Thermodynamics of p-Bond-Forming Ring-Closing Metathesis Reactions
FULL PAPER
tion yields from the synthetic literature to test their predic-
tions.[13] However, to our knowledge, there has been no com-
bined electronic structure calculation and quantitative (or
even semi-quantitative) solution experimental approach to
date.
nene 3e was not observed by RCM, even at concentrations
as low as [1e]0 =0.5 mm. Instead, only a mixture of oligo-
mers and unreacted diene was obtained (confirmed by GC-
MS with chemical ionisation using methane).
Two very surprising results arose during this study. Firstly,
in the RCM of 1,8-nonadiene 1c, cycloheptene 3c was ac-
companied by a significant quantity of cyclohexene 3b (re-
1
Results and Discussion
vealed by the alkene H signal, dH (CDCl3)=5.69 ppm). At
higher [1c]0 (about 1m), more cyclohexene 3b was obtained
than cycloheptene 3c. Diene isomerisation in the presence
of ruthenium–alkylidene catalysts is well known and has
been exploited effectively in synthesis[19] but is uncommon
at room temperature.[20] Pre-catalyst 2 is known to favour
metathesis over isomerisation,[21] with isomerisation
common with “stressed” catalysts arising from high reaction
temperatures, high dilution or forced high turnover.[22] None
of these factors would appear to be relevant to the RCM re-
actions of 1c reported here. The 1H NMR spectrum of a
concentrated reaction ([1c]0 =2m in CDCl3) does contain a
peak consistent with the presence of diruthenium hydride 6
at ꢀ8.77 ppm (lit. dH (CD2Cl2)=ꢀ8.61 ppm)[23] but the
signal-to-noise ratio indicates that 6 is present in very low
concentration. There is significantly more 7 (the species
An experimental method that would minimise perturbation
of the reaction mixtures before analysis was essential to in-
terrogate the system shown in Scheme 1. Dienes 1a–f are all
commercially available and most cycloalkenes 3 are either
commercially available (3a–d and E- and Z-3 f) or known in
the literature (3e).[14] In addition, many of the dimers, prod-
ucts of cross-metathesis, are known (linear dimer 4a[15] and
cyclic dimers 5c–f).[16] The experimental approach was de-
scribed in our previous Communication, and utilises non-in-
vasive 1H NMR analysis to quickly quantify reaction out-
comes without processing the reaction mixture.[10] RCM of
each diene (1a–f) was carried out at a number of initial con-
centrations [1]0 in [D2]dichloromethane or [D]chloroform in
GC vials with an internal standard. Although the reactions
were not carried out under pressure, ethene did have the op-
portunity to accumulate in solution and was seen clearly in
a number of reaction product mixtures (dH =5.43 ppm in
CD2Cl2, 5.41 ppm in CDCl3) even after 18 h. Hence, the en-
ergetic consequences of ethene evolution were not included
in our subsequent calculations. The internal disubstituted
alkene resonances for dimers 4 and 5 all appear at d
ꢃ5.4 ppm and were observed by 1H NMR for all systems
except the RCM of 1b. End groups, arising from unreacted
diene and from dimers and higher oligomers, could be dis-
tinguished unambiguously using a range of 2D NMR tech-
from which 6 forms) and a reservoir of benzylidene 2, as
usual for these small scale experiments. If 6 is the sole cata-
lyst of the isomerisation reaction, it is a remarkably efficient
one. Further exploration of this chemistry forms the subject
of ongoing experiments in our laboratory. Ethylidene 8 was
identified at the end of these high [1c]0 reactions as a quar-
tet in the 1H NMR spectrum (dH (CDCl3)=18.6 ppm (J=
5.5 Hz)) with a single cross-peak in the 2D [1H,1H] CO-
SY NMR spectrum to a doublet signal at dH =1.6 ppm.[24] It
is likely that 8 is a product of the metathesis of isomerised
dienes (for example, 1,7-nonadiene RCM would yield cyclo-
hexene 3b and ethylidene 8).
Secondly, Z-cyclooctene 3d was formed during the RCM
of 1,9-decadiene 1d and was seen clearly in the 1H NMR
spectrum (dH (CD2Cl2)=5.65 ppm), albeit in low conversion,
so accurate quantification of [3d] by 1H NMR integration
was not possible. However, observation of 3d in these reac-
tions is surprising as the literature suggests that Z-cyclooc-
tene cannot be formed from 1d by RCM. Non-annelative
closure of eight-membered rings is usually an unfavourable
reaction[25] and reactions that form Z-cyclooctenes usually
require either appropriate vicinal ring substitution, often re-
ferred to as “gearing”,[26] or fusion to other ring systems.[27]
We could also clearly see cyclohexene 3b (dH (CD2Cl2)=
1
niques including [1H,13C] HSQC-TOCSY,[17a] and ge-1D H
TOCSY[17b–d] (see the Supporting Information for illustrative
examples). The T1 relaxation times were measured for the
dienes and all commercially available cycloalkenes (typically
6–7 s for the olefinic resonances) to ensure reliable integra-
1
tion (sample H NMR spectra can be found in the Support-
ing Information).
There were marked differences in behaviour between dif-
ferent systems. 1,7-Octadiene 1b forms only cyclohexene 3b
when exposed to 2, even at [1b]0 =4m; we have previously
estimated a kinetic EM for cyclohexene 3b at about 80m
based on theoretical and experimental studies, which shows
that this is a remarkably efficient RCM reaction.[10] Mando-
lini calculated a value of 912m for the EMT of 3b based on
measured symmetry-corrected thermodynamic parameters
for 3b, hexane and hydrogen.[18] In stark contrast, cyclono-
Chem. Eur. J. 2011, 17, 13087 – 13094
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