Biarylmethane and fused heterocyclic arene synthesis via in situ generated o - And/or p -naphthoquinone methides

Article abstract of DOI:10.1021/acs.joc.5b00434

o- and/or p-naphthoquinone methides (NQMs) can be selectively prepared by the ring opening of 1-(siloxymethyl)-1,4-epoxy-1,4-dihydronaphthalene derivatives based on a substituent effect at the 4 position of the substrates. The 4-alkyl- or silyl-substitute

Full text of DOI:10.1021/acs.joc.5b00434

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Article
Biarylmethane and Fused Heterocyclic Arene Synthesis via in
situ-Generated ortho- and/or para-Naphthoquinone Methides
Yoshinari Sawama, Takahiro Kawajiri, Shota Asai, Naoki
Yasukawa, Yuko Shishido, Yasunari Monguchi, and Hironao Sajiki
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b00434 • Publication Date (Web): 04 May 2015
Downloaded from http://pubs.acs.org on May 5, 2015
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The Journal of Organic Chemistry
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Biarylmethane and Fused Heterocyclic Arene Synthesis
via in situꢀGenerated orthoꢀ and/or paraꢀ
Naphthoquinone Methides
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Yoshinari Sawama,* Takahiro Kawajiri, Shota Asai, Naoki Yasukawa, Yuko Shishido, Yasunari
Monguchi and Hironao Sajiki*
Laboratory of Organic Chemistry, Gifu Pharmaceutical University, 1ꢀ25ꢀ4 Daigakuꢀnishi, Gifu 501ꢀ
1196, Japan
Phone/Fax: (+81)ꢀ58ꢀ230ꢀ8109; email: sawama@gifuꢀpu.ac.jp, sajiki@gifuꢀpu.ac.jp
CORRESPONDING AUTHOR
Yoshinari Sawama and Hironao Sajiki
*Eꢀmail: sajiki@gifuꢀpu.ac.jp; sawama@gifuꢀpu.ac.jp
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ABSTRACT
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Ortho- and/or paraꢀnaphthoquinone methides (NQMs) can be selectively prepared by the ring opening
of 1ꢀsiloxymethylꢀ1,4ꢀepoxyꢀ1,4ꢀdihydronaphthalene derivatives based on a substituent effect at the 4
position of the substrates. The 4ꢀalkyl or silyl substituted 1ꢀsiloxymethylꢀ1,4ꢀepoxyꢀ1,4ꢀ
dihydronaphthalene was transformed to oꢀNQM (1ꢀnaphthoquinoneꢀ2ꢀmethide), which underwent the
FriedelꢀCrafts 1,4ꢀaddition of the α,βꢀunsaturated carbonyl moiety to provide the 2ꢀbenzylꢀ1ꢀnaphthol as
the biarylmethane and [4+2]ꢀcycloaddition with a dienophile to give the fused heterocyclic arene.
Meanwhile, the 4ꢀunsubstituted 1ꢀsiloxymethylꢀ1,4ꢀepoxyꢀ1,4ꢀdihydronaphthalene could be converted
to the corresponding 4ꢀbenzylꢀ1ꢀnaphthol by the FriedelꢀCrafts 1,6ꢀaddition of pꢀNQM (1ꢀ
naphthoquinoneꢀ4ꢀmethide) generated by the siteꢀselective ring opening of the 1,4ꢀepoxy moiety.
Furthermore, the 4ꢀsiloxymethyl (1,4ꢀdisiloxymethyl) 1,4ꢀepoxyꢀ1,4ꢀdihydronaphthalene was
transformed into a 2,4ꢀbisbenzyl 1ꢀnaphthol or pentacyclic derivative via both the oꢀ and pꢀNQMs
intermediates.
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INTRODUCTION
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Naphthoquinone methides (NQMs) are reactive intermediates possessing a quinone methide (QM)
backbone, which is composed of a cyclohexadiene core bearing the carbonyl and exomethylene
functionalities. These are traditionally prepared from the corresponding phenol derivative possessing an
activated benzylic carbon.1,2 While the reactions utilizing QM intermediates have been widely
investigated,1,2 a limited number of synthetic methods via the NQMs has been reported.3ꢀ6 NQMs are
categorized by several subtypes, such as 1ꢀnaphthoquinoneꢀ2ꢀmethide,3 2ꢀnaphthoquinoneꢀ1ꢀmethide4
and 2ꢀnaphthoquinoneꢀ3ꢀmethide5ꢀ6, based on the substitution site and pattern of the carbonyl and
exomethylene groups, and can be prepared from naphthol derivatives. Among them, the orthoꢀNQM (1ꢀ
naphthoquinoneꢀ2ꢀmethide) is regarded as an efficient synthetic precursor to construct a
pharmaceutically useful fused heterocyclic arene7 (e.g., rubioncolin B7fꢀh possessing a potent cytotoxic
and antitumor activity) via the [4+2]ꢀcycloaddition with an electronꢀsufficient dienophile and 2ꢀbenzylꢀ
1ꢀnaphthol as a biarylmethane possessing various bioactivities8 by the 1,4ꢀaddition of the arene
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nucleophile into the α,βꢀunsaturated carbonyl moiety of the oꢀNQM (Figure 1, top). Additionally, the
paraꢀNQM (1ꢀnaphthoquinoneꢀ4ꢀmethide) could also be a good precursor to provide 4ꢀbenzylꢀ1ꢀ
naphthol derivatives possessing a biarylmethane function9 via the 1,6ꢀaddition by a nucleophilic arene
into pꢀNQM (Figure 1, bottom).
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Figure 1. Orthoꢀ and paraꢀnaphthoquinone methide (NQM) intermediates
used to construct a wide variety of backbones of bioactive compounds.
We have recently revealed that various benzylic CꢀO bonds could be activated by the safe and
inexpensive FeCl3 as a catalyst10 and the FeCl3ꢀcatalyzed ringꢀopening nucleophilic addition using 1,4ꢀ
disubstitutedꢀ1,4ꢀepoxyꢀ1,4ꢀdihydronaphthalenes, which are easily prepared by the DielsꢀAlder reaction
between benzynes and furans, providing the highly functionalized naphthalene derivatives.11
Additionally, the 1ꢀsiloxymethylꢀ4ꢀalkylꢀ1,4ꢀepoxyꢀ1,4ꢀdihydronaphthalenes (1: R1 = alkyl) were found
to be transformed into oꢀNQM (A), which underwent annulation with allyl silanes.12 We now
demonstrate the new FeCl3ꢀcatalyzed synthetic methods of biarylmethane (2: 2ꢀbenzylꢀ1ꢀnaphthol) via
the FriedelꢀCrafts 1,4ꢀaddition of arenes to the α,β
ꢀunsaturated carbonyl moiety of oꢀNQM (A)13 and the
fused heterocyclic arenes (3) by the [4+2]ꢀcycloaddition of A with dienophiles (e.g., benzofuran and
indole as heteroarenes) except for the allyl silanes (Scheme 1). Furthermore, the novel trifluoroacetic
anhydride (TFAA)ꢀmediated preparation of pꢀNQM using 4ꢀunsubstituted 1ꢀsiloxymethylꢀ1,4ꢀepoxyꢀ
1,4ꢀdihydronaphthalenes (4: R1 = H) is also developed to construct the different types of biarylmethanes
(5: 4ꢀbenzylꢀ1ꢀnaphthols) by the FriedelꢀCrafts 1,6ꢀaddition. Additionally, the 1,4ꢀdibenzylated 1ꢀ
naphthols14 (7) and the highly functionalized heterocycles (8) can be easily prepared by the double
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functionalization of arenes or heteroarenes via both the oꢀ and pꢀNQMs derived from the 1,4ꢀ
disiloxymethyl 1,4ꢀepoxyꢀ1,4ꢀdihydronaphthalenes (6: R1 = CH2OTBS).
Scheme 1. Synthesis of biarylmethanes and fused heterocyclic arenes via
orthoꢀ and/or paraꢀnaphthoquinone methides (NQMs).
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RESULTS AND DISCUSSION
We initially investigated the catalyst (5 mol%) efficiency for the syntheses of 2ꢀbenzylꢀ1ꢀnaphthol
derivatives
via
oꢀNQM
using
1ꢀtertꢀbutyldimethylsiloxymethylꢀ4ꢀmethylꢀ1,4ꢀepoxyꢀ1,4ꢀ
dihydronaphthalene (1a)15 as a substrate and 1,3,5ꢀtrimethoxybenzene (2 equiv.) as an arene nucleophile
in CH2Cl2 at room temperature (Table 1). The reaction using catalytic FeCl3 or AuCl316 gave the desired
product (2a) in good yields (78% and 81%, respectively, for entries 1 and 2), while the other Lewis
acids, such as FeBr3, ZnCl2, BF3•Et2O, TMSOTf and AlCl3, were somewhat less effective (entries 3ꢀ7).
From the viewpoint of the cost performance and general versatility in comparison to AuCl3, the solvent
effect was next investigated under the FeCl3ꢀcatalyzed conditions. Consequently, (CH2Cl)2 was the most
efficient among the tested solvents including CH2Cl2, CHCl3, CH3CN, CH3NO2 and THF (entries 8 vs. 1
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and 10ꢀ13), and the increased amount of 1,3,5ꢀtrimethoxybenzene to 4 equiv. could improve the reaction
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efficiency to give 2a in 88% yield (entry 9).
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Table 1. Optimization using 1ꢀsiloxylmethylꢀ4ꢀmethyl substrate (1a).
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entry
catalyst
solvent
time (h)a
Yield (%)
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2
3
4
5
6
7
8
FeCl3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
(CH2Cl)2
(CH2Cl)2
CHCl3
0.5
0.5
0.5
2
0.5
0.5
0.5
0.5
0.5
0.25
0.25
0.5
30
78
81
67
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AuCl3
FeBr3
ZnCl2
BF3•Et2O
TMSOTf
AlCl3
FeCl3
FeCl3
FeCl3
FeCl3
9b
10
11
12
13
CH3CN
CH3NO2
THF
FeCl3
FeCl3
a
The reaction was stopped when 1a was completely consumed by
checking using TLC. b 4 equiv. of 1.3.5ꢀtrimethoxybenzene were used.
