Bi(OTf)3-Mediated (4+1) Annulation of α-Sulfonyl o-Hydroxyacetophenones with α-Hydroxy Arylketones to Access Sulfonyl 2-Aroylbenzofurans

Article abstract of DOI:10.1002/adsc.202100143

In this paper, a high-yield, facile route for the scalable synthesis of sulfonyl 2-aroylbenzofurans via a Bi(OTf)₃-mediated intermolecular double cyclocondensation of α-sulfonyl o-hydroxyacetophenones with substituted α-hydroxy arylketones under mild open-vessel reaction conditions is described. In the overall reaction, water is generated as the only byproduct. Various metal triflate-promoted reactions and conditions are investigated for the efficient one-pot (4+1) annulation reaction. (Figure presented.).

Full text of DOI:10.1002/adsc.202100143

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DOI: 10.1002/adsc.202100143
Bi(OTf)3-Mediated (4+1) Annulation of α-Sulfonyl
o-Hydroxyacetophenones with α-Hydroxy Arylketones to Access
Sulfonyl 2-Aroylbenzofurans
Meng-Yang Changa, b,* and Kuan-Ting Chena
a
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan
E-mail: mychang@kmu.edu.tw
Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
b
Manuscript received: February 1, 2021; Revised manuscript received: March 8, 2021;
Version of record online: ■■■, ■■■■
Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.202100143
Abstract: In this paper, a high-yield, facile route for the scalable synthesis of sulfonyl 2-aroylbenzofurans via
a Bi(OTf)3-mediated intermolecular double cyclocondensation of α-sulfonyl o-hydroxyacetophenones with
substituted α-hydroxy arylketones under mild open-vessel reaction conditions is described. In the overall
reaction, water is generated as the only byproduct. Various metal triflate-promoted reactions and conditions are
investigated for the efficient one-pot (4+1) annulation reaction.
Keywords: 2-Aroylbenzofurans; Double Cyclocondensation; o-Hydroxyacetophenones; α-Hydroxy Arylketones;
(4+1) Annulation
Introduction
Among the one-step methods for constructing hetero-
cycle-containing five-membered rings, the (4+1)
annulation reaction has attracted the attention of many
chemists. The Xiao group summarized and analysed
the elegant synthetic applications of the (4+1)
annulation reaction.[1] Recently, a number of transition
metal-catalysed methods (e.g., with Rh(III),[2–7] Au-
(I),[8–9] Re(I)[10] and Ir(III)[11]) have emerged as (4+1)
annulation routes to provide a structurally diverse
range of molecules. The use of other promoters,
including organophosphines,[12–14] organoamines[15] and
K2CO3, has been reported.[16] These articles demon-
strated that (4+1) annulations could proceed via
numerous unique synthetic routes to construct func-
tionalized core systems, including organic functional-
ized materials, biologically active molecules and useful
Scheme 1. (4+1) Annulation routes of benzofurans.
synthetic building blocks. After investigating the studied the tBuOK-mediated cyclization of o-hydrox-
elegant studies on (4+1) annulations, we understand yacetophenones with 1,1-dichloroethylene.[19] Osyanin
that only few reports were documented in the con- et al. demonstrated the Et3N-mediated annulation of
struction of functionalized benzofurans.[17–20] As shown benzyl ammonium salts with potassium trinitrometha-
in Scheme 1, Wang et al. found the Cu(I)/tBuOK- nide (a 1,1-ambiphilic equivalent).[20] For the synthetic
mediated one-pot coupling/cyclization of terminal route of benzofurans, a wide selection of methods and
alkynes with hydrozones.[17] Li and Fu reported the different annulation reactions are available in review
Cu(I)/Cs2CO3-promoted tandem cyclization of calcium articles.[21–24]
carbide with hydrozones.[18] Schevenels and Markó
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Despite these impressive achievements, to the best 10 h (Table 1, entry 1). With these results in mind, the
of our knowledge no bismuth(III)-catalysed (4+1) optimal reaction time was studied by using 20 mol%
annulation reactions to produce benzofurans currently Bi(OTf)3 as the promoter and 5 mL of MeNO2 as the
exist. Among bismuth(III) salts,[25–27] Bi(OTf)3 belongs solvent. To increase the isolated yield, elongation times
to a group of efficient and environmentally benign were investigated. In entries 2–3, we found that two
promoters for catalysing various functional group reaction times (12 and 15 h) provided yields of nearly
transformations and establishing carbon-carbon/car- 75% and 70%, respectively. The results revealed that
bon-heteroatom bond formations. In continuation of longer reaction times did not enhance the yield of 4a.
the recent research on a diverse set of Bi(OTf)3- Furthermore, reaction temperature screening was per-
promoted reactions[28–31] and the related synthetic formed. By elevating the temperature to 60 C and
°
°
applications
of
α-sulfonyl
o-hydroxy- 80 C, better yields (85% and 78%) of 4a were
acetophenones,[32–33] we present a Bi(OTf)3-mediated obtained, but when the reaction was run at a reflux
°
one-pot (4+1) annulation route (called the Rap- temperature (101 C), the yield of 4a quickly decreased
Stoermer reaction) to 3-sulfonylmethyl 2-aroylbenzo- to 69% (entries 4–6). It is obvious that the reaction
furans; this route involves intermolecular double cyclo- was appropriate for warm MeNO2-dependent condi-
condensation of α-sulfonyl o-hydroxyacetophenones tions. On the basis of the abovementioned data, the
with substituted α-hydroxy arylketones and the for- volumes of MeNO2 were studied. After increasing the
mation of one carbon-carbon double (C=C) bond and reaction volume from 5 mL to 10 mL, a slightly lower
one carbon-oxygen single (CÀ O) bond (green bonds, yield (82%) was obtained (entry 7). Under trace
Scheme 1).
solvent conditions, however, the solution system
Three interesting examples of the synthesis of 2- provided similar yields (80%, entry 8). Compared with
sulfonylmethyl 3-aroylbenzofurans were described as entry 4 (5 mL MeNO2), neither entry 7 nor 8 provided
follows (Scheme 2):[34–36] (1) Jiang et al. investigated higher yields of 4a.
the Ag(I)-catalysed one-pot oxidative cyclization of
In entry 9, when the catalytic amount of Bi(OTf)3
1,6-enynes and RSO2Na;[34] (2) Wei and co-workers was increased (from 20 to 30 mol%), the same yield
documented the I2O5/TBHP-mediated oxidative cycli- (85%) of 4a was isolated. By decreasing the amount of
zation of 1,6-enynes and arylsulfonylhydrazides;[35] Bi(OTf)3 used (from 20 to 10 mol%), the isolated yield
and (3) Sun et al. explored NH4I-promoted cyclizations of 4a was decreased to 75% (entry 10). This meant
of 1,6-enynes with DMSO/H2O.[36] These authors that 20 mol% Bi(OTf)3 was enough to produce a high
showed novel radical addition cascade cyclization yield of 4a. By changing the solvent to (CH2Cl)2 (1,2-
routes for the formation of sulfonyl 3-aroylbenzofur- dichloroethane), a low yield of 4a (60%) was obtained
ans.
(entry 11). However, toluene resulted in only an 8%
yield, and 2a was recovered as the major component
(entry 12). With the use of DMF as the solvent, a
complex mixture resulted instead of the desired 4a
Results and Discussion
The initial study commenced with the treatment of α- (entry 13). Subsequently, other trivalent metal triflates
sulfonyl o-hydroxyacetophenone 2a (Ar=Ph, 870 mg, (M=In, Fe, Sc) were used. When the reaction was run
3.0 mmol, prepared from CuBr2-mediated α-bromina- with In(OTf)3 or Fe(OTf)3, the resulting yields (61%
tion of o-hydroxyacetophenone 1a followed by nucle- and 58%) were lower than those with Bi(OTf)3
ophilic substitution of the resulting α-bromo-o-hydrox- (entries 14–15). However, no reaction was detected
yacetophenone with TolSO2Na) and α-hydroxy with the use of Sc(OTf)3 (entry 16). On the other hand,
phenylketone 3a (Ar’=Ph; 420 mg, 3.1 mmol). First, divalent metal triflates (M=Cu, Hg, Sn) were tested
using Bi(OTf)3 (20 mol%), a 72% yield of 4a was next. However, Cu(OTf)2 provided 4a in a low yield
°
obtained in the presence of MeNO2 (5 mL) at 25 C for (52%) along with a 10% yield of a complex unknown
mixture (entry 17). Hg(OTf)2 provided a 24% yield of
4a and major unidentified components (48%, en-
try 18). Like Sc(OTf)3, Sn(OTf)2 did not catalyse the
formation of 4a (entry 19). Among monovalent metal
triflates, AgOTf provided a 35% yield of 4a (entry 20).
According to the abovementioned results, we found
that Bi(OTf)3 was the optimal metal triflate for
catalysing (4+1) annulation. Furthermore, other
Brønsted acids were examined. In entry 21, CF3SO2H
(TfOH) provided 4a in a 67% yield. However,
CF3CO2H and CH3CO2H could not promote the
Scheme 2. Synthetic routes of 2-sulfonylmethyl 3-aroylbenzo-
generation of 4a due to the low acidity that resulted
from the reaction (entries 22 and 23). From these
furans.
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Table 1. Reaction conditions.[a]
entry
promoter
(mol%)
solvent
(mL)
time
(h)
temp
4a
( C)
(%)[b]
°
1
2
3
4
5
6
7
8
Bi(OTf)3 (20)
Bi(OTf)3 (20)
Bi(OTf)3 (20)
Bi(OTf)3 (20)
Bi(OTf)3 (20)
Bi(OTf)3 (20)
Bi(OTf)3 (20)
Bi(OTf)3 (20)
Bi(OTf)3 (30)
Bi(OTf)3 (10)
Bi(OTf)3 (20)
Bi(OTf)3 (20)
Bi(OTf)3 (20)
In(OTf)3 (20)
Fe(OTf)3 (20)
Sc(OTf)3 (20)
Cu(OTf)2 (20)
Hg(OTf)2 (20)
Sn(OTf)2 (20)
AgOTf (20)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (10)
MeNO2 (1)
MeNO2 (5)
MeNO2 (5)
(CH2Cl)2 (5)
toluene (5)
DMF (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
10
12
15
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
25
25
25
60
80
reflux
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
72
75
70
85
78
69
82
80
85
75
60
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
[c]
–
61
58
[d]
–
52[e]
24[e]
[d]
–
35
67
CF3SO2H (20)
CF3CO2H (20)
CH3CO2H (20)
[d]
–
[d]
–
[a] Reactions were run on a 3.0 mmol scale with 2a (870 mg), 3a (420 mg, 3.1 mmol), promoter (20 mol%), solvent (5 mL).
[b] Isolated yields.
[c] No detection.
[d] No reaction.
[e] Complex and unidentified products.
observations, we concluded that entry 4 provided
optimal conditions for the formation of 4a (85%) via
Bi(OTf)3-promoted intermolecular (4+1) annulation
of 2a with 3a. In the overall reaction processes, water
was generated as the only byproduct.
On the basis of the optimal reaction conditions, a
plausible mechanism for the formation of 4a is
illustrated in Scheme 3. Initially, Bi(OTf)3 coordinates
3a to yield A. With the involvement of 2a, the o-
hydroxy group on 2a could attack the α-position of A,
yielding B and causing the removal of Bi(OTf)3(OH)-.
