Asymmetric Dearomatization of 1-Aminonaphthalene Derivatives through C-C Bond Formation with Electron-Rich Heterocycles as Nucleophiles

Article abstract of DOI:10.1002/ejoc.201500486

A cationic gold(I)/axially chiral biaryl bis(phosphine) complex has been employed to catalyze the asymmetric dearomatization reactions of 1-aminonaphthalene derivatives through a C-C bond-forming reaction with electron-rich heterocycles as the nucleophiles. These reactions afford pentacyclic heterocycles in good yields with moderate enantiomeric excess (ee) values. A cationic gold(I)/axially chiral biaryl bis(phosphine) complex has been employed to catalyze the asymmetric dearomatization of 1-aminonaphthalene derivatives through a C-C bond-forming reaction with electron-rich heterocycles as the nucleophiles. These reactions afford pentacyclic heterocycles in good yields with moderate enantiomeric excess (ee) values.

Full text of DOI:10.1002/ejoc.201500486

FULL PAPER
DOI: 10.1002/ejoc.201500486
Asymmetric Dearomatization of 1-Aminonaphthalene Derivatives through C–C
Bond Formation with Electron-Rich Heterocycles as Nucleophiles
[a]
[a]
[b]
[a,c,d]
Takafumi Baba, Junko Oka, Keiichi Noguchi, and Ken Tanaka*
Keywords: Asymmetric catalysis / Heterocycles / Dearomatization / Arenes / Gold / Enantioselectivity
A cationic gold(I)/axially chiral biaryl bis(phosphine) com- erocycles as the nucleophiles. These reactions afford penta-
plex has been employed to catalyze the asymmetric de-
aromatization reactions of 1-aminonaphthalene derivatives
through a C–C bond-forming reaction with electron-rich het-
cyclic heterocycles in good yields with moderate enantio-
meric excess (ee) values.
Introduction
bond-forming reactions with electron-rich heterocycles as
the nucleophiles.
The catalytic asymmetric C–C bond-forming dearomati-
zation of arenes is an attractive method for the synthesis of
[
1]
chiral carbocycles. A number of transition-metal-cata-
[
2–4]
and organocatalytic[5] asymmetric dearomatiza-
lyzed
tions that occur through an oxidative single C–C bond-
forming reaction at the ortho- or para-position of a substit-
uent have been reported for the synthesis of chiral cyclo-
hexadiene derivatives. However, our group recently reported
the gold(I)-catalyzed asymmetric dearomatization reactions
of 3-benzyl-substituted propiolic acid 1-naphthylamides
(Scheme 1) and N-benzyl-substituted propiolic acid 1-
naphthylamide (Scheme 2) through redox-neutral double
C–C bond formation at the ipso- and ortho- or para-posi-
[6–9]
tions of the amino substituent
to give chiral dihydro-
The former reactions af-
naphthalene derivatives.[
10–12]
forded the corresponding dearomatization products with
moderate to high enantiomeric excess (ee) values
Scheme 1. Gold-catalyzed asymmetric dearomatization of 3-
benzyl-substituted propiolic acid 1-naphthylamides {(R)-xyl-binap
(Scheme 1), whereas the latter reaction afforded the corre-
sponding dearomatization product with a low ee value = (R)-2,2Ј-bis[di(3,5-xylyl)phosphino]-1,1Ј-binaphthyl}.
[
10]
(Scheme 2).
In these reactions, alkoxy-substituted elec-
tron-rich benzenes were employed as nucleophiles. Herein,
we disclose the asymmetric dearomatization of 1-amino-
naphthalene derivatives, which proceeds through C–C
[
[
[
a] Department of Applied Chemistry, Graduate School of
Engineering, Tokyo University of Agriculture and Technology,
Koganei, Tokyo 184-8588, Japan
Scheme 2. Gold-catalyzed asymmetric dearomatization of N-
benzyl-substituted propiolic acid 1-naphthylamide {(R)-H -binap
(R)-2,2Ј-bis(diphenylphosphino)-5,5Ј,6,6Ј,7,7Ј,8,8Ј-octahydro-
,1Ј-binaphthyl}.
b] Instrumentation Analysis Center, Tokyo University of
Agriculture and Technology,
8
=
1
Koganei, Tokyo 184-8588, Japan
c] Department of Applied Chemistry, Graduate School of Science
and Engineering, Tokyo Institute of Technology,
Ookayama, Meguro-ku, Tokyo 152-8550, Japan
E-mail: ktanaka@apc.titech.ac.jp
http://www.apc.titech.ac.jp/~ktanaka/
d] ACT-C, Japan Science and Technology Agency (JST),
Results and Discussion
[
4
-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
We first examined the reaction of N-(3-furanylmeth-
ylene)-substituted propiolic acid 1-naphthylamide 1a as
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500486.
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Eur. J. Org. Chem. 2015, 4374–4382

Asymmetric Dearomatization of 1-Aminonaphthalene Derivatives
shown in Table 1. The use of the cationic gold(I)/(R)-H8- cantly decreased the product yields and ee values (Table 1,
binap catalyst (20 mol-% Au), which was the optimal Entries 15 and 16, respectively). Thus, the details provided
catalyst when N-benzyl-substituted propiolic acid 1-naphth- in Entry 13 were selected as the optimal reaction condi-
[10]
ylamide was the substrate (Scheme 2),
afforded the de- tions.
sired dearomatization product 2a in excellent yield with an
ee value of 43% (Table 1, Entry 1). Although this reaction
proceeded with moderate enantioselectivity, the ee value is
higher than that of the example in Scheme 2, which em-
ployed an electron-rich benzene as the nucleophile. The
screening of axially chiral biaryl bis(phosphine) ligands
(Figure 1, Table 1, Entries 1–7) revealed that (R)-2,2Ј-bis(di-
phenylphosphino)-1,1Ј-binaphthyl [(R)-binap] afforded 2a
in high yield in combination with a high ee value (Table 1,
Entry 2). We then screened the silver salts (Table 1, En-
tries 2 and 8–12) and found that AgBF and AgOTf (OTf
4
=
trifluoromethanesulfonate) afforded 2a with the highest
Figure 1. Structures of axially chiral biaryl bis(phosphine) ligands.
With the optimized conditions in hand, the substrate
ee values (Table 1, Entries 8 and 9). AgOTf (Table 1, En-
try 13) performed better than AgBF (Table 1, Entry 14)
4
when the catalyst loading was decreased to 5 mol-%. Low- scope was examined (Table 2). Not only the furan moiety
ering the reaction temperature (0 °C) and employing the of 1a (Table 2, Entry 1) but also the benzofuran unit of 1b
isolated chiral gold(I) catalyst (R)-binap-(AuCl)2 signifi- (Table 2, Entry 2), and the thiophene of 1c (Table 2, En-
try 3) were employed as nucleophiles to give the corre-
sponding dearomatization products 2a, 2b, and 2c in high
Table 1. Gold-catalyzed asymmetric dearomatization of 1-amino-
naphthalene derivative 1a.[
a]
yields with moderate ee values. However higher catalyst
[
13]
loadings were required in the latter two cases.
Import-
antly, the C–C bond formation between naphthalene and
the highly nucleophilic 2-position of furan 1a proceeded in
high yield (Table 2, Entry 1), whereas that between naphth-
alene and the less nucleophilic 3-position of furan 1d did
not proceed at all (Table 2, Entry 4). With regard to substit-
uents, we successfully incorporated the phenyl, cyclohexyl,
and alkyl groups at the alkyne terminus in high yields, but
the ee values of these products were significantly lower
Entry Ligand
MX
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
AgBF
AgOTf
AgNTf
% Conv. % Yield 2a[b] [% ee]
1
2
3
4
5
6
7
8
9
(R)-H
(R)-binap
(R)-segphos
(R)-tol-binap
(R)-xyl-binap
8
-binap
6
100
100
100
100
100
64
100
100
100
100
12
Ͼ99 (43)
Ͼ99 (46)
Ͼ99 (13)
80 (47)
57 (43)
49 (14)
61 (34)
Ͼ99 (48)
Ͼ99 (48)
93 (40)
–
(Table 2, Entries 5–7).
6
The structure of the dearomatization product was unam-
[
c]
6
[c]
biguously confirmed by the X-ray crystallographic analysis
6
[
14]
of compound (Ϯ)-2f (Figure 2).
