Borderline metal-catalyzed carboarylation of alkynylarenes using N,O-acetals

Article abstract of DOI:10.1039/c2cc32715e

Borderline metal catalysts, Bi(OTf)₃ and Fe(OTf)₃, were proven to work as dual activators for alkynes and N,O-acetals via σ,π-chelation, which achieved a new carboarylation reaction of alkynylarenes with N,O-acetals.

Full text of DOI:10.1039/c2cc32715e

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COMMUNICATION
Borderline metal-catalyzed carboarylation of alkynylarenes using
N,O-acetalsw
Kimihiro Komeyama,* Takahiro Yamada, Ryoichi Igawa and Ken Takaki*
Received 17th April 2012, Accepted 8th May 2012
DOI: 10.1039/c2cc32715e
Borderline metal catalysts, Bi(OTf)3 and Fe(OTf)3, were proven
to work as dual activators for alkynes and N,O-acetals via
r,p-chelation, which achieved a new carboarylation reaction of
alkynylarenes with N,O-acetals.
in which these catalysts were able to activate the alkyne moiety.7
With this in mind, we envisaged that the s,p-chelation might be
also applied to the dual activation of alkynes and N,O-acetals.
Herein, we report borderline metal-catalyzed carboarylation of
alkynylarenes 1 with N,O-acetal 2 (Scheme 1B).
To prove the viability of the carboarylation, we first
examined the reaction of 1,4-diphenylbut-1-yne (1a) with
N-benzyl-3-hydroxyisoindoline-1-one (2a)8 by using various
Lewis acid catalysts (Table 1). When 1a was treated with 1.1
equivalents of 2a in the presence of Bi(OTf)3 or Fe(OTf)3
catalysts (10 mol%) in 1,2-dichloroethane (DCE) for 5 h at
80 1C, the carboarylated product 3aa was obtained in 96% or
95% yields, respectively (entries 1 and 2). Although Cu(OTf)2,
Fe(OTf)2, and Zn(OTf)2 also afforded 3aa, the yields were
much lower than Bi and Fe catalysts (entries 3–5). PtCl2 and
AgOTf provided negligible yields of 3aa, wherein a large
amount of both substrates remained unchanged after the
reaction (entries 6 and 7). If the generation of the iminium
ion is a driving force to direct this carboarylation, it would
N-Acyliminium ions can be easily derived from N,O-acetals,
and are widely recognized as useful synthetic intermediates for
the construction of carbon–carbon bonds due to their high
electrophilic character.1 These reactions typically employ
electron-rich aromatic nucleophiles as well as allyl, vinyl,
and alkynyl metal species,2 whereas unactivated olefins and
alkynes are less reactive to N-acyliminium ions under catalytic
conditions.3 Recently, we have demonstrated a borderline
metal-catalyzed cyclization of alkenyl N,O-acetals to afford a
diverse set of nitrogen-containing heterocycles (Scheme 1A).4
In the cyclization, the alkene and the hydroxyl group of
N,O-acetal were dually activated by Fe or Bi catalysts via
s,p-chelation,5 allows the two reaction sites to be close enough
to interact with each other.6 In contrast, we have also
described a Fe- or Bi-catalyzed hydroarylation of alkynylarenes,
Table 1 Screening of catalystsa
Entry
Catalyst
Time/h
Yieldb/%
1
2
3
4
5
6
7
8
Bi(OTf)3
Fe(OTf)3
Cu(OTf)2
Fe(OTf)2
Zn(OTf)2
PtCl2
5
5
5
96
95
58
50
30
12
11
20
16
14
0
5
18
18
18
18
18
18
18
18
18
Scheme 1
AgOTf
Ga(OTf)3
Yb(OTf)3
Sc(OTf)3
AlCl3
9
10
11
12
13
Department of Applied Chemistry, Graduate School Engineering,
Hiroshima University, 1-4-1 Kagamiyama, Higashi-Hiroshima City,
Hiroshima 739-8527, Japan. Fax: +81 82 424 5494;
BF3ꢀOEt2
0
5
TfOH
Tel: +81 82 424 7747; E-mail: kkome@hiroshima-u.ac.jp
w Electronic supplementary information (ESI) available: Experimental
details and characterization data. See DOI: 10.1039/c2cc32715e
a
b
Conditions: 1a (0.5 mmol), 2a (0.55 mmol). NMR yield.
c
6372 Chem. Commun., 2012, 48, 6372–6374
This journal is The Royal Society of Chemistry 2012