Following the deprotonation process, C is generated,
and Bi(OTf)3 is recovered. Water would be formed in
this pathway.[37] Furthermore, after accomplishing Bi-
(OTf)3-mediated coordination, C, D1 and D2 (with an
enol form), could be produced. Then, by intramolecu-
Scheme 3. Plausible mechanism.
lar aldol condensation, D1 could convert into benzofur-
an 4a with a five-membered aromatic ring. Subse-
quently, more water could be removed along the
reaction pathway.[38–39] However, the intramolecular
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aldol condensation of D2 could not occur to produce hydroxy arylketones 3a–3l to afford functionalized
benzo[b]oxepin-5-one 4a’ with a seven-membered ring sulfonyl 2-aroylbenzofurans 4a–4ag in the presence of
since the efficiency of the ring formation is rather Bi(OTf)3, as shown in Table 2. With optimal conditions
°
lower than that of the five-membered ring. Finally, established (MeNO2, 12 h, 60 C) and a plausible
Bi(OTf)3 could be recovered for the next cycle of the mechanism proposed (Scheme 2), we found that this
intermolecular (4+1) annulation.
synthetic route could produce direct intermolecular
To investigate the substrate scope and related etherification and intramolecular aldol condensation
limitations of the (4+1) annulation synthetic route, a under mild open-vessel and scalable (3.0 mmol) con-
diverse group of α-sulfonyl o-hydroxyacetophenones ditions with a range of moderate to good yields (70%–
2a–2v was reacted with commercially available α- 85%). In entries 1–11, when using phenyl (Ph) as the
Table 2. Synthesis of 4a–4ag.[a]
4r (X-Ray)
entry
2, Ar=, R=
3, Ar’=,
4 (%)[b]
1
2
3
4
5
6
7
8
2a, Ph, Tol
2b, Ph, 3-MeC6H4
2c, Ph, Ph
2d, Ph, Me
2e, Ph, nBu
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3b, 4-FC6H4
3c, 4-MeOC6H4
3d, Tol
3e, 4-CF3C6H4
3f, 4-BrC6H4
3g, 4-PhC6H4
3h, 3,4-(MeO)2C6H3
3i, 3,4-CH2O2C6H3
3j, 3,4,5-(MeO)3C6H2
3k, 2-naphthyl
3l, 2-thienyl
4a, 85
4b, 80
4c, 80
4d, 76
4e, 70
4f, 78
4g, 82
4h, 84
4i, 80
2f, Ph, 4-FC6H4
2g, Ph, 4-MeOC6H4
2h, Ph, 4-EtC6H4
2i, Ph, 4-iPrC6H4
2j, Ph, 4-nBuC6H4
2k, Ph, 4-tBuC6H4
2l, 4-FC6H3, Tol
2m, 4-ClC6H3, Tol
2n, 4-BrC6H3, Tol
2o, 4-MeC6H3, Tol
2p, 4-MeOC6H3, Tol
2q, 4,6-Cl2C6H3, Tol
2r, 5-MeOC6H3, Tol
2s, 5-Br-2-naphthyl, Tol
2t, 4-PhC6H3, Tol
2u, 4,6-F2C6H2, Tol
2v, 2-naphthyl, Tol
2a, Ph, Tol
2a, Ph, Tol
2a, Ph, Tol
2a, Ph, Tol
2a, Ph, Tol
2a, Ph, Tol
2a, Ph, Tol
2a, Ph, Tol
2a, Ph, Tol
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
4j, 74
4k, 70
4l, 76
4m, 70
4n, 81
4o, 83
4p, 84
4q, 80
4r, 78
4s, 74
4t, 70
4u, 72
4v, 73
4w, 75
4x, 80
4y, 81
4z, 82
4aa, 78
4ab, 76
4ac, 74
4ad, 74
4ae, 78
4af, 74
4ag, 70
2a, Ph, Tol
2a, Ph, Tol
[a] Reactions were run on a 3.0 mmol scale with 2a–2v, 3a–3l (3.1 mmol), Bi(OTf)3 (400 mg, 20 mol%), MeNO2 (5 mL), 12 h,
°
60 C.
[b] Isolated yields.
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Ar (for 2) and Ar’ group (for 3), different substituents electron-neutral, electron-donating or electron-with-
R on the sulfonyl group, including aliphatic (Me, n- drawing groups. Furthermore, this was a facile and
Bu) and aromatic (alkylphenyl, fluorophenyl, meth- scalable route for the synthesis of sulfonyl 2-aroylben-
oxyphenyl) groups, did not affect the efficient for- zofurans 4a–4ag via Bi(OTf)3-mediated double cyclo-
mation of 4a–4j. After controlling R on the sulfonyl condensation of 2a–2v with 3a–3l.
group of 2 and Ar’ of 3 as Tol and Ph groups
Encouraged by the above experimental results, the
(entries 12–22), a diverse range of substituents (fluoro, Bi(OTf)3-mediated Rap-Stoermer reaction of 2-aroyl-
chloro, bromo, methoxy, methyl, dichloro, difluoro) on benzofurans without a sulfonyl substituent was next
the Ar (phenyl and naphthyl) group provided 4k–4v in studied under the optimal conditions.[41–43] To distin-
modest yields (70%–84%). The molecular structure of guish the reactivity between o-hydroxyacetophenones
4r was determined by single-crystal X-ray analysis.[40] 1 and sulfonyl o-hydroxyacetophenones 2, the Bi-
On the other hand, when using 2a as the starting (OTf)3-mediated double cyclocondensation of 1 with 3
substrate (Ar=Ph, R=Tol) and different Ar’ groups (for was examined, as seen in Table 3, entries 1–21. Under
3), containing a halide (F and Br), electron-with- similar conditions, by choosing 1a–1f, 1h, or 1k–1m
drawing trifluoromethyl or electron-donating oxygen- (3.0 mmol) and 3a–3l (3.1 mmol) as starting materials,
ated substituents, compounds 4w–4ae were generated, 5a–5u were produced in moderate to good yields. In
as shown in entries 23–31. In particular, when the Ar’ addition, 5t–5u with naphthyl groups were isolated in
group was the bicyclic 2-naphthyl or heterocyclic 2- slightly low yields (60% and 65%); others were
thienyl group, 4af and 4ag were obtained in 74% and provided in the range of 70%–90% yields.
70% yields, respectively (entries 32–33). On the basis
In particular, without the α-sulfonyl substituent, 3-
of the experimental results, we understood that the methyl-2-aroylbenzofurans 5a–5u were obtained with
electronic properties of the Ar substituent of 2 and the low yields in many entries (60%–84%, Table 3).
Ar’ substituent of 3 could include those of different Compared with the formation of 5a–5u, however, 4a–
Table 3. Synthesis of 5a–5u.[a]
5s (X-Ray)
entry
1, Ar=
3, Ar’=
5 (%)[b]
1
2
3
4
5
6
7
8
1a, Ph
1a, Ph
1a, Ph
1a, Ph
1a, Ph
1a, Ph
1a, Ph
1a, Ph
1a, Ph
1a, Ph
1a, Ph
1a, Ph
1b, 4-FC6H3
1c, 4-ClC6H3
1d, 4-BrC6H3
1e, 4-MeC6H3
1f, 4-MeOC6H3
1h, 5-MeOC6H3
1k, 4,6-F2C6H2
1l, 2-naphthyl
1m, 1-naphthyl
3a, Ph
5a, 90
5b, 84
5c, 82
5d, 80
5e, 84
5f, 80
5g, 76
5h, 80
5i, 74
5j, 74
5k, 70
5l, 76
5m, 80
5n, 81
5o, 80
5p, 73
5q, 74
5r, 70
5s, 70
5t, 60
5u, 65
3b, 4-FC6H4
3c, 4-MeOC6H4
3d, Tol
3e, 4-CF3C6H4
3f, 4-BrC6H4
3g, 4-PhC6H4
3h, 3,4-(MeO)2C6H3
3i, 3,4-CH2O2C6H3
3j, 3,4,5-(MeO)3C6H2
3k, 2-naphthyl
3l, 2-thienyl
3a, Ph
3a, Ph
3a, Ph
3a, Ph
3a, Ph
9
10
11
12
13
14
15
16
17
18
19
20
21
3a, Ph
3a, Ph
3a, Ph
3a, Ph
[a] Reactions were run on a 3.0 mmol scale with 1a–1f, 1h, 1k–1m, 3a–3l (3.1 mmol), Bi(OTf)3 (400 mg, 20 mol%), MeNO2
°
(5 mL), 12 h, 60 C.
[b] Isolated yields.
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4ag (70%–85%, Table 2) were produced with a for the acetoxy (for 3n) group, the present route still
slightly higher distribution of average yields. A exhibited a novel, chemoselective synthesis of the
possible reason could be that the electron-withdrawing benzofuran core skeleton.
α-sulfonyl group could induce the electron density to
As an extension of the Bi(OTf)3-mediated (4+1)
increase the relative polarity of the neighbouring annulation of 2a, we tried to synthesize the 2,2-
carbonyl group such that intramolecular cycloconden- disubstituted benzofuran skeleton, as shown in
sation was easier to carry out on the pathway from D1 Scheme 5, eq 1. For the treatment of 2a with benzoin
to 4 (see Scheme 2). For the electronic influences of (3o), however, a 47% yield of 4aj–1 was provided,
substituents on the Ar and Ar’ groups of 1 and 3, and the desired 2,3-diphenylbenzofuran skeleton was
different electron-neutral, electron-donating and elec- not detected. A possible reason for these low-yield
tron-withdrawing groups were well tolerated. The results could be that the steric hindrance of the α-
results show that Bi(OTf)3 was an excellent catalytic phenyl group on 3o affected the conversion from
protomer for constructing the core skeleton of aroyl- intermediate C to D1 (see Scheme 2) such that the
benzofurans via a one-pot efficient (4+1) annulation. intramolecular dehydration of 2a and 3o was initiated.
The molecular structures of 5s and 5u were confirmed After 3o was displaced as α-hydroxytetralone (3p),
by single-crystal X-ray analysis.[40] Herein, we have however, low yields (36%) were observed for the
developed a one-pot Bi(OTf)3-mediated transformation generation of 4ak–1 (Scheme 5, eq. 2). We envisioned
for converting o-hydroxyacetophenone to 3-methyl-2- that with Bi(OTf)3 coordinated, the secondary alcohol
aroylbenzofuran. 3-Methyl-2-aroylbenzofuran is a ver- group on 3p was a bulky leaving group and 2a could
satile skeleton commonly seen in useful synthetic not displace it directly. After intramolecular carbonyl-
blocks.[44–45]
mediated cyclization and the removal of Bi(OTf)3OH,
After exchanging the aryl (Ar’) group in 3 with an 2a could attack E to generate 4ak–1 with an oxirane
aliphatic group (hydroxyacetone 3m, R’=Me) and an moiety. From these observations, we understood that
ester group (ethyl hydroxyacetate, 3n, R’=OEt), 2- treatment of 2a with 3o or 3p could not provide the
acetylbenzofuran 5v was obtained in 66% yield desired 2,2-disubstituted benzofurans. However, for
(Scheme 4, eq 1). For the reaction of 1a with 3n, the treatment of 2a with 3q containing a 4-nitrophenyl
however, the predicted carbethoxybenzofuran 5w was group (Scheme 5, eq 3), no desired product was
not generated, and only 5w–1 was afforded in a 16% isolated and only a complex unknown mixture was
yield. On the other hand, similar results were also detected due to the stronger electron-withdrawing
observed in the Bi(OTf)3-mediated cyclocondensation effect. Although 3o, 3p and 3q provided unexpected
of 2a with 3m or 3n (Scheme 4, eq. 2). In the reaction products, the Bi(OTf)3-mediated route still provided a
of 2a with 3m, 4ah was isolated in a 65% yield, and novel synthesis of the benzofuran skeleton.
no 4ai was detected. From the unsuccessful attempts at
After changing the α-substituent of the o-hydrox-
the formation of 5w and 4ai, we thought that yacetophenone from sulfonyl to benzoyl (2v), no 6a
Bi(OTf)3-mediated chelation of 1a or 2a with 3n was detected (Scheme 6, eq 1), and only 6a–1 was
could not promote intramolecular dehydration easily obtained in a 68% yield via a four-step pathway
(for D1, Scheme 3). The less acidic α-proton of the involving (1) esterification of 2v and 3a, (2) Bi(OTf)3-
ester group (for 3n) did not make enolization easy
enough that Bi(OTf)3-initiated intramolecular cyclo-
condensation could occur efficiently. The above results
mean that the substrate scope for 3 includes aromatic
(for 3a–3l) and aliphatic (for 3m) groups. Although
the Bi(OTf)3-mediated methodology was inappropriate
Scheme 4. Synthesis of 4ah–4ai, 5v and 5w–1.
