Angewandte
Communications
Chemie
tions of alkynes (Scheme 1b). The desired process would have
ability of guanidine to form stable ruthenium(II) com-
plexes.[21] A thorough solvent screening revealed that a 10:1
mixture of AmOH and H2O gives the highest yields and
selectivities (entry 10; see the Supporting Information).
Substrates 1a and 2a were best employed in a 1:1.5 ratio
(entries 11 and 12).
À
to be initiated by a carboxylate-directed ortho-C H alkyne
t
insertion step. The resulting vinyl–metal species would then
need to be forced towards a reductive elimination step to
yield alkenylbenzoic acids, despite the abundance of facile
pathways leading to cyclized products.
To probe the feasibility of this concept, we investigated
the reaction of 2-methylbenzoic acid (1a) with 1-phenyl-1-
propyne (2a) in the presence of various metal catalysts
(Table 1). Many complexes known for their ability to mediate
The scope of the hydroarylation reaction with regard to
the acid component was investigated using 1-phenyl-1-pro-
pyne (2a) as the coupling partner (Table 2). Benzoic acids
Table 2: Substrate scope of the directed hydroarylation.[a]
Table 1: Optimization of the directed hydroarylation conditions.[a]
Entry [M] (mol%)
Base
Yield [%]
(3aa/
3aa’)[b]
1
2
3
4
5
6
7
8
9
[Ru(p-cym)Cl2]2 (4) 0.3 equiv K2CO3
[Ru(p-cym)I2]2 (4) 0.3 equiv K2CO3
[Ru(p-cym)I2]2 (2) 0.3 equiv K2CO3
[Ru(p-cym)I2]2 (2) 0.1 equiv K2CO3
[Ru(p-cym)I2]2 (2) 0.5 equiv K2CO3
[Ru(p-cym)I2]2 (2) 1.0 equiv K2CO3
[Ru(p-cym)I2]2 (2) 0.5 equiv Cs2CO3
[Ru(p-cym)I2]2 (2) 0.5 equiv Li2CO3
43:5
52:10
60:6
39:7
46:trace
n.d.
53:14
44:9
[Ru(p-cym)I2]2 (2) 0.5 equiv guanidine carbonate 68:7
10[c] [Ru(p-cym)I2]2 (2) 0.5 equiv guanidine carbonate 74:5
11[c,d] [Ru(p-cym)I2]2 (2) 0.5 equiv guanidine carbonate 73:6
12[c,e] [Ru(p-cym)I2]2 (2) 0.5 equiv guanidine carbonate 90 (93):5
[a] Reaction conditions: 1a–l (0.5 mmol), 2a–f (0.75 mmol), [Ru(p-
cym)l2]2 (2 mol%), guanidine carbonate (0.5 equiv.), tAmOH/
H2O=10:1 (1.1 mL), 1008C, 12–24 h. Yields of the corresponding
methyl ester isolated after derivatization with MeI. [b] 2 f (0.5 mmol).
[a] Reaction conditions: 1a (0.5 mmol), 2a (0.5 mmol), [M] (4 mol%),
base, 1,4-dioxane:H2O (10:1, 1.1 mL), 1008C, 12 h. [b] Yields of
corresponding methyl esters determined by GC after esterification with
K2CO3 (2 equiv) and MeI (5 equiv) in MeCN using n-tetradecane as the
internal standard. Yields of isolated products are given within paren-
theses. [c] tAmOH/H2O=10:1 as solvent. [d] 0.6 mmol 1a.
[e] 0.75 mmol 2a. n.d.=not determined. cym=cymene.
bearing various functional groups, including halides (1b–c),
electron-withdrawing groups such as CF3, Ac, CO2Me (1d–
e,j), or electron-donating moieties (1a,f–g) all gave good to
moderate yields. Multisubstituted benzoic acids (1i,k,l)were
also suitable substrates for this transformation. Next, several
alkynes were evaluated as coupling partners in combination
with toluic acid (1a). All gave reasonable yields, with best
results being obtained with diphenylacetylene (2 f). Unpro-
tected hydroxy groups remained intact when at a distance
À
C H functionalizations, including Pd(OAc)2, [{IrCp*Cl2}2],
[{Ir(cod)2Cl}2], and [{Rh(cod)2Cl}2] were investigated, but
none of them gave the hydroarylation product 3aa in the
desired selectivity (see the Supporting Information for
details). However, the simple ruthenium complex [Ru(p-
cym)Cl2]2, usually an efficient hydroacyloxylation catalyst,[19]
surprisingly furnished 3aa in an encouraging 48% yield with
a high 7:1 regioselectivity in favor of the methyl-branched
stilbene derivative (entry 1). The iodine-bridged analogue
[Ru(p-cym)I2]2 proved to be an even more active and
selective catalyst (entries 2 and 3). The process requires the
presence of substoichiometric amounts of base, ideally
50 mol%, thus giving the best balance between conversion
and selectivity. If stoichiometric amounts of base are present,
the reaction is completely suppressed, thus indicating that
protons are required in the overall process (entries 4–6).
Carbonate bases, and guanidinium carbonate in particular,
were found to be most effective (entries 7–9). The remarkable
reactivity of the guanidinium base may result from the known
À
from the C C triple bond (2e).
À
With propargylic alcohols (2g–k) as substrates, the C H
hydroarylation was followed by intramolecular lactonization,
so that g-alkylidene-d-lactones were formed in high yields
À
(Table 3). This reaction nicely complements the oxidative C
H functionalizations/lactonizations, which lead to endocyclic
À
C C double bonds (Scheme 1). The broad scope spans from
electron-rich to electron-deficient benzoic acids bearing
a wealth of functional groups in the para-, ortho-, or meta-
position (Table 3; 1m–v). Various propargylic alcohols were
smoothly converted into the corresponding lactones (2h–k).
Not only benzoic acid, but also methacrylic acid (1w) was
successfully converted. During the optimization of the
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Angew. Chem. Int. Ed. 2016, 55, 6933 –6937