The oꢀNQM derivative (A) derived from the FeCl3ꢀcatalyzed transformation of 1a efficiently
reacted with various arene nucleophiles (1,3ꢀdimethoxybenzene17, anisole17, 2ꢀ or 1ꢀ
methoxynaphthalene and Nꢀphenylindole18) at room temperature to give the corresponding 2ꢀ
(hetero)arylmethylꢀ1ꢀnaphthols (2) in moderate to good yields for 0.5 h (Table 2, entries 1ꢀ5).
Meanwhile, benzofuran worked as a dienophile in the reaction with oꢀNQM (A), and the fused
pentacyclic arene derivative including the heterocyclic component (3a) was obtained in 74% yield (entry
6). While indene and styrene also underwent the same annulation with oꢀNQM (entries 7 and 8), the
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reaction of benzothiophene gave 2ꢀbenzothienylmethylꢀ1ꢀnaphthol (2g) (entry 9).19 Furthermore, the 4ꢀ
silylated substrate (1b; 1ꢀtertꢀbutyldimethylsiloxymethylꢀ4ꢀtriethylsilylꢀ1,4ꢀepoxyꢀ1,4ꢀ
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2
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4
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8
dihydronaphthalene) was also applied to the FeCl3ꢀcatalyzed reaction using 1,3,5ꢀtrimethoxybenzene as
a nucleophile to give the corresponding 2ꢀbenzylꢀ4ꢀsilylꢀ1ꢀnaphthol derivative (2ha) (entry 10). During
the reaction, the TES group was partially cleaved probably by the nucleophilic attack of the chloride
anion derived from FeCl3 on the silicon atom, and the 2ꢀbenzylꢀ4ꢀhydroꢀ1ꢀnaphthol derivative (2hb
shown in eq. 1) was obtained as a byproduct. The use of FeBr3 as a stronger Lewis acid could complete
the subsequent cleavage of the TES group after the formation of 2ha to give 2hb as the sole product (eq.
1). The stability of the TESꢀAr bond strongly depended on the characteristic feature of the product, and
the FeCl3ꢀcatalyzed reaction of 1b in the presence of Nꢀphenyl indole and the 6,7ꢀbismethoxyꢀ4ꢀsilyl
substituent (1c) with 1,3,5ꢀtrimethoxybenzene provided the desilylated products (2i and 2j) (entries 11
and 13), while the TES group remained during the reaction using benzofuran (entry 12).
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Table 2. 2ꢀArylmethylꢀ1ꢀnaphthol syntheses.
R1
arene or dienophile (4 equiv.)
FeCl3 (5 mol%)
R2
O
Product
(CH2Cl)2, rt, 0.5 h
R2
1
OTBS
entry
1
substrate
R1
arene or
dienophile
product
R2
Me
H (1a)
2b: 71%
2c: 55%
2
Me
Me
H (1a)
H (1a)
3a
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2d: 83%
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5
4a
Me
H (1a)
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7
2e: 47%
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Me
Me
Me
H (1a)
H (1a)
H (1a)
2f: 64%
3a: 74%
3b: 90%
8b
Me
H (1a)
3c: 77%
2g: 34%
2ha: 75%
9a
Me
H (1a)
H (1b)
H (1b)
H (1b)
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11
12b
TES
TES
TES
2i: 72%
3d: 14%
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1
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13
TES
MeO (1c)
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7
2j: 63%
a 2 equiv. of arene were used. b For 2 h.
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While the reaction of the 4ꢀalkylꢀ or silylꢀ1ꢀsiloxymethyl substrates (1) and nucleophilic arenes gave
the 2ꢀbenzylꢀ1ꢀnaphthol derivatives (2) (Tables 1 and 2), the 4ꢀbenzylꢀ1ꢀnaphthol derivative (5a) was
obtained by the use of 1ꢀtertꢀbutyldimethylsiloxymethylꢀ1,4ꢀepoxyꢀ1,4ꢀdihydronaphthalene (4a) as a 4ꢀ
unsubstituted substrate with 1,3,5ꢀtrimethoxybenzene (Table 3). BF3•Et2O was an effective Lewis acid
catalyst in comparison to FeCl3 and AuCl3 (Entries 3 vs. 1 and 2). Although the catalytic use (5 mol%)
of trifluoroacetic acid (TFA) as a Brønsted acid was less effective (Entry 4), the stoichiometric amount
(1 equiv.) of TFA efficiently facilitated the desired reaction to give 5a in 78% yield (Entry 5).
Intriguingly, the reaction using trifluoroacetic anhydride (TFAA: 1 equiv.) as a neutral additive also
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effectively provided 5a in quantitative yield
accompanied by the formation of 2ꢀ
trifluoromethylcarbonylꢀ1,3,5ꢀtrimethoxybenzene (9: 37% yield) (Entry 6), which indicated that TFA
(ca. 40 mol%) was gradually generated as a consequence of the trifluoroacetylation and moderately
facilitated the desired reaction in the presence of an excessive amount of 1,3,5ꢀtrimethoxybenzene (see
Scheme 2). Furthermore, the reaction efficiency became significantly diminished with the decreasing
amount of the use of TFA or TFAA, and the substrate was never completely consumed even after 24 h
(Entries 7 and 8). Meanwhile, the equivalent use of acetic anhydride (Ac2O) instead of TFAA was not
effective (Entry 9).
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Table 3. Reaction using 1ꢀsiloxymethyl substrate (1b).
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entry
reagent
FeCl3
AuCl3
BF3•Et2O
TFA
TFA
TFAA
TFA
X
5
5
5
time (h)
0.5
0.5
0.5
24
2
2
24
24
yield (%)
37
61
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3
4
5
6
7
8
9
80
5
trace
78
100
100
40
40
100
quant.a
71b
TFAA
Ac2O
65c
24
no reaction
a
37% of 1ꢀtrifluoroacetylꢀ2,4,6ꢀtrimethoxybenzene (9;
b
Scheme 2) was obtained as a byproduct. 29% of 4a was
c
recovered.
15% of 4a was recovered.; TFAA:
trifluoroacetic anhydride, TFA: trifluoroacetic acid.
The reactions of various 4ꢀunsubstitutedꢀ1ꢀsiloxymethyl substrates (4) and arenes were applicable
under the TFAAꢀmediated reaction conditions (Table 4). 1ꢀMethoxynaphthalene, 2ꢀmethoxynaphthalene
and Nꢀphenyl indole were reacted with 4a to give the corresponding 4ꢀ(hetero)arylmethylꢀ1ꢀnaphthol
derivatives (5bꢀd) (Entries 1ꢀ3) and the substrate possessing bromines at the 6 and 7 positions (4b) was
also applied to provide the 6,7ꢀdibromoꢀ1ꢀnaphthol derivative (5e) (Entry 4). Meanwhile, benzofuran
and benzothiophene as the nucleophiles were insufficient for the reactions using 4a to give the complex
mixtures.
Table 4. 4ꢀArylmethylꢀ1ꢀnaphthol syntheses.
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1
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entry
1
R
arene
product
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H (4a)
5b: 74% (2 h)
2
H (4a)
5c: 36% (2 h)
[30% (2.5 h)]a
3
4
H (4a)
5d: quant. (3 h)
5e: 52% (3 h)
Br (4b)
a BF3•Et2O (5 mol%) was used instead of TFAA.
The TFAAꢀmediated system could be adapted for the reaction of the 4ꢀalkyl or silyl 1ꢀsiloxymethyl
substrates (1), and the comparative study for the reaction efficiency using the catalytic FeCl3 are both
described by eqs. 2ꢀ5. The reaction efficiency by the addition of TFAA was strongly affected by the
property and combination of the substrate (1) and arene/dienophile. While the yields of the products (2a
and 2f) derived from 1a and 1,3,5ꢀtrimethoxybenzene or Nꢀphenyl indole were improved (eqs. 2 and 3)
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using a stoichiometric amount of TFAA, the reaction efficiency between 1a and benzofuran or 1b and
Nꢀphenyl indole slightly decreased (eqs. 4 and 5).
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The reactions using the 4ꢀsubstituted and unsubstituted substrates can proceed via the different
carbocation intermediates (Scheme 2). The 1,4ꢀepoxy moiety of the 4ꢀmethylated substrate (1a) is siteꢀ
selectively cleaved via a fiveꢀmembered transition state by the coordination between two oxygen atoms
of the 1,4ꢀepoxy moiety and the siloxy group to give the carbocation intermediate C. The subsequent
rearrangement of the siloxymethyl group to the 2 position (C→D) and the aromatization provides a 2ꢀ
siloxymethylꢀ1ꢀnaphthol intermediate (E).20 The further FeCl3ꢀcatalyzed elimination of the siloxy
group21 gives oꢀNQM (A), which reacts with an arene by nucleophilic attack or a dienophile via the
[4+2]ꢀcycloaddition into the corresponding 2ꢀbenzylꢀ1ꢀnaphthol or the condensed heterocyclic arene
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derivative, respectively. Among the coupling partners bearing olefin moieties connected to the benzene
nucleus, benzofuran, indene, styrene and benzothiophene preferentially act as dienophiles towards oꢀ
NQM, while the indole derivatives possessing the relatively high nucleophilicity promote the 1,4ꢀ
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addition of the α,βꢀunsaturated carbonyl moiety of oꢀNQM. Furthermore, HCl derived from FeCl3 can
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also catalyze the present reactions. On the other hand, TFA generated by the reaction of TFAA and an
arene facilitates the ring opening of the 1ꢀunsubstituted substrate (4a) to give two different carbocation
intermediates (F and G). The favorable tertꢀcarbocation (G) was formed and undergoes a hydride shift
to the neighboring 2ꢀposition. The following aromatization gives the 4ꢀsiloxymethylꢀ1ꢀnaphthol
intermediate (I).20 The pꢀNQM can be generated by the subsequent acidꢀcatalyzed elimination of the
siloxy group21 and reacts with an arene to give the corresponding 4ꢀbenzylꢀ1ꢀnaphthol derivative.
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Scheme 2. Proposed reaction mechanism for the formation of orthoꢀ and
paraꢀnaphthoquinone methides. TFAA: trifluoroacetic anhydride, TFA:
trifluoroacetic acid, NQM: naphthoquinone methide.