Scheme 5. Reactions of 2a with 3o-3q.
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To understand the reaction procedure, stepwise
control experiments were performed, as shown in
Scheme 8. Initially, Bi(OTf)3-mediated etherification
of 1a with 3a produced C1 in a 95% yield after
°
heating at 60 C for 1 h. With C1 in hand, the
formation of 5a was studied. By using catalytic
amounts of Bi(OTf)3, C1 was converted to 5a in a
°
92% yield after heating at 60 C for 11 h. Compared
with the one-pot process (Table 3, entry 1, 90% yield),
the stepwise route provided a lower total yield of 5a
(87%). The two-step experiments shows that Bi(OTf)3
is an optimal catalyst to efficiently promote the overall
reaction procedure.
Conclusion
In summary, we developed a one-step, novel, scalable,
facile and environmentally friendly route for the
synthesis of functionalized 2-aroylbenzofurans via Bi-
(OTf)3-mediated intermolecular double cyclocondensa-
Scheme 6. Synthesis of 6a–1 and 6b–1.
mediated intramolecular annulation of I, (3) oxy- tion of sulfonyl or o-hydroxyacetophenones with
promoted intramolecular pinacol-type rearrangement substituted α-hydroxyketones. Related plausible mech-
of II and sequential ring-opening of the dihydrobenzo- anisms were proposed. The structures of the key
furan ring and (4) a retro-aldol reaction promoted by products were confirmed by X-ray crystallography.
the o-hydroxyl group of III. Salicylic acid was isolated Various metal triflate-mediated reactions and various
from the reaction process in a 40% yield via hydrolysis conditions for efficient transformation were investi-
of the benzoxetone intermediate. Furthermore, α-cyano gated. Further investigations regarding the synthetic
o-hydroxyacetophenone (2w) was tested. However, no application of sulfonyl o-hydroxyacetophenones will
desired 6b was detected, and only 6b–1 was formed in be conducted and published in the future.
a 68% yield via an intramolecular cyclization of 2w
(Scheme 6, eq. 2).
Experimental Section
Indole is an important core skeleton for medicinal
General. Commercially available reagents and solvents were
used without further purification. All reactions were carried by
standard procedures under an air atmosphere (an open-vessel
condition). All products in EtOAc and CH2Cl2 were dried with
anhydrous magnesium sulfate before concentration in vacuo
under reduced pressure. The heating mantle is used to provide a
stable heat source. Melting points (mp) were recorded with a
SMP3 melting apparatus. 1H NMR (400 MHz) and 13C{1H}
NMR (100 MHz) spectroscopic data were measured on a Varian
INOVA-400 spectrometer, respectively. Chemical shift values
(δ) are reported in ppm relative to CDCl3 as the internal
standards, and coupling contants (J values) are reported in Hertz
(Hz). High-resolution mass spectroscopic data (HRMS) were
measured with a double focusing mass spectrometer by ESI
chemistry. Therefore, with this as a synthesis goal, the
Bi(OTf)3-mediated (4+1) annulation of o-aminoaceto-
phenone 1n with 3a was investigated. However, the
expected 7a was not obtained, and only a complex
mixture of unidentified products was obtained
(Scheme 7, eq. 1). On the other hand, the reaction of
2x[46] with 3a did not produce 7b under the standard
conditions (Scheme 7, eq. 2). Although the substrate
was limited to o-aminoacetophenone, it still provided a
novel and efficient synthesis of a sulfonyl 2-aroylben-
zofuran skeleton.
Scheme 7. Reactions of 1n, 2x and 3a.
Scheme 8. Stepwise control experiment.
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using a hybrid ion-trap. X-ray single crystal structures were
determined with a diffractometer (CAD4, Kappa CCD).
136.5, 133.7, 133.1, 129.7 (2×), 128.73 (3×), 128.67 (2×),
128.2 (2×), 127.3, 124.5, 122.8, 117.2, 112.2, 52.3.
For the starting substrates 1a–1n and 3a–3q, these materials
were purchased commercially and were used without further
purification.
(3-Methanesulfonylmethylbenzofuran-2-yl)
phenylmethanone (4d). 4d was prepared according to general
synthetic procedure from 2d (642 mg, 3.0 mmol) and 3a
(442 mg, 3.1 mmol); Yield=76% (716 mg); White solid; mp=
For the starting substrates 2a–2x, these compounds were
°
161–163 C (recrystallized from hexanes and EtOAc); HRMS
1
known and their related analytical data (e.g., HRMS, H NMR
(ESI-TOF) m/z: [M+H]+ calcd for C17H15O4S 315.0691, found
and 13C{1H} NMR) were identical with those in the references
33 and 46.
1
315.0697; H NMR (400 MHz, CDCl3): δ 8.18-8.15 (m, 2H),
7.97 (dt, J=1.2, 8.0 Hz, 1H), 7.67 (dt, J=1.2, 8.0 Hz, 1H),
7.62–7.55 (m, 4H), 7.44 (dt, J=1.6, 8.0 Hz, 1H), 4.98 (s, 2H),
2.97 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 185.3, 154.4,
149.7, 136.5, 133.5, 130.0 (2×), 129.2, 128.6 (2×), 127.4,
124.7, 122.9, 118.3, 112.3, 51.4, 39.8.
General synthetic procedure of skeleton 4is as follows:
Bi(OTf)3 (400 mg, 20 mol%) was added to a stirred solution of
°
2 (3.0 mmol) in MeNO2 (4 mL) at 25 C. The reaction mixture
°
was stirred at 25 C for 10 min. 3 (3.1 mmol) in MeNO2 (1 mL)
°
was added to the reaction mixture at 25 C. The reaction mixture
[3-(n-Butane-1-sulfonylmethyl)benzofuran-2-yl]
°
was stirred at 60 C for 12 h. The reaction mixture was cooled
to 25 C and the solvent was concentrated. The residue was
phenylmethanone (4e). 4e was prepared according to general
synthetic procedure from 2e (768 mg, 3.0 mmol) and 3a
(442 mg, 3.1 mmol); Yield=70% (748 mg); Colorless oil;
HRMS (ESI-TOF) m/z: [M+H]+ calcd for C20H21O4S
357.1161, found 357.1165; 1H NMR (400 MHz, CDCl3): δ
8.17–8.14 (m, 2H), 7.99 (dt, J=1.2, 8.0 Hz, 1H), 7.69–7.65 (m,
1H), 7.61–7.54 (m, 4H), 7.43 (dt, J=1.6, 8.0 Hz, 1H), 4.98 (s,
2H), 3.10 (dt, J=2.0, 6.4 Hz, 2H), 1.90–1.82 (m, 2H), 1.46–
1.36 (m, 2H), 0.89 (t, J=7.6 Hz, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ 185.4, 154.4, 149.6, 136.7, 133.4, 130.0
(2×), 129.0, 128.5 (2×), 127.5, 124.6, 123.0, 118.1, 112.2, 51.9,
50.2, 23.3, 21.7, 13.5.
°
diluted with water (10 mL) and the mixture was extracted with
CH2Cl2 (3×30 mL). The combined organic layers were washed
with brine, dried, filtered and evaporated to afford crude
product under reduced pressure. Purification on silica gel
(hexanes/EtOAc=20/1~8/1) afforded 4.
Phenyl-[3-(toluene-4-sulfonylmethyl)benzofuran-2-yl]
methanone (4a). 4a was prepared according to general
synthetic procedure from 2a (870 mg, 3.0 mmol) and 3a
(442 mg, 3.1 mmol); Yield=85% (995 mg); White solid; mp=
°
167–170 C (recrystallized from hexanes and EtOAc); HRMS
(ESI-TOF) m/z: [M+H]+ calcd for C23H19O4S 391.1004, found
391.1010; 1H NMR (400 MHz, CDCl3): δ 7.96 (dt, J=0.8,
7.6 Hz, 1H), 7.80–7.78 (m, 2H), 7.61–7.57 (m, 1H), 7.55–7.52
(m, 4H), 7.49–7.44 (m, 2H), 7.43 (t, J=8.0 Hz, 1H), 7.07 (d,
J=8.0 Hz, 2H), 5.13 (s, 2H), 2.15 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ 184.7, 154.0, 149.6, 144.7, 136.4, 134.3,
133.0, 129.7 (2×), 129.4 (2×), 128.74 (2×), 128.65, 128.2 (2×),
127.3, 124.4, 122.8, 117.4, 112.2, 52.3, 21.3.
[3-(4-Fluorobenzenesulfonylmethyl)benzofuran-2-yl]
phenylmethanone (4f). 4f was prepared according to general
synthetic procedure from 2f (882 mg, 3.0 mmol) and 3a
(442 mg, 3.1 mmol); Yield=78% (922 mg); White solid; mp=
°
139–141 C (recrystallized from hexanes and EtOAc); HRMS
(ESI-TOF) m/z: [M+H]+ calcd for C22H16FO4S 395.0753,
1
found 395.0759; H NMR (400 MHz, CDCl3): δ 7.95 (dt, J=
1.2, 8.0 Hz, 1H), 7.86–7.83 (m, 2H), 7.73–7.68 (m, 2H), 7.63–
7.59 (m, 1H), 7.58–7.55 (m, 2H), 7.50–7.42 (m, 3H), 7.01–6.95
(m, 2H), 5.16 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3): δ
184.7, 165.8 (d, J=254.8 Hz), 154.1, 149.6, 136.4, 133.5,
133.3, 131.6 (d, J=9.8 Hz, 2×), 129.6 (2×), 128.9, 128.3 (2×),
127.2, 124.6, 122.7, 117.2, 116.0 (d, J=22.0 Hz, 2×), 112.3,
52.4.
Phenyl-[3-(toluene-3-sulfonylmethyl)benzofuran-2-yl]
methanone (4b). 4b was prepared according to general
synthetic procedure from 2b (870 mg, 3.0 mmol) and 3a
(442 mg, 3.1 mmol); Yield=80% (936 mg); White solid; mp=
°
148–150 C (recrystallized from hexanes and EtOAc); HRMS
(ESI-TOF) m/z: [M+H]+ calcd for C23H19O4S 391.1004, found
391.1013; 1H NMR (400 MHz, CDCl3): δ 7.89 (dt, J=0.8,
8.0 Hz, 1H), 7.80–7.77 (m, 2H), 7.58–7.54 (m, 1H), 7.52–7.49
(m, 2H), 7.48–7.36 (m, 5H), 7.18–7.12 (m, 2H), 5.11 (s, 2H),
2.16 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 184.8, 154.0,
149.7, 139.0, 137.4, 136.5, 134.4, 133.1, 129.7 (2×), 128.9,
128.6 (2×), 128.2 (2×), 127.3, 125.7, 124.4, 122.7, 117.1,
112.2, 52.2, 21.0.