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occur with other Lewis acid catalysts having high affinity to
the hydroxyl group of 2a. But, no or negligible yields of the
product were detected by Ga(OTf)3, Yb(OTf)3, Sc(OTf)3,
AlCl3, BF3ꢀOEt2, and TfOH catalysts (entries 8–13). More-
over, to confirm the occurrence of the iminium ion in entries 1
and 13, the reaction of 1a with 2a in the presence of allyl-
trimethylsilane (3.0 equiv.) using TfOH or Bi(OTf)3 catalyst
was carried out.2b,9 As a result, TfOH afforded an allylated
isoindolinone at the 3-position as a sole product, whereas
Bi(OTf)3 produced 3aa in 60% yield with a trace amount of
the allylated product. These results would indicate that
Bi(OTf)3 worked not only in the generation of the iminium,
but also in the cyclization step. In addition, we confirmed that
no reaction took place in the absence of the catalyst.
desired products as a mixture of two regioisomers of about
50 : 50 ratio (entries 16–20). An electron-rich terminal aryl
group at the R2-position accelerated the reaction (entry 2). An
alkynylarene having an alkyl substituent at the R2-position
participated in the reaction, leading to a 4-alkylchromene
adduct without detection of other cyclized products (entry 9).
This transformation was not limited to alkynylarenes with ether
and simple methylene tethers, nitrogen functionalized all-
carbon tethers 1w–y also took part in the reaction (eqn (1)).
Moreover, the present reaction was compatible with other types
of N,O-acetals like 2c and 2d to give the corresponding products
3ac and 3ad, respectively (eqn (2) and (3)). Particularly for 3ac,
the conversion of the phthalimidyl group to an amino one by
Gabriel reaction could construct some ligands for histamine
H1-receptors.10 Regarding the formation of 3ad, it would be
derived from the carboarylated product 3ad0 through an intra-
molecular hydroarylation of the olefin moiety.
Next, with our optimized conditions in hand, we investi-
gated the substituent effect of the aryl nucleophiles of the
alkynylarenes 1 at the para-, ortho- and meta-positions. These
results are summarised in Table 2. A wide range of electron-
deficient aryl groups could successfully participate in the
reaction, providing the corresponding carboarylated products
3 in good yields (entries 1–6 and 10–13). In contrast, electron-
rich ones resulted in the formation of hydroarylation products
(40–50% yields) with low yields of the desired products
(entries 7–8 and 14–15). meta-Substituents produced the
Table 2 Substituent effecta
ð1Þ
ð2Þ
Alkynylarenes 1
Yield of 3b/%
R1
R2
Entry
Time/h
1
2
3
4
5
6
7
8
1b
1c
1d
1e
1f
1g
1h
1i
4-CO2Me
4-CO2Me
4-C(O)Ph
4-CN
4-F
4-Br
4-OMe
4-Me
4-Br
2-NO2
2-CN
2-F
2-Br
2-OMe
2-Me
3-NO2
3-NO2
3-CO2Me
3-F
Ph
22 (57)c
4
5
30
5
24
24
23
22
5
58 (63)c
84
68
67
84
99
29
37
39
58
55
80
70
27
11
4-MeC6H4
4-MeC6H4
Ph
4-MeC6H4
Ph
Ph
Ph
n-Bu
4-MeC6H4
4-MeC6H4
4-MeC6H4
Ph
Ph
Ph
Ph
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
9
1j
1k
1l
10
11
12
13
14
15
16
17
18
19
20
ð3Þ
4
4
1m
1n
1o
1p
1q
1r
1s
1t
22
24
25
24
9
5
7
5
Notably, we observed different modes of reactions depending
on the catalyst used in the reaction of an alkynylarene containing
a hydroxyl group 4a with N,O-acetal 2b (Scheme 1). Thus,
when hard Lewis acids such as Sc(OTf)3 or AlCl3 were used,
condensation reaction of the hydroxyl group of 2b with an
alcoholic function of 4a exclusively occurred to give 5 as a sole
product. No other products were detected even after a longer
reaction time (96 h). A reaction using soft Lewis acids like
PdCl2, PtCl2, or AgOTf selectively afforded a carboalkoxylated
product 6. In contrast, borderline metal catalysts, Bi(OTf)3 or
70 [49 : 51]d
75 [52 : 48]d
82 [49 : 51]d
81 [49 : 51]d
64 [48 : 52]d
1u
3-Br
a
Conditions: 1 (0.50 mmol), 2b (0.55 mmol), Bi(OTf)3 (0.05 mmol), DCE
b
(1.0 mL), DCE (1.0 mL). Isolated yield. Fe(OTf)3 was used instead of
d
Bi(OTf)3. Regioisomer ratio of adducts at 2- and 6-positions.
c
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 6372–6374 6373

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of the alkyne11 and a subsequent reaction of the C–Bi bond with
the N-acyliminium ion.
In conclusion, we have demonstrated a novel carboarylation
of alkynylarenes with the N-acyliminium ions generated from
N,O-acetals by means of borderline metal catalysts like
Bi(OTf)3 and Fe(OTf)3. This functionalization well tolerated
a wide range of alkynylarenes, particularly, possessing non-
protected heteroatom nucleophiles, and various N,O-acetals.
In this reaction, the excellent catalytic activity of borderline
metal complexes such as bismuth and iron would be attribu-
table to the unique activation mode: s,p-chelation. Further
investigation of the mechanistic detail and the extension of
this protocol to other types of double functionalization using
N,O-acetals are in progress.
This work was partially supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology of Japan. K.K. also acknowl-
edges financial support from Kinki Invention Center and
Furukawa Technical Foundation.
Scheme 2 Different reactivities of hard, soft, and borderline metal
catalysts.
Notes and references
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s,p-chelated intermediate B, which would prefer the addition of
aromatic nucleophile rather than that of the oxygen atom to
afford the carboarylation products via the carbobismuthination
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c
6374 Chem. Commun., 2012, 48, 6372–6374
This journal is The Royal Society of Chemistry 2012