Angewandte
Communications
Chemie
a ruthenium(0) species, and that HCO Na works as a reduc-
2
tant to promote the transformation of high-valent ruthenium
species into an active ruthenium(0) species, which is effective
[
8f,i,12]
for the first step, the [2+2+1] cycloaddition.
Ruthenium
catalysts supported on SiO , Al O , TiO , and ZrO showed
2
2
3
2
2
[13]
no activities (entry 8). Xantphos was also indispensable for
the present reaction and the other phosphines listed in
entries 9–12 were totally ineffective. No consumption of
substrates was observed under pressurized CO conditions
(entry 13). This observation implies that an excess of CO
inhibits the coordination of the substrates to the active
ruthenium center. The present Ru/CeO2 catalytic system
could be employed on a gram scale to furnish 4a in a yield of
58% (2.08 g of 4a was isolated; entry 14). Note that 3a,
formed through the [2+2+1] cycloaddition, was completely
converted during overnight oxidation under air.
Scheme 2. Synthesis of the g-hydroxybutenolide 4a by the [2+2+1]
carbonylative cycloaddition of an aldehyde and alkyne, with subsequent
oxidation by Ru/CeO2.
During the reaction, the hydroacylated product 5a was also
Under the optimized reaction conditions, a variety of g-
hydroxybutenolides was synthesized by the intermolecular
[2+2+1] carbonylative cycloaddition of aldehydes with
alkynes, and subsequent oxidation with the catalytic system
of Ru/CeO , HCO Na, and Xantphos (Table 2). Note that
[10]
formed in 19% yield (GC) as a byproduct.
Table 1 shows the results of the optimization of the
[11]
reaction conditions. Ru/CeO gave a higher yield of 4a than
2
did [Ru(acac) ], [{RuCl (p-cymene)} ], and [Ru (CO) ]
3
2
2
3
12
2
2
(
entries 1–4). This outcome is probably because of the
byproducts were formed through hydrogenation and hydro-
acylation of alkynes in all the following cases (see below). The
reaction of substituted aromatic aldehydes smoothly pro-
ceeded to give the corresponding g-hydroxybutenolides (4b–
i) in moderate to good yields. In contrast, the reaction of 2,4,6-
trimethylaldehyde (1p) did not give the corresponding g-
hydroxybutenolide, while the hydroacylated product 5p was
macro-ligand nature of CeO , such as basic properties and
steric effects, which enhance the selectivity and stability of
active ruthenium species. When HCO Na is absent, the
reaction with either Ru/CeO2 or [{RuCl (p-cymene)} ]
resulted in no conversion of the substrates (entries 5 and 6).
In contrast, a zero-valent ruthenium complex, namely [Ru3-
(
(
2
2
2
2
[
8i]
CO) ], showed moderate activity without HCO Na
obtained as a major product (Scheme 3). Symmetrical
1
2
2
entry 7), thus suggesting that the active species is
[a,b]
Table 2: Scope with respect to the substrates.
Table 1: Optimization of the reaction conditions.
[
a]
[b]
Entry Variation from the standard reaction conditions
Yield [%]
1
2
3
4
5
6
none
72
62
50
64
[{RuCl (p-cymene)} ] in place of Ru/CeO
2
[Ru(acac) ] in place of Ru/CeO
2
2
3
2
[Ru (CO) ] in place of Ru/CeO
2
3
12
[
c]
without HCO Na
[{RuCl (p-cymene)} ] in place of Ru/CeO , without
0
0
2
[c]
2
2
2
HCO Na
2
7
8
[Ru (CO) ] in place of Ru/CeO , without HCO Na
36
0
3
12
2
2
[
c]
SiO -, Al O -, TiO -, or ZrO -supported Ru catalyst
2
2
3
2
2
in place of Ru/CeO2
[
[
[
[
c]
c]
c]
c]
9
0
1
2
3
4
PPh in place of Xantphos
0
0
0
0
0
3
1
1
1
1
1
dppb in place of Xantphos
dppf in place of Xantphos
DPEphos in place of Xantphos
[
d]
[c]
CO (3 atm)
gram-scale reaction
[
e]
58
[
a] Reaction conditions: 1) 1a (3.0 mmol), 2a (1.0 mmol), Ru/CeO2
(
(
125 mg, 2.5 mol% as Ru), HCO Na (0.15 mmol), Xantphos
2
0.10 mmol), DMA (2.0 mL), 1608C, 3 h, CO (1 atm, balloon); 2) stirring
overnight at RT under air. [b] Yield of the isolated product. [c] No
conversion of 2a was observed. [d] Reaction in a stainless steel
autoclave. [e] Reaction run at 10 times the scale as that used in the
standard reaction conditions.
[a] Reaction conditions: 1) 1a (3.0 mmol), 2a (1.0 mmol), Ru/CeO2
(125 mg, 2.5 mol% as Ru), HCO Na (0.15 mmol), Xantphos
2
(0.10 mmol), DMA (2.0 mL), 1608C, 3 h, CO (1 atm, balloon); 2) stirring
overnight at RT under air. [b] Yield of the isolated product.
Angew. Chem. Int. Ed. 2016, 55, 278 –282
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
279