[3-(4-Methoxybenzenesulfonylmethyl)benzofuran-2-yl]
phenylmethanone (4g). 4g was prepared according to general
synthetic procedure from 2g (918 mg, 3.0 mmol) and 3a
(442 mg, 3.1 mmol); Yield=82% (999 mg); White solid; mp=
°
128–130 C (recrystallized from hexanes and EtOAc); HRMS
(ESI-TOF) m/z: [M+H]+ calcd for C23H19O5S 407.0953, found
407.0959; 1H NMR (400 MHz, CDCl3): δ 7.95 (dt, J=1.2,
8.0 Hz, 1H), 7.83–7.80 (m, 2H), 7.62–7.53 (m, 5H), 7.49–7.40
(3-Benzenesulfonylmethylbenzofuran-2-yl)phenylmethanone
(4c). 4c was prepared according to general synthetic procedure
from 2c (828 mg, 3.0 mmol) and 3a (442 mg, 3.1 mmol);
(m, 3H), 6.72 (d, J=8.8 Hz, 2H), 5.13 (s, 2H), 3.61 (s, 3H); 13
C
{1H} NMR (100 MHz, CDCl3): δ 184.7, 163.7, 154.0, 149.6,
136.5, 133.0, 130.9 (2×), 129.7 (2×), 128.8, 128.6, 128.2 (2×),
127.3, 124.4, 122.8, 117.6, 113.9 (2×), 112.2, 55.4, 52.4.
°
Yield=80% (903 mg); White solid; mp=151–152 C (recrys-
tallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M
+H]+ calcd for C22H17O4S 377.0848, found 377.0851; 1H NMR
(400 MHz, CDCl3): δ 7.94 (dt, J=1.2, 8.0 Hz, 1H), 7.83–7.80
(m, 2H), 7.72–7.69 (m, 2H), 7.61–7.57 (m, 1H), 7.55–7.54 (m,
2H), 7.49–7.38 (m, 4H), 7.35–7.31 (m, 2H), 5.17 (s, 2H); 13C
{1H} NMR (100 MHz, CDCl3): δ 184.8, 154.1, 149.6, 137.5,
[3-(4-Ethylbenzenesulfonylmethyl)benzofuran-2-yl]
phenylmethanone (4h). 4h was prepared according to general
synthetic procedure from 2h (912 mg, 3.0 mmol) and 3a
(442 mg, 3.1 mmol); Yield=84% (1018 mg); White solid;
°
mp=138–140 C (recrystallized from hexanes and EtOAc);
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HRMS (ESI-TOF) m/z: [M+H]+ calcd for C24H21O4S
405.1161, found 405.1154; H NMR (400 MHz, CDCl3): δ 7.94
129.5 (2×), 128.7 (2×), 128.2 (2×), 117.3, 117.2 (d, J=
26.7 Hz), 113.2 (d, J=9.2 Hz), 108.0 (d, J=25.2 Hz), 52.2,
21.4.
1
(dt, J=1.2, 8.0 Hz, 1H), 7.81–7.78 (m, 2H), 7.60–7.53 (m, 5H),
7.48–7.40 (m, 3H), 7.11 (d, J=8.4 Hz, 2H), 5.15 (s, 2H), 2.46
(q, J=7.6 Hz, 2H), 1.01 (d, J=7.2 Hz, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ 184.7, 154.0, 150.8, 149.5, 136.4, 134.5,
133.0, 129.7 (2×), 128.8 (2×), 128.7, 128.18 (2×), 128.16 (2×),
127.3, 124.4, 122.8, 117.4, 112.2, 52.3, 28.6, 14.7.
[5-Chloro-3-(toluene-4-sulfonylmethyl)benzofuran-2-yl]
phenylmethanone (4m). 4m was prepared according to
general synthetic procedure from 2m (972 mg, 3.0 mmol) and
3a (442 mg, 3.1 mmol); Yield=70% (891 mg); White solid;
°
mp=167–168 C (recrystallized from hexanes and EtOAc);
[3-(4-Isopropylbenzenesulfonylmethyl)benzofuran-2-yl]
phenylmethanone (4i). 4i was prepared according to general
synthetic procedure from 2i (954 mg, 3.0 mmol) and 3a
(442 mg, 3.1 mmol); Yield=80% (1003 mg); White solid;
HRMS (ESI-TOF) m/z: [M+H]+ calcd for C23H18ClO4S
425.0614, found 425.0618; 1H NMR (400 MHz, CDCl3): δ
7.81–7.78 (m, 3H), 7.63–7.58 (m, 1H), 7.56 (d, J=8.4 Hz, 2H),
7.49–7.45 (m, 4H), 7.10 (d, J=8.0 Hz, 2H), 5.07 (s, 2H), 2.18
(s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 184.5, 152.2,
150.8, 145.0, 136.1, 134.2, 133.3, 130.3, 129.7 (2×), 129.5
(2×), 129.0, 128.7 (2×), 128.5, 128.2 (2×), 122.1, 116.6, 113.3,
52.1, 21.4.
°
mp=149–151 C (recrystallized from hexanes and EtOAc);
HRMS (ESI-TOF) m/z: [M+H]+ calcd for C25H23O4S
419.1317, found 419.1322; 1H NMR (400 MHz, CDCl3): δ 7.93
(dt, J=1.2, 8.0 Hz, 1H), 7.83–7.80 (m, 2H), 7.61–7.53 (m, 5H),
7.48–7.39 (m, 3H), 7.15 (d, J=8.0 Hz, 2H), 5.15 (s, 2H), 2.77–
2.70 (m, 1H), 1.02 (d, J=6.8 Hz, 6H); 13C{1H} NMR
(100 MHz, CDCl3): δ 184.7, 155.4, 154.0, 149.5, 136.5, 134.6,
133.0, 129.7 (2×), 128.9 (2×), 128.7, 128.2 (2×), 127.4, 126.8
(2×), 124.4, 122.8, 117.5, 112.2, 52.3, 34.0, 23.3 (2×).
[5-Bromo-3-(toluene-4-sulfonylmethyl)benzofuran-2-yl]
phenylmethanone (4n). 4n was prepared according to general
synthetic procedure from 2n (1104 mg, 3.0 mmol) and 3a
(442 mg, 3.1 mmol); Yield=81% (1137 mg); White solid;
°
mp=170–172 C (recrystallized from hexanes and EtOAc);
[3-(4-n-Butylbenzenesulfonylmethyl)benzofuran-2-yl]
HRMS (ESI-TOF) m/z: [M+H]+ calcd for C23H18BrO4S
1
phenylmethanone (4j). 4j was prepared according to general
synthetic procedure from 2j (996 mg, 3.0 mmol) and 3a
(442 mg, 3.1 mmol); Yield=74% (959 mg); White solid; mp=
469.0109, found 469.0115; H NMR (400 MHz, CDCl3): δ 7.94
(d, J=2.0 Hz, 1H), 7.81–7.79 (m, 2H), 7.62–7.59 (m, 2H), 7.55
(d, J=8.0 Hz, 2H), 7.49–7.45 (m, 2H), 7.42 (t, J=8.8 Hz, 1H),
7.10 (d, J=8.0 Hz, 2H), 5.06 (s, 2H), 2.19 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3): δ 184.5, 152.6, 150.6, 145.0, 136.2,
134.3, 133.3, 131.7, 129.7 (2×), 129.5 (2×), 129.1, 128.7 (2×),
128.3 (2×), 125.2, 117.7, 116.5, 113.7, 52.1, 21.4.
°
125–127 C (recrystallized from hexanes and EtOAc); HRMS
(ESI-TOF) m/z: [M+H]+ calcd for C26H25O4S 433.1474, found
433.1478; 1H NMR (400 MHz, CDCl3): δ 7.94 (dt, J=1.2,
8.4 Hz, 1H), 7.83–7.80 (m, 2H), 7.61–7.52 (m, 5H), 7.48–7.40
(m, 3H), 7.10 (d, J=8.4 Hz, 2H), 5.15 (s, 2H), 2.42 (t, J=
7.6 Hz, 2H), 1.37–1.28 (m, 2H), 1.25–1.16 (m, 2H), 0.84 (d,
J=7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 184.7,
154.0, 149.6, 149.5, 136.5, 134.5, 133.0, 129.7 (2×), 128.74
(2×), 128.68 (2×), 128.6, 128.2 (2×), 127.4, 124.4, 122.8,
117.5, 112.2, 52.3, 35.4, 32.6, 22.2, 13.8.
[5-Methyl-3-(toluene-4-sulfonylmethyl)benzofuran-2-yl]
phenylmethanone (4o). 4o was prepared according to general
synthetic procedure from 2o (912 mg, 3.0 mmol) and 3a
(442 mg, 3.1 mmol); Yield=83% (1006 mg); White solid;
°
mp=157–159 C (recrystallized from hexanes and EtOAc);
HRMS (ESI-TOF) m/z: [M+H]+ calcd for C24H21O4S
405.1161, found 405.1153; 1H NMR (400 MHz, CDCl3): δ
7.80–7.77 (m, 2H), 7.67–7.66 (m, 1H), 7.60–7.53 (m, 3H),
7.48–7.44 (m, 2H), 7.41 (d, J=8.4 Hz, 1H), 7.34 (dd, J=2.0,
8.4 Hz, 1H), 7.07 (d, J=8.4 Hz, 2H), 5.11 (s, 2H), 2.51 (s, 3H),
2.15 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 184.7, 152.6,
149.8, 144.7, 136.5, 134.3, 134.2, 132.9, 130.4, 129.7 (2×),
129.3 (2×), 128.8 (2×), 128.1 (2×), 127.4, 122.0, 117.1, 111.7,
52.3, 21.5, 21.3.
[3-(4-t-Butylbenzenesulfonylmethyl)benzofuran-2-yl]
phenylmethanone (4k). 4k was prepared according to general
synthetic procedure from 2k (996 mg, 3.0 mmol) and 3a
(442 mg, 3.1 mmol); Yield=70% (907 mg); White solid; mp=
°
181–183 C (recrystallized from hexanes and EtOAc); HRMS
(ESI-TOF) m/z: [M+H]+ calcd for C26H25O4S 433.1474, found
433.1470; 1H NMR (400 MHz, CDCl3): δ 7.93 (dt, J=1.2,
8.0 Hz, 1H), 7.82–7.80 (m, 2H), 7.62–7.53 (m, 5H), 7.47–7.40
(m, 3H), 7.31 (d, J=8.4 Hz, 2H), 5.16 (s, 2H), 1.01 (s, 9H); 13
C
[5-Methoxy-3-(toluene-4-sulfonylmethyl)benzofuran-2-yl]
phenylmethanone (4p). 4p was prepared according to general
synthetic procedure from 2p (960 mg, 3.0 mmol) and 3a
(442 mg, 3.1 mmol); Yield=84% (1059 mg); White solid;
{1H} NMR (100 MHz, CDCl3): δ 184.6, 157.7, 154.0, 149.5,
136.5, 134.3, 133.0, 129.7 (2×), 128.7, 128.6 (2×), 128.2 (2×),
127.4, 125.7 (2×), 124.4, 122.8, 117.5, 112.2, 52.2, 35.0, 30.7
(3×).