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It is noteworthy that the FeCl3ꢀcatalyzed double functionalizations via both the oꢀ and pꢀNQMs
derived from the 1,4ꢀbis(siloxymethyl) 1,4ꢀepoxyꢀ1,4ꢀdihydronaphthalenes (6) gave the corresponding
bifunctionalized products (7 and 8) (Table 5). The simple substrate (6a) could be transformed into the
1,4ꢀbis(arylmethyl)ꢀ1ꢀnaphthol derivative (7aꢀc) in the presence of 1,3,5ꢀtrimethoxybenzene, 1ꢀ
methoxynaphthalene or Nꢀphenyl indole as an arene nucleophile (Entries 1ꢀ3). The reaction of 6a and
benzofuran provided a highly functionalized heterocycle (8a) by the nucleophilic attack on the pꢀNQM
and the [4+2]ꢀcycloaddition to the oꢀNQM (Entry 4). The unsymmetrical substrate (6b) bearing a
methoxy group on the aromatic nucleus could also be siteꢀselectively converted to the corresponding
1,4ꢀbis(arylmethyl)ꢀ1ꢀnaphthol derivative (7d) or fused heterocyclic product (8b) in the presence of
1,3,5ꢀtrimethoxybenzene or benzofuran, respectively (Entries 5 and 6).22
Table 5. Double functionalization of 1,4ꢀsiloxymethyl substrate.
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entry substrate
arene
product
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1
R1, R2 = H (6a)
7a: 65% (77%)a
2
R1, R2 = H (6a)
7b: 84%
N
Ph
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R1, R2 = H (6a)
N
Ph
OH
7c: 68%
R1, R2 = H (6a)
8a: 54%
7d: 72%
R1 = H
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R2 = MeO (6b)
R1 = H
R2 = MeO (6b)
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8b: 21%
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a TFAA (1 equiv.) for 2 h was used instead of FeCl3.
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Two possible reaction mechanisms are considered (Scheme 3). First, the FeCl3ꢀcatalyzed ringꢀ
opening reaction of the 1,4ꢀepoxy moiety of the substrate (6a), the subsequent rearrangement and
aromatization produced the 1,4ꢀdisiloxymethylꢀ1ꢀnaphthol (J) intermediate as shown in Scheme 2. oꢀ
NQM (K) is then initially generated to provide a 2ꢀbenzylꢀ1ꢀnaphthol, which is transformed into pꢀ
NQM (L). Alternatively, the reaction via the initial generation of pꢀNQM (M) is also plausible.
Scheme 3. Proposed reaction mechanisms of the double functionalization.
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In conclusion, we have developed a selective preparation method of the reactive oꢀ and pꢀNQM
intermediates by the substitution effect at the 4ꢀposition of the 1ꢀtertꢀbutyldimethylsiloxymethylꢀ1,4ꢀ
epoxyꢀ1,4ꢀdihydronaphthalenes as substrates. The selective transformation to oꢀNQM could be achieved
by the introduction of an alkyl or silyl substituent at the 4ꢀposition, while the 4ꢀunsubstituted substrate
was converted to pꢀNQM. The combination of the nucleophilic attack of arenes on the oꢀ and/or pꢀ
NQMs and [4+2]ꢀcycloaddition of dienophiles with oꢀNQM could construct various types of
pharmaceutically useful biarylmethanes (2ꢀbenzylꢀ1ꢀnaphthol, 4ꢀbenzylꢀ1ꢀnaphthol and 2,4ꢀbisbenzylꢀ1ꢀ
naphthol derivatives) and highly functionalized fused heteroaromatic arenes, respectively.
EXPERIMENTAL SECTION
1. General Information
All reactions were performed in ovenꢀdried glassware under argon. Anhydrous (CH2Cl)2 as a solvent was
purchased from a commercial source and used without further purification. Flash column chromatography was
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performed with silica gel. 1H and 13C NMR spectra were recorded at room temperature in CDCl3 or CD3OD as a
solvent and internal standard (1H NMR: δ= 7.26; 13C NMR:δ= 77.0 for CDCl3; 1H NMR: δ = 3.4, 4.8; 13C NMR:
δ = 49.3 for CD3OD) with tetramethylsilane as an internal standard. ESI high resolution mass spectra (HRMS)
were measured by ITꢀTOF.
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2. Procedures to prepare the substratesand their spectroscopic data.
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Substrates (1a and 6a) were prepared according to reference 12.
2ꢀ1. Synthetic procedure of 5ꢀtertꢀButyldimethylsiloxymethylꢀ2ꢀtriethylsilylfuran.
Step 1: To a solution of the 2ꢀtriethylsilylfuran (1.82 g, 10.0 mmol) in anhydrous DMF (30mL) was added
o
o
POCl3 (1.0 mL, 10.8 mmol) at 0 C. The reaction mixture was subsequently heated at 95 C. After being stirred
for 5 h, the reaction mixture was cooled to room temperature and 4N NaOH aq. (25 mL) was added for the
hydrolysis. After dilution with AcOEt, the organic layer was washed with water, dried with Na2SO4 and filtrated.
The filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography using
hexane–AcOEt (10/1) as a eluent to give 5ꢀformylꢀ2ꢀtriethylsilylfuran (1.25 g, 5.92 mmol) in 59 % yield.
5ꢀFormylꢀ2ꢀtriethylsilylfuran: Colorless oil; IR (ATR) cmꢀ1: 2956, 2877, 1683, 1560, 1461, 1106, 1019, 805,
760; 1H NMR (400 MHz, CDCl3): δ 9.69 (s, 1H), 7.22 (d, J = 3.6 Hz, 1H), 6.76 (d, J = 3.6 Hz, 1H), 1.00 (t, J =
7.2 Hz, 9H), 0.83 (q, J = 7.2 Hz, 6H); 13C NMR (100 MHz, CDCl3): δ178.0, 167.1, 156.4, 122.5, 120.5, 7.2, 2.9;
ESIꢀHRMS m/z: 233.0963 ([M+Na]+); Calcd for C11H18O2SiNa: 233.0968.
Step 2: To a solution of 5ꢀformylꢀ2ꢀtriethylsilylfuran (1.21 g, 5.75 mmol) in MeOH (5 mL) was added sodium
borohydride (262 mg, 6.91mmol) at 0 oC. The reaction mixture was subsequently stirred at room temperature for
12 h. The reaction was quenched with water. After MeOH was removed in vacuo, the residue was diluted with
AcOEt, dried with Na2SO4 and filtrated. The filtrate was concentrated in vacuo. The residue was purified by
silica gel column chromatography using hexane–AcOEt (10/1) as a eluent to give 5ꢀhydroxymethylꢀ2ꢀ
triethylsilylfuran (1.13 g, 5.32 mmol) in 93 % yield.
5ꢀHydroxymethylꢀ2ꢀtriethylsilylfuran: Colorless oil; IR (ATR) cmꢀ1: 3310, 2954, 2876, 1459, 1415, 1238,
1180, 1012, 792, 723; 1H NMR (400 MHz, CDCl3): δ 6.58 (d, J = 3.6 Hz, 1H), 6.27 (d, J = 3.6 Hz, 1H), 4.63 (d,
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J = 5.6 Hz, 2H), 1.72 (t, J = 5.6 Hz, 1H), 0.98 (t, J = 8.0 Hz, 9H), 0.76 (q, J = 8.0 Hz, 6H); 13C NMR (100 MHz,
CDCl3): δ 158.7, 158.1, 121.5, 107.5, 57.8, 7.3, 3.2; ESIꢀHRMS m/z: 211.1163 ([MꢀH]ꢀ); Calcd for C11H19O2Si:
211.1160.
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Step 3: To a solution of the 5ꢀhydroxymethylꢀ2ꢀtriethylsilylfuran (1.14 g, 5.36 mmol) in anhydrous DMF (10
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mL) was added imidazole (552 mg, 8.10 mmol in 5 ml of anhydrous DMF) at 0 C. The reaction mixture was
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stirred at room temperature for 0.5 h. TBSCl (1.22 g, 8.09 mmol in 5 ml of anhydrous DMF) was subsequently
added at 0 oC. The reaction mixture was stirred at room temperature for 19 h. The reaction mixture was quenched
with sat. NaHCO3 and extracted with diethyl ether. The obtained organic layers were dried over Na2SO4 and
concentrated in vacuo. The residue was purified by silica gel column chromatography using hexane–AcOEt
(45/1) as a eluent to give 5ꢀtertꢀbutyldimethylsiloxymethylꢀ2ꢀtriethylsilylfuran (1.57 g, 4.81 mmol) in 90 % yield.
5ꢀtertꢀButyldimethylsiloxymethylꢀ2ꢀtriethylsilylfuran: Colorless oil; IR (ATR) cmꢀ1: 2954, 1462, 1254,
1
1080, 834, 720; H NMR (400 MHz, CDCl3): δ 6.55 (d, J = 3.2Hz, 1H), 6.21 (d, J = 3.2Hz, 1H), 4.67 (s, 2H),
0.98 (t, J = 8.4Hz, 9H), 0.90 (s, 9H), 0.78―0.72 (m, 6H), 0.07 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 158.5,
157.8, 121.3, 107.1, 58.4, 25.8, 18.4, 7.3, 3.2, ꢀ5.2; ESIꢀHRMS m/z: 349.1981 ([M+Na]+); Calcd for
C17H34O2Si2Na: 349.1990.
2ꢀ2. Synthetic procedure of 1b.
To a solution of the 5ꢀtertꢀbutyldimethylsiloxymethylꢀ2ꢀtriethylsilylfuran (170 mg, 0.52 mmol) in anhydrous
THF (10 mL) was added anthranilic acid (105 mg, 0.79 mmol in 10 mL of anhydrous THF) and isoamylnitrite
o
(0.20 mL, 1.50 mmol in 10 mL of anhydrous THF) at 95 C. After being stirred for 1ꢀ2 h, the reaction mixture
was cooled to room temperature and water was added. After dilution with diethylether, the organic layers were
washed with sat. NaHCO3, dried with Na2SO4 and filtrated. The filtrate was concentrated in vacuo. The residue
was purified by silica gel column chromatography using hexane–AcOEt (30/1) as a eluent to give 1b (119 mg,
0.30 mmol) in 57 % yield.
