Catalytic [3 + 2] annulation of ketimines with alkynes via C-H activation by a cationic iridium(cod) complex

Article abstract of DOI:10.1039/c4cc01874e

[3 + 2] Annulation of ketimines with internal and terminal alkynes proceeded via C-H activation to give aminoindene derivatives in high yields, which is catalyzed by a cationic iridium complex coordinated with 1,5-cyclooctadiene (cod). This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc01874e

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Catalytic [3 + 2] annulation of ketimines with
alkynes via C–H activation by a cationic
iridium(cod) complex†
Cite this: Chem. Commun., 2014,
50, 6274
Received 13th March 2014,
Accepted 16th April 2014
Midori Nagamoto and Takahiro Nishimura*
DOI: 10.1039/c4cc01874e
www.rsc.org/chemcomm
Table 1 Ir-catalyzed annulation of 3-phenyl-3-hydroxyisoindolin-1-one
(1a) with diphenylacetylene (2m)a
[3 + 2] Annulation of ketimines with internal and terminal alkynes
proceeded via C–H activation to give aminoindene derivatives in
high yields, which is catalyzed by a cationic iridium complex
coordinated with 1,5-cyclooctadiene (cod).
Transition metal-catalyzed ortho-C–H functionalization of aromatic
compounds has been achieved by use of appropriate directing
groups such as carbonyl groups and imines.1 The annulation
reaction via the C–H bond activation involving a transformation
of the directing group offers a straightforward route to the synthesis
of complicated cyclic compounds,2 and in particular, a redox-
neutral annulation3 enables an atom-efficient reaction.4 For exam-
ple, the catalytic annulation reactions of aromatic ketones or imines
with C–C unsaturated bonds leading to indene derivatives have
been developed by use of Re,5 Ru,6 Rh,7 and Ir8 catalysts. There have
also been several reports on the oxidative coupling reactions of
aromatic imines or ketones to give indene or indane derivatives.9
Recently, we reported the Ir-catalyzed annulation of ketimines
with 1,3-dienes giving 1-aminoindanes (eqn (1)).10,11 The reaction
proceeds via ortho-C–H activation forming an aryliridium(I) species I
as a key intermediate in the presence of 1,4-diazabicyclo[2.2.2]octane
Entry
Change from the optimized condition
Yieldb (%)
1
2
3
4
5
6
7
8
With DABCO (5 mol%)
With DABCO (10 mol%)
None
21
0
97c
0
Without NaBArF
4
AgPF6 instead of NaBArF
31
0
9
4
[IrCl(coe)2]2 instead of [IrCl(cod)]2
[IrCl(coe)2]2/(R)-binap instead of [IrCl(cod)]2
[RhCl(cod)]2 instead of [IrCl(cod)]2
0
a
Reaction conditions: 1a (0.20 mmol), 2m (0.30 mmol), Ir catalyst
(5 mol% of Ir), NaBArF (10 mol%) in toluene (0.8 mL) at 80 1C for 20 h.
4
b Determined by 1H NMR analysis. Isolated yield.
c
Treatment of 3-hydroxy-3-phenylisoindolin-1-one (1a), which in situ
(DABCO) as a base for a successive oxidative cyclization with generates the corresponding ketimine by dehydration,10b with diphenyl-
1,3-dienes. Here we report that cyclic N-acyl ketimines react with acetylene (2m) in toluene in the presence of [IrCl(cod)]2 (5 mol%
alkynes to give annulation products in the presence of the Ir catalyst of Ir, cod = 1,5-cyclooctadiene), NaBArF (ArF = 3,5-(CF3)2C6H3), and
4
without the use of any bases.
DABCO at 80 1C for 20 h gave 1-aminoindene 3am in 21% yield
(Table 1, entry 1). The reaction conditions are the optimized ones in
the annulation of 1a with 1,3-dienes, where it is proposed that
the formation of the aryliridium(I) species from an initially formed
cationic Ir(III)-hydride species occurred by deprotonation promoted by
DABCO.8 The use of an increased amount of DABCO (10 mol%)
completely inhibited the formation of 3am (entry 2). On the other
hand, the catalytic activity was greatly improved by removing DABCO
from the previous reaction system to give 3am in 97% yield (entry 3).