°
mp=167–169 C (recrystallized from hexanes and EtOAc);
[5-Fluoro-3-(toluene-4-sulfonylmethyl)benzofuran-2-yl]
phenylmethanone (4l). 4l was prepared according to general
synthetic procedure from 2l (870 mg, 3.0 mmol) and 3a
(442 mg, 3.1 mmol); Yield=76% (930 mg); White solid; mp=
HRMS (ESI-TOF) m/z: [M+H]+ calcd for C24H21O5S
421.1110, found 421.1106; 1H NMR (400 MHz, CDCl3): δ
7.78–7.75 (m, 2H), 7.60–7.52 (m, 3H), 7.48–7.43 (m, 2H), 7.42
(dd, J=0.4, 9.2 Hz, 1H), 7.29 (d, J=2.4 Hz, 1H), 7.14 (dd, J=
2.4, 9.2 Hz, 1H), 7.07 (d, J=8.0 Hz, 2H), 5.12 (s, 2H), 3.92 (s,
3H), 2.15 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 184.5,
157.0, 150.2, 149.1, 144.7, 136.5, 134.2, 132.9, 129.7 (2×),
129.3 (2×), 128.8 (2×), 128.1 (2×), 127.9, 119.5, 117.4, 112.9,
102.8, 55.9, 52.4, 21.3.
°
160–162 C (recrystallized from hexanes and EtOAc); HRMS
(ESI-TOF) m/z: [M+H]+ calcd for C23H18FO4S 409.0910,
1
found 409.0905; H NMR (400 MHz, CDCl3): δ 7.80–7.78 (m,
2H), 7.63–7.54 (m, 4H), 7.51–7.45 (m, 3H), 7.26 (dt, J=2.8,
9.2 Hz, 1H), 7.11–7.08 (m, 2H), 5.08 (s, 2H), 2.17 (s, 3H); 13C
{1H} NMR (100 MHz, CDCl3): δ 184.5, 159.8 (d, J=
240.9 Hz), 151.1, 150.2, 144.9, 136.2, 134.2, 133.2, 129.7 (3×),
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[5,7-Dichloro-3-(toluene-4-sulfonylmethyl)benzofuran-2-yl]
phenylmethanone (4q). 4q was prepared according to general
synthetic procedure from 2q (1074 mg, 3.0 mmol) and 3a
(442 mg, 3.1 mmol); Yield=80% (1099 mg); White solid;
(2×), 128.4, 128.2 (2×), 127.8, 127.54 (2×), 127.46, 120.8,
117.5, 112.3, 52.3, 21.3.
[5,7-Difluoro-3-(toluene-4-sulfonylmethyl)benzofuran-2-yl]
phenylmethanone (4u). 4u was prepared according to general
synthetic procedure from 2u (978 mg, 3.0 mmol) and 3a
(442 mg, 3.1 mmol); Yield=72% (920 mg); White solid; mp=
°
mp=223–225 C (recrystallized from hexanes and EtOAc);
HRMS (ESI-TOF) m/z: [M+H]+ calcd for C23H17Cl2O4S
459.0225, found 459.0231; 1H NMR (400 MHz, CDCl3): δ
7.89–7.86 (m, 2H), 7.74 (d, J=2.4 Hz, 1H), 7.64–7.60 (m, 1H),
7.56 (d, J=8.0 Hz, 2H), 7.52 (d, J=2.0 Hz, 1H), 7.51–7.47 (m,
2H), 7.11 (d, J=8.4 Hz, 2H), 5.05 (s, 2H), 2.17 (s, 3H); 13C
{1H} NMR (100 MHz, CDCl3): δ 183.8, 151.1, 148.4, 145.1,
135.8, 134.1, 133.6, 130.5, 129.9 (2×), 129.6 (2×), 129.5, 128.7
(2×), 128.5, 128.4 (2×), 120.8, 118.4, 117.2, 52.1, 21.4.
°
182–184 C (recrystallized from hexanes and EtOAc); HRMS
(ESI-TOF) m/z: [M+H]+ calcd for C23H17F2O4S 427.0816,
1
found 427.0822; H NMR (400 MHz, CDCl3): δ 7.83–7.81 (m,
2H), 7.64–7.59 (m, 1H), 7.56 (d, J=8.4 Hz, 2H), 7.50–7.46 (m,
2H), 7.41 (ddd, J=0.8, 2.4, 7.6 Hz, 1H), 7.10 (d, J=8.0 Hz,
2H), 7.07 (dt, J=2.0, 8.0 Hz, 1H), 5.06 (s, 2H), 2.16 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3): δ 183.0, 159.1 (dd, J=8.4,
243.3 Hz), 151.6, 147.5 (dd, J=13.7, 254.0 Hz), 146.1, 138.0
(d, J=10.6 Hz), 135.7, 134.1, 133.5, 130.3 (d, J=8.4 Hz),
129.8 (2×), 129.5 (2×), 128.7 (2×), 128.3 (2×), 117.6 (d, J=
2.3 Hz), 104.4 (dd, J=19.8, 30.4 Hz), 103.9 (dd, J=4.6,
25.1 Hz), 52.1, 21.3.
[6-Methoxy-3-(toluene-4-sulfonylmethyl)benzofuran-2-yl]
phenylmethanone (4r). 4r was prepared according to general
synthetic procedure from 2r (960 mg, 3.0 mmol) and 3a
(442 mg, 3.1 mmol); Yield=78% (983 mg); White solid; mp=
°
214–216 C (recrystallized from hexanes and EtOAc); HRMS
(ESI-TOF) m/z: [M+H]+ calcd for C24H21O5S 421.1110, found
Phenyl-[3-(toluene-4-sulfonylmethyl)naphtho[1,2-b]furan-2-
yl]methanone (4v). 4v was prepared according to general
synthetic procedure from 2v (1020 mg, 3.0 mmol) and 3a
(442 mg, 3.1 mmol); Yield=73% (964 mg); White solid; mp=
1
421.1118; H NMR (400 MHz, CDCl3): δ 7.81 (d, J=8.8 Hz,
1H), 7.77–7.75 (m, 2H), 7.59–7.52 (m, 3H), 7.47–7.43 (m, 2H),
7.08–7.03 (m, 3H), 6.99 (d, J=2.0 Hz, 1H), 5.11 (s, 2H), 3.89
(s, 3H), 2.16 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ
184.2, 161.4, 155.5, 149.2, 144.7, 136.5, 134.3, 132.7, 129.5
(2×), 129.3 (2×), 128.7 (2×), 128.1 (2×), 123.3, 120.8, 118.0,
114.8, 95.3, 55.8, 52.4, 21.3. Single-crystal X-Ray diagram:
crystal of compound 4r was grown by slow diffusion of EtOAc
into a solution of compound 4r in CH2Cl2 to yield colorless
prisms. The compound crystallizes in the orthorhombic crystal
system, space group P212121, a=12.1688(4) Å, b=12.6853(3)
°
232–234 C (recrystallized from hexanes and EtOAc); HRMS
(ESI-TOF) m/z: [M+H]+ calcd for C27H21O4S 441.1161, found
1
441.1152; H NMR (400 MHz, CDCl3): δ 8.27–8.25 (m, 1H),
8.01–7.99 (m, 1H), 7.92 (d, J=8.8 Hz, 1H), 7.86–7.85 (m, 2H),
7.80 (d, J=8.8 Hz, 1H), 7.66–7.60 (m, 3H), 7.58–7.49 (m, 4H),
7.06 (d, J=8.0 Hz, 2H), 5.22 (s, 2H), 2.15 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3): δ 184.0, 150.7, 149.3, 144.7, 136.8,
134.2, 133.7, 133.0, 132.8, 129.8 (2×), 129.5, 129.3 (2×), 128.8
(2×), 128.7, 128.2 (2×), 127.3, 127.0, 125.5, 120.7, 119.5,
118.8, 52.4, 21.3.
Å, c=13.1517(4) Å, V=2030.16(10) Å3, Z=4, dcalcd =1.376 g/
3
°
cm , F(000)=880, 2θ range 2.231~27.016 , R indices (all
data) R1=0.0871, wR2=0.1796.
(4-Fluorophenyl)-[3-(toluene-4-sulfonylmethyl)benzofuran-
2-yl]methanone (4w). 4w was prepared according to general
synthetic procedure from 2a (870 mg, 3.0 mmol) and 3b
(477 mg, 3.1 mmol); Yield=75% (918 mg); White solid; mp=
[5-Bromo-3-(toluene-4-sulfonylmethyl)naphtho[1,2-b]furan-
2-yl]phenylmethanone (4s). 4s was prepared according to
general synthetic procedure from 2s (1254 mg, 3.0 mmol) and
3a (442 mg, 3.1 mmol); Yield=74% (1150 mg); White solid;
°
162–164 C (recrystallized from hexanes and EtOAc); HRMS
°
mp=224–226 C (recrystallized from hexanes and EtOAc);
(ESI-TOF) m/z: [M+H]+ calcd for C23H18FO4S 409.0910,
HRMS (ESI-TOF) m/z: [M+H]+ calcd for C27H20BrO4S
519.0266, found 519.0274; 1H NMR (400 MHz, CDCl3): δ 8.39
(dd, J=1.2, 8.0 Hz, 1H), 8.27 (dd, J=1.6, 8.4 Hz, 1H), 8.11 (s,
1H), 7.89–7.87 (m, 2H), 7.76–7.62 (m, 3H), 7.57 (d, J=8.4 Hz,
2H), 7.54–7.50 (m, 2H), 7.10 (d, J=8.4 Hz, 2H), 5.17 (s, 2H),
2.19 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 183.9, 150.1,
149.7, 145.0, 136.6, 134.3, 133.1, 131.5, 129.8 (2×), 129.5
(2×), 128.8 (2×), 128.6, 128.4, 128.3 (2×), 127.9, 124.0, 123.0,
121.8, 121.1, 119.4, 118.0, 52.3, 21.4.
1
found 409.0916; H NMR (400 MHz, CDCl3): δ 7.94–7.87 (m,
3H), 7.55–7.53 (m, 4H), 7.44–7.40 (m, 1H), 7.17–7.13 (m, 2H),
7.08 (d, J=8.4 Hz, 2H), 5.12 (s, 2H), 2.18 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3): δ 182.9, 165.6 (d, J=254.0 Hz),
154.0, 149.5, 144.7, 134.4, 132.7 (d, J=3.1 Hz), 132.5 (d, J=
9.1 Hz, 2×), 129.3 (2×), 128.8, 128.7 (2×), 127.3, 124.5, 122.8,
117.6, 115.4 (d, J=22.0 Hz, 2×), 112.1, 52.3, 21.4.
(4-Methoxyphenyl)-[3-(toluene-4-sulfonylmethyl)
benzofuran-2-yl]methanone (4x). 4x was prepared according
to general synthetic procedure from 2a (870 mg, 3.0 mmol) and
3c (515 mg, 3.1 mmol); Yield=80% (1008 mg); White solid;
Phenyl-[5-phenyl-3-(toluene-4-sulfonylmethyl)benzofuran-2-
yl]methanone (4t). 4t was prepared according to general
synthetic procedure from 2t (1098 mg, 3.0 mmol) and 3a
(442 mg, 3.1 mmol); Yield=70% (979 mg); White solid; mp=
°
mp=146–148 C (recrystallized from hexanes and EtOAc);
HRMS (ESI-TOF) m/z: [M+H]+ calcd for C24H21O5S
°
188–190 C (recrystallized from hexanes and EtOAc); HRMS
1
421.1110, found 421.1118; H NMR (400 MHz, CDCl3): δ 7.93
(ESI-TOF) m/z: [M+H]+ calcd for C29H23O4S 467.1317, found
(dt, J=1.2, 8.0 Hz, 1H), 7.86 (d, J=9.2 Hz, 2H), 7.56–7.50 (m,
4H), 7.41 (dt, J=2.0, 8.0 Hz, 1H), 7.05 (d, J=8.4 Hz, 2H),
6.94 (d, J=8.8 Hz, 2H), 5.12 (s, 2H), 3.90 (s, 3H), 2.15 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3): δ 183.0, 163.6, 153.8, 150.1,
144.6, 134.3, 132.3 (2×), 129.3 (2×), 128.7 (3×), 128.3, 127.3,
124.3, 122.6, 116.6, 113.5 (2×), 112.0, 55.5, 52.2, 21.3.