1ꢀtertꢀButyldimethylsiloxymethylꢀ4ꢀtriethylsilylꢀ1,4ꢀepoxyꢀ1,4ꢀdihydoronaphthalene (1b); Yellow oil; IR
1
(ATR) cmꢀ1: 2953, 1462, 1253, 1097, 1006, 835, 752; H NMR (500 MHz, CDCl3): δ 7.26 (dd, J = 6.0, 2.0 Hz,
1H), 7.15 (dd, J = 6.0, 2.0 Hz, 1H), 6.97―6.89 (m, 4H), 4.45 (d, J = 10.5 Hz, 1H), 4.27 (d, J = 10.5 Hz, 1H),
13
1.04 (t, J = 8.0 Hz, 9H), 0.93 (s, 9H), 0.84 (q, J = 8.0 Hz, 6H), 0.13 (s, 6H); C NMR (125 MHz, CDCl3):δ
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154.7, 151.2, 147.6, 142.6, 124.2, 124.1, 120.1, 119.8, 93.1, 85.9, 61.8, 25.8, 18.3, 7.6, 2.6, ꢀ5.3; ESIꢀHRMS m/z:
425.2312 ([M+Na]+); Calcd for C23H38O2Si2Na: 425.2303.
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2ꢀ3. Synthetic procedure of 1c.
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To a solution of 5ꢀtertꢀbutyldimethylsiloxymethylꢀ2ꢀtriethylsilylfuran (1.30g, 3.98 mmol) and 1,2ꢀdibromoꢀ4,5ꢀ
dimethoxybenzen (590 mg, 1.99 mmol) in anhydrous THF (10 mL) was added 1.0 mL (2.6mmol) of nꢀBuLi (2.6
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M in hexanes) at –78 C. After being stirred until reaction was completed, the reaction mixture was added to
water, diluted with diethyl ether and washed with brine. After the solution was dried over Na2SO4 and filtrated,
the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography using
hexane–AcOEt (15/1) as a eluent to give 1c (47mg, 0.10 mmol) in 5 % yield.
1ꢀtertꢀButyldimethylsiloxymethyꢀ6,7ꢀdimethoxyꢀlꢀ4ꢀtriethylsilylꢀ1,4ꢀepoxyꢀ1,4ꢀdihydoronaphthalene (1c);
Yellow pale oil; IR (ATR) cmꢀ1:2952, 1463, 1324, 1247, 1209, 1119, 1096, 834, 777, 730, 691; 1H NMR (400
MHz, CDCl3): δ 7.04 (s, 1H), 6.98 (d, J = 5.6 Hz, 1H), 6.95 (d, J = 5.6 Hz, 1H), 6.85 (s, 1H), 4.40 (d, J = 11.2
Hz, 1H), 4.27 (d, J = 11.2 Hz, 1H), 3.83 (s, 3H), 3.82 (s, 3H), 1.05 (t, J = 8.0 Hz, 9H), 0.94 (s, 9H), 0.84 (q, J =
8.0 Hz, 6H), 0.14 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 148.0, 147.3, 145.3, 145.0, 144.3, 143.0, 107.4, 106.7,
93.2, 86.2, 62.0, 56.8, 56.2, 25.8, 18.2, 7.6, 2.6, ꢀ5.4; ESIꢀHRMS m/z: 461.2550 ([MꢀH]ꢀ); Calcd for C25H41O4Si2:
461.2549.
2ꢀ4. Synthetic procedure of 4a.
To a solution of the 2ꢀtertꢀbutyldimethylsiloxymethylfuran (1.06 g, 4.99 mmol; synthesized accoroding to
reference 23) in anhydrous THF (20 mL) was added anthranilic acid (1.05 g, 7.66 mmol in 5 mL of anhydrous
o
THF) and isoamylnitrite (1.45 mL, 10.9 mmol in 5 mL of anhydrous THF) at 95 C. After being stirred for 5 h,
the reaction mixture was cooled to room temperature and water was added. After dilution with diethylether, the
organic layer was washed with sat. NaHCO3, dried with Na2SO4 and filtrated. The filtrate was concentrated in
vacuo. The residue was purified by silica gel column chromatography using hexane–AcOEt (30/1) as a eluent to
give 4a (0.62 g, 2.16 mmol) in 43 % yield.
1ꢀtertꢀButyldimethylsiloxymethylꢀ1,4ꢀepoxyꢀ1,4ꢀdihydoronaphthalene (4a); Colorless oil; IR (ATR) cmꢀ1:
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2928, 2856, 1254, 1137, 1006, 978, 947, 835, 777, 755; H NMR (500 MHz, CDCl3): δ 7.28―7.26 (m, 1H),
7.22―7.21 (m, 1H), 7.03 (dd, J = 6.0, 1.5 Hz, 1H), 6.97―6.95 (m, 3H), 5.69 (d, J = 1.5 Hz, 1H), 4.46 (d, J =
11.0 Hz, 1H), 4.31 (d, J = 11.0 Hz, 1H), 0.95 (s, 9H), 0.16 (s, 6H); 13C NMR (125 MHz, CD3OD): δ 152.4, 150.4,
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145.5, 144.1, 126.2, 126.2, 121.2, 121.2, 94.8, 83.7, 62.7, 26.7, 19.5, ꢀ4.9; ESIꢀHRMS m/z: 287.1474 ([MꢀH]ꢀ);
Calcd for C17H23O2Si: 287.1473.
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2ꢀ5. Synthetic procedure of 4b.
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To a solution of 2ꢀtertꢀbutyldimethylsiloxymethylfuran (779 mg, 3.67 mmol) and 1,2,4,5ꢀtetrabromobenzene
(963 mg, 2.45 mmol) in anhydrous THF (30 mL) was added 1.17 mL (3.10 mmol) of n-BuLi (2.6M in hexane) at
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–78 C. After being stirred until reaction was completed, the reaction mixture was added to water, diluted with
diethyl ether and washed with brine. After the solution was dried over Na2SO4 and filtrated, the filtrate was
concentrated in vacuo. The residue was purified by silica gel column chromatography using hexane–AcOEt
(20/1) as a eluent to give 1c (397 mg, 0.86 mmol) in 35 % yield.
1ꢀtertꢀButyldimethylsiloxymethylꢀ6,7ꢀdibromoꢀ1,4ꢀepoxyꢀ1,4ꢀdihydoronaphthalene (4b);Yellow pale oil;
IR (ATR) cmꢀ1: 2928, 1255, 1099, 834, 776, 576; H NMR (400 MHz, CDCl3): δ 7.51 (s, 1H), 7.43 (s, 1H), 7.00
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(dd, J = 5.4, 2.0 Hz, 1H), 6.92 (d, J = 5.4 Hz, 1H), 5.63 (d, J = 2.0 Hz, 1H), 4.37 (d, J = 11.6 Hz, 1H), 4.27 (d, J
= 11.6 Hz, 1H), 0.94 (s, 9H), 0.15 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 151.7, 150.7, 143.6, 142.8, 125.5,
125.1, 120.6, 120.4, 92.5, 81.6, 61.1, 25.8, 18.3, ꢀ5.4; ESIꢀHRMS m/z: 466.9648 ([M+Na]+); Calcd for
C17H22O2SiBr2Na: 466.9648.
2ꢀ6. Synthetic procedure of 6b.
To a solution of 2,5ꢀdiꢀtertꢀbutyldimethylsiloxymethylfuran (1.50 mL, 3.89 mmol) and 3,4ꢀdibromoanisole
(0.3 mL, 2.05 mmol) in anhydrous THF (10 mL) was added 1.0 mL (2.60 mmol) of n-BuLi (2.6 M in hexane) at
o
–78 C. After being stirred until reaction was completed, the reaction mixture was added to water, diluted with
diethyl ether and washed with brine. After the solution was dried with Na2SO4 and filtrated, the filtrate was
concentrated in vacuo. The residue was purified by silica gelꢀcolumn chromatography using hexane–AcOEt
(30/1) as a eluent to give 1c (159mg, 0.34 mmol) in 17 % yield.
1,4ꢀDiꢀtertꢀbutyldimethylsiloxymethylꢀ6ꢀmethoxyꢀ1,4ꢀepoxyꢀ1,4ꢀdihydoronaphthalene (6b); Colorless oil;
IR (ATR) cmꢀ1: 2928, 2856, 1464, 1254, 1206, 1097, 1005, 832, 775; 1H NMR (400 MHz, CDCl3): δ 7.11 (d, J =
8.0 Hz, 1H), 6.97 (d, J = 5.2 Hz, 1H), 6.94 (d, J = 5.2 Hz, 1H), 6.93 (d, J = 2.4 Hz, 1H), 6.41 (dd, J = 8.0, 2.4 Hz,
1H), 4.41―4.37 (m, 2H), 4.27―4.23 (m, 2H), 3.76 (s, 3H), 0.94 (s, 9H), 0.93 (s, 9H), 0.14 (s, 6H), 0.13 (s, 6H);
13C NMR (100 MHz, CDCl3): δ 157.3, 153.2, 144.3, 143.1, 142.7, 119.6, 108.8, 107.3, 92.1, 91.9, 61.7, 61.7,
55.5, 25.9, 18.3, ꢀ5.3, ꢀ5.4; ESIꢀHRMS m/z: 485.2523 ([M+Na]+); Calcd for C25H42O4Si2Na: 485.2514.
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3. General synthetic procedures of biarylmethanes and fused heterocyclic arenes.
Typical procedure using catalytic FeCl3: To a solution of the 4ꢀsubstituted 1ꢀsiloxymethylꢀ1,4ꢀepoxyꢀ1,4ꢀ
dihydronaphthalene (1: 0.2 mmol) in (CH2Cl)2 (1 mL) was added an arene (0.8 mmol) and FeCl3 (0.01 mmol: 5
mol% of the substrate) and stirred at room temperature under argon. After an adequate reaction time, the mixture
was quenched with water and extracted with CH2Cl2. The combined organic layers were dried over Na2SO4, and
concentrated in vacuo. The residue was purified by a silica gel column chromatography to give the biarylmethane
(2) or fused heterocyclic arene (3).
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Typical procedure using TFAA: To a solution of a 4ꢀsubstituted or unsubstituted 1ꢀsiloxymethylꢀ1,4ꢀepoxyꢀ
1,4ꢀdihydronaphthalene (1 or 4: 0.2 mmol) in (CH2Cl)2 (1 mL) was added an arene (0.8 mmol) and TFAA (0.2
mmol: 1 equiv. of the substrate) and stirred at room temperature under argon. After an adequate reaction time,
the mixture was quenched with water and extracted with CH2Cl2. The combined organic layers were dried over
Na2SO4, and concentrated in vacuo. The residue was purified by a silica gel column chromatography to give the
biarylmethane (2 or 5).