The formation of the annulation product 3am was not observed at all
in the reaction without NaBArF4 (entry 4). These results indicate that a
cationic Ir(I) complex efficiently catalyzes the present reaction and the
Ir(III)-hydride species would be involved as a key intermediate for a
successive alkyne insertion (vide infra). The counter anion of the
(1)
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo,
Kyoto 606-8502, Japan. E-mail: tnishi@kuchem.kyoto-u.ac.jp;
Fax: +81 75 753 3988; Tel: +81 75 753 3987
† Electronic supplementary information (ESI) available: Experimental proce-
dures, and compound characterization data. See DOI: 10.1039/c4cc01874e
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Scheme 2 Annulation of 3-hydroxy-3-phenylisoindolin-1-one with
alkynes. Reaction conditions: 1a (0.20 mmol), 2 (0.30 mmol), [IrCl(cod)]2
(5 mol% of Ir), NaBArF (10 mol%), and toluene (0.8 mL) at 80 1C for 20 h.
Scheme 1 Annulation of ketimines with diphenylacetylene. Reaction
conditions: 1 (0.20 mmol), 2m (0.30 mmol), [IrCl(cod)]2 (5 mol% of Ir),
and NaBArF4 (10 mol%) in toluene (0.8 mL) at 80 1C for 20 h. Isolated yields
are shown. a For 48 h.
4
Isolated yields are shown. a Performed with 1a (0.24 mmol) and 2q
(0.20 mmol). b Ratio of atropisomers: 44 : 36 : 13 : 7. c Performed with
[IrCl(cod)]2 (10 mol% of Ir) and NaBArF (20 mol%). d 1 : 1 mixture of
4
regioisomers. e Ratio of isomers: 54 : 23 : 23.
cationic iridium plays a certain role in the catalytic activity: the use of
AgPF6 gave a lower yield (31%) of 3am (entry 5) than that obtained
using NaBArF4 (entry 3). The use of [IrCl(coe)2]2 (coe = cyclooctene) as a
catalyst gave no annulation product (entry 6), indicating that cod (entry
3) works as a chelating ligand. On the other hand, the catalytic activity
coordinated with a bisphosphine ligand, binap, was low, resulting in a
low yield (9%) of 3am (entry 7). [RhCl(cod)]2 did not promote the
present reaction (entry 8).
The results obtained for the Ir-catalyzed annulation of several
hemiaminals or ketimines 1 with diphenylacetylene (2m) are sum-
marized in Scheme 1. The reactions of hemiaminals having para-
substituted phenyl groups 1b–1e gave high yields of annulation
products 3bm–3em. Not only the cyclic N-acyl ketimines, but also a
cyclic N-sulfonyl ketimine 1f and acyclic N-tosyl ketimines 1g and 1h
are good substrates to give the corresponding aminoindenes 3fm–
3hm in high yields. It should be noted that the selective C–H bond
activation of the 2-methylphenyl group of 1h occurred to give 3hm
as a single isomer. This is probably because the E-geometry of 1h,
which is stabilized by the steric hindrance of the 2-methylphenyl
group, allows the coordination of the imine nitrogen to the Ir center
directing toward the 2-methylphenyl group.
Scheme 2 summarizes the results obtained for the reaction of
3-hydroxy-3-phenylisoindolin-1-one (1a) with several alkynes 2. Sym-
metrically substituted diaryl alkynes 2n–2r reacted with 1a to give
the corresponding annulation products 3an–3ar in 76–96% yields.
