CH2Cl2, room temperature) converts styrene quantitatively into
stilbene after 18 h. However, the presence of 1 equiv. (relative to
styrene) of DEM, DEF, or MeOAc slowed stilbene formation
(after 24 h, y 30% with DEM or DEF, 50% with MeOAc),
suggesting competition between styrene, and DEM, DEF, or
MeOAc for PCy3-dissociated 2. Attempts to observe cyclopro-
panation with EDA and catalyst 2, by increasing the amount of
styrene (to 2 equiv.) or by slow (syringe pump) addition of EDA
proved fruitless. Ethyl cinnamate was also not detected in any of
these experiments. It therefore appears that catalyst 2 is able to
promote two different carbene transformations in the same flask,
with no carbene crossover.11
With catalyst 2 (1 mol%) and unsaturated diazoacetates 11
(0.07 mol dm23 in CH2Cl2) it was found that maleate formation
was complete after 14–18 h at room temperature, but only a small
amount of alkene metathesis had occurred. This presumably
reflects the lower metathesis activity of alkyl-substituted terminal
alkenes compared with styrene. Thus, an additional 1 mol% of
catalyst 2 was added and the reaction heated to reflux to promote
ring-closing metathesis.{ cis-Alkenes14 were preferentially formed
by metathesis when leading to 12- and 14-membered dilactones,
whereas trans stereochemistry was increasingly favoured for larger
rings (16–26-membered).
In summary, Grubbs’ 2nd-generation ruthenium carbene is
shown to act as an efficient catalyst for highly stereoselective
homocoupling of diazoacetates; in the presence of additional
alkene functionality cyclopropanation is not observed but rather
metathetical activity is retained, and can be exploited with
unsaturated diazoacetates giving dienyl dilactones. The contrasting
stereo- and regiochemical outcomes between (unsaturated) acryl-
ates and diazoacetates with catalyst 2 are noteworthy. Studies with
other unsaturated diazocompounds are under investigation.
We thank the University of Oxford for a full Clarendon Fund
bursary award (to D. A.) and the EPSRC National Mass
Spectrometry Service Centre for mass spectra.
A
tentative catalytic cycle which rationalises the above
observations concerning EDA homocoupling is outlined in
Scheme 3. The coordinatively unsaturated intermediate 7 reacts
with EDA to generate ester carbene 8. Ester carbene 8 does not
display propensity for cyclopropanation (or metathesis), but pre-
ferentially undergoes reaction with further EDA (8 A 9 A 10).
Highly diastereoselective attack by EDA on a (Cu-based) ester
carbene followed by anti-elimination of the metal and N2 has been
suggested as the origin of the stereoselectivity for maleate over
fumarate in EDA homocoupling.12 DEM dissociation from 10
then completes the catalytic cycle. With EDA, styrene and catalyst
2, the cycle shown in Scheme 3 preferentially (but not exclusively)
operates alongside the well-established metathesis catalytic cycle1,9
involving common intermediate 7 and styrene [with the difference
that after one metathesis turnover a ruthenium methylidene rather
than benzylidene (i.e., H rather than Ph) is involved].
Notes and references
{ Typical procedure for dilactone formation: Grubbs’ 2nd-generation
catalyst 2 (3 mg, 3.5 mmol) was added to a stirred solution of but-3-enyl
diazoacetate 11 (n 5 2) (49 mg, 0.35 mmol) in CH2Cl2 (5 cm3) at rt. After
14 h, further catalyst 2 (3 mg, 3.5 mmol) was added and the reaction
mixture heated to reflux for 14 h. The mixture was then concentrated under
reduced pressure and purified by flash chromatography (SiO2, 5 A 10%
EtOAc in hexane) to afford a yellow oil, dilactone 12 (n 5 2) (15.5 mg,
45%, E : Z 7 : 93); Rf 0.56 (50% EtOAc in hexane); nmax(neat)/cm21 2962w,
1794s, 1382w, 1261m and 1100s; dH(400 MHz; CDCl3) Z-isomer: 6.18 (1H,
s, LCHCO), 5.62–5.54 (1H, m, LCHCH2), 4.32–4.24 (2H, m, OCH2) and
2.51 (2H, q, J 5.5, LCHCH2); discernible data for E-isomer: 6.16 (1H, s,
LCHCO), 5.42–5.38 (1H, m, LCHCH2) and 2.46–2.38 (2H, m, LCHCH2);
dC(100 MHz, CDCl3) Z-isomer: 165.1 (CLO), 128.8 (LCH), 128.7 (LCH),
64.8 (OCH2) and 26.4 (LCHCH2); discernible data for E-isomer: 129.2
(LCH), 63.3 (OCH2) and 32.5 (LCHCH2); m/z (ES) 197 (M + H+, 30%),
214 (100) and 215 (10); Found M + H, 197.0816. C10H13O4 requires M
197.0814.
1 Handbook of Metathesis, ed. R. H. Grubbs, Wiley-VCH, Weinheim,
2003.
2 T.-L. Choi, C. W. Lee, A. K. Chatterjee and R. H. Grubbs, J. Am.
Chem. Soc., 2001, 123, 10417–10418.
3 C. W. Lee and R. H. Grubbs, J. Org. Chem., 2001, 66, 7155–7158. See
also: A. Fu¨rstner, O. R. Thiel, L. Ackermann, H.-J. Schanz and
S. P. Nolan, J. Org. Chem., 2000, 65, 2204–2207.
Scheme 3
4 H. M. L. Davies and E. G. Antoulinakis, Org. React., 2001, 57, 1–326.
5 Intriguingly, homocoupling is completely suppressed using a Cu
N-heterocyclic carbene system: M. R. Fructos, T. R. Belderrain,
M. C. Nicasio, S. P. Nolan, H. Kaur, M. M. D´ıaz-Requejo and
P. J. Pe´rez, J. Am. Chem. Soc., 2004, 126, 10846–10847.
6 M. P. Doyle, M. A. McKervey and T. Ye, Modern Catalytic Methods
for Organic Synthesis with Diazo Compounds, John Wiley and Sons,
New York, 1998, pp. 624–627. For a recent example in synthesis, see:
G.-Y. Li and C.-M. Che, Org. Lett., 2004, 6, 1621–1623.
The ability of Grubbs’ catalyst 2 to catalyse both diazoacetate
dimerisation and alkene metathesis led us to examine head-to-head
dimerisation of unsaturated diazoacetates 11 (readily available
from the corresponding unsaturated alcohol and glyoxylic acid
chloride Ts hydrazone),13 as a route to dienyl dilactones 12
(Scheme 4).
7 (a) W. Baratta, A. Del Zotto and P. Rigo, Chem. Commun., 1997,
2163–2164; (b) W. Baratta, A. Del Zotto and P. Rigo, Organometallics,
1999, 18, 5091–5096; (c) A. Del Zotto, W. Baratta, G. Verado and
P. Rigo, Eur. J. Org. Chem., 2000, 2795–2801.
8 W. Baratta, W. A. Herrmann, R. M. Kratzer and P. Rigo,
Organometallics, 2000, 19, 3664–3669. See also: B. C¸ entinkaya,
¨
I. Ozdemir and P. H. Dixneuf, J. Organomet. Chem., 1997, 534,
153–158.
Scheme 4
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Chem. Commun., 2005, 4902–4904 | 4903