4. Spectroscopic data of products.
4ꢀMethylꢀ2ꢀ[(2’,4’,6’ꢀtrimethoxyphenyl)methyl]naphthalenꢀ1ꢀol (2a): 1a (60.0 mg, 0.20 mmol), FeCl3 (1.6
mg, 0.01 mmol) and (CH2Cl)2 (1.0 mL) were used, and the reaction was carried out at room temperature for 0.5 h.
After purification of the crude product by a silica gel column chromatography using hexane–AcOEt (10/1) as a
o
eluent, 2a (59.3 mg, 0.18 mmol) was obtained in 88%. Colorless solid; M.p. 122ꢀ127 C; IR (ATR) cmꢀ1: 3397,
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2932, 2838, 1591, 1204, 1111, 944, 757; H NMR (400 MHz, CDCl3): δ 8.27―8.25 (m, 1H), 7.84―7.82 (m,
1H), 7.77 (s, 1H), 7.43―7.40 (m, 2H), 7.39 (s, 1H), 6.17 (s, 2H), 3.96 (s, 2H), 3.95 (s, 6H), 3.77 (s, 3H), 2.58 (s,
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3H); C NMR (125 MHz, CDCl3):δ 159.7, 157.7, 147.9, 132.2, 130.3, 125.2, 125.1, 124.7, 124.3, 123.7, 122.6,
119.5, 109.5, 91.1, 55.9, 55.3, 23.4, 18.8; ESIꢀHRMS m/z: 361.1424 ([M+Na]+); Calcd for C21H22O4Na:
361.1410.
2ꢀ[(2’,4’ꢀDimethoxyphenyl)methyl]ꢀ4ꢀmethylnaphthalenꢀ1ꢀol (2b): 1a (56.6 mg, 0.19 mmol), FeCl3 (1.6 mg,
0.01 mmol) and (CH2Cl)2 (1.0 mL) were used, and the reaction was carried out at room temperature for 0.5 h.
After purification of the crude product by a silica gel column chromatography using hexane–AcOEt (10/1) as an
eluent, 2b (40.8 mg, 0.13 mmol) was obtained in 71%. Colorless oil; IR (ATR) cmꢀ1: 3383, 2937, 1613, 1582,
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1506, 1207, 1148, 1029, 760; H NMR (400 MHz, CDCl3): δ 8.28―8.26 (m, 1H), 7.85―7.83 (m, 1H),
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7.45―7.43 (m, 2H), 7.34 (s, 1H), 7.25 (t, J = 8.0 Hz, 1H), 7.17 (s, 1H), 6.48―6.46 (m, 2H), 3.97 (s, 3H), 3.95 (s,
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2H), 3.76 (s, 3H), 2.57 (s, 3H); C NMR (100 MHz, CDCl3): δ 159.6, 156.2, 147.5, 132.4, 130.7, 128.9, 125.8,
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125.5, 125.4, 124.7, 123.8, 122.7, 121.1, 119.7, 105.5, 98.9, 55.9, 55.4, 30.3, 18.7; ESIꢀHRMS m/z: 331.1294
([M+Na]+); Calcd for C20H20O3Na: 331.1305.
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2ꢀ[(4’ꢀMethoxyphenyl)methyl]ꢀ4ꢀmethylnaphthalenꢀ1ꢀol (2c): 1a (57.8 mg, 0.19 mmol), FeCl3 (1.6 mg, 0.01
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mmol) and (CH2Cl)2 (1.0 mL) were used, and the reaction was carried out at room temperature for 0.5 h. After
purification of the crude product by a silica gel column chromatography using hexane–AcOEt (15/1) as an eluent,
2c (28.9 mg, 0.10 mmol) was obtained in 55%. Red oil; IR (ATR) cmꢀ1: 3501, 2926, 1510, 1387, 1245, 1033,
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759; H NMR (400 MHz, CDCl3): δ 8.15―8.12 (m, 1H), 7.93―7.91 (m, 1H), 7.52―7.45 (m, 2H), 7.17 (d, J =
8.8 Hz, 2H), 7.12 (s, 1H), 6.84 (d, J = 8.8 Hz, 2H), 4.99 (s, 1H), 4.07 (s, 2H), 3.78 (s, 3H), 2.61 (s, 3H);13C NMR
(100 MHz, CDCl3): δ 158.4, 147.5, 132.5, 131.2, 129.5, 129.3, 126.4, 125.5, 125.1, 125.0, 124.1, 121.7, 119.6,
114.3, 55.3, 36.0, 18.7; ESIꢀHRMS m/z: 277.1237 ([MꢀH]ꢀ); Calcd for C19H17O2: 277.1234.
2ꢀ[(1’ꢀMethoxynaphthalenꢀ4’ꢀyl)methyl]ꢀ4ꢀmethylnaphthalenꢀ1ꢀol (2d): 1a (62.0 mg, 0.20 mmol), FeCl3 (1.6
mg, 0.01 mmol) and (CH2Cl)2 (1.0 mL) were used, and the reaction was carried out at room temperature for 0.5 h.
After purification of the crude product by a silica gel column chromatography using hexane–AcOEt (10/1) as an
eluent, 2d (61.8 mg, 0.17 mmol) was obtained in 83%. Red oil; IR (ATR) cmꢀ1: 3480, 2932, 1583, 1461, 1386,
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1268, 1089, 906, 756; H NMR (400 MHz, CDCl3): δ 8.33―8.30 (m, 1H), 8.16―8.13 (m, 1H), 8.01―7.99 (m,
1H), 7.91―7.89 (m, 1H), 7.50―7.43 (m, 4H), 7.11 (d, J = 8.0 Hz, 1H), 7.08 (s, 1H), 6.64 (d, J = 8.0 Hz, 1H),
5.22 (s, 1H), 4.42 (s, 2H), 3.93 (s, 3H), 2.56 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 154.9, 147.7, 132.8, 132.5,
129.2, 126.8, 126.4, 126.4,126.2, 126.0, 125.5, 125.3, 125.1, 125.0, 124.1, 123.6, 122.7, 121.8, 118.6, 103.3,
55.4, 33.7, 18.8,;ESIꢀHRMS m/z: 351.1365 ([M+Na]+); Calcd for C23H20O2Na: 351.1356.
2ꢀ[(2’ꢀMethoxynaphthalenꢀ1’ꢀyl)methyl]ꢀ4ꢀmethylnaphthalenꢀ1ꢀol (2e): 1a (31.2 mg, 0.10 mmol), FeCl3 (0.8
mg, 0.005 mmol) and (CH2Cl)2 (0.5 mL) were used, and the reaction was carried out at room temperature for 0.5
h. After purification of the crude product by a silica gel column chromatography using hexane–AcOEt (10/1) as
an eluent, 2e (18.6 mg, 0.05 mmol) was obtained in 47%. Colorless oil; IR (ATR) cmꢀ1: 3352, 2938, 1579, 1512,
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1465, 1386, 1247, 1079, 807, 760; H NMR (400 MHz, CDCl3): δ 8.36 (d, J = 8.8 Hz, 1H), 8.26―8.24 (m, 1H),
7.83―7.76 (m, 4H), 7.56 (dt, J = 7.2, 1.6 Hz, 1H), 7.44―7.39 (m, 3H), 7.36 (t, J = 7.2 Hz, 1H), 7.32 (d, J = 8.8
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Hz, 1H), 4.50 (s, 2H), 4.14 (s, 3H), 2.56 (s, 3H); C NMR (100 MHz, CDCl3): δ 152.6, 148.4, 133.1, 132.3,
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130.0, 129.4, 128.8, 128.7, 126.8, 125.4, 125.3, 124.6, 123.9,123.8, 123.8, 123.7, 122.6, 121.3, 118.4, 112.9,
57.1, 26.2, 18.8; ESIꢀHRMS m/z: 327.1377 ([MꢀH]ꢀ); Calcd for C23H19O2: 327.1391.
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3ꢀ[(1’ꢀHydroxyꢀ4’ꢀmethylnaphthalenꢀ2’ꢀyl)methyl]ꢀNꢀphenylindole (2f): 1a (59.7 mg, 0.19 mmol), FeCl3 (1.5
mg, 0.01 mmol) and (CH2Cl)2 (1.0 mL) were used, and the reaction was carried out at room temperature for 0.5 h.
After purification of the crude product by a silica gel column chromatography using hexane–AcOEt (10/1) as an
eluent, 2f (44.1 mg, 0.12 mmol) was obtained in 64%. Yellow oil; IR (ATR) cmꢀ1: 3469, 3063, 1596, 1499, 1455,
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1218, 907, 734, 696; H NMR (400 MHz, CDCl3): δ 8.17 (dd, J = 7.6, 2.0 Hz, 1H), 7.91 (dd, J = 7.6, 2.0 Hz,
1H), 7.62 (d, J = 8.0 Hz, 1H), 7.54 (d, J = 8.0 Hz, 1H), 7.49―7.38 (m, 6H), 7.27―7.20 (m, 3H), 7.14 (t, J = 8.0
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Hz, 1H), 7.04 (s, 1H), 5.42 (s, 1H), 4.24 (s, 2H), 2.61 (s, 3H); C NMR (100 MHz, CDCl3): δ 147.9, 139.4,
136.6, 132.5, 129.5, 129.2, 128.5, 126.3, 126.3, 125.5, 125.2, 124.9, 124.1, 124.0, 123.0, 121.9, 120.3, 119.5,
118.4, 114.4, 110.7, 27.2, 18.8; ESIꢀHRMS m/z: 386.1511 ([M+Na]+); Calcd for C26H21NONa: 386.1515.
