and [Ru]-II18 (HoveydaꢀGrubbs) (Table 1, entries 1 and 2).
1
The reaction was monitored by TLC and H NMR and
Scheme 3. Proposed Catalytic System for Ultrasound Olefin CMa
showed the rapid formation and accumulation of homo-
dimer 70 which does not undergo a secondary metathesis
reaction with Type III olefin 4 to give the expected cross-
coupling product. After 24 h, both catalysts showed their
limitations for CM with only 4% of conversion and a high
amount of homodimer 70 detected by 1H NMR and TLC.
Unfortunately, no improvement was observed when using
a catalystloading ashighas15mol % (addedinthree equal
portions, entries 3 and 4).
We thenturnedour attention tomicrowave irradiation19
(entries 5 and 6), which has resulted in many cases in a
short reaction time, a low loading of catalyst, and a higher
yield compared with classical thermal conditions.20 In our
hands, CM under microwave irradiation at 100 °C in DCE
with 10 mol % [Ru]-II gave 70% (entry 6) conversion after
4 h while [Ru]-I gave a modest 38% yield (entry 5). Note-
worthy, under these conditions, larger amounts of impu-
rities were formed, probably due to the more significant
thermal decomposition of the ruthenium complex that
leads to tedious purification.
Ultrasound applications have been recently reported
for latent [Ru] metathesis catalyst activation containing
N-heterocyclic carbene ligands (NHC) in ROMP.21 Thus,
we investigated the effects of ultrasound irradiation in
CM and we found that its use had a positive influence
on the conversion. In fact, sonication at 55 °C of the
reaction mixture with 15 mol % [Ru]-I (added in three
equal portions) permitted reaching a 92% conversion
(entry 7). The catalyst loading was then gradually de-
creased from 15 mol % [Ru]-I to 3 mol % [Ru]-I to
determine the optimal loading. Surprisingly, no significant
decrease was observed in the conversion until 6 mol %
[Ru]-I with 86% (entry 9). When the more reactive catalyst
[Ru]-II was used at this loading, a 93% conversion was
obtained (entry 10). Even under ultrasonication, the se-
quential catalyst addition was critical. In fact, when the
reaction was carried out following one addition of 5 mol %
[Ru]-I, only 49% of product was detected (entry 11).
Finally, it should be noted that the conversion was stopped
if sonication was suspended. We therefore hypothesized
the following (Scheme 3): (1) The mechanical force brought
by ultrasonication could potentially enhance the ligand
dissociation of the latent precatalyst (a) to generate the
active species (b); (2) the “degassing effect” of ultrasounds
permits efficient expulsion of the ethylene gas generated
during the reaction avoiding the regeneration of the term-
inal olefin (cycle I). In many cases, removal of ethylene was
found to be essential for achieving high conversions;22 (3)
the sonication permits the less reactive homodimer to react
a Ligand dissociation (from a to b); formation of homodimer (cycle I);
formation of desired heterodimer (cycle II).
toward the formation of the desired product (cycle II).
Thus, the use of ultrasonication offers a very effective
protocol leading to trisubstituted olefins via CM using
either [Ru]-I and [Ru]-II catalysts.
Diacetate 6 was then subjected to the lipase catalyzed
hydrolysis of the targeted trans acetyl group (Table 2).
Table 2. Lipase-Catalyzed Hydrolysis of Diacetate 7a
entry
lipaseb
PPL
time (h)
8 (%)c
9 (%)c
10 (%)c
1c
2c
3c
24
48
16
21
32
83
41
33
0
traces
traces
11
Amano PS
CAL-B
a Reactions were performed with diacetate 7 in 0.1 M phosphate
buffer pH 7.0 and appropriate lipase (100% w/w). b Porcine Poncreas
lipase (PPL), Burkholderiacepacia lipase (Amano PS), Candida antarc-
tica lipase B (CAL-B). c Isolated yield.
Takabe,23 Imai,24 and Deska25 have already reported
several examples of desymmetrization of prochiral diols
(18) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H.
J. Am. Chem. Soc. 2000, 122, 8168.
(19) Fuwa, H.; Noto, K.; Sasaki, M. Org. Lett. 2010, 12, 1636.
(20) Coquerel, Y.; Rodriguez, J. Eur. J. Org. Chem. 2008, 7, 1125.
(21) (a) Jakobs, R. T. M.; Sijbesmas, R. P. Organometallics 2012, 31,
2476. (b) Piermattei, A.; Karthikeyan, S.; Sijbesma, R. P. Nat. Chem.
2009, 1, 133–137.
(23) Hisano, T.; Onodera, K.; Toyabe, Y.; Mase, N.; Yoda, H.;
Takabe, K. Tetrahedron Lett. 2005, 46, 6293.
(24) Miura, T.; Umetsu, S.; Kanamori, D.; Tsuyama, N.; Jyo, Y.;
Kawashima, Y.; Koyata, N.; Murakami, Y.; Imai, N. Tetrahedron 2008,
64, 9305.
(22) Pietraszuk, C.; Marciniec, B.; Fischer, H. Organometallics 2000,
19, 913–917.
4392
Org. Lett., Vol. 15, No. 17, 2013