6
[
c]
(S)-dtbm-binap
(S)-xyl-H
6
We next examined the reaction of 3-(3-furanylmethyl-
ene)-substituted propiolic acid 1-naphthylamide 3a
[c]
8
-binap
6
(R)-binap
(R)-binap
(R)-binap
(R)-binap
(R)-binap
(R)-binap
(R)-binap
(R)-binap
(R)-binap
4
(
Table 3). The cationic gold(I)/(R)-H -binap complex
8
(20 mol-% Au) catalyzed the double C–C bond formation
1
0
2
[
c]
1
1
AgOTs
NaBArF
AgOTf
AgBF
not only at the ipso- and ortho-positions but also at the
ipso- and para-positions to give 4a in 88% yield with 49%ee
and eight-membered ring product 5a in 12% yield (Table 3,
Entry 1). Compound 5a, however, could not be isolated in
pure form because of its instablity. Screening the axially
chiral biaryl bis(phosphine) ligands (Table 3, Entries 1–6)
revealed that (R)-xyl-binap afforded 4a with the highest ee
1
2
4
53
–
[
d]
1
3
100
100
34
99 (47)
81 (47)
30 (27)
30 (12)
[d]
1
4
4
[e]
1
5
AgOTf
AgOTf
[f]
16
65
[
(
a] AuCl(SMe
0.010 mmol), 1a (0.05 mmol), and (CH
2
) (0.010 mmol), ligand (0.0050 mmol), MX
Cl) (2.0 mL) were used.
2
2
The relative configuration is shown for 2a. [b] Isolated yield. value (Table 3, Entry 5). Screening the silver salts (Table 3,
[
c] (R)-segphos = (R)-5,5Ј-bis(diphenylphosphino)-4,4Ј-bi-1,3-
Entries 5 and 7–11) revealed that AgSbF afforded 4a in
6
benzodioxole, (R)-tol-binap = (R)-2,2Ј-bis(di-p-tolylphosphino)-
high yield in combination with a high ee value (Table 3,
Entry 5). Lowering the reaction temperature (0 °C) and em-
1
4
,1Ј-binaphthyl, (S)-dtbm-binap = (S)-2,2Ј-bis[di-(3,5-di-tert-butyl-
-methoxyphenyl)phosphino]-1,1Ј-binaphthyl, (S)-xyl-H -binap =
8
(
S)-2,2Ј-bis[di(3,5-xylyl)phosphino]-5,5Ј,6,6Ј,7,7Ј,8,8Ј-octahydro- ploying the isolated chiral gold(I) catalyst (R)-xyl-binap-
1
,1Ј-binaphthyl, and OTs para-toluenesulfonate. [d] AuCl(SMe
0.010 mmol), (R)-binap (0.0050 mmol), AgOTf or AgBF
0.010 mmol), 1a (0.20 mmol), and (CH Cl)
2
)
4
(AuCl) resulted in a decreased product yield (Table 3, En-
tries 12 and 13). Lowering the catalyst loading to 10 mol-
2
(
(
2
2
(2.0 mL) were used.
%
Au maintained the product yield and ee value (Table 3,
[e] The reaction was conducted at 0 °C. [f] Isolated (R)-binap-
Entry 14), but further decreasing the catalyst loading to
5 mol-% Au significantly lowered both the product yield
(
(
AuCl)
CH Cl)
2
(0.010 mmol), AgOTf (0.020 mmol), 1a (0.050 mmol), and
2
2
(2.0 mL) were used.
Eur. J. Org. Chem. 2015, 4374–4382
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4375

T. Baba, J. Oka, K. Noguchi, K. Tanaka
FULL PAPER
Table 2. Gold-catalyzed asymmetric dearomatization of 1-amino-
naphthalene derivative 1a–1g.[
a]
Figure 2. ORTEP diagram of (Ϯ)-2f with ellipsoids at 50% prob-
ability.
Table 3. Gold-catalyzed enantioselective dearomatization of 1-
aminonaphthalene derivative 3a.[
a]
Entry Ligand
MX
% Conv.
% Yield[b]
a [% ee]
4
5a
1
2
3
4
5
6
7
8
9
(R)-H
(R)-binap
(R)-segphos
(R)-tol-binap
(R)-xyl-binap
(S)-dtbm- binap
8
-binap
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
6
100
100
100
100
100
59
100
86
49
100
22
71
68
100
69
88 (49)
77 (41)
72 (48)
80 (51)
78 (61)
39 (30)
74 (53)
55 (59)
54 (63)
80 (59)
19 (62)
53 (62)
53 (63)
74 (60)
53 (50)
12
19
26
20
22
9
10
14
13
16
2
6
6
6
6
6
(R)-xyl-H
8
-binap
6
(R)-xyl-binap
(R)-xyl-binap
(R)-xyl-binap
(R)-xyl-binap
(R)-xyl-binap
(R)-xyl-binap
(R)-xyl-binap
(R)-xyl-binap
AgBF
4
AgOTf
1
0
AgNTf
NaBArF
AgSbF
AgSbF
AgSbF
AgSbF
2
1
1
4
[
c]
1
2
6
18
8
15
9
[d]
1
3
6
[e]
1
4
6
[f]
15
6
[
(
a] AuCl(SMe
0.010 mmol), 3a (0.05 mmol), and (CH
2
)
(0.010 mmol), ligand (0.0050 mmol), MX
Cl) (2.0 mL) were used.
2
2
Relative configurations are shown for 4a and 5a. [b] Determined
by H NMR spectroscopic analysis. [c] The reactions were con-
1
ducted at 0 °C. [d] Isolated (R)-xyl-binap-(AuCl)
AgSbF (0.020 mmol), 3a (0.050 mmol), and (CH
were used. [e] The reaction was conducted with AuCl(SMe
0.010 mmol), (R)-xyl-binap (0.0050 mmol), AgSbF (0.010 mmol),
a (0.10 mmol), and (CH Cl) (2.0 mL) at 25 °C for 72 h. [f] The
reaction was conducted with AuCl(SMe ) (0.010 mmol), (R)-xyl-
binap (0.0050 mmol), AgSbF (0.010 mmol), 3a (0.20 mmol), and
CH Cl) (2.0 mL) at 25 °C for 72 h.
2
(0.010 mmol),
6
2
Cl) (2.0 mL)
2
[
a] The reactions were conducted by using AuCl(SMe
2
) (0.010–
.040 mmol), (R)-binap (0.0050–0.020 mmol), AgOTf (0.010–
.040 mmol), 1 (0.20 mmol), and (CH Cl) (2.0 mL) at 25 °C. The
2
)
0
0
(
3
6
2
2
2
2
relative configurations are shown for 2. [b] Isolated yield. [c] At
0 °C. [d] 1 (0.10 mmol) was used.
2
8
6
(
2
2
and ee value (Table 3, Entry 15). Thus, the details provided
in Entry 14 were selected as the optimal reaction condi- ethyl group (i.e., 3a, Table 4, Entry 1) but also a methyl (i.e.,
tions. 3b, Table 4, Entry 2), isobutyl (i.e., 3c, Table 4, Entry 3),
With the optimized conditions in hand, the scope of sub- and benzyl group (i.e., 3d, Table 4, Entry 4) could be em-
strates was examined (Table 4). Taking the substituent on ployed to give the corresponding dearomatization products
the nitrogen into consideration, we found that not only an 4a–4d in good to high yields with moderate ee values. In
4376
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Eur. J. Org. Chem. 2015, 4374–4382

Asymmetric Dearomatization of 1-Aminonaphthalene Derivatives
Table 4. Gold-catalyzed enantioselective dearomatization of 1-ami- gold(I) complex to the alkyne triple bond of 1a induces the
nonaphthalene derivatives 3a–3e.[
a]
ipso-cyclization to generate cationic intermediate A. A Frie-
del–Crafts type reaction followed by deprotonation gives in-
termediate B, and protonation of B affords 2a and regener-
ates the cationic gold(I) catalyst.
Scheme 3. Possible mechanism for the formation of 2a from 1a.
A possible mechanism for the formation of 4a and 5a
from 3a is shown in Scheme 4, which is similar to that for
2a (Scheme 3). An ipso-cyclization through the coordina-
tion of a cationic gold(I) complex to the alkyne triple bond
of 3a affords cationic intermediate C. A Friedel–Crafts-type
reaction at the ortho- and para-positions followed by depro-
tonation gives intermediate D and E, respectively. Proton-
ation of D and E then affords 4a and 5a, respectively, and
regenerates the cationic gold(I) catalyst.
Conclusions
In summary, we have established that a cationic gold(I)/
axially chiral biaryl bis(phosphine) complex catalyzes asym-
metric dearomatization reactions of 1-aminonaphthalene
derivatives through a C–C bond-forming reaction with elec-
tron-rich heterocycles as nucleophiles. These reactions af-
ford pentacyclic heterocycles in good yields with moderate
ee values.
Experimental Section
General Methods: The H and 13C NMR spectroscopic data were
1
recorded with JEOL AL-300 (300 MHz) and JEOL JNM-ECA500
(
500 MHz) spectrometers at ambient temperature. HRMS data
were obtained on a Bruker micrOTOF Focus II mass spectrometer.