2ꢀ[(1’ꢀHydroxyꢀ4’ꢀmethylnaphthalenꢀ2’ꢀyl)methyl]ꢀbenzo[b]thiophene (2g): 1a (61.4 mg, 0.20 mmol), FeCl3
(1.6 mg, 0.01 mmol) and (CH2Cl)2 (1.0 mL) were used, and the reaction was carried out at room temperature for
0.5 h. After purification of the crude product by a silica gel column chromatography using hexane–AcOEt (20/1)
as an eluent, 2g (21.5 mg, 0.07 mmol) was obtained in 34%. Red oil; IR (ATR) cmꢀ1: 3494, 3066, 1580, 1425,
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1385, 1201, 906, 753, 725; H NMR (500 MHz, CDCl3): δ 8.15 (dd, J = 7.5, 2.0 Hz, 1H), 7.93 (dd, J = 7.5, 2.0
Hz, 1H), 7.86―7.84 (m, 1H), 7.81―7.79 (m, 1H), 7.51 (dt, J = 7.0, 2.0 Hz, 1H), 7.49 (dt, J = 7.0, 2.0 Hz, 1H),
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7.38―7.34 (m, 2H), 7.15 (s, 1H), 6.98 (s, 1H), 5.15 (s, 1H), 4.27 (s, 2H), 2.59 (s, 3H); C NMR (125 MHz,
CDCl3): δ 147.5, 140.9, 138.5, 133.9, 132.6, 129.0, 126.7, 125.7, 125.1, 125.0, 124.6, 124.2, 124.2, 123.1, 122.9,
121.9, 121.6, 117.6, 30.2, 18.8; ESIꢀHRMS m/z: 303.0852 ([MꢀH]ꢀ); Calcd for C20H15OS: 303.0849.
4ꢀTriethylsilylꢀ2ꢀ[(2’,4’,6’ꢀTrimethoxyphenyl)methyl]ꢀnaphthalenꢀ1ꢀol (2ha): 1b (58.3 mg, 0.14 mmol),
FeCl3 (1.2 mg, 0.007 mmol) and (CH2Cl)2 (1.0 mL) were used, and the reaction was carried out at room
temperature for 0.5 h. After purification of the crude product by a silica gel column chromatography using
hexane–AcOEt (10/1) as an eluent, 2ha (46.1 mg, 0.11 mmol) was obtained in 75%. Colorless solid; M.p. 119ꢀ
121 C; IR (ATR) cmꢀ1: 3387, 2943, 1593, 1327, 1142, 1104, 758, 723; H NMR (400 MHz, CDCl3): δ
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2H), 3.94 (s, 6H), 3.78 (s, 3H), 0.98 (s, 15H); C NMR (100 MHz, CDCl3): δ 159.8, 157.8, 151.0, 139.3, 137.7,
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127.3, 125.3, 125.0, 124.1, 124.0, 122.9, 119.1, 109.4, 91.1,55.9, 55.4, 23.8, 7.8, 4.7, 0.0; ESIꢀHRMS m/z:
461.2126 ([M+Na]+); Calcd for C26H34O4SiNa: 461.2119.
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2ꢀ[(2’,4’,6’ꢀTrimethoxyphenyl)methyl]ꢀnaphthalenꢀ1ꢀol (2hb): 1b (81.8 mg, 0.20 mmol), FeBr3 (3.0 mg, 0.01
mmol) and (CH2Cl)2 (1.0 mL) were used, and the reaction was carried out at room temperature for 3.0 h. After
purification of the crude product by a silica gel column chromatography using hexane–AcOEt (5/1) as an eluent,
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2hb (42.7 mg, 0.13 mmol) was obtained in 66%. Colorless solid; M.p. 122ꢀ126 C; IR (ATR) cmꢀ1: 3377, 2940,
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1591, 1452, 1142, 1110, 944, 781; H NMR (400 MHz, CDCl3): δ 8.24―8.21 (m, 1H), 7.94 (s, 1H), 7.70―7.69
(m, 1H), 7.55 (d, J = 8.4 Hz, 1H), 7.40―7.35 (m, 2H), 7.30 (d, J = 8.4 Hz, 1H), 6.16 (s, 2H), 3.99 (s, 2H), 3.93
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(s, 6H), 3.76 (s, 3H); C NMR (100 MHz, CDCl3): δ 159.9, 157.9, 149.7, 133.6, 130.1, 127.2, 125.4, 125.2,
124.7, 122.3, 120.1, 119.0, 109.5, 91.3, 56.1, 55.5, 23.7;ESIꢀHRMS m/z: 347.1256 ([M+Na]+); Calcd for
C20H20O4Na: 347.1254.
3ꢀ[(1’ꢀHydroxynaphthalenꢀ2’ꢀyl)methyl]ꢀNꢀphenylindol (2i): 1b (81.0 mg, 0.20 mmol), FeCl3 (1.6 mg, 0.01
mmol) and (CH2Cl)2 (1.0 mL) were used, and the reaction was carried out at room temperature for 0.5 h. After
purification of the crude product by a silica gel column chromatography using hexane–AcOEt (10/1) as an eluent,
2i (69.2 mg, 0.15 mmol) was obtained in 72%. Red oil; IR (ATR) cmꢀ1: 3052, 2292, 1657, 1594, 1499, 1455,
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1329, 906, 727; H NMR (400 MHz, CDCl3): δ 8.16―8.13 (m, 1H), 8.04―8.02 (m, 1H), 7.75―7.70 (m, 2H),
7.56 (t, J = 7.2 Hz, 2H), 7.53―7.46 (m, 5H), 7.37―7.33 (m, 1H), 7.28 (s, 1H), 7.23 (dt, J = 8.0, 1.2 Hz, 1H),
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7.16 (dt, J = 8.0, 1.2 Hz, 1H), 6.73 (s, 1H), 4.11 (s, 2H); C NMR (100 MHz, CDCl3): δ 185.4, 185.3, 150.2,
136.2, 139.5, 135.3, 133.7, 133.6, 132.3, 132.2, 129.6, 128.4, 127.2, 126.6, 126.4, 126.1, 124.2, 122.8, 120.4,
119.1, 111.6, 110.8, 25.2; ESIꢀHRMS m/z: 348.1392 ([MꢀH]ꢀ); Calcd for C25H18NO: 348.1394.
6,7ꢀDimethoxyꢀ2ꢀ[(2’,4’,6’ꢀtrimethoxyphenyl)methyl]ꢀnaphthalenꢀ1ꢀol (2j): 1c (47.0 mg, 0.10 mmol), FeCl3
(0.8 mg, 0.005 mmol) and (CH2Cl)2 (0.5 mL) were used, and the reaction was carried out at room temperature for
0.5 h. After purification of the crude product by a silica gel column chromatography using hexane–AcOEt (5/1)
as an eluent, 2j (24.1 mg, 0.06 mmol) was obtained in 63% Yellow oil; IR (ATR) cmꢀ1:3381, 2940, 2836, 1609,
1953, 1510, 1487, 1456, 1253, 1230, 1156, 1111, 728; 1H NMR (400 MHz, CDCl3): δ 7.89 (s,1H), 7.51 (s, 1H),
7.42 (d, J = 8.0 Hz, 1H), 7.15 (d, J = 8.0 Hz, 1H), 7.01 (s, 1H), 6.16 (s, 2H), 4.00 (s, 3H), 3.96 (s, 2H), 3.95 (s,
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3H), 3.94 (s, 6H), 3.76 (s, 3H); C NMR (125 MHz, CDCl3): δ 159.7, 157.7, 149.0, 148.7, 148.5, 129.2, 128.3,
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120.0, 118.8, 117.5, 109.5, 105.8, 101.1, 91.1, 55.9, 55.8, 55.7, 55.4, 23.5; ESIꢀHRMS m/z: 407.1456 ([M+Na]+);
Calcd for C22H24O6Na: 407.1465.
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Product 3a: 1a (57.2 mg, 0.19 mmol), FeCl3 (1.5 mg, 0.01 mmol) and (CH2Cl)2 (1.0 mL) were used, and the
reaction was carried out at room temperature for 0.5 h. After purification of the crude product by a silica gel
column chromatography using hexane–AcOEt (20/1) as an eluent, 3a (40.4 mg, 0.14 mmol) was obtained in 74%.
Pale yellow solid; M.p.116ꢀ117oC; IR (ATR) cmꢀ1: 2891, 1596, 1509, 1417, 1241, 1178, 1148, 1096, 1013, 743;
1H NMR (400 MHz, CDCl3): δ 8.14―8.12 (m, 1H), 7.86―7.83 (m, 1H), 7.58 (d, J = 6.8 Hz, 1H), 7.43 (t, J = 3.8
Hz, 1H), 7.40 (t, J = 3.8 Hz, 1H), 7.12 (dt, J = 7.8, 1.2 Hz, 1H), 7.09 (s, 1H), 6.86 (t, J = 7.6 Hz, 1H), 6.66 (d, J =
8.0 Hz, 1H), 5.92 (d, J = 7.6 Hz, 1H), 5.42―5.39 (m, 1H), 3.29 (dd, J = 15.6, 4.2 Hz, 1H), 3.23 (dd, J = 15.6, 4.2
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Hz, 1H), 2.57 (s, 3H); C NMR (100 MHz, CDCl3): δ 160.7, 148.5, 132.3, 130.9, 127.8, 127.5, 126.3, 126.1,
125.9, 125.4, 125.1, 124.0, 121.7, 120.9, 117.6, 109.9, 82.8, 79.3, 29.1, 18.8; ESIꢀHRMS m/z: 287.1081([MꢀH]ꢀ);
Calcd for C20H15O2: 287.1078.
Product 3b: 1a (60.8 mg, 0.20 mmol), FeCl3 (1.6 mg, 0.01 mmol) and (CH2Cl)2 (1.0 mL) were used, and the
reaction was carried out at room temperature for 0.5 h. After purification of the crude product by a silica gel
column chromatography using hexane–AcOEt (30/1) as an eluent, 3b (51.4 mg, 0.18 mmol) was obtained in 90%.
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Colorless oil; IR (ATR) cmꢀ1: 2931, 1582, 1417, 1107, 755, 730; H NMR (400 MHz, CDCl3): δ 8.27―8.25 (m,
1H), 7.86―7.83 (m, 1H), 7.59―7.58 (m, 1H), 7.44―7.42 (m, 2H), 7.23―7.21 (m, 3H), 6.97 (s, 1H), 5.64 (d, J
= 6.4 Hz, 1H), 3.14―3.00 (m, 3H), 2.85―2.80 (m, 1H), 2.66―2.60 (m, 1H), 2.55 (s, 3H);13C NMR (100 MHz,
CDCl3): δ 148.4, 143.0, 142.5, 132.1, 128.6, 127.9, 126.8, 125.7, 125.5, 125.2, 125.2, 125.1, 124.8, 123.9, 122.0,
115.9, 81.4, 37.7, 37.1, 27.8, 18.7; ESIꢀHRMS m/z: 285.1276 ([MꢀH]ꢀ); Calcd for C21H17O: 285.1285.
