Angewandte
Chemie
Table 1: Development of the catalytic reactions.[a]
studied stoichiometric reactions between benzophenone
imine (1a) and selected RhI and RuII catalyst precursors
(Scheme 2). [(cod)Rh(OH)]2 and 1,3-bis(diphenylphosphi-
no)propane (dppp) ligand did not react with 1a at 808C,
which is comparable to the high reaction temperatures
required for similar RhI catalyzed reactions.[11,14] In contrast,
Entry Ru Catalyst
Ligand Solvent Yield [%][b]
1
2
3
4
5
6
7
8
[(cod)Ru(C,N-ketimine)2] (6) none
toluene
toluene
toluene
toluene
toluene
toluene
hexane
hexane
Et2O
THF
DMF
hexane
hexane
<2
45
44
57
<2
5
95
68
64
9
6
7a
7a
7b
8a
8b
7a
7b
7a
7a
7a
none
7a
[Ru(cod)(h3-C4H7)2] (5a)
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
9
10
11
12
13[c]
<2
<2
23
[a] Reaction conditions: 2a (0.10 mmol, 1 equiv), 1a (1.1 equiv), Ru
catalyst (0.030 equiv), ligand (0.033 equiv), solvent (0.5 mL), room
temperature (20–228C), 24 h. [b] Determined by GC with n-dodecane as
internal standard. [c] Using 1.0 mol% 5a and 1.1 mol% 7a.
Scheme 2. Attempted cyclometalation of benzophenone imine (1a)
with RhI and RuII complexes. cod=cyclooctadiene.
the RuII/p-allyl complex [(cod)Ru(h3-methallyl)2][21] (5a)
reacted with 1a at room temperature quantitatively to form
the doubly cyclometalated RuII bis(imine) complex [Ru(cod)-
{h2-HNC(C6H5)C6H4}2] (6). The solid-state structure of com-
plex 6 was determined by single crystal X-ray diffraction,
which shows a near-octahedral RuII center with the two N
À
atoms of the imine ligands trans to each other, and two Ru C
tion (Scheme 3). High yields and regioselectivity were
achieved for reactions between 1a and nonsymmetrical
phenylacetylene derivatives having an alkyl, alkenyl, or 2-
thiophenyl substituent (products 3b–f).[26] Reactions between
1a and aliphatic internal alkynes required the use of IMes
(7b) as ligand and toluene as solvent (3g, 3h). Heating to
608C was necessary to form the diethyl-substituted 3g in high
yield. Among ketimine substrates, diaryl ketimines with
electron-withdrawing F, Cl, and CF3 groups at para and
meta positions readily reacted with 2a to give [3+2] adducts in
high yields (3i, 3j, 3l–n).[27] In comparison, lower reactivity
was observed for imines with a para- or meta-methoxy group,
the reactions of which were carried out at 608C to achieve
high yields (3o and 3p). A temperature of 608C was also
necessary for 3,3’-(bis)CF3-substituted benzophenone imine
to form product 3k in 91% yield. Nonsymmetrical diaryl
ketimines coupled to 2a with moderate regioselectivity (ca.
bonds at cis to each other.[22]
II
À
The Ru -mediated activation of an imine C H bond at
room temperature encouraged us to evaluate RuII catalyst
precursors for a ligand-assisted [3+2] ketimine/alkyne carbo-
cyclization at room temperature (Table 1). In toluene, ruth-
enacycle 6 did not catalyze the coupling between 1a and
diphenylacetylene (2a; entry 1). However, coupling was
promoted at room temperature by 3 mol% of 6 in combina-
tion with 3.3 mol% of IPr ligand (7a), to selectively form the
[3+2] annulation product 3a in 45% yield after 24 h (entry 2).
Replacing 6 with commercially available p-allyl complex 5a
as catalyst gave similar results (entry 3), thus suggesting that 6
is generated in situ from 5a by the elimination of isobutene.
Thus, 5a was further evaluated as a catalyst precursor in
combination with other NHC ligands.[23] The use of IMes
ligand (7b) gave comparable yield to 7a (entry 4), whereas
when saturated analogues SIPr (8a) and SIMes (8b) were
used poor results were obtained (entries 5 and 6). In terms of
solvent effect, better results were observed with nonpolar
solvents rather than polar solvents (entries 7–11). Thus,
coupling between 1a (1.1 equiv) and 2a (1.0 equiv) pro-
ceeded smoothly at room temperature in hexane with
3.0 mol% of 5a and 3.3 mol% of 7a, to give 3a as the only
product in 95% yield (entry 7). Only a trace amount of 3a was
detected from reactions in the absence of ligand 7a (entry 12).
Lastly, lower catalyst loading led to diminished catalytic
reactivity (entry 13).[24]
À
2:1 to 4:1); C H activation at the more electron-deficient aryl
(3l–3o) was favored. This electronic influence on regioselec-
À
tive C H bond activation was most pronounced with product
3p, which was formed by exclusive reaction at the meta-CF3
substituted phenyl ring over the meta-methoxy substituted
one.[11]
The substrate scope and substituent effects provide
significant insights into the reaction mechanism. Firstly, high
regioselectivity with nonsymmetric alkyne substrates sup-
À
ported the proposed alkyne insertion into a Ru aryl rather
than a Ru H linkage.[21] Secondly, the relatively low reactivity
À
With the standard reaction conditions established, various
of 3-hexyne (product 3g) compared to aromatic alkynes was
consistent with a rate-limiting alkyne insertion.[28] Thus, the
remarkable reactivity enhancement by NHC ligands is likely
internal alkyne[25] and diaryl N H ketimine substrates were
À
studied for RuII-catalyzed room-temperature [3+2] annula-
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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