Anhydrous (CH Cl) (no. 28,450–5) and CH CN (no. 27,100-4)
2
2
3
[
(
a] The reactions were conducted by using AuCl(SMe
0.010 mmol), (R)-xyl-binap (0.0050 mmol), AgSbF (0.010 mmol),
(0.10 mmol), and (CH Cl) (2.0 mL) at 25 °C for 72 h. Relative
2
)
were obtained from Aldrich and used as received. Solvents that
were used for the preparation of the substrates were dried over
molecular sieves (4 Å, Wako) prior to use. H -binap and segphos
8
derivatives were obtained from Takasago International Corpora-
tion. All other reagents were obtained from commercial sources
and used as received. All reactions were carried out under argon
or nitrogen in oven-dried glassware with magnetic stirring.
6
3
2
2
configurations are shown for 4 and 5. [b] Isolated yield. [c] Mix-
tures of 4 and 5 were isolated. Ratios of 4/5 were determined by
1
H NMR spectroscopic analysis.
addition, both electron-rich furan as well as thiophene (i.e.,
3
e, Table 4, Entry 5) could be employed in this reaction.
N-[(Furan-3-yl)methyl]-3-(2-methoxyphenyl)-N-(naphthalen-1-yl)-
propynamide (1a): To a stirred solution of 3-(2-methoxyphenyl)
prop-2-ynoic acid (0.706 g, 4.00 mmol) and 4-methylmorpholine
In reactions of highly nucleophilic furan derivatives, eight-
membered ring byproducts 5a–5d were generated but could
not be isolated in pure form because of their instability.
[15]
(
0.607 g, 6.00 mmol) in tetrahydrofuran (THF, 20 mL) was added
A possible mechanism for the conversion of 1a into 2a is isobutyl chloroformate (0.656 g, 4.80 mmol) in THF (3 mL) at
depicted in Scheme 3. The coordination of the cationic 0 °C, and the mixture was stirred at 0 °C for 0.5 h. 1-Naphth-
Eur. J. Org. Chem. 2015, 4374–4382
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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4377

T. Baba, J. Oka, K. Noguchi, K. Tanaka
FULL PAPER
Scheme 4. Possible mechanism for the formation of 4a and 5a from 3a.
ylamine (0.687 g, 4.80 mmol) in THF (2 mL) was added at 0 °C,
and the mixture was then stirred at 0 °C for 1 h and at room tem-
perature for 16 h. The reaction was quenched with water, and the
87.4, 86.3, 55.0, 42.7 ppm. HRMS (ESI): calcd. for C25
[M + Na]+ 404.1263; found 404.1264.
H19NNaO
3
N-[(Benzofuran-3-yl)methyl]-3-(2-methoxyphenyl)-N-(naphthalen-1-
yl)propynamide (1b): By following the procedure used to prepare
resulting mixture was extracted with CH
washed with brine, dried with Na SO , and concentrated to furnish
the corresponding crude 3-(2-methoxyphenyl)-N-(naphthalen-1-yl)-
2 2
Cl . The organic layer was
2
4
1
(
a, 3-(2-methoxyphenyl)-N-(naphthalen-1-yl)propiolamide and 3-
bromomethyl)benzofuran[ afforded 1b [53 % yield from 3-(2-
16]
[
11a]
propiolamide
0.294 g, 3.00 mmol), PPh
bromide (1.193 g, 3.60 mmol) in CH
(1.055 g). A mixture of (furan-3-yl)methanol
(1.023 g, 3.90 mmol), and carbon tetra-
Cl (15 mL) was stirred at
1
methoxyphenyl)prop-2-ynoic acid] as a pale orange, sticky oil. H
(
3
NMR (500 MHz, CDCl
3
): δ = 7.94–7.86 (m, 2.4 H), 7.85–7.80 (m,
2
2
0
7
7
0
.8 H), 7.74–7.69 (m, 0.2 H), 7.63 (dd, J = 7.6, 1.7 Hz, 0.2 H),
room temperature for 3 h. The mixture was then poured into hex-
ane (200 mL), and the resulting precipitate was removed by vacuum
filtration through a pad of Celite. The filtrate was concentrated,
and any additional precipitate was removed by filtration. The fil-
trate, which contained the 3-(bromomethyl)furan, was used without
further purification. To a suspension of 55 % sodium hydride
.55–7.50 (m, 1.8 H), 7.49–7.46 (m, 0.2 H), 7.43–7.37 (m, 1 H),
.23–7.20 (m, 0.8 H), 7.17–7.09 (m, 2 H), 7.07 (dd, J = 5.0, 1.3 Hz,
.8 H), 7.04–7.01 (m, 1 H), 6.99 (td, J = 7.6, 0.9 Hz, 0.2 H), 6.93
(
(
d, J = 8.4 Hz, 0.2 H), 6.68 (dd, J = 7.6, 1.9 Hz, 0.8 H), 6.66–6.61
m, 0.8 H), 6.58 (d, J = 8.4 Hz, 0.8 H), 5.76 (d, J = 15.1 Hz, 0.2
H), 5.58 (d, J = 14.2 Hz, 0.8 H), 4.91 (d, J = 15.1 Hz, 0.2 H), 4.51
(96 mg, 2.2 mmol) in THF (10 mL) was added a portion of the
1
3
(
d, J = 14.2 Hz, 0.8 H), 3.82 (s, 0.6 H), 3.42 (s, 2.4 H) ppm.
C
above crude 3-(2-methoxyphenyl)-N-(naphthalen-1-yl)propiolam-
ide (0.602 g) in THF (10 mL) at 0 °C, and the mixture was then
stirred at 0 °C for 0.5 h. The above 3-(bromomethyl)furan in THF
3
NMR (125 Hz, CDCl ): δ = 160.7, 155.0, 137.4, 137.2, 134.3, 134.1,
1
1
31.3, 130.7, 128.7, 128.5, 128.1, 127.5, 127.0, 126.2, 125.6, 125.2,
24.3, 122.5, 119.9, 110.3, 109.2, 87.5, 86.3, 55.1, 46.7 ppm. HRMS
19NNaO
S [M + Na]+ 420.1034; found
(5 mL) was added at 0 °C, and the mixture was stirred at room
(
ESI): calcd. for C25
H
2
temperature for 16 h. The reaction was quenched with water, and
the resulting solution was extracted with EtOAc (3ϫ). The yellow
420.1033.
layer was washed with brine and dried with Na
solution was concentrated and purified by a silica gel column
chromatography (hexane/EtOAc, 3:1), to furnish 1a [0.505 g,
2
SO
4
. The resulting
3-(2-Methoxyphenyl)-N-(naphthalen-1-yl)-N-[(thiophen-3-yl)meth-
yl]propynoic Acid amide (1c): By following the procedure used to
prepare 1a, 3-(2-methoxyphenyl)-N-(naphthalen-1-yl)propiolamide
and 3-(bromomethyl)thiophene[ afforded 1b [73% yield from 3-
17]
1
. 3 2 m m o l , 5 8 % y i e l d f r o m 3 - ( 2 - m e t h o x y p h e ny l ) -
1
prop-2-ynoic acid] as a pale yellow, sticky oil. H NMR (500 MHz,
CDCl ): δ = 7.99–7.84 (m, 3 H), 7.82 (d, J = 8.2 Hz, 0.2 H), 7.78–
(2-methoxyphenyl)prop-2-ynoic acid as a pale orange, sticky oil.
1
3
3
H NMR (500 MHz, CDCl ): δ = 7.94–7.86 (m, 2.4 H), 7.85–7.80
7
.73 (m, 0.2 H), 7.62 (dd, J = 7.6, 1.7 Hz, 0.2 H), 7.55–7.50 (m, 2 (m, 0.8 H), 7.74–7.69 (m, 0.2 H), 7.63 (dd, J = 7.6, 1.7 Hz, 0.2 H),
H), 7.50–7.46 (m, 0.2 H), 7.45–7.39 (m, 1 H), 7.36–7.31 (m, 0.8 H), 7.55–7.50 (m, 1.8 H), 7.49–7.46 (m, 0.2 H), 7.43–7.37 (m, 1 H),
.26 (d, J = 8.4 Hz, 0.2 H), 7.24–7.20 (m, 1.6 H), 7.15–7.11 (m, 0.8 7.23–7.20 (m, 0.8 H), 7.17–7.09 (m, 2 H), 7.07 (dd, J = 5.0, 1.3 Hz,
H), 6.98 (t, J = 7.5 Hz, 0.2 H), 6.92 (d, J = 8.4 Hz, 0.2 H), 6.68 0.8 H), 7.04–7.01 (m, 1 H), 6.99 (td, J = 7.6, 0.9 Hz, 0.2 H), 6.93
dd, J = 7.6, 1.8 Hz, 0.8 H), 6.65–6.60 (m, 0.8 H), 6.57 (d, J = (d, J = 8.4 Hz, 0.2 H), 6.68 (dd, J = 7.6, 1.9 Hz, 0.8 H), 6.66–6.61
.4 Hz, 0.8 H), 6.47 (d, J = 1.7 Hz, 0.2 H), 6.41 (d, J = 1.7 Hz, 0.8 (m, 0.8 H), 6.58 (d, J = 8.4 Hz, 0.8 H), 5.76 (d, J = 15.1 Hz, 0.2
H), 5.60 (d, J = 15.3 Hz, 0.2 H), 5.40 (d, J = 14.4 Hz, 0.8 H), 4.75 H), 5.58 (d, J = 14.2 Hz, 0.8 H), 4.91 (d, J = 15.1 Hz, 0.2 H), 4.51
d, J = 15.3 Hz, 0.2 H), 4.35 (d, J = 14.4 Hz, 0.8 H), 3.84 (s, 0.6
7
(
8
1
3
(
(d, J = 14.2 Hz, 0.8 H), 3.82 (s, 0.6 H), 3.42 (s, 2.4 H) ppm.