1
467.1324; H NMR (400 MHz, CDCl3): δ 8.01 (d, J=2.0 Hz,
1H), 7.84–7.82 (m, 2H), 7.77 (dd, J=2.0, 8.4 Hz, 1H), 7.66–
7.55 (m, 6H), 7.51–7.47 (m, 4H), 7.41–7.37 (m, 1H), 7.08 (d,
J=8.0 Hz, 2H), 5.17 (s, 2H), 2.14 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ 184.7, 153.6, 150.3, 144.8, 140.6, 138.1,
136.5, 134.4, 133.1, 129.8 (2×), 129.4 (2×), 128.9 (2×), 128.8
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[3-(Toluene-4-sulfonylmethyl)benzofuran-2-yl]-p–tolylme-
thanone (4y). 4y was prepared according to general synthetic
procedure from 2a (870 mg, 3.0 mmol) and 3d (633 mg,
3.1 mmol); Yield=81% (982 mg); White solid; mp=151–
451.1215, found 451.1223; 1H NMR (400 MHz, CDCl3): δ 7.93
(dt, J=0.8, 8.0 Hz, 1H), 7.63 (dd, J=2.0, 8.4 Hz, 1H), 7.57–
7.53 (m, 4H), 7.44–7.40 (m, 2H), 7.08 (d, J=8.4 Hz, 2H), 6.92
(d, J=8.4 Hz, 1H), 5.12 (s, 2H), 3.99 (s, 3H), 3.95 (s, 3H), 2.18
(s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 182.9, 153.9,
153.6, 150.2, 148.8, 144.6, 134.5, 129.4 (2×), 129.3, 128.7
(2×), 128.4, 127.4, 125.4, 124.4, 122.7, 116.7, 112.0, 111.8,
109.8, 56.2, 56.0, 52.3, 21.4.
°
153 C (recrystallized from hexanes and EtOAc); HRMS (ESI-
TOF) m/z: [M+H]+ calcd for C24H21O4S 405.1161, found
405.1170; 1H NMR (400 MHz, CDCl3): δ 7.95 (dt, J=0.8,
8.0 Hz, 1H), 7.71 (d, J=8.4 Hz, 2H), 7.54–7.52 (m, 4H), 7.42
(dt, J=2.8, 8.0 Hz, 1H), 7.26 (d, J=8.0 Hz, 2H), 7.06 (d, J=
8.0 Hz, 2H), 5.12 (s, 2H), 2.45 (s, 3H), 2.15 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3): δ 184.3, 154.0, 149.9, 144.7, 144.0,
134.3, 133.9, 129.9 (2×), 129.4 (2×), 128.9 (2×), 128.7 (2×),
128.5, 127.4, 124.4, 122.8, 117.0, 112.1, 52.3, 21.7, 21.3.
Benzo[1,3]dioxol-5-yl-[3-(toluene-4-sulfonylmethyl)
benzofuran-2-yl]methanone (4ad). 4ad was prepared accord-
ing to general synthetic procedure from 2a (870 mg, 3.0 mmol)
and 3i (558 mg, 3.1 mmol); Yield=74% (964 mg); White solid;
°
mp=160–162 C (recrystallized from hexanes and EtOAc);
[3-(Toluene-4-sulfonylmethyl)benzofuran-2-yl]-(4-
HRMS (ESI-TOF) m/z: [M+H]+ calcd for C24H19O6S
1
trifluoromethylphenyl)methanone (4z). 4z was prepared
according to general synthetic procedure from 2a (870 mg,
3.0 mmol) and 3e (633 mg, 3.1 mmol); Yield=82% (1127 mg);
435.0902, found 435.0911; H NMR (400 MHz, CDCl3): δ 7.93
(dt, J=0.8, 8.0 Hz, 1H), 7.56–7.50 (m, 5H), 7.42 (dt, J=2.0,
8.0 Hz, 1H), 7.30 (d, J=1.6 Hz, 1H), 7.08 (d, J=8.0 Hz, 2H),
6.87 (d, J=8.0 Hz, 1H), 6.08 (s, 2H), 5.11 (s, 2H), 2.20 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3): δ 182.6, 153.9, 151.9, 149.9,
147.7, 144.7, 134.4, 130.9, 129.4 (2×), 128.7 (2×), 128.4,
127.3, 126.7, 124.4, 122.7, 117.0, 112.1, 109.6, 107.8, 101.9,
52.3, 21.4.
°
White solid; mp=145–147 C (recrystallized from hexanes and
EtOAc); HRMS (ESI-TOF) m/z: [M+H]+ calcd for
1
C24H18F3O4S 459.0878, found 459.0885; H NMR (400 MHz,
CDCl3): δ 7.95 (dt, J=0.8, 8.0 Hz, 1H), 7.92 (d, J=8.0 Hz,
2H), 7.74 (d, J=8.4 Hz, 2H), 7.60–7.53 (m, 4H), 7.44 (dt, J=
2.0, 8.4 Hz, 1H), 7.11 (d, J=8.0 Hz, 2H), 5.14 (s, 2H), 2.19 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3): δ 183.6, 154.2, 149.0,
144.8, 139.3, 134.5, 134.0, 130.0 (2×), 129.4 (2×), 129.2, 128.8
(2×), 127.2, 125.2 (q, J=3.8 Hz, 2×), 124.7, 124.3 (q, J=
283.5 Hz), 123.0, 118.4, 112.2, 52.3, 21.3.
[3-(Toluene-4-sulfonylmethyl)benzofuran-2-yl]-(3,4,5-
trimethoxyphenyl)methanone (4ae). 4ae was prepared ac-
cording to general synthetic procedure from 2a (870 mg,
3.0 mmol) and 3j (701 mg, 3.1 mmol); Yield=78% (1123 mg);
°
White solid; mp=156–158 C (recrystallized from hexanes and
(4-Bromophenyl)-[3-(toluene-4-sulfonylmethyl)benzofuran-
2-yl]methanone (4aa). 4aa was prepared according to general
synthetic procedure from 2a (870 mg, 3.0 mmol) and 3f
(663 mg, 3.1 mmol); Yield=78% (1095 mg); White solid;
EtOAc); HRMS (ESI-TOF) m/z: [M+H]+ calcd for C26H25O7S
481.1321, found 481.1328; 1H NMR (400 MHz, CDCl3): δ 7.93
(dt, J=0.8, 8.0 Hz, 1H), 7.59 (d, J=8.4 Hz, 2H), 7.55–7.52 (m,
2H), 7.43 (dt, J=1.6, 8.0 Hz, 1H), 7.17 (s, 2H), 7.11 (d, J=
8.0 Hz, 2H), 5.12 (s, 2H), 3.96 (s, 3H), 3.91 (s, 6H), 2.22 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3): δ 183.3, 153.9, 152.7
(2×), 149.9, 144.7, 134.7, 131.4, 129.5, 129.4 (2×), 128.7 (2×),
128.6, 127.3, 124.5, 122.8, 117.2, 112.0, 107.6 (2×), 61.0, 56.3
(2×), 52.3, 21.4.
°
mp=182–184 C (recrystallized from hexanes and EtOAc);
HRMS (ESI-TOF) m/z: [M+H]+ calcd for C23H18BrO4S
1
469.0109, found 469.0118; H NMR (400 MHz, CDCl3): δ 7.94
(dt, J=0.8, 8.0 Hz, 1H), 7.70 (d, J=8.8 Hz, 2H), 7.61 (d, J=
8.8 Hz, 2H), 7.56–7.53 (m, 4H), 7.43 (dt, J=1.6, 8.0 Hz, 1H),
7.09 (d, J=8.0 Hz, 2H), 5.12 (s, 2H), 2.19 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3): δ 183.5, 154.0, 149.3, 144.8, 135.1,
134.4, 131.5 (2×), 131.2 (2×), 129.4 (2×), 128.9, 128.7 (2×),
128.3, 127.3, 124.6, 122.9, 117.8, 112.2, 52.3, 21.4.
Naphthalen-2-yl-[3-(toluene-4-sulfonylmethyl)benzofuran-2-
yl]methanone (4af). 4af was prepared according to general
synthetic procedure from 2a (870 mg, 3.0 mmol) and 3k
(577 mg, 3.1 mmol); Yield=74% (977 mg); White solid; mp=
°
Biphenyl-4-yl-[3-(toluene-4-sulfonylmethyl)benzofuran-2-yl]
methanone (4ab). 4ab was prepared according to general
synthetic procedure from 2a (870 mg, 3.0 mmol) and 3g
(657 mg, 3.1 mmol); Yield=76% (1063 mg); White solid;
189–191 C (recrystallized from hexanes and EtOAc); HRMS
(ESI-TOF) m/z: [M+H]+ calcd for C27H21O4S 441.1161, found
1
441.1157; H NMR (400 MHz, CDCl3): δ 8.32 (s, 1H), 8.00–
7.89 (m, 4H), 7.82 (dd, J=1.6, 8.4 Hz, 1H), 7.66–7.54 (m, 6H),
7.45 (dt, J=2.0, 8.4 Hz, 1H), 7.02 (d, J=8.4 Hz, 2H), 5.16 (s,
2H), 1.94 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 184.6,
154.0, 149.9, 144.7, 135.4, 134.2, 133.6, 132.1, 132.0, 129.7,
129.3 (2×), 128.8, 128.7 (2×), 128.6, 128.0, 127.8, 127.4,
126.9, 125.0, 124.5, 122.8, 117.2, 112.2, 52.2, 21.1.
°
mp=190–192 C (recrystallized from hexanes and EtOAc);
HRMS (ESI-TOF) m/z: [M+H]+ calcd for C29H23O4S
467.1317, found 467.1322; 1H NMR (400 MHz, CDCl3): δ 7.97
(dt, J=0.8, 8.0 Hz, 1H), 7.91 (d, J=8.4 Hz, 2H), 7.61–7.65 (m,
4H), 7.57–7.41 (m, 8H), 7.08 (d, J=8.0 Hz, 2H), 5.16 (s, 2H),
2.15 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 184.1, 154.0,
149.8, 145.8, 144.7, 139.8, 135.1, 134.3, 130.4 (2×), 129.4
(2×), 129.0 (2×), 128.8 (2×), 128.6, 128.4, 127.3, 127.3 (2×),
126.8 (2×), 124.5, 122.8, 117.3, 112.2, 52.3, 21.4.
