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regioselectivity (Table 3, entry 2). Thus, [Cl2IPrCuF] was
synthesized[9] in a similar way to [IPrCuF][10] using the
known NHC ligand Cl2IPr.[11] The reaction of 1m in the
presence of [Cl2IPrCuF] (2.5 mol%) in n-hexane as a
solvent afforded 2m and 2m’ in much higher yield (88%)
even at 708C with moderate regioselectivity (Table 3,
entry 3). The regioselectivity was considerably improved
by replacing the methyl group of 1m with a butyl group
(1n) or secondary alkyl groups (1o). In these cases, the
major regioisomers (2n and 2o) were readily isolated in
analytically pure form by column chromatography on silica
gel. Gratifyingly, alkynes with cyclohexyl (1p) and tert-
butyl groups (1q–s) afforded single regioisomers in good to
high yields (Table 3, entries 6–9). Here, bromo (Table 3,
entry 8) and alkoxycarbonyl (entry 9) functionalities on the
phenyl ring were tolerated in the reaction. In the present
reaction, simple internal aliphatic alkynes such as 5-decyne
were much less reactive (conv. < 5%) and did not give the
corresponding carboxylic acid under the present reaction
conditions. However, it was found that 1-methoxy-2-decyne
(1t) gave a product in good yield with high regioselectivity
(Table 3, entry 10). A similar effect was evident for the b-
methoxy (1u and 1v) and benzyloxy groups (1w; Table 3,
entries 11–13), suggesting that coordination of the ether
moieties to a copper center would be important in the
reaction. 1,4-Dimethoxy-2-butyne (1x) and 2,5-dimethoxy-3-
hexyne (1y) bearing the two b-ether functionalities also
afforded the corresponding products (2x and 2y, respectively)
in good yields (Table 3, entries 14 and 15). As for terminal
alkynes, phenylacetylene (1z) afforded cinnamic acid (2z) in
44% yield using [IPrCuF] as the catalyst at 1008C in 1,4-
dioxane (Table 3, entry 16). The yield was modest owing to
considerable formation of the styrene in 28% yield.
Scheme 3. Stoichiometric reactions relevant to the catalysis.
es S5 and S6 in the Supporting Information). Finally, C’
reacted with an excess (4 equiv) of HSi(OEt)3 at room
temperature and the copper hydride complex A’ was afforded
cleanly. The isolated B’ and C’ were active catalysts, affording
2q in 80% and 74% yields, respectively, under the same
reaction condition as those used in entry 7, Table 3.
On the basis of the stoichiometric reactions shown in
Scheme 3, a possible catalytic cycle is shown in Scheme 4. A
copper(I) hydride species (A)[13] is generated in situ from
[LCuF] (L = IMes, IPr, or Cl2IPr) and a hydrosilane by the aid
of the strong silicon–fluorine interaction[10] (step a). Syn
addition of A to an alkyne (1) initiates the catalytic cycle and
affords a copper alkenyl intermediate (B) stereoselectively
(step b).[12] Then, insertion of CO2 takes place to provide the
corresponding copper carboxylate intermediate C[4c,14]
(step c). Finally, s-bond metathesis of C with a hydrosilane
provides the corresponding silyl ester 2si and regenerates A
(step d). All the catalytic were confirmed by the stoichio-
metric reactions in Scheme 3, in which only the insertion of
CO2 requires the higher reaction temperature (658C),
whereas other stoichiometric reactions proceeded at room
To gain insight into reaction mechanism, fundamental
catalytic steps in the present hydrocarboxylation were
examined by stoichiometric reactions (Scheme 3). When
[Cl2IPrCuF], the catalyst precursor used the examples
shown in Table 3, was treated with an excess of the silane
(4 equiv), such as PMHS or HSi(OEt)3 in [D6]C6H6, an
immediate color change from colorless to bright orange was
1
observed. The H NMR spectrum indicated clean formation
of [Cl2IPrCuH] (A’) with a diagnostic proton resonance of
Cu-H at d = 2.39 ppm (see Figure S2 in the Supporting
Information), which is consistent with a reported value of
[IPrCuH] at d = 2.63 ppm.[12]
An aromatic alkyne such as 1q reacted with A’ smoothly
in 2.5 hours at room temperature to afford the corresponding
copper alkenyl complex (B’). In contrast, an aliphatic alkyne
such as 5-decyne did not react with A’, which was decomposed
rapidly under the reaction conditions. This low reactivity of
the internal aliphatic alkyne is very reminiscent of the
catalytic reaction. The copper alkenyl complex B’ was isolated
1
in 70% yield and fully characterized by H and 13C NMR
methods (see Figures S3 and S4 in the Supporting Informa-
tion). The reaction of B’ with CO2 (balloon) was very slow at
room temperature, but took place smoothly at a higher
reaction temperature (658C) after 12 hours. The copper
carboxylato complex C’ was also isolated in 84% yield and
1
fully characterized by H and 13C NMR analysis (see Figur-
Scheme 4. Plausible catalytic cycle.
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ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Angew. Chem. Int. Ed. 2011, 50, 523 –527