1-Octyne (2s) also reacted with 1a to give the annulation product 3as
although the yield was modest (52%). The reactions of unsymme-
trically substituted diaryl alkynes 2t and 2u proceeded to give 3at
and 3au in 93 and 89% yields, respectively. Unfortunately, however,
no regioselectivity was observed for 3at and 3au. The reaction of
1-phenyl-1-propyne (2v) gave a mixture of regioisomers 3av in 87%
yield. These results indicate that the regioselectivity of the alkyne
insertion is less affected by electronic and steric differences of the
substituents of alkynes. Terminal alkynes 2w and 2x were also
applicable to give 3aw and 3ax as the single regioisomers in
38 and 21% yields, respectively.12
The regio- and atropisomeric mixture of 3au was transformed
into a fused aromatic compound 5 by Pd-catalyzed intramolecular
C–H arylation (eqn (2)).13
To gain some insight into the mechanism of the C–H activation,
we conducted a substoichiometric reaction of 1b (2 equiv. to Ir) with
[IrCl(cod)]2 in CDCl3 in the presence of NaBArF (Scheme 3a). The
4
reaction at room temperature for 3 h brought about the formation
of a small amount (1.3%) of a new hydridoiridium complex 6, which
showed a singlet peak at ꢀ12.2 ppm by 1H NMR analysis. The
hydridoiridium complex stabilized by the coordination of PPh3 was
also formed in modest yield (Scheme 3b). The reaction of 1b
(1 equiv. to Ir) with [IrCl(cod)]2 in the presence of NaBArF and
4
PPh3 (1 equiv. to Ir) in CDCl3 at room temperature for 20 h gave
complex 7, whose yield was estimated to be 57% by 1H NMR
analysis. The 1H NMR spectrum of the isolated complex 7 passing
through a short alumina column showed a doublet peak at
(2)
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cyclization without activation by the cationic iridium species due to
the high reactivity of the imine moiety.
In summary, we have developed an annulation reaction
of ketimines with alkynes via C–H activation catalyzed by a
cationic iridium complex coordinated with 1,5-cyclooctadiene.
A variety of alkynes including a terminal alkyne were success-
fully employed to give 1-aminoindene derivatives. The NMR
experiments indicated that the Ir(III)-hydride species as an
intermediate is formed via a directed C–H activation under
chelation assistance of N-acyl and N-sulfonyl imines.
Scheme 3 Stoichiometric reactions. (a) 1b (2 equiv. to Ir), [IrCl(cod)]2, and
NaBArF in CDCl3 at room temperature for 3 h. (b) 1b (1 equiv. to Ir),
4
[IrCl(cod)]2, NaBArF4, and PPh3 (1 equiv. to Ir) in CDCl3 at room tempera-
ture for 20 h.
This work was supported by a Grant-in-Aid for Scientific
Research on Innovative Areas ‘‘Molecular Activation Directed
toward Straightforward Synthesis’’, from the MEXT, Japan.
ꢀ13.5 ppm (JP–H = 11.3 Hz), which was assigned to a hydridoiridium
complex coordinated with PPh3 cis to the hydride.14 These results
indicate that the ortho-C–H activation forms the aryl-hydrido-
iridium(III) species as a key intermediate in the present reaction.
Shibata and co-workers reported sequential catalytic reactions of
aromatic ketones with alkynes using an iridium–binap complex,
where the iridium complex operates as a catalyst in the ortho-C–H
bond alkenylation of aromatic ketones and as a Lewis acid catalyst
in the cyclization of the alkenylated products leading to benzo-
fulvenes.8 In a similar manner, the present annulation reaction may
involve the sequential steps, ortho-C–H alkenylation and cycliza-
tion.15 The catalytic cycle is postulated as illustrated in Scheme 4.
ortho-C–H activation of ketimine 1a0, which involves oxidative
addition of the C–H bond to Ir, forms arylhydridoiridium(III) inter-
mediate B. The alkyne insertion to the Ir–H bond forms
alkenyliridium(III) C and the successive reductive elimination gives
ortho-alkenylated product D, which may be activated by coordina-
tion to the cationic iridium center. An intramolecular cyclization
via intermediate E gives aminoindene 3am and regenerates the
cationic iridium A. Alternatively, alkenylated product D undergoes
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Scheme 4 Proposed catalytic cycle.
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sulfonylketimine 1f with 2m at 60 1C for 15 min. See the ESI† for details.
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