Thiophen-2-yl-[3-(toluene-4-sulfonylmethyl)benzofuran-2-
yl]methanone (4ag). 4ag was prepared according to general
synthetic procedure from 2a (870 mg, 3.0 mmol) and 3l
(440 mg, 3.1 mmol); Yield=70% (832 mg); White solid; mp=
°
(3,4-Dimethoxyphenyl)-[3-(toluene-4-sulfonylmethyl)
197–199 C (recrystallized from hexanes and EtOAc); HRMS
benzofuran-2-yl]methanone (4ac). 4ac was prepared accord-
ing to general synthetic procedure from 2a (870 mg, 3.0 mmol)
and 3h (608 mg, 3.1 mmol); Yield=74% (999 mg); White
(ESI-TOF) m/z: [M+H]+ calcd for C21H17O4S2 397.0568, found
397.0562; 1H NMR (400 MHz, CDCl3): δ 8.17 (dd, J=1.2,
4.0 Hz, 1H), 7.94 (dt, J=0.8, 8.0 Hz, 1H), 7.73 (dd, J=1.2,
4.8 Hz, 1H), 7.61–7.52 (m, 4H), 7.43 (dt, J=1.6, 8.0 Hz, 1H),
7.20 (dd, J=4.0, 4.8 Hz, 1H), 7.08 (d, J=8.4 Hz, 2H), 5.13 (s,
°
solid; mp=173-175 C (recrystallized from hexanes and
EtOAc); HRMS (ESI-TOF) m/z: [M+H]+ calcd for C25H23O6S
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2H), 2.18 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 175.2,
154.0, 148.9, 144.8, 142.4, 135.0, 134.9, 134.2, 129.3 (2×),
128.8 (3×), 128.3, 127.4, 124.5, 122.9, 117.4, 112.0, 52.2, 21.4.
(3-Methylbenzofuran-2-yl)phenylmethanone (5a). 5a was
prepared according to general synthetic procedure from 1a
(408 mg, 3.0 mmol) and 3a (422 mg, 3.1 mmol); Yield=90%
(637 mg); Colorless oil; HRMS (ESI-TOF) m/z: [M+H]+ calcd
1-[3-(Toluene-4-sulfonylmethyl)benzofuran-2-yl]ethanone
(4ah). 4ah was prepared according to general synthetic
procedure from 2a (870 mg, 3.0 mmol) and 3m (229 mg,
3.1 mmol); Yield=65% (640 mg); White solid; mp=200–
1
for C16H13O2 237.0916, found 237.0922; H NMR (400 MHz,
CDCl3): δ 8.13–8.10 (m, 2H), 7.69 (d, J=7.6 Hz, 1H), 7.62–
7.58 (m, 1H), 7.54–7.46 (m, 4H), 7.35–7.31 (m, 1H), 2.65 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3): δ 185.7, 154.1, 148.2,
137.7, 132.4, 129.6 (2×), 129.0, 128.2 (2×), 128.1, 126.7,
123.2, 121.3, 112.1, 9.90.
°
202 C (recrystallized from hexanes and EtOAc); HRMS (ESI-
TOF) m/z: [M+H]+ calcd for C18H17O4S 329.0848, found
329.0857; 1H NMR (400 MHz, CDCl3): δ 7.87 (dt, J=1.2,
7.6 Hz, 1H), 7.57 (d, J=8.4 Hz, 2H), 7.53–7.52 (m, 2H), 7.38
(dt, J=4.0, 7.6 Hz, 1H), 7.22 (d, J=8.0 Hz, 2H), 5.03 (s, 2H),
2.40 (s, 3H), 2.39 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ
190.4, 153.9, 149.2, 144.7, 134.9, 129.3 (2×), 128.7 (2×),
128.7, 127.5, 124.3, 123.0, 114.8, 112.1, 52.2, 27.2, 21.6.
(4-Fluorophenyl)-(3-methylbenzofuran-2-yl)methanone
(5b). 5b was prepared according to general synthetic procedure
from 1a (408 mg, 3.0 mmol) and 3b (477 mg, 3.1 mmol);
Yield=84% (640 mg); Colorless oil; HRMS (ESI-TOF) m/z:
1
[M+H]+ calcd for C16H12FO2 255.0821, found 255.0826; H
NMR (400 MHz, CDCl3): δ 8.20–8.15 (m, 2H), 7.71 (dt, J=
0.8, 8.0 Hz, 1H), 7.54 (dt, J=0.8, 8.4 Hz, 1H), 7.50 (dt, J=1.2,
8.4 Hz, 1H), 7.35 (dt, J=1.2, 8.0 Hz, 1H), 7.23–7.17 (m, 2H),
2.66 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 184.1, 165.4
(d, J=252.5 Hz), 154.2, 148.1, 134.0 (d, J=3.1 Hz), 132.4 (d,
J=9.1 Hz, 2×), 129.1, 128.3, 127.2, 123.4, 121.4, 115.4 (d, J=
22.0 Hz, 2×), 112.2, 10.0.
1,2-Diphenyl-2-{2-[2-(toluene-4-sulfonyl)acetyl]phenoxy}
ethanone (4aj–1). 4aj–1 was prepared according to general
synthetic procedure from 2a (870 mg, 3.0 mmol) and 3o
(657 mg, 3.1 mmol); Yield=47% (683 mg); White solid; mp=
°
154–156 C (recrystallized from hexanes and EtOAc); HRMS
(ESI-TOF) m/z: [M+H]+ calcd for C29H25O5S 485.1423, found
1
485.1436; H NMR (400 MHz, CDCl3): δ 8.00–7.98 (m, 2H),
7.67 (d, J=8.4 Hz, 2H), 7.61 (dd, J=1.6, 7.6 Hz, 1H), 7.59–
7.53 (m, 3H), 7.47–7.33 (m, 6H), 7.23 (d, J=8.4 Hz, 2H), 6.98
(dt, J=0.4, 7.6 Hz, 1H), 6.79 (d, J=8.8 Hz, 1H), 6.60 (s, 1H),
5.22 (d, J=14.4 Hz, 1H), 4.97 (d, J=14.4 Hz, 1H), 2.40 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3): δ 193.8, 189.7, 156.7,
144.5, 136.7, 134.6, 134.2, 134.0, 133.9, 131.4, 129.5 (3×),
129.4 (2×), 128.9 (2×), 128.8 (2×), 128.4 (2×), 128.2 (2×),
127.6, 121.8, 113.5, 82.4, 67.2, 21.6.
(4-Methoxyphenyl)-(3-methylbenzofuran-2-yl)methanone
(5c). 5c was prepared according to general synthetic procedure
from 1a (408 mg, 3.0 mmol) and 3c (515 mg, 3.1 mmol);
°
Yield=82% (655 mg); White solid; mp=91–93 C (recrystal-
lized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M+
1
H]+ calcd for C17H15O3 267.1021, found 267.1028; H NMR
(400 MHz, CDCl3): δ 8.16 (d, J=9.2 Hz, 2H), 7.69 (dt, J=0.4,
8.0 Hz, 1H), 7.54 (dt, J=0.4, 8.4 Hz, 1H), 7.47 (dt, J=1.2,
8.4 Hz, 1H), 7.33 (dt, J=1.2, 8.0 Hz, 1H), 7.01 (d, J=9.2 Hz,
2H), 3.90 (s, 3H), 2.66 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3): δ 181.3, 163.3, 154.1, 148.6, 132.2 (2×), 130.5, 129.2,
127.8, 126.1, 123.2, 121.2, 113.6 (2×), 112.1, 55.4, 9.9.
1-[2-(2,3-Dihydro-1aH-1-oxacyclopropa[a]naphthalen-7b-
yloxy)phenyl]-2-(toluene-4-sulfonyl)ethanone (4ak–1). 4ak–
1 was prepared according to general synthetic procedure from
2a (870 mg, 3.0 mmol) and 3p (502 mg, 3.1 mmol); Yield=
°
36% (469 mg); White solid; mp=168–169 C (recrystallized
(3-Methylbenzofuran-2-yl)-p-tolylmethanone (5d). 5d was
prepared according to general synthetic procedure from 1a
(408 mg, 3.0 mmol) and 3d (465 mg, 3.1 mmol); Yield=80%
(600 mg); Colorless oil; HRMS (ESI-TOF) m/z: [M+H]+ calcd
from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M+H]+
calcd for C25H23O5S 435.1266, found 435.1274; 1H NMR
(400 MHz, CDCl3): δ 8.05 (dd, J=0.8, 7.6 Hz, 1H), 7.76 (d,
J=8.0 Hz, 2H), 7.52 (dt, J=1.2, 7.2 Hz, 1H), 7.35–7.23 (m,
6H), 6.95 (dt, J=1.2, 7.6 Hz, 1H), 6.81 (d, J=8.4 Hz, 1H),
4.60 (d, J=14.0 Hz, 1H), 4.43 (br s, 1H), 3.94 (d, J=13.6 Hz,
1H), 3.48–3.39 (m, 1H), 3.12–3.00 (m, 2H), 2.88–2.83 (m, 1H),
2.44 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 191.2, 157.0,
145.4, 143.6, 136.9, 133.7, 131.7, 131.23, 131.16, 130.0 (2×),
128.5, 128.3, 127.8 (2×), 126.8, 123.1, 121.7, 111.1, 91.8, 80.6,
59.2, 27.9, 25.7, 21.7.
1
for C17H15O2 251.1072, found 251.1078; H NMR (400 MHz,
CDCl3): δ 8.04 (d, J=8.0 Hz, 2H), 7.68 (dt, J=0.8, 8.0 Hz,
1H), 7.54 (dt, J=0.8, 8.4 Hz, 1H), 7.47 (dt, J=1.2, 8.0 Hz,
1H), 7.35-7.31 (m, 3H), 2.65 (s, 3H), 2.45 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3): δ 185.4, 154.1, 148.3, 143.3, 135.1,
129.8 (2×), 129.1, 128.9 (2×), 127.9, 126.3, 123.1, 121.2,
112.0, 21.6, 9.9.
(3-Methylbenzofuran-2-yl)-(4-trifluoromethylphenyl)
General synthetic procedure of skeleton 5is as follows:
Bi(OTf)3 (400 mg, 20 mol%) was added to a stirred solution of
methanone (5e). 5e was prepared according to general
synthetic procedure from 1a (408 mg, 3.0 mmol) and 3e
(633 mg, 3.1 mmol); Yield=84% (766 mg); White solid; mp=
°
1 (3.0 mmol) in MeNO2 (4 mL) at 25 C. The reaction mixture
°
°
was stirred at 25 C for 10 min. 3 (3.1 mmol) in MeNO2 (1 mL)
92–94 C (recrystallized from hexanes and EtOAc); HRMS
was added to the reaction mixture at 25 C. The reaction mixture
(ESI-TOF) m/z: [M+H]+ calcd for C17H12F3O2 305.0789, found
°
1
°
was stirred at 60 C for 12 h. The reaction mixture was cooled
to 25 C and the solvent was concentrated. The residue was
305.0796; H NMR (400 MHz, CDCl3): δ 8.21-8.18 (m, 2H),
°
7.81–7.78 (m, 2H), 7.73 (dt, J=1.2, 8.0 Hz, 1H), 7.55-7.50 (m,
2H), 7.36 (dt, J=0.8, 8.0 Hz, 1H), 2.69 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ 184.7, 154.4, 147.8, 140.71, 140.70,
133.7 (q, J=32.9 Hz), 130.0 (2×), 129.0, 128.7, 128.2, 125.3
(q, J=3.8 Hz, 2×), 123.7 (q, J=271.1 Hz), 123.5, 121.6, 10.1.
diluted with water (10 mL) and the mixture was extracted with
CH2Cl2 (3×30 mL). The combined organic layers were washed
with brine, dried, filtered and evaporated to afford crude
product under reduced pressure. Purification on silica gel
(hexanes/EtOAc=20/1~8/1) afforded 5.
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(4-Bromophenyl)-(3-methylbenzofuran-2-yl)methanone (5f).
5f was prepared according to general synthetic procedure from
1a (408 mg, 3.0 mmol) and 3f (663 mg, 3.1 mmol); Yield=
184.5, 154.2, 152.9 (2×), 148.3, 142.3, 132.7, 129.2, 128.2,
126.8, 123.4, 121.4, 112.0, 107.5 (2×), 61.0, 56.3 (2×), 10.1.