3,4ꢀDihydroꢀ6ꢀmethylꢀ2ꢀphenylꢀ2Hꢀnaphtho[1,2-b]pyran (3c): 1a (60.9 mg, 0.20 mmol), FeCl3 (1.6 mg, 0.01
mmol) and (CH2Cl)2 (1.0 mL) were used, and the reaction was carried out at room temperature for 2.0 h. After
purification of the crude product by a silica gel column chromatography using hexane–AcOEt (15/1) as an eluent,
3c (38.8 mg, 0.16 mmol) was obtained in 77%. Colorless oil; IR (ATR) cmꢀ1: 2924, 1580, 1416, 1386, 1107, 756,
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696; H NMR (400 MHz, CDCl3): δ 8.28 (d, J = 6.8 Hz, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.51―7.45 (m, 4H),
7.42―7.38 (m, 2H), 7.33 (t, J = 7.2 Hz, 1H), 7.01 (s, 1H), 5.21 (dd, J = 9.6, 2.4 Hz, 1H), 3.10―3.02 (m, 1H),
2.84―2.78 (m, 1H), 2.59 (s, 3H), 2.35―2.28 (m, 1H), 2.20―2.10 (m, 1H); 13C NMR (100 MHz, CDCl3): δ
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148.2, 142.1, 132.1, 128.4, 127.9, 127.6, 125.8, 125.5, 125.5, 125.4, 124.9, 123.9, 122.0, 114.9, 77.5, 30.1, 24.9,
18.6; ESIꢀHRMS m/z: 273.1286 ([MꢀH]ꢀ); Calcd for C20H17O: 273.1285.
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Product 3d: 1b (61.2 mg, 0.15 mmol), FeCl3 (1.3 mg, 0.007 mmol) and (CH2Cl)2 (1.0 mL) were used, and the
reaction was carried out at room temperature for 2.0 h. After purification of the crude product by a silica gel
column chromatography using hexane–AcOEt (20/1) as an eluent, 3d (8.3 mg, 0.02 mmol) was obtained in 14%.
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Yellow oil; IR (ATR) cmꢀ1: 2952, 1599, 1478, 1240, 978, 728; H NMR (400 MHz, CDCl3): δ 8.19―8.16 (m,
1H), 7.98―7.94 (m, 1H), 7.60 (dd, J = 7.2, 1.6 Hz, 1H), 7.42―7.36 (m, 3H), 7.17 (dt, J = 7.5, 1.4 Hz, 1H), 6.90
(dt, J = 7.5, 1.4 Hz, 1H), 6.70 (d, J = 8.4 Hz, 1H), 5.88 (d, J = 7.2 Hz, 1H), 5.40―5.36 (m, 1H), 3.34 (dd, J =
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15.6, 4.2 Hz, 1H), 3.27 (dd, J = 15.6, 4.2 Hz, 1H), 0.96―0.94 (m, 15H); C NMR (100 MHz, CDCl3): δ 160.6,
151.3, 137.7, 135.8, 131.0, 127.9, 127.6, 126.3, 126.2, 125.8, 125.3, 124.8, 122.0, 121.0, 116.2, 110.1, 82.5, 78.9,
28.9, 7.7, 4.5; ESIꢀHRMS m/z: 387.1783 ([MꢀH]ꢀ); Calcd for C25H28O2Si: 387.1786.
4ꢀ[(2’,4’,6’ꢀTrimethoxyphenyl)methyl]ꢀnaphthalenꢀ1ꢀol (5a): 4a (58.6 mg, 0.20 mmol), TFAA (28 µl, 0.20
mmol) and (CH2Cl)2 (1.0 mL) were used, and the reaction was carried out at room temperature for 2.0 h. After
purification of the crude product by a silica gel column chromatography using hexane–AcOEt (5/1) as an eluent,
5a (65.6 mg, 0.20 mmol) was obtained in quantitative yield. Colorless solid; M.p. 126ꢀ129 C; IR (ATR) cmꢀ1:
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3374, 1590, 1200, 1144, 1116, 812, 761; 1H NMR (400 MHz, CDCl3): δ 8.27 (d, J = 8.2 Hz, 1H), 8.19 (d, J = 8.2
Hz, 1H), 7.58―7.54 (m, 1H), 7.51―7.47 (m, 1H), 6.73 (d, J = 7.6 Hz, 1H), 6.63 (d, J = 7.6 Hz, 1H), 6.21 (s,
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2H), 4.96 (s, 1H), 4.29 (s, 2H), 3.85 (s, 3H), 3.72 (s, 6H); C NMR (125 MHz, CDCl3): δ 159.8, 159.3, 149.5,
133.2, 129.5, 126.0, 124.6, 124.5, 123.9, 123.8, 122.0, 108.8, 108.2, 90.7,55.7, 55.3, 24.7; ESIꢀHRMS m/z:
347.1245 ([M+Na]+); Calcd for C20H20O4Na: 347.1254.
4ꢀ[(1’ꢀMethoxynaphthalenꢀ4’ꢀyl)methyl]ꢀnaphthalenꢀ1ꢀol (5b): 4a (60.9 mg, 0.21 mmol), TFAA (28 µl, 0.20
mmol) and (CH2Cl)2 (1.0 mL) were used, and the reaction was carried out at room temperature for 2.0 h. After
purification of the crude product by a silica gel column chromatography using hexane–AcOEt (5/1) as an eluent,
5b (48.9 mg, 0.16 mmol) was obtained in 74%. Colorless solid; M.p. 126ꢀ129 C; IR (ATR) cmꢀ1: 3519, 1585,
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1463, 1381, 1267, 1242, 1091, 757; H NMR (400 MHz, CDCl3): δ 8.35―8.32 (m, 1H), 8.27―8.24 (m, 1H),
8.00―7.94 (m, 2H), 7.52―7.46 (m, 4H), 6.96 (d, J = 7.8 Hz, 1H), 6.85 (d, J = 7.8 Hz, 1H), 6.67―6.64 (m, 2H),
4.69 (s, 2H), 3.95 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 154.3, 150.2, 133.2, 133.0, 128.8, 128.2, 126.8, 126.8,
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126.5, 125.9, 125.0, 124.9, 124.7, 124.0, 123.8, 122.5, 122.2, 108.2, 103.5,55.4, 34.8; ESIꢀHRMS m/z: 337.1188
([M+Na]+); Calcd for C22H18O2Na: 337.1199.
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4ꢀ[(2’ꢀMethoxynaphthalenꢀ1’ꢀyl)methyl]ꢀnaphthalenꢀ1ꢀol (5c): 4a (55.1 mg, 0.19 mmol), TFAA (27 µl, 0.19
mmol) and (CH2Cl)2 (1.0 mL) were used, and the reaction was carried out at room temperature for 2.0 h. After
purification of the crude product by a silica gel column chromatography using hexane–AcOEt (10/1) as an eluent,
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5c (22.1 mg, 0.07 mmol) was obtained in 36%. Colorless solid; M.p. 145ꢀ148 C; IR (ATR) cmꢀ1: 3380, 2926,
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1586, 1511, 1384, 1250, 1089, 743; H NMR (400 MHz, CDCl3): δ 8.35 (d, J = 8.6 Hz, 1H), 8.25 (d, J = 8.6 Hz,
1H), 7.86 (d, J = 8.8 Hz, 1H), 7.84―7.82 (m, 1H), 7.69―7.64 (m, 2H), 7.56 (t, J = 7.6 Hz, 1H), 7.38 (d, J = 8.8
Hz, 1H), 7.34―7.29 (m, 2H), 6.47 (d, J = 7.6 Hz, 1H), 6.41 (d, J = 7.6 Hz, 1H), 5.00 (s, 1H), 4.81 (s, 2H), 3.89
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(s, 3H); C NMR (100 MHz, CDCl3): δ 155.3, 149.7, 133.8, 133.1, 129.3, 128.6, 128.4, 128.3, 126.4, 124.9,
124.6, 124.4,124.4, 124.0, 123.4, 123.4,122.3, 120.8, 113.7, 108.2, 56.8, 27.0; ESIꢀHRMS m/z: 337.1195
([M+Na]+); Calcd for C22H18O2Na: 337.1199.
3ꢀ[(1’ꢀHydroxynaphthalenꢀ4ꢀyl)methyl]ꢀNꢀphenylindol (5d): 4a (56.7 mg, 0.19 mmol), TFAA (28 µl, 0.20
mmol) and (CH2Cl)2 (1.0 mL) were used, and the reaction was carried out at room temperature for 3.0 h. After
purification of the crude product by a silica gel column chromatography using hexane–AcOEt (10/1) as an eluent,
5d (78.8 mg, 0.19 mmol) was obtained in quantitative yield. Red oil: IR (ATR) cmꢀ1: 3508, 3046, 1499, 1455,
905, 728; 1H NMR (500 MHz, CDCl3): δ 8.23―8.22 (m, 1H), 8.06―8.05 (m, 1H), 7.68 (d, J = 7.0 Hz, 1H), 7.57
(d, J = 8.0 Hz, 1H), 7.47―7.45 (m, 2H), 7.41―7.35 (m, 4H), 7.25―7.20 (m, 3H), 7.17 (t, J = 7.0 Hz, 1H), 6.81
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(s, 1H), 6.69 (d, J = 7.5 Hz, 1H), 5.27 (s, 1H), 4.49 (s, 2H); C NMR (125 MHz, CDCl3): δ 150.3, 139.7, 136.0,
133.1, 129.4, ,129.4, 128.9, 128.7, 126.4, 126.4, 126.0, 124.9, 124.7, 124.4, 124.0, 122.5, 122.1, 119.9, 119.4,
116.8, 110.5, 108.1, 28.4; ESIꢀHRMS m/z: 372.1360 ([M+Na]+); Calcd for C25H19NONa: 372.1359.