C
13
H), 3.39 (s, 2.4 H) ppm. C NMR (125 Hz, CDCl
3
): δ = 160.7, NMR (125 Hz, CDCl ): δ = 160.7, 155.0, 137.4, 137.2, 134.3, 134.1,
3
1
1
55.0, 142.8, 141.4, 137.3, 134.3, 134.1, 131.3, 130.7, 128.7, 128.1,
27.5, 126.9, 126.3, 125.2, 122.6, 120.5, 119.8, 111.2, 110.3, 109.1,
131.3, 130.7, 128.7, 128.5, 128.1, 127.5, 127.0, 126.2, 125.6, 125.2,
124.3, 122.5, 119.9, 110.3, 109.2, 87.5, 86.3, 55.1, 46.7 ppm. HRMS
4378
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 4374–4382

Asymmetric Dearomatization of 1-Aminonaphthalene Derivatives
(
4
ESI): calcd. for C25
20.1033.
H
19NNaO
2
S [M + Na]+ 420.1034; found
H), 7.12 (dd, J = 7.2, 1.1 Hz, 0.9 H), 7.06 (dd, J = 7.2, 1.1 Hz, 0.1
H), 6.41 (dd, J = 1.8, 0.8 Hz, 0.1 H), 6.34 (dd, J = 1.8, 0.8 Hz, 0.9
H), 5.39 (d, J = 15.4 Hz, 0.1 H), 5.35 (d, J = 14.4 Hz, 0.9 H), 4.60
N-[(Furan-2-yl)methyl]-3-(2-Methoxyphenyl)-N-(naphthalen-1-yl)-
propynamide (1d): By following the procedure used to prepare 1a,
3
(
d, J = 15.4 Hz, 0.1 H), 4.25 (d, J = 14.4 Hz, 0.9 H), 2.16 (s, 0.3
1
3
H), 1.49 (s, 2.7 H) ppm. C NMR (125 Hz, CDCl
3
): δ = 155.0,
43.0, 141.5, 137.4, 134.4, 130.6, 128.9, 128.4, 127.5, 127.1, 126.4,
25.2, 122.6, 120.5, 111.3, 89.7, 74.0, 42.7, 3.7 ppm. HRMS (ESI):
15NNaO
[M + Na]+ 312.1000; found 312.1005.
-(2-methoxyphenyl)-N-(naphthalen-1-yl)propiolamide and 2-
1
1
(
bromomethyl)furan[18] afforded 1d [32 % yield from 3-(2-meth-
1
oxyphenyl)prop-2-ynoic acid] as a pale yellow, sticky oil. H NMR
calcd. for C19
H
2
3
(500 MHz, CDCl ): δ = 7.94–7.85 (m, 2 H), 7.83 (d, J = 8.6 Hz,
0
0
7
.2 H), 7.82–7.77 (m, 1 H), 7.68 (s, 0.2 H), 7.63 (dd, J = 7.7, 1.4 Hz, Representative Procedure for Gold-Catalyzed Asymmetric Dearoma-
.2 H), 7.52 (td, J = 6.6, 3.2 Hz, 1.6 H), 7.49–7.40 (m, 1 H), 7.33–
tization: (Table 2) AuCl(SMe
(3.1 mg, 0.0050 mmol), and AgOTf (2.6 mg, 0.010 mmol) were dis-
solved in (CH Cl) (1.5 mL). The resulting mixture was added to a
solution of 1a (76.2 mg, 0.200 mmol) in (CH Cl) (0.5 mL) at room
.4 Hz, 0.8 H), 5.66 (d, J = 15.8 Hz, 0.2 H), 5.47 (d, J = 14.9 Hz, temperature and then stirred at 25 °C for 16 h. The resulting solu-
.8 H), 5.01 (d, J = 15.8 Hz, 0.2 H), 4.67 (d, J = 14.9 Hz, 0.8 H), tion was concentrated, and the residue was purified by preparative
.87 (s, 0.6 H), 3.43 (s, 2.4 H) ppm. 13C NMR (125 Hz, CDCl
): δ TLC (hexane/EtOAc/toluene/CH Cl /CH Cl, 1:1:1:1:1) to furnish
160.8, 155.1, 150.0, 142.2, 137.5, 134.3, 131.4, 131.1, 128.8, 128.2, (–)-2a (75.2 mg, 0.197 mmol, 99% yield, 47%ee).
2
) (2.9 mg, 0.010 mmol), (R)-binap
.28 (m, 1 H), 7.27–7.21 (m, 1 H), 7.19–7.12 (m, 1 H), 6.99 (dd, J
=
8.6, 7.4 Hz, 0.2 H), 6.94 (d, J = 8.6 Hz, 0.2 H), 6.72–6.62 (m, 1.8
2
2
H), 6.60 (d, J = 8.6 Hz, 0.8 H), 6.27–6.22 (m, 1 H), 6.17 (d, J =
2
2
3
0
3
3
2
2
3
=
1
1
C
27.4, 127.0, 126.3, 125.4, 122.6, 120.0, 110.42, 110.37, 109.6,
(
–)-5-(2-Methoxyphenyl)-9,12b-dihydro-7H-benzo[h]furo[3,2-c]pyrr-
09.4, 87.7, 86.3, 55.2, 44.5 ppm. HRMS (ESI): calcd. for
olo[2,1-j]quinolin-7-one [(–)-2a]: Pale yellow solid (75.2 mg, 99%
+
25
H
19NNaO
3
[M + Na] 404.1263; found 404.1275.
2
5
yield, 47%ee); m.p. 62.3–62.5 °C. [α]
D
= –116 (c = 1.50, CHCl
3
).
1
N-[(Furan-3-yl)methyl]-N-(naphthalen-1-yl)-3-phenylpropynamide
1e): By following the procedure used to prepare 1a, phenyl-
H NMR (500 MHz, CDCl ): δ = 7.28–7.18 (m, 4 H), 7.15 (dd, J
3
(
= 7.5, 1.3 Hz, 1 H), 6.87 (dd, J = 7.3, 1.3 Hz, 1 H), 6.80 (d, J =
8.3 Hz, 1 H), 6.59 (td, J = 7.5, 0.9 Hz, 1 H), 6.17 (d, J = 1.9 Hz, 1
H), 6.00–5.95 (m, 3 H), 5.91 (s, 1 H), 5.10 (dd, J = 16.0, 2.0 Hz, 1
propiolic acid, 1-naphthylamine, and 3-(bromomethyl)furan af-
forded 1e [39% yield from phenylpropiolic acid] as a pale orange,
sticky oil. H NMR (500 MHz, CDCl
7
7
1
3
): δ = 7.96–7.82 (m, 3 H), H), 4.05 (s, 1 H), 3.93 (dd, J = 16.0, 2.6 Hz, 1 H), 3.69 (s, 3 H) ppm.
