Dearomatization of fused arenes using platinum-catalyzed intramolecular formation of two C-C bonds

Article abstract of DOI:10.1002/anie.201202165

The (de)aroma of success: A cationic platinum(II) complex generated in situ catalyzes dearomatization of fused arenes by forming two intramolecular C-C bonds (see scheme). Mechanistic studies reveal that this reaction could proceed through alkyne activation by the cationic platinum(II) complex followed by a Friedel-Crafts-type reaction. Copyright

Full text of DOI:10.1002/anie.201202165

Angewandte
Chemie
DOI: 10.1002/anie.201202165
Dearomatization Reaction
Dearomatization of Fused Arenes Using Platinum-Catalyzed
À
Intramolecular Formation of Two C C Bonds**
Tetsuro Shibuya, Keiichi Noguchi, and Ken Tanaka*
The dearomatization of arenes has been extensively studied
to make simple aromatic compounds useful for the prepara-
tion of complex aliphatic compounds.[1] The catalytic dear-
ortho or para positions of the substituent Z to produce
cyclohexadienes has not been reported to date (Scheme 1,
type 2).[7]
Herein, we present the platinum(II)-catalyzed dearoma-
À
omatization by way of C C bond formation is particularly
attractive. As shown in Scheme 1, previous reports have
tization of N-benzyl-N-(1-naphthyl)propiolamide derivatives
À
À
focused on C C bond formation at the ortho or para position
through the formation of two intramolecular C C bonds at
the ipso and ortho positions of the acylamino group
À
(Scheme 2). Several intramolecular C C bond-forming ipso
iodocyclizations of N-arylpropiolamides have been
reported;[8] however, these reactions are not catalytic and
À
did not involve the formation of two C C bonds.
À
Scheme 1. Catalytic dearomatization by forming either one or two C C
bonds.
Scheme 2. Platinum-catalyzed dearomatization by way of the formation
À
of two C C bonds.
À
of the substituent (X Y) through the elimination of the
leaving group (Y) to produce substituted cyclohexadienes
(Scheme 1, type 1).[2–6] Three p-bonds still remain after the
dearomatization in this transformation, which stabilizes the
dearomatization products. For example, a number of metal-
Our research group recently reported the enantioselective
intramolecular 6-endo hydroarylation of N-arylpropiol-
amides, which was catalyzed by palladium(II)/xyl-H8-binap
(xyl-H8-binap = 2,2’-bis[di(3,5-xylyl)phosphine]-5,5’,6,6’,7,7’,-
8,8’-octahydro-1,1’-binaphthyl). This system furnishes axially
chiral 4-aryl-2-quinolinones with good yields and ee
values.[9–11] In this reaction, N-(2-naphthyl)propiolamides
showed high reactivity. Consequently, we also investigated
the reaction of N-(1-naphthyl)propiolamide 1a in the pres-
ence of a cationic palladium(II)/binap complex (binap = 2,2’-
bis(diphenylphosphino)-1,1’-binaphthyl). Although the cor-
responding 6-endo hydroarylation product 3a was not
obtained, the corresponding 5-exo hydroarylation product
4a was obtained in good yield (Table 1, entry 1). Interestingly,
the use of cationic gold(III), gold(I), silver(I), rhodium(III),
and platinum(II) complexes as catalysts produced dearoma-
tization product 2a in low yields along with 6-endo and 5-exo
hydroarylation products 3a and 4a (entries 2–6). As the
cationic platinum(II) complex showed the highest yield and
selectivity for the formation of 2a (entry 6), further optimi-
zation was conducted to improve the yield of 2a. Prolonged
reaction time gave 73% conversion of 1a (entry 7), and
screening of silver salts (entries 7–10) revealed that the use of
AgOTf showed the highest selectivity for the formation of 2a
(entry 10). The use of CH3CN as a solvent significantly
increased the yield of 2a (entry 11) and could reduce the
required catalyst loading to 5 mol% (entry 12).