6,7ꢀDibromoꢀ4ꢀ[(2’,4’,6’ꢀtrimethoxyphenyl)methyl]ꢀnaphthalenꢀ1ꢀol (5e): 4b (83.3 mg, 0.19 mmol), TFAA
(28 µl, 0.20 mmol) and (CH2Cl)2 (1.0 mL) were used, and the reaction was carried out at room temperature for
2.0 h. After purification of the crude product by a silica gel column chromatography using hexane–AcOEt (2/1)
as an eluent, 5e (45.0 mg, 0.10 mmol) was obtained in 52%. Yellow oil; IR (ATR) cmꢀ1: 3396, 2937, 2837, 1596,
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1454, 1416, 1203, 1148, 1118, 812, 732; H NMR (400 MHz, CDCl3): δ 8.67 (s, 1H), 8.46 (s, 1H), 6.97 (d, J =
8.0 Hz, 1H), 6.63 (d, J = 8.0 Hz, 1H), 6.17 (s, 2H), 5.09 (s, 1H), 4.18 (s, 2H), 3.82 (s, 3H), 3.77 (s, 6H); 13C NMR
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(100 MHz, CDCl3); δ 160.0, 159.0, 148.7, 133.1, 129.5, 129.5,127.1, 126.8, 124.5, 122.5, 120.6, 109.4, 108.6,
90.7, 55.7, 55.3, 25.0; ESIꢀHRMS m/z: 502.9457 ([M+Na]+); Calcd for C20H18O4Br2Na: 502.9464.
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2,4ꢀBis[(2’,4’,6’ꢀtrimethoxyphenyl)methyl]ꢀnaphthalenꢀ1ꢀol (7a): 6a (83.6 mg, 0.19 mmol), FeCl3 (1.6 mg,
0.01 mmol) and (CH2Cl)2 (1.0 mL) were used, and the reaction was carried out at room temperature for 0.5 h.
After purification of the crude product by a silica gel column chromatography using hexane–AcOEt (5/1) as an
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eluent, 7a (62.4 mg, 0.13 mmol) was obtained in 65%. Colorless solid; M.p. 117ꢀ118 C; IR (ATR) cmꢀ1:3486,
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2937, 1623, 1584, 1513, 1421, 1387, 1269, 1091, 904, 726; H NMR (500 MHz, CDCl3): δ 8.25 (d, J = 7.8 Hz,
1H), 8.14 (d, J = 7.8 Hz, 1H), 7.74 (s, 1H), 7.45 (t, J = 7.0 Hz, 1H), 7.41 (t, J = 7.0 Hz, 1H), 6.94 (s, 1H), 6.25 (s,
2H), 6.08, (s, 1H), 4.26 (s, 3H), 3.88 (s, 3H), 3.83 (s, 2H), 3.76―3.74 (m, 9H), 3.70 (s, 6H); 13C NMR (100
MHz, CDCl3): δ 159.7, 159.5, 157.7, 147.7, 132.0, 127.8, 127.6, 125.2, 124.9, 124.0, 123.3, 122.6, 119.4, 109.7,
109.4, 90.9, 90.7, 90.6, 55.8, 55.7, 55.6, 55.4, 24.6, 23.5; ESIꢀHRMS m/z: 527.2037 ([M+Na]+); Calcd for
C30H32O7Na: 527.2040.
2,4ꢀBis[(1’ꢀmethoxynaphthalenꢀ4’ꢀyl)methyl]ꢀnaphthalenꢀ1ꢀol (7b): 6a (43.2 mg, 0.10 mmol), FeCl3 (0.8 mg,
0.005 mmol) and (CH2Cl)2 (0.5 mL) were used, and the reaction was carried out at room temperature for 0.5 h.
After purification of the crude product by a silica gel column chromatography using hexane–AcOEt (5/1) as an
eluent, 7b (40.7 mg, 0.08 mmol) was obtained in 84%.. Pale yellow oil; IR (ATR) cmꢀ1: 2394, 1584, 1461, 1387,
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1267, 1090, 760; H NMR (500 MHz, CDCl3): δ 8.31 (d, J = 8.0 Hz, 1H), 8.27 (d, J = 8.0 Hz, 1H), 8.19 (d, J =
9.0 Hz, 1H), 7.93 (t, J = 7.0 Hz, 2H), 7.83 (d, J = 7.0 Hz, 1H), 7.49―7.41 (m, 5H), 7.39 (t, J = 8.0 Hz, 1H), 7.09
(d, J = 8.0 Hz, 1H), 6.92―6.91 (m, 2H), 6.61 (d, J = 8.0 Hz, 2H), 5.29 (s, 1H), 4.67 (s, 2H), 4.32 (s, 2H), 3.94 (s,
6H); 13C NMR (125 MHz, CDCl3): δ 154.9, 154.2, 148.4, 132.8, 132.7, 132.2, 130.1, 128.6, 128.2, 126.7, 126.4,
126.2, 126.1, 125.8, 125.8, 125.2, 125.0, 124.9, 124.9, 124.0, 124.0, 123.7, 123.7, 122.6, 122.5, 122.0, 118.6,
103.3, 103.1, 55.4, 55.4, 34.7, 34.2; ESIꢀHRMS m/z: 507.1930 ([M+Na]+); Calcd for C34H28O3Na: 507.1931.
2,4ꢀBis[(3’ꢀNꢀphenylindlyl)methyl]ꢀnaphthalenꢀ1ꢀol (7c): 6a (32.3 mg, 0.07 mmol), FeCl3 (0.6 mg, 0.004
mmol) and (CH2Cl)2 (0.5 mL) were used, and the reaction was carried out at room temperature for 0.5 h. After
purification of the crude product by a silica gel column chromatography using hexane–AcOEt (15/1) as an eluent,
7c (26.5 mg, 0.05 mmol) was obtained in 68%. Yellow oil; IR (ATR) cmꢀ1: 3481, 3051, 1596, 1498, 1455, 906,
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730; H NMR (400 MHz, CDCl3): δ 8.20―8.18 (m, 1H), 8.07―8.04 (m, 1H), 7.69 (d, J = 7.6 Hz, 1H),
7.57―7.51 (m, 3H), 7.43―7.34 (m, 11H), 7.28―7.17 (m, 4H), 7.13 (dt, J = 4.4, 1.2 Hz, 1H), 7.08―7.05 (m,
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2H), 6.84 (s, 1H), 5.49 (s, 1H), 4.53 (s, 2H), 4.25 (s, 2H); C NMR (100 MHz, CDCl3): δ 148.5, 139.8, 139.4,
136.6, 136.1, 132.2, 129.6, 129.5, 129.4, 128.9, 128.5, 128.4, 126.4, 126.3, 126.0, 125.9, 125.7, 125.4, 124.9,
124.3, 124.1, 124.0, 123.0, 122.5, 122.0, 120.3, 120.0, 119.5, 119.4, 118.5, 117.0, 114.4, 110.7, 110.5, 28.4,
27.3; ESIꢀHRMS m/z: 577.2246 ([M+Na]+); Calcd for C40H30N2ONa: 577.2250.
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2,4ꢀBis[(2’,4’,6’ꢀtrimethoxyphenyl)methyl]ꢀ7ꢀmethoxyꢀnaphthalenꢀ1ꢀol (7d): 6b (46.7 mg, 0.10 mmol), FeCl3
(0.8 mg, 0.005 mmol) and (CH2Cl)2 (0.5 mL) were used, and the reaction was carried out at room temperature for
0.5 h. After purification of the crude product by a silica gel column chromatography using hexane–AcOEt (5/1)
as an eluent, 7d (38.4 mg, 0.07 mmol) was obtained in 72%. Pale yellow oil; IR (ATR) cmꢀ1: 3411, 2936, 1590,
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2.6 Hz, 1H), 7.11 (dd, J = 9.2, 2.6 Hz, 1H), 6.83 (s, 1H), 6.24 (s, 2H), 6.09 (s, 2H), 4.23 (s, 2H), 3.93 (s, 3H),
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3.87 (s, 3H), 3.82 (s, 2H), 3.76 (s, 6H), 3.74 (s, 3H), 3.70 (s, 6H); C NMR (125 MHz, CDCl3): δ 159.6, 159.5,
159.5, 157.7, 156.6, 146.8, 127.8, 127.5, 126.1, 125.6, 125.1, 120.1, 117.3, 109.8, 109.6, 100.9, 90.9, 90.7, 55.8,
55.7,55.5, 55.4, 55.3, 24.6, 23.6; ESIꢀHRMS m/z: 557.2138 ([M+Na]+); Calcd for C31H34O8Na: 557.2146.
Product 8a: 6a (41.2 mg, 0.10 mmol), FeCl3 (0.8 mg, 0.005 mmol) and (CH2Cl)2 (0.5 mL) were used, and the
reaction was carried out at room temperature for 0.5 h. After purification of the crude product by a silica gel
column chromatography using hexane–AcOEt (15/1) as an eluent, 8a (19.8 mg, 0.05 mmol) was obtained in 54%.
Yellow oil; IR (ATR) cmꢀ1: 3065, 2925, 1600, 1511, 1478, 1388, 1241, 1106, 750; 1H NMR (500 MHz, CDCl3):
δ 8.16 (d, J = 7.5 Hz, 1H), 7.89 (d, J = 7.5 Hz, 1H), 7.60 (d, J = 7.5 Hz, 1H), 7.43―7.37 (m, 4H), 7.21―7.18 (m,
2H), 7.17―7.13 (m, 2H), 6.88 (t, J = 7.5 Hz, 1H), 6.69 (d, J = 9.0 Hz, 1H), 6.19 (s, 1H), 5.94 (d, J = 7.5 Hz, 1H),
5.43―5.39 (m, 1H), 4.48 (d, J = 16.5 Hz, 1H), 4.39 (d, J = 16.5 Hz, 1H), 3.30 (dd, J = 15.8, 4.0 Hz, 1H), 3.25
(dd, J = 15.8, 4.0 Hz, 1H), 13C NMR (125 MHz, CDCl3): δ 160.6, 157.8, 154.7, 149.5, 131.7, 131.0, 128.8, 128.4,
126.5, 126.3, 126.2, 126.0, 125.9, 125.3, 123.8, 123.3, 122.4, 121.9, 121.0, 120.3 117.4, 110.9, 110.0, 103.6,
82.5, 79.2, 32.0, 29.0; ESIꢀHRMS m/z: 403.1330 ([MꢀH]ꢀ); Calcd for C28H19O3: 403.1340.
Product 8b: 6b (26.7 mg, 0.06 mmol), FeCl3 (0.8 mg, 0.005 mmol) and (CH2Cl)2 (0.5 mL) were used, and the
reaction was carried out at room temperature for 0.5 h. After purification of the crude product by a silica gel
column chromatography using hexane–AcOEt (10/1) as an eluent, 8b (6.4 mg, 0.01 mmol) was obtained in 21%.
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Hz, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 2.8 Hz, 1H), 7.40 (dt, J = 5.6, 1.2 Hz, 2H), 7.21―7.13 (m, 3H),
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