1
3
.78–7.73 (m, 0.1 H), 7.68–7.64 (m, 0.2 H), 7.58–7.50 (m, 2 H),
.49–7.40 (m, 1.3 H), 7.38 (t, J = 1.7 Hz, 0.1 H), 7.37–7.33 (m, 0.9
C NMR (125 Hz, CDCl
3
): δ = 170.1, 162.5, 156.3, 147.0, 142.4,
134.0, 129.7, 129.3, 128.7, 128.6, 127.3, 124.3, 124.0, 122.7, 122.3,
H), 7.25–7.17 (m, 2.7 H), 7.13 (dd, J = 7.3, 1.1 Hz, 0.1 H), 7.11– 119.5, 114.6, 110.0, 107.9, 70.3, 55.3, 37.3, 35.0 ppm. HPLC (CHI-
–
1
7
.03 (m, 1.8 H), 6.79–6.70 (m, 1.8 H), 6.48 (dd, J = 1.8, 0.8 Hz, 0.1
H), 6.41 (dd, J = 1.8, 0.8 Hz, 0.9 H), 5.49 (d, J = 15.5 Hz, 0.1 H),
.38 (d, J = 14.4 Hz, 0.9 H), 4.71 (d, J = 15.5 Hz, 0.9 H), 4.42 (d, (ESI): calcd. for C25
RALPAK AD-H; hexane/2-PrOH, 90:10; 1.0 mL min ): t
19.3 min (major isomer) and t = 27.6 min (minor isomer). HRMS
19NNaO
[M + Na]+ 404.1263; found
R
=
R
5
H
3
13
3
J = 14.5 Hz, 0.1 H) ppm. C NMR (125 Hz, CDCl ): δ = 155.0, 404.1261.
1
1
4
3
43.1, 141.6, 137.5, 134.4, 132.3, 130.8, 129.8, 129.1, 128.4, 128.1,
27.6, 127.2, 126.5, 125.3, 122.6, 120.5, 120.0, 111.3, 90.6, 82.5,
2.8 ppm. HRMS (ESI): calcd. for C24
74.1157; found 374.1151.
(
[
–)-7-(2-Methoxyphenyl)-11,16b-dihydro-9H-benzo[h]benzofuro-
3,2-c]pyrrolo[2,1-j]quinolin-9-one [(–)-2b]: Pale yellow solid
H17NNaO
2
[M + Na]+
2
5
(
36.1 mg, 84% yield, 44%ee); m.p. 72.5–74.0 °C. [α]
D
= –213 (c =
1
1
.00, CHCl ). H NMR (400 MHz, CDCl ): δ = 7.41–7.33 (m, 2
3
3
3
-Cyclohexyl-N-[(furan-3-yl)methyl]-N-(naphthalen-1-yl)propyn- H), 7.29–7.26 (m, 1 H), 7.25–7.14 (m, 4 H), 6.86 (dd, J = 7.4,
amide (1f): By following the procedure used to prepare 1a, 3-cyclo-
1.0 Hz, 1 H), 6.83 (dd, J = 8.4, 0.7 Hz, 1 H), 6.62 (td, J = 7.4,
1.0 Hz, 1 H), 6.09–5.99 (m, 3 H), 5.98 (s, 1 H), 5.36 (dd, J = 16.0,
hexylprop-2-ynoic acid,[
11a]
1-naphthylamine, and 3-(bromometh-
yl)furan afforded 1f [54 % yield from 3-cyclohexylprop-2-ynoic
acid] as an orange solid; m.p. 68.5–70.0 °C. H NMR (500 MHz,
2.2 Hz, 1 H), 4.26–4.21 (m, 1 H), 4.15 (dd, J = 16.0, 2.8 Hz, 1 H),
3.73 (s, 3 H) ppm. C NMR (125 Hz, CDCl ): δ = 170.1, 162.7,
3
1
13
CDCl
.75 (m, 1 H), 7.69 (t, J = 4.9 Hz, 0.2 H), 7.59–7.44 (m, 2 H), 7.40 127.4, 125.7, 124.3, 123.9, 123.5, 122.8, 122.7, 122.2, 119.5, 118.6,
t, J = 7.7 Hz, 0.8 H), 7.37 (q, J = 1.7 Hz, 0.2 H), 7.32 (t, J = 111.2, 110.7, 110.1, 70.3, 55.4, 37.9, 34.2 ppm. HPLC (CHI-
3
): δ = 7.91–7.86 (m, 1 H), 7.84 (d, J = 8.6 Hz, 0.8 H), 7.82–
156.4, 155.2, 150.1, 134.0, 129.8, 129.7, 129.3, 128.8, 128.7, 127.8,
7
(
–
1
1
7
1
0
0
1
.7 Hz, 0.8 H), 7.20 (s, 0.8 H), 7.14 (dd, J = 6.9, 1.1 Hz, 0.8 H),
.05 (dd, J = 7.4, 1.1 Hz, 0.2 H), 6.46–6.31 (m, 1 H), 5.40 (d, J = 24.6 min (minor isomer) and t
4.9 Hz, 0.2 H), 5.29 (d, J = 14.9 Hz, 0.8 H), 4.60 (d, J = 15.5 Hz, (ESI): calcd. for C29 21NNaO
RALPAK AD-H; hexane/2-PrOH, 90:10; 1.0 mL min ): t
= 28.7 min (major isomer). HRMS
[M + Na]+ 454.1414; found
R
=
R
H
3
.2 H), 4.36 (d, J = 14.3 Hz, 0.8 H), 2.14 (s, 0.8 H), 2.01–1.90 (s,
.2 H), 1.77 (s, 0.2 H), 1.61 (s, 0.2 H), 1.39 (t, J = 8.6 Hz, 0.4 H),
.31–1.19 (m, 0.2 H), 1.18–1.00 (m, 3.2 H), 0.96–0.75 (m, 4.8
454.1411.
–)-5-(2-Methoxyphenyl)-9,12b-dihydro-7H-benzo[h]pyrrolo[2,1-j]-
thieno[3,2-c]quinolin-7-one [(–)-2c]: Pale yellow solid (35.0 mg, 88%
(
13
H) ppm. C NMR (125 Hz, CDCl
3
): δ = 155.3, 143.0, 141.5, 137.9,
34.5, 130.9, 128.8, 128.2, 127.3, 127.0, 126.4, 125.2, 122.8, 120.7,
11.4, 97.1, 75.2, 42.7, 30.6, 28.1, 25.4, 23.3 ppm. HRMS (ESI):
2
5
yield, 54%ee); m.p. 56.5–57.6 °C. [α]
D
= –124 (c = 0.67, CHCl
): δ = 7.27–7.22 (m, 2 H), 7.22–7.15
m, 2 H), 7.09 (dd, J = 5.2, 1.0 Hz, 1 H), 6.86 (dd, J = 7.4, 0.9 Hz,
H), 6.80 (d, J = 8.2 Hz, 1 H), 6.70 (d, J = 5.2 Hz, 1 H), 6.59 (td,
N-[(Furan-3-yl)methyl]-N-(naphthalen-1-yl)but-2-ynamide (1g): By J = 7.4, 0.9 Hz, 1 H), 6.03 (dd, J = 9.7, 6.2 Hz, 1 H), 5.99–5.90
3
).
1
1
1
H NMR (500 MHz, CDCl
3
(
+
2
calcd. for C24H23NNaO [M + Na] 380.1626; found 380.1621.
1
following the procedure used to prepare 1a, 2-butynoic acid, 1-
(m, 3 H), 5.28 (dd, J = 16.5, 1.7 Hz, 1 H), 4.11 (dd, J = 16.5,
1
3
naphthylamine, and 3-(bromomethyl)furan afforded 1g [36% yield
2.3 Hz, 1 H), 4.06 (d, J = 6.2 Hz, 1 H), 3.69 (s, 3 H) ppm.
NMR (125 Hz, CDCl ): δ = 170.0, 162.8, 156.3, 135.2, 134.1, 131.9,
130.1, 129.6, 129.3, 128.7, 128.6, 127.4, 127.2, 124.3, 123.8, 122.9,
.71–7.65 (m, 0.1 H), 7.58–7.51 (m, 2 H), 7.50–7.47 (m, 0.2 H), 122.6, 119.4, 110.0, 70.0, 55.4, 39.0, 37.8 ppm. HPLC (CHI-
.41 (dd, J = 8.3, 7.2 Hz, 0.9 H), 7.38–7.35 (m, 0.1 H), 7.32 (t, J =
.7 Hz, 0.9 H), 7.17 (q, J = 0.7 Hz, 0.9 H), 7.14 (d, J = 0.8 Hz, 0.1 103.0 min (minor isomer) and t
C
1
from 2-butynoic acid] as a black oil. H NMR (500 MHz, CDCl
3
):
3
δ = 7.93–7.88 (m, 1 H), 7.88–7.84 (m, 0.9 H), 7.83–7.75 (m, 1 H),
7
7
1
–
1
R
RALPAK AD-H; hexane/2-PrOH, 97:3; 1.0 mL min ): t =
R
= 111.4 min (major isomer).
4379
Eur. J. Org. Chem. 2015, 4374–4382
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org

T. Baba, J. Oka, K. Noguchi, K. Tanaka
FULL PAPER
HRMS (ESI): calcd. for C25
found 420.1029.