À
catalyzed C C bond-forming dearomatization reactions of
[2,3]
À
À
À
À
phenol (X Y= O H)
or aniline derivatives (X Y= NR’
H)[4] to produce cyclohexadienones or iminocyclohexadienes
have been reported. The palladium-catalyzed allylative
dearomatization reactions of substituted benzyl or cinnamyl
À
À
=
À
chlorides (X Y= CH(R’) Cl or CH CHCH2 Cl) to produce
methylenecyclohexadienes have also been reported.[5] How-
À
ever, the catalytic formation of two C C bonds at the ipso and
[*] T. Shibuya, Prof. Dr. K. Tanaka
Department of Applied Chemistry, Graduate School of Engineering
Tokyo University of Agriculture and Technology
Koganei, Tokyo 184-8588 (Japan)
E-mail: tanaka-k@cc.tuat.ac.jp
Homepage: http://www.tuat.ac.jp/-tanaka-k/
Prof. Dr. K. Noguchi
Instrumentation Analysis Center, Tokyo University of Agriculture
and Technology
Koganei, Tokyo 184-8588 (Japan)
[**] This work was supported partly by Grants-in-Aid for Scientific
Research (Nos. 23105512 and 20675002) from MEXT (Japan).
Supporting information for this article (experimental details) is
available on the WWW under http://dx.doi.org/10.1002/anie.
201202165.
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Table 1: Optimization of reaction conditions for the formation of two
Table 2: Dearomatization of fused arenes 1a–l by way of platinum-
[a]
À
À
C C bonds on N-(1-naphthyl)propiolamide 1a.
catalyzed intramolecular formation of two C C bonds.
Entry Ligand
Catalyst Time Conv.
Yield
[%][a]
[mol%] [h]
[%]
2a 3a
4a
1
[Pd(CH3CN)4](BF4)2/ 20
16
92
0
0
70
binap
2
3
4
5
6
7
8
9
AuCl3/3AgBF4
AuCl(SMe2)/AgBF4
AgBF4
20
20
20
16
16
16
16
16
72
72
72
72
72
72
100
28
19
24
55
73
100
80
100
100
96
11 13
77
8
5
7
5
5
10
4
5
[Cp*RhCl2]2/4AgBF4 20
5
PtCl2/2AgBF4
PtCl2/2AgBF4
PtCl2/2AgSbF6
PtCl2/2AgPF6
PtCl2/2AgOTf
20
20
20
20
20
20
5
13 13
26 18
14 44
21 22
36 25
63 15
69 12
15
21
28
26
20
13
9
10
11[b] PtCl2/2AgOTf
12[b] PtCl2/2AgOTf
[a] Yield of isolated product. [b] Solvent: CH3CN. Cp*=C5Me5.
With the conditions optimized, the scope of the plati-
num(II)-catalyzed dearomatization reactions was examined
(Table 2). The reactions of substrates 1b–d possessing alkoxy-
substituted electron-rich benzyl groups (entries 2–4) showed
higher reactivity than 1a, with a nonsubstituted benzyl group
(entry 1). In the reaction of 1b, the sterically less-demanding
regioisomer 2b was obtained as a major product along with
the minor regioisomer 2b’ (entry 2). The substrate 1c
possessing the 2-methoxyphenyl group at the alkyne terminus
showed higher reactivity than 1e with a nonsubstituted
phenyl group (entry 3 versus 5). Not only aryl groups but
also alkyl groups could be incorporated at the alkyne
terminus, although high catalyst loadings and/or long reaction
times were required (1 f-i, entries 6–9). Other fused arenes
were also examined, which revealed that 9-aminophena-
threne derivative 1j produced the corresponding dearomati-
zation product 2j in moderate yield owing to the formation of
a 6-endo hydroarylation product as a byproduct (entry 10).[12]
6-Aminochrysene derivatives 1k,l were particularly suitable
substrates for this process, and the desired dearomatization
products 2k,l were obtained in high yields (entries 11 and 12).
In all cases, the reaction products 2a–l were obtained as
a single diastereomer. The structure of the dearomatization
product was unambiguously confirmed by X-ray crystallo-
graphic analysis of the crystalline compound 2d.[13]
Scheme 3 depicts a possible mechanism for the present
dearomatization reactions. We believe that the coordination
of the cationic platinum(II) complex to the alkyne triple bond
of N-(1-naphthyl)propiolamide 1 would induce the endo
[a] Yield of isolated product. [b] Solvent: CH3CN.
Cp*=C5Me5.[a] Reactions were conducted using PtCl2/2AgOTf as
a catalyst in CH3CN at 808C. [b] Yield of isolated product. Cy=cyclo-
hexyl.
