bicycle 18a, which
was accompanied by the fused endo-bicycle 18a9 (see Scheme 2). In
contrast, pro-bicyclic diene 19 was a poor substrate—only 30%
conversion was recorded with extensive regio-isomerisation of 20a.
Pro-bicyclic diene 21, possessing a gem-dimethyl group on the
cyclohexene fragment, thwarts b-hydride elimination from the
cyclohexyl ring, i.e. the endo-bicycle cannot be formed, providing
22a as the sole cycloisomerisation product. Nitrogen-tethered 1,6-
dienes (23, 25, and 27) undergo efficient cycloisomerisation. Here
the greatest enhancement in yield and selectivity was observed. For
example, yields for 24a and 26a were improved from 65 and 62%,
from conventional heating, to 99 and 82% under microwave
heating, respectively. Higher selectivity was seen using unsymme-
trical 1,6-diene 29.
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Several 1,6-dienes failed to undergo microwave-assisted cycloi-
somerisation (Fig. 2). A co-mixture of 1 with 31 gave 2a as the sole
cycloisomerisation product after 0.25 h. The experiment confirms
that 31 does not undergo cycloisomerisation in the presence of
catalyst ‘‘Cl-Ru-H’’, propagated through cycloisomerisation of 1.
The formation of 18a9 in the reaction of 17 A 18a is intriguing
as it indicates that a hydroruthenation/carboruthenation/b-hydride
elimination process is not favoured, as hydroruthenation would
occur on both hindered and non-hindered alkenes—the formation
of exo-bicycle 18a would occur through initial addition of ‘‘H-Ru-
Cl’’ to cyclopentene, the more substituted alkene, which is
kinetically less favoured. The oxidative ruthenation/reductive
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elimination/b-hydride elimination pathway provides
a more
adequate explanation, and supports the mechanistic proposal
based on cycloisomerisation of 29.5a Oxidative ruthenation gives
Ru(IV) intermediate I, which then reductively eliminates to give II
(pathway a) or III (pathway b). b-Hydride elimination reveals 18a
and 18a9, respectively. Pathway a dominates to give 18a.
13 In the absence of ruthenium, cycloisomerisation was not observed under
conventional or microwave heating.
In conclusion, we have shown that microwave heating
accelerates Ru-mediated cycloisomerisation of 1,6-dienes.
Enhanced rates are also seen in 1,6-enyne cycloisomerisation.14
Generally, selectivity for the cycloisomerisation product is at least
equal to or superior in several examples. Other cycloisomerisation
processes, including alkene dimerisation leading to acyclic
isomerisation products,15 could benefit from microwave heating.
We thank the EPSRC (GR/S94926/01) for funding G.P.M, and
ERASMUS for supporting F.W. Dr C. T. O’Brien is thanked for
help and discussion. We are very grateful to Drs A. F. Lee and
K. Wilson for discussion and use of HRGC equipment.
14 Microwave dielectric heating increases the rate in cationic
Ru(II)-mediated cycloisomerisation of 1,6-enynes.
For details of the conventionally heated reaction, see: B. M. Trost and
F. D. Toste, J. Am. Chem. Soc., 2002, 124, 5025.
15 (a) T. V. RajanBabu, Chem. Rev., 2003, 103, 2845; (b) R. B. Bedford,
M. Betham, M. E. Blake, A. Garce´s, S. L. Millar and S. Prashar,
Tetrahedron, 2005, 61, 9799.
990 | Chem. Commun., 2006, 988–990
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