H
19NNaO
2
S [M + Na]+ 420.1034; J = 7.2, 1.2 Hz, 1 H), 7.10 (t, J = 1.7 Hz, 1 H), 6.25–6.21 (m, 1 H),
5.62–5.61 (m, 1 H), 4.25 (dq, J = 7.2, 14.3 Hz, 1 H), 3.62–3.49 (dq,
J = 7.2, 14.3 Hz, 1 H), 3.07 (t, J = 1.3 Hz, 2 H), 1.19 (t, J = 7.2 Hz,
(
–)-5-Phenyl-9,12b-dihydro-7H-benzo[h]furo[3,2-c]pyrrolo[2,1-j]quin-
1
3
3
1
1
3
H) ppm. C NMR (125 MHz, CDCl ): δ = 154.6, 142.7, 139.2,
olin-7-one [(–)-2e]: Orange solid (63.8 mg, 91% yield, 13%ee); m.p.
1
(
7
37.7, 134.6, 131.0, 129.0, 128.4, 127.3, 127.2, 126.6, 125.4, 122.7,
18.2, 109.9, 89.4, 75.7, 43.5, 15.3, 13.2 ppm. HRMS (ESI): calcd.
43.2–144.0 °C. [α]2
500 MHz, CDCl ): δ = 7.33–7.26 (m, 3 H), 7.24–7.19 (m, 2 H),
.19–7.14 (m, 2 H), 7.02–6.97 (m, 1 H), 6.72–6.67 (m, 2 H), 6.16
5
1
D 3
= –43.7 (c = 2.80, CHCl ). H NMR
3
NNa [M + Na]+ 326.1151; found 326.1151.
for C20
H
17
O
2
(d, J = 1.9 Hz, 1 H), 6.10 (d, J = 9.8 Hz, 1 H), 5.99–5.95 (m, 1 H),
4-(Furan-3-yl)-N-methyl-N-(naphthalen-1-yl)but-2-ynamide (3b): By
5
2
.95 (s, 1 H), 5.10 (dd, J = 16.0, 2.0 Hz, 1 H), 3.88 (dd, J = 16.0,
following the procedure used to prepare 3a, N-methyl-N-
.5 Hz, 1 H), 3.78–3.72 (m, 1 H) ppm. 13C NMR (125 Hz, CDCl
[10]
): (naphthalen-1-yl)propiolamide
and 3-(bromomethyl)furan af-
3
1
δ = 169.6, 165.8, 146.8, 142.6, 134.2, 133.2, 129.1, 129.0, 128.8,
forded 3b (32% yield) as an orange solid; m.p. 52.0–53.5 °C.
H
1
3
1
27.74, 127.72, 127.6, 124.7, 124.0, 121.1, 115.0, 107.8, 69.4, 38.2,
4.7 ppm. HPLC (CHIRALPAK AD-H; hexane/2-PrOH, 90:10;
NMR (500 MHz, CDCl ): δ = 7.96–7.87 (m, 2 H), 7.86–7.79 (m, 1
H), 7.61–7.53 (m, 2 H), 7.52–7.47 (m, 1 H), 7.43 (dd, J = 7.2,
3
–1
.0 mLmin ): t
R
= 21.1 min (minor isomer) and t
R
= 24.9 min 1.1 Hz, 1 H), 7.10 (t, J = 1.7 Hz, 1 H), 6.25–6.24 (m, 1 H), 5.62–
1
3
(
major isomer). HRMS (ESI): calcd. for C24
H
17NNaO
2
[M + Na] 5.61 (m, 1 H), 3.42 (s, 3 H), 3.08 (s, 2 H) ppm. C NMR
(125 MHz, CDCl ): δ = 154.9, 142.7, 139.4, 139.2, 134.5, 130.5,
28.9, 128.5, 127.4, 126.7, 126.1, 125.6, 122.4, 118.2, 109.9, 89.7,
5.4, 36.5, 15.2 ppm. HRMS (ESI): calcd. for C19 NNa [M +
+
3
74.1157; found 374.1158.
–)-5-Cyclohexyl-9,12b-dihydro-7H-benzo[h]furo[3,2-c]pyrrolo[2,1-j]-
quinolin-7-one [(–)-2f]: White solid (71.5 mg, Ͼ99% yield, 14%ee);
3
1
7
(
15 2
H O
+
Na] 312.1000; found 312.1005.
m.p. 204.5–206.2 °C. [α]2
5
= –57.6 (c = 2.90, CHCl
): δ = 7.23 (dd, J = 1.9, 1.1 Hz, 1 H), 7.22–7.19
m, 1 H), 7.19–7.15 (m, 1 H), 7.09 (dd, J = 7.2, 1.5 Hz, 1 H), 6.99–
1
D
3
). H NMR
4
-(Furan-3-yl)-N-isobutyl-N-(naphthylen-1-yl)but-2-ynamide (3c):
(500 MHz, CDCl
3
By following the procedure used to prepare 3a, N-isobutyl-N-
(
10]
(
naphthalen-1-yl)propiolamide[ and 3-(bromomethyl)furan af-
6
1
.94 (m, 1 H), 6.56 (d, J = 9.8 Hz, 1 H), 6.41 (dd, J = 9.8, 6.1 Hz,
H), 6.14 (d, J = 1.9 Hz, 1 H), 5.75 (d, J = 0.5 Hz, 1 H), 4.99 (dd,
1
forded 3c (44% yield) as an orange sticky oil. H NMR (500 MHz,
CDCl
3
): δ = 7.98–7.92 (m, 1 H), 7.90 (d, J = 8.2 Hz, 1 H), 7.87–
J = 16.0, 2.0 Hz, 1 H), 3.77 (dd, J = 16.0, 2.5 Hz, 1 H), 3.72–3.64
m, 1 H), 2.37–2.30 (m, 1 H), 1.91–1.86 (m, 1 H), 1.78–1.73 (m, 1
H), 1.63–1.58 (m, 1 H), 1.55–1.48 (m, 1 H), 1.30–1.08 (m, 3 H),
7.80 (m, 1 H), 7.60–7.53 (m, 2 H), 7.51–7.46 (m, 1 H), 7.42 (dd, J
(
=
7.2, 1.2 Hz, 1 H), 7.10 (t, J = 1.7 Hz, 1 H), 6.25–6.24 (m, 1 H),
.02–0.86 (m, 3 H) ppm. 1 C NMR (125 Hz, CDCl
3
5.62–5.61 (m, 1 H), 4.22 (dd, J = 13.3, 9.3 Hz, 1 H), 3.17 (dd, J =
1
1
1
2
1
3
): δ = 174.6,
1
3.3, 5.6 Hz, 1 H), 3.07 (s, 2 H), 1.90–1.82 (m, 1 H), 1.03 (d, J =
70.7, 146.9, 142.5, 133.1, 130.3, 129.0, 128.7, 128.3, 127.8, 124.8,
24.6, 116.8, 115.0, 107.8, 68.5, 38.1, 36.9, 34.4, 34.3, 34.1, 26.5,
6 . 4, 2 5. 7 ppm . H PLC (CH I RAL PAK AD -H , EtOH,
1
3
6
.7 Hz, 3 H), 0.90 (d, J = 6.7 Hz, 3 H) ppm. C NMR (125 MHz,
): δ = 155.3, 142.7, 139.2, 138.2, 134.6, 130.7, 128.9, 128.5,
127.3, 126.6, 125.3, 122.6, 118.2, 109.9, 89.8, 75.6, 55.2, 27.5, 20.3,
0.1, 15.3 ppm. HRMS (ESI): calcd. for C22 NNa [M +
CDCl
3
–1
.0 mLmin ): t
R
= 23.2 min (minor isomer) and t
R
= 51.1 min
[M + Na]
2
21 2
H O
(
major isomer). HRMS (ESI): calcd. for C24
H
23NNaO
2
+
+
Na] 354.1465; found 354.1474.
380.1626; found 380.1621.
N-Benzyl-4-(furan-3-yll)-N-(naphthalen-1-yl)but-2-ynamide (3d): By
following the procedure used to prepare 3a, N-benzyl-N-
(naphthalen-1-yl)propiolamide[ and 3-(bromomethyl)furan af-
(
–)-5-Methyl-9,12b-dihydro-7H-benzo[h]furo[3,2-c]pyrrolo[2,1-j]-
quinolin-7-one [(–)-2g]: Pale yellow solid (50.0 mg, 86 % yield,
1
NMR (500 MHz, CDCl
7
6
10]
2%ee); m.p. 173.4–175.0 °C. [α]2
5
1
D
= –99.1 (c = 1.68, CHCl ). H
3
1
forded 3d (Ͼ99% yield) as a yellow sticky oil. H NMR (500 MHz,
3
): δ = 7.24–7.16 (m, 3 H), 7.09 (dd, J =
.1, 1.8 Hz, 1 H), 7.01–6.96 (m, 1 H), 6.55 (d, J = 9.8 Hz, 1 H),
.36 (dd, J = 9.8, 6.2 Hz, 1 H), 6.15 (d, J = 1.9 Hz, 1 H), 5.69 (q,
CDCl
3
): δ = 7.96–7.75 (m, 3 H), 7.57–7.51 (m, 2 H), 7.33 (dd, J =
8
7
1
.3, 7.3 Hz, 1 H), 7.27–7.17 (m, 5 H), 7.08 (t, J = 1.7 Hz, 1 H),
.00 (dd, J = 7.3, 1.1 Hz, 1 H), 6.23–6.20 (m, 1 H), 5.65 (d, J =
4.1 Hz, 1 H), 5.61–5.57 (m, 1 H), 4.35 (d, J = 14.1 Hz, 1 H), 5.60–
J = 1.5 Hz, 1 H), 5.01 (dd, J = 16.0, 2.1 Hz, 1 H), 3.83 (dd, J =
1
6.0, 2.5 Hz, 1 H), 3.59 (m, 1 H), 1.90 (d, J = 1.5 Hz, 3 H) ppm.