2
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Scheme 5. Platinum-catalyzed reaction of 1a in the presence of
CD3OD.
dearomatization product 2b–d in excellent yields (entries 2–
4). However, the reaction of substrate 1m with a trifluoro-
methyl substituted electron-deficient benzyl group did not
give the corresponding dearomatization product 2m, but
hydroarylation products 3m and 4m (Scheme 6). These
results suggest that the initial formation of intermediate C is
reversible and the Friedel–Crafts-type reaction of the elec-
tron-rich benzyl group proceeds through intermediate C to
form dearomatization product 2.
Scheme 3. Possible mechanism for the formation of 2 from 1.
cyclization to generate intermediate A.[14] Subsequent skel-
etal rearrangement through intermediate B would afford
intermediate C, although direct formation of C from 1 through
ipso cyclization cannot be excluded at the present stage.
Friedel–Crafts-type reaction followed by deprotonation gives
intermediate D. Protonation of D affords the dearomatization
product 2 and regenerates the platinum catalyst.
To confirm this deprotonation–protonation sequence,
deuterium-labeling studies were conducted. The reaction of
deuterated phenyl substituted N-(1-naphthyl)propiolamide
[D5]-1a produced partially deuterated product [D5]-2a with
selective incorporation of deuterium in the vinylic position
(Scheme 4).
Scheme 6. Platinum-catalyzed reaction of 1m with a trifluoromethyl
substituted electron-deficient benzyl group.
Finally, hydrogenation of dearomatized product 2a was
examined as shown in Scheme 7. Chemoselective hydrogena-
tion of the 1,2-dihydronaphthalene moiety of 2a proceeded
by using Pd/C as a catalyst to give dihydropyrroloisoquinoline
derivative 5 in good yield. On the other hand, hydrogenation
of both the 1,2-dihydronaphthalene and a,b-unsaturated g-
lactam moieties of 2a occurred when Pt/C was used as the
catalyst to give tetrahydropyrroloisoquinoline derivative 6 in
moderate yield as a single diastereomer. From a synthetic
point of view, various biologically active multicyclic alkaloids
contain hydropyrroloisoquinoline structures.[15] The dearo-
Scheme 4. Platinum-catalyzed reaction of [D5]-1a.
À
matization–hydrogenation sequence that forms two C C
Furthermore, the reaction of nondeuterated phenyl sub-
stituted N-(1-naphthyl)propiolamide 1a in the presence of
a large excess of external deuterium source (CD3OD) also
gave partially deuterated product [D]-2a with selective
incorporation of deuterium in the vinylic position
(Scheme 5). These results are consistent with the formation
of 2 by way of the proposed deprotonation–protonation
mechanism.
To confirm the Friedel–Crafts-type reaction of the benzyl
group with the naphthyl group, the electronic effect of the
benzyl group was examined. As shown in Table 2, the
reactions of substrates 1b–d possessing alkoxy-substituted
electron-rich benzyl groups produced the corresponding
Scheme 7. Hydrogenation of dearomatized product 2a.
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In conclusion, we have established that a cationic plati-
num(II) complex generated in situ catalyzes dearomatization
À
of fused arenes using intramolecular formation of two C C
bonds. The results of the deuterium-labeling studies were
consistent with a mechanism involving alkyne activation by
the cationic platinum(II) complex, followed by a Friedel–
Crafts-type reaction. Future work will focus on asymmetric
and/or intermolecular variants of this reaction.
Received: March 19, 2012
Published online: && &&, &&&&
À
Keywords: alkynes · arenes · C C bond formation ·
dearomatization · platinum
.
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4
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Angew. Chem. Int. Ed. 2012, 51, 1 – 5
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Chemie
Communications
Dearomatization Reaction
T. Shibuya, K. Noguchi,
K. Tanaka*
&&&& — &&&&
Dearomatization of Fused Arenes Using
Platinum-Catalyzed Intramolecular
À
Formation of Two C C Bonds
The (de)aroma of success: A cationic
platinum(II) complex generated in situ
catalyzes dearomatization of fused
arenes by forming two intramolecular C
C bonds (see scheme). Mechanistic
studies reveal that this reaction could
proceed through alkyne activation by the
cationic platinum(II) complex followed by
a Friedel–Crafts-type reaction.
À
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!