1
3
1
3
3
5.59 (m, 2 H) ppm. C NMR (125 MHz, CDCl ): δ = 154.9, 142.7,
C NMR (125 Hz, CDCl
3
): δ = 170.4, 164.4, 146.5, 142.5, 132.9,
1
1
39.2, 137.4, 136.7, 134.5, 130.7, 129.3 (2 C), 129.0, 128.5, 128.4,
27.7, 127.6, 127.3, 126.5, 125.3, 122.5, 118.1, 109.9, 90.1, 75.4,
1
6
2
t
C
30.6, 129.0, 128.6, 128.5, 127.8, 124.3, 124.1, 118.9, 115.1, 107.9,
8.6, 37.8, 34.7, 13.7 ppm. HPLC (CHIRALPAK AD-H; hexane/
–1
19 2
52.0, 15.3 ppm. HRMS (ESI): calcd. for C25H O NNa [M +
-PrOH, 90:10; 1.0 mLmin ): t
R
= 18.6 min (minor isomer) and
+
Na] 388.1308; found 388.1322.
R
= 27.4 min (major isomer). HRMS (ESI): calcd. for
+
19
H
15NNaO
2
[M + Na] 312.1000; found 312.0995.
N-Ethyl-N-(naphthalen-1-yl)-4-(thiophen-3-yl)but-2-ynamide (3e):
By following the procedure used to prepare 3a, N-ethyl-N-
N-Ethyl-4-(furan-3-yl)-N-(naphthalen-1-yl)but-2-ynamide (3a): N-
[
10]
Ethyl-N-(naphthalen-1-yl)propiolamide[
10]
(naphthalen-1-yl)propiolamide
and 3-(bromomethyl)thio-
(0.670 g, 3.00 mmol)
phene[ afforded 3e (23% yield) as an orange sticky oil. H NMR
500 MHz, CDCl ): δ = 8.00–7.79 (m, 3 H), 7.61–7.53 (m, 2 H),
.49 (dd, J = 8.2, 7.2 Hz, 1 H), 7.41 (dd, J = 7.2, 1.2 Hz, 1 H), 6.99
dd, J = 4.9, 3.0 Hz, 1 H), 6.25 (dd, J = 4.9, 1.3 Hz, 1 H), 5.86–
17]
1
was added to a mixture of 3-(bromomethyl)furan (0.483 g,
.00 mmol), copper(I) iodide (0.628 g, 3.33 mmol), potassium carb-
onate (0.456 g, 3.33 mmol), and tetrabutylammonium iodide
1.219 g, 3.33 mmol) in dry acetonitrile (40 mL). The resulting
(
3
3
7
(
(
5
7
.84 (m, 1 H), 4.25 (dq, J = 14.4, 7.2 Hz, 1 H), 3.58 (dq, J = 14.4,
.2 Hz, 1 H), 3.31–3.26 (m, 2 H), 1.20 (t, J = 7.2 Hz, 3 H) ppm.
C NMR (125 MHz, CDCl ): δ = 154.6, 137.7, 134.6, 134.0, 131.1,
3
slurry was stirred at 40 °C for 2 d and then diluted with saturated
aqueous ammonium chloride. The resulting mixture was extracted
with diethyl ether (2ϫ). The combined organic layers were dried
with Na SO and passed through a filter to remove the drying
2 4
agent. The filtrate was concentrated, and the residue was purified
by silica gel column chromatography (hexane/EtOAc/toluene, 3:1:3)
1
3
1
8
C
29.0, 128.5, 127.4, 127.2, 126.8, 126.6, 125.5, 125.5, 122.7, 121.0,
9.8, 76.4, 43.5, 20.1, 13.2 ppm. HRMS (ESI): calcd. for
17NOSNa [M + Na]+ 342.0929; found 342.0939.
20
H
to afford 3a (0.119 g, 0.330 mmol, 11% yield) as an orange solid;
Representative Procedure for Gold-Catalyzed Asymmetric Dearoma-
) (2.9 mg, 0.010 mmol), (R)-xyl-
binap (3.7 mg, 0.0050 mol), and AgSbF (3.4 mg, 0.010 mmol)
1
m.p. 50.3–50.9 °C. H NMR (500 MHz, CDCl
3
): δ = 7.97–7.81 (m, tization: (Table 4): AuCl(SMe
2
3
H), 7.60–7.54 (m, 2 H), 7.50 (dd, J = 8.2, 7.2 Hz, 1 H), 7.40 (dd,
6
4380
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 4374–4382

Asymmetric Dearomatization of 1-Aminonaphthalene Derivatives
were dissolved in (CH
of 3a (35.9 mg, 0.10 mmol) in (CH
ture. The mixture was stirred at 25 °C for 72 h. The resulting solu-
tion was concentrated, and the residue was purified by preparative
TLC (hexane/EtOAc, 1:1) to furnish a mixture of (+)-4a (60%ee)
and 5a (31.9 mg, 89% yield, 4a/5a = 83:17).
2
Cl)
2
(1.0 mL) and then added to a solution
Cl) (1.0 mL) at room tempera-
3
(500 MHz, CDCl ): δ = 7.23 (td, J = 7.4, 1.3 Hz, 1 H), 7.20–7.13
2
2
(m, 5 H), 7.12–7.08 (m, 2 H), 7.07 (dd, J = 7.4, 1.3 Hz, 1 H), 7.02
(d, J = 7.4 Hz, 1 H), 6.56 (d, J = 9.6 Hz, 1 H), 6.38 (d, J = 1.9 Hz,
1 H), 6.08 (d, J = 1.9 Hz, 1 H), 5.97 (dd, J = 9.6, 6.2 Hz, 1 H),
4.73 (d, J = 15.8 Hz, 1 H), 3.76 (d, J = 15.8 Hz, 1 H), 3.62 (dd, J
= 17.9, 1.6 Hz, 1 H), 3.47–3.41 (m, 1 H), 3.35 (dt, J = 17.9, 2.5 Hz,
1
3
1
1
1
3
H) ppm. C NMR (125 MHz, CDCl ): δ = 160.8, 160.6, 147.4,
(
[
+)-5-Ethyl-8,11b-dihydrofuro[3,2-f]naphtho[2,1-h]indol-6(5H)-one
(+)-4a]: The solid mixture of 4a and 5a was washed with Et O and
filtered to give pure 4a (95% ee) as an orange solid; m.p. 212.2–
42.7, 138.1, 133.2, 129.2, 128.9, 127.8, 127.7, 127.4, 127.3, 126.7,
25.9, 125.5, 114.7, 109.2, 67.0, 43.4, 41.6, 23.8 ppm. HRMS (ESI):
2
19 2
H O
NNa [M + Na]+ 388.1308; found 388.1304.
calcd. for C25
HPLC (CHIRALPAK AD-H; hexane/2-PrOH, 90:10;
13.5 °C. [α]2
CDCl ): δ = 7.28 (td, J = 7.4, 1.1 Hz, 1 H), 7.25–7.23 (m, 1 H),
.20 (td, J = 7.4, 1.5 Hz, 1 H), 7.15 (dd, J = 7.4, 1.1 Hz, 1 H), 7.01
d, J = 7.4 Hz, 1 H), 6.69 (d, J = 9.7 Hz, 1 H), 6.52 (dd, J = 9.5,
5
1
2
D 3
= +444 (c = 0.18, CHCl ). H NMR (500 MHz,
3
–
1
1
.0 mLmin ): t
R R
= 20.0 min (major isomer) and t = 25.2 min
7
(
(
minor isomer).
6
3
2
.0 Hz, 1 H), 6.26 (d, J = 1.7 Hz, 1 H), 6.11 (d, J = 1.7 Hz, 1 H), (+)-5-Ethyl-8,11b-dihydronaphtho[2,1-h]thieno[3,2-f]indol-6(5H)-one
.72–3.65 (m, 1 H), 3.60 (dd, J = 17.5, 1.4 Hz, 1 H), 3.41–3.28 (m,
[(+)-4e]: Following the representative procedure above afforded 4e
H), 3.00 (dq, J = 14.3, 7.1 Hz, 1 H), 0.85 (t, J = 7.1 Hz, 3 H) ppm. (37.8 mg, 59 % yield, 43 % ee) as an orange solid; m.p. 171.4–
1
3
25
1
C NMR (125 MHz, CDCl
3
): δ = 169.0, 160.0, 147.5, 142.8, 133.0, 173.2 °C. [α]
D
= +222 (c = 1.57, CDCl
3
). H NMR (500 MHz,
1
6
C
30.0, 129.2, 129.1, 127.9, 127.6, 126.0, 125.1, 123.5, 115.0, 109.3,
CDCl ): δ = 7.27 (td, J = 7.5, 1.4 Hz, 1 H), 7.20 (td, J = 7.5, 1.4 Hz,
3
6.7, 42.2, 35.4, 23.7, 14.4 ppm. HRMS (ESI): calcd. for
1 H), 7.14 (dd, J = 7.5, 1.0 Hz, 1 H), 7.11 (dd, J = 5.2, 1.0 Hz, 1
H), 7.01 (d, J = 7.5 Hz, 1 H), 6.69 (d, J = 9.5 Hz, 1 H), 6.64 (d, J
= 5.2 Hz, 1 H), 6.58 (dd, J = 9.5, 6.2 Hz, 1 H), 6.26 (d, J = 2.3 Hz,
1 H), 3.84 (dd, J = 18.1, 1.0 Hz, 1 H), 3.76–3.65 (m, 1 H), 3.52 (dt,
J = 18.1, 2.3 Hz, 1 H), 3.37 (dq, J = 14.2, 7.1 Hz, 1 H), 3.00 (dq,
+
20
H
17
O
2
NNa [M + Na] 326.1151; found 326.1151. HPLC (CHI-
–
1
RALPAK IE-3; hexane/2-PrOH, 90:10; 0.6 mL min ): t
9.6 min (major isomer) and t = 100.2 min (minor isomer).
R
=
8
R
(+)-5-Methyl-8,11b-dihydrofuro[3,2-f]naphtho[2,1-h]indol-6(5H)-one
1
3
J = 14.2, 7.1 Hz, 1 H), 0.87 (t, J = 7.1 Hz, 3 H) ppm. C NMR
125 MHz, CDCl ): δ = 169.2, 159.6, 136.1, 133.2, 132.3, 130.2,
29.2, 129.1, 128.4, 128.0, 127.5, 126.1, 125.4, 124.9, 123.2, 66.6,
3.8, 35.4, 27.3, 14.5 ppm. HRMS (ESI): calcd. for C20 17NOSNa
[(+)-4b]: Following the representative procedure above afforded a
(
3
mixture of (+)-4b (24.0 mg, 84% yield, 61%ee) and 5b (27.4 mg).
Leaving the mixture of 4b and 5b under Ar for 3 d followed by
preparative TLC afforded pure 4b as an orange solid; m.p. 154.3–
1
4
[
H
M + Na]+ 342.0923; found 342.0923. HPLC (CHIRALPAK AD-
55.2 °C. [α]2
CDCl
5
= +349 (c = 0.45, CHCl
): δ = 7.28 (td, J = 7.6, 1.3 Hz, 1 H), 7.24 (dd, J = 1.9,
.3 Hz, 1 H), 7.21 (td, J = 7.6, 1.3 Hz, 1 H), 7.15 (dd, J = 7.6,
.3 Hz, 1 H), 6.99 (d, J = 7.6 Hz, 1 H), 6.67 (d, J = 9.7 Hz, 1 H), Supporting Information (see footnote on the first page of this arti-
1
1
D
3
). H NMR (500 MHz,
–
1
H; hexane/2-PrOH, 80:20; 1.0 mLmin ): t
mer) and t = 12.2 min (minor isomer).
R
= 8.5 min (major iso-
3
R
1
1
6
1
13
.49 (dd, J = 9.7, 6.1 Hz, 1 H), 6.28 (d, J = 1.9 Hz, 1 H), 6.12 (d,
cle): Chiral HPLC chromatograms and H and C NMR spectra.
J = 1.9 Hz, 1 H), 3.62 (dd, J = 13.1, 1.3 Hz, 1 H), 3.60 (s, 1 H),
1
3
3
.40–3.33 (m, 1 H), 3.65 (s, 3 H) ppm. C NMR (125 MHz,
Acknowledgments
CDCl ): δ = 168.7, 160.0, 147.3, 142.9, 133.0, 129.5, 129.2, 129.1,
3
1
2
3
27.8, 127.5, 126.0, 124.7, 123.4, 115.2, 109.3, 66.7, 41.6, 25.4,
NNa [M + Na]+
This work was partly supported by the Japanese Ministry of Educa-
tion, Culture, Sports, Science, and Technology (MEXT) through a
Grant-in-Aid for Scientific Research (grant number 25105714) and
the ACT-C from the Japan Science and Technology Agency (JST,
Japan). The authors thank the Takasago International Corporation
3.8 ppm. HRMS (ESI): calcd. for C19H O
15 2
12.0995; found 312.1006. HPLC (CHIRALPAK IA; hexane/
–1
3 R R
CHCl , 60:40; 0.4 mLmin ): t = 34.0 min (major isomer) and t
=
52.9 min (minor isomer).
(
+)-5-Isobutyl-8,11b-dihydrofuro[3,2-f]naphtho[2,1-h]indol-6(5H)- for the gift of the H -binap, binap, and segphos derivatives.
8
one [(+)-4c]: Following the representative procedure above afforded
4
c (52.1 mg, 0.0741 mmol, 74% yield, 53%ee) as an orange solid;
[
1] For reviews, see: a) C.-X. Zhuo, C. Zheng, S.-L. You, Acc.
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25
1
m.p. 158.3–160.0 °C. [α]
D 3
= +231 (c = 1.57, CDCl ). H NMR
3
): δ = 7.27 (td, J = 7.5, 1.4 Hz, 1 H), 7.23 (dd, J
1.9, 1.2 Hz, 1 H), 7.19 (td, J = 7.5, 1.4 Hz, 1 H), 7.12 (dd, J =
(500 MHz, CDCl
=
2013, 45, 1; d) C.-X. Zhuo, W. Zhang, S.-L. You, Angew. Chem.
7
1
6
1
8
0
.5, 1.2 Hz, 1 H), 7.01 (d, J = 7.5 Hz, 1 H), 6.64 (d, J = 10.3 Hz,
H), 6.49 (dd, J = 9.6, 6.1 Hz, 1 H), 6.26 (d, J = 1.9 Hz, 1 H),
.10 (d, J = 1.9 Hz, 1 H), 3.75–3.63 (m, 1 H), 3.59 (dd, J = 17.8,
.6 Hz, 1 H), 3.31 (dt, J = 17.8, 2.5 Hz, 1 H), 3.06 (dd, J = 14.1,
.2 Hz, 1 H), 2.75 (dd, J = 14.1, 7.1 Hz, 1 H), 1.57–1.43 (m, 1 H),
.73 (d, J = 6.6 Hz, 3 H), 0.66 (d, J = 6.6 Hz, 3 H) ppm. 1 C NMR
Int. Ed. 2012, 51, 12662; Angew. Chem. 2012, 124, 12834; e) H.
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(125 MHz, CDCl ): δ = 169.8, 159.8, 147.5, 142.7, 133.0, 130.1,
1
4
29.1, 128.9, 127.4, 127.3, 126.0, 125.4, 123.2, 114.9, 109.2, 66.9,
8.0, 41.9, 28.2, 23.7, 20.3, 20.0 ppm. HRMS (ESI): calcd. for
12, 5020; b) Q.-F. Wu, W.-B. Liu, C.-X. Zhuo, Z.-Q. Rong, K.-
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C
22
H
21
O
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–
1
RALPAK AD-H; hexane/2-PrOH, 80:20; 1.0 mL min ): t
.0 min (major isomer) and t = 8.2 min (minor isomer).
R
=
7
R
133, 9282; d) M. Yoshida, T. Nemoto, Z. Zhao, Y. Ishige, Y.
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[(+)-4d]: Following the representative procedure above afforded 4d
(
23.9 mg, 0.0654 mmol, 66 % yield, 52 % ee) as a colorless solid;
25
1
m.p. 99.2–101.0. [α]
D 3
= +144 (c = 1.25, CDCl ). H NMR
Eur. J. Org. Chem. 2015, 4374–4382
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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1
1
Received: April 16, 2015
492.
Published Online: June 5, 2015
4382
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© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 4374–4382