(3-Methylbenzofuran-2-yl)naphthalen-2-ylmethanone (5k).
5k was prepared according to general synthetic procedure from
1a (408 mg, 3.0 mmol) and 3k (577 mg, 3.1 mmol); Yield=
°
80% (754 mg); White solid; mp=100–102 C (recrystallized
from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M+H]+
calcd for C16H12BrO2 315.0021, found 315.0014; 1H NMR
(400 MHz, CDCl3): δ 7.98 (d, J=8.8 Hz, 2H), 7.68 (dt, J=0.8,
8.8 Hz, 1H), 7.65 (d, J=8.8 Hz, 2H), 7.53–7.47 (m, 2H), 7.33
(dt, J=1.6, 8.0 Hz, 1H), 2.65 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ 184.4, 154.1, 147.9, 136.3, 131.5 (2×),
131.2 (2×), 129.0, 128.3, 127.6, 127.4, 123.3, 121.4, 112.1,
10.0.
°
70% (601 mg); White solid; mp=84–86 C (recrystallized from
hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M+H]+ calcd
1
for C20H15O2 287.1072, found 287.1080; H NMR (400 MHz,
CDCl3): δ 8.68 (s, 1H), 8.14 (dd, J=2.0, 8.4 Hz, 1H), 8.01 (d,
J=8.4 Hz, 1H), 7.97 (d, J=8.8 Hz, 1H), 7.92 (d, J=8.4 Hz,
1H), 7.73 (d, J=8.0 Hz, 1H), 7.63 (dt, J=1.6, 8.0 Hz, 1H),
7.59 (dd, J=1.2, 8.0 Hz, 1H), 7.57 (dt, J=1.6, 8.0 Hz, 1H),
7.52 (dt, J=1.2, 8.4 Hz, 1H), 7.37 (dt, J=1.6, 7.6 Hz, 1H),
2.68 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 185.8, 154.3,
148.5, 135.3, 135.1, 132.4, 131.6, 129.7, 129.2, 128.3, 128.2,
128.1, 127.8, 126.8, 126.6, 125.4, 123.3, 121.4, 112.2, 10.1.
Biphenyl-4-yl-(3-methylbenzofuran-2-yl)methanone (5g). 5g
was prepared according to general synthetic procedure from 1a
(408 mg, 3.0 mmol) and 3g (657 mg, 3.1 mmol); Yield=76%
(712 mg); Colorless oil; HRMS (ESI-TOF) m/z: [M+H]+ calcd
1
for C22H17O2 313.1229, found 313.1233; H NMR (400 MHz,
(3-Methylbenzofuran-2-yl)thiophen-2-ylmethanone (5l). 5l
was prepared according to general synthetic procedure from 1a
(408 mg, 3.0 mmol) and 3l (440 mg, 3.1 mmol); Yield=76%
(552 mg); Colorless oil; HRMS (ESI-TOF) m/z: [M+H]+ calcd
CDCl3): δ 8.23 (d, J=8.0 Hz, 2H), 7.78–7.68 (m, 5H), 7.58 (dt,
J=0.8, 8.4 Hz, 1H), 7.53–7.48 (m, 3H), 7.43 (dt, J=1.2,
8.0 Hz, 1H), 7.36 (dt, J=1.2, 8.0 Hz, 1H), 2.70 (s, 3H); 13C
{1H} NMR (100 MHz, CDCl3): δ 185.2, 154.1, 148.3, 145.2,
139.9, 136.4, 130.3 (2×), 129.1, 128.8 (2×), 128.09, 128.06,
127.2 (2×), 126.9 (2×), 126.8, 123.2, 121.3, 112.1, 10.0.
1
for C14H11O2S 243.0480, found 243.0485; H NMR (400 MHz,
CDCl3): δ 8.39 (dd, J=1.2, 4.0 Hz, 1H), 7.72 (dd, J=0.8,
4.8 Hz, 1H), 7.67 (dt, J=1.2, 8.0 Hz, 1H), 7.55 (dt, J=0.8,
8.4 Hz, 1H), 7.49 (dt, J=1.2, 8.4 Hz, 1H), 7.32 (dt, J=1.2,
8.4 Hz, 1H), 7.22 (dd, J=4.0, 4.8 Hz, 1H), 2.69 (s, 3H); 13C
{1H} NMR (100 MHz, CDCl3): δ 176.4, 154.1, 147.4, 143.4,
134.3, 134.2, 129.1, 128.20, 128.18, 127.1, 123.3, 121.3, 112.0,
9.8.
(3,4-Dimethoxyphenyl)-(3-methylbenzofuran-2-yl)
methanone (5h). 5h was prepared according to general
synthetic procedure from 1a (408 mg, 3.0 mmol) and 3h
(608 mg, 3.1 mmol); Yield=80% (711 mg); White solid; mp=
°
57–59 C (recrystallized from hexanes and EtOAc); HRMS
(ESI-TOF) m/z: [M+H]+ calcd for C18H17O4 297.1127, found
297.1136; 1H NMR (400 MHz, CDCl3): δ 7.89 (dd, J=2.0,
8.4 Hz, 1H), 7.66 (d, J=2.0 Hz, 1H), 7.65 (dt, J=1.6, 8.4 Hz,
1H), 7.51 (dt, J=0.8, 8.4 Hz, 1H), 7.44 (dt, J=1.2, 8.4 Hz,
1H), 7.29 (dt, J=1.2, 8.0 Hz, 1H), 6.94 (d, J=8.4 Hz, 1H),
3.94 (s, 6H), 2.61 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ
183.9, 153.9, 153.0, 148.7, 148.4, 130.4, 129.1, 127.8, 126.1,
124.8, 123.1, 121.1, 111.9 (2×), 109.9, 55.9, 55.8, 9.9.
(5-Fluoro-3-methylbenzofuran-2-yl)phenylmethanone (5m).
5m was prepared according to general synthetic procedure from
1b (462 mg, 3.0 mmol) and 3a (422 mg, 3.1 mmol); Yield=
80% (610 mg); Colorless oil; HRMS (ESI-TOF) m/z: [M+H]+
calcd for C16H12FO2 255.0821, found 255.0812; 1H NMR
(400 MHz, CDCl3): δ 8.09–8.06 (m, 2H), 7.63–7.59 (m, 1H),
7.54–7.50 (m, 2H), 7.46 (dd, J=4.0, 8.8 Hz, 1H), 7.31 (dd, J=
2.4, 8.4 Hz, 1H), 7.20 (dt, J=2.4, 8.8 Hz, 1H), 2.59 (s, 3H); 13
C
Benzo[1,3]dioxol-5-yl-(3-methylbenzofuran-2-yl)methanone
(5i). 5i was prepared according to general synthetic procedure
from 1a (408 mg, 3.0 mmol) and 3i (558 mg, 3.1 mmol);
{1H} NMR (100 MHz, CDCl3): δ 185.6, 159.3 (d, J=
238.8 Hz), 150.3, 149.6, 137.5, 132.7, 129.9 (d, J=9.9 Hz),
129.7 (2×), 128.3 (2×), 126.5 (d, J=4.6 Hz), 116.3 (d, J=
26.5 Hz), 113.1 (d, J=9.1 Hz), 106.4 (d, J=24.3 Hz), 9.91.
°
Yield=74% (622 mg); White solid; mp=115–117 C (recrys-
tallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M
(5-Chloro-3-methylbenzofuran-2-yl)phenylmethanone (5n).
5n was prepared according to general synthetic procedure from
1c (510 mg, 3.0 mmol) and 3a (422 mg, 3.1 mmol); Yield=
1
+H]+ calcd for C17H13O4 281.0814, found 281.0821; H NMR
(400 MHz, CDCl3): δ 7.80 (dd, J=1.6, 8.0 Hz, 1H), 7.67 (dt,
J=0.8, 8.0 Hz, 1H), 7.62 (d, J=1.6 Hz, 1H), 7.53 (dt, J=0.8,
8.0 Hz, 1H), 7.46 (dt, J=1.2, 8.0 Hz, 1H), 7.31 (dt, J=0.8,
8.0 Hz, 1H), 6.91 (d, J=8.0 Hz, 1H), 6.05 (s, 2H), 2.62 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3): δ 183.6, 154.0, 151.4, 148.2,
147.7, 132.0, 129.1, 127.9, 126.35, 126.29, 123.2, 121.2, 112.0,
109.7, 107.8, 101.7, 9.9.
°
81% (656 mg); White solid; mp=77–79 C (recrystallized from
hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M+H]+ calcd
1
for C16H12ClO2 271.0526, found 271.0533; H NMR (400 MHz,
CDCl3): δ 8.08–8.05 (m, 2H), 7.66–7.59 (m, 2H), 7.55–7.50 (m,
2H), 7.46 (dd, J=0.8, 8.8 Hz, 1H), 7.42 (dd, J=2.0, 8.8 Hz,
1H), 2.60 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 185.7,
152.5, 149.3, 137.5, 132.8, 130.5, 129.7 (2×), 129.1, 128.4
(2×), 128.3, 125.9, 120.9, 113.3, 9.9.
(3-Methylbenzofuran-2-yl)-(3,4,5-trimethoxyphenyl)
methanone (5j). 5j was prepared according to general
synthetic procedure from 1a (408 mg, 3.0 mmol) and 3j
(701 mg, 3.1 mmol); Yield=74% (724 mg); Colorless oil;
HRMS (ESI-TOF) m/z: [M+H]+ calcd for C19H19O5 327.1233,
(5-Bromo-3-methylbenzofuran-2-yl)phenylmethanone (5o).
5o was prepared according to general synthetic procedure from
1d (642 mg, 3.0 mmol) and 3a (422 mg, 3.1 mmol); Yield=
1
found 327.1228; H NMR (400 MHz, CDCl3): δ 7.71 (d, J=
°
80% (754 mg); White solid; mp=102–104 C (recrystallized
7.6 Hz, 1H), 7.54 (d, J=8.4 Hz, 1H), 7.50 (dt, J=1.2, 8.0 Hz,
1H), 7.43 (s, 2H), 7.35 (dt, J=1.2, 8.0 Hz, 1H), 3.96 (s, 3H),
3.94 (s, 6H), 2.65 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ
from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M+H]+
calcd for C16H12BrO2 315.0021, found 315.0028; 1H NMR
(400 MHz, CDCl3): δ 8.08–8.05 (m, 2H), 7.82 (d, J=2.0 Hz,
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1H), 7.64–7.59 (m, 1H), 7.57–7.50 (m, 3H), 7.41 (dd, J=0.4,
8.4 Hz, 1H), 2.59 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ
185.6, 152.8, 149.1, 137.4, 132.8, 131.1, 131.0, 129.7 (2×),
128.3 (2×), 125.8, 124.1, 116.4, 113.7, 9.9.
(3-Methylnaphtho[1,2-b]furan-2-yl)phenylmethanone (5t).
5t was prepared according to general synthetic procedure from
1l (558 mg, 3.0 mmol) and 3a (422 mg, 3.1 mmol); Yield=
°
60% (515 mg); White solid; mp=111–113 C (recrystallized
from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M+H]+
calcd for C20H15O2 287.1072, found 287.1065; 1H NMR
(400 MHz, CDCl3): δ 8.29 (dd, J=1.2, 8.0 Hz, 1H), 8.22-8.19
(m, 2H), 7.93 (dd, J=1.6, 7.6 Hz, 1H), 7.69–7.54 (m, 7H), 2.73
(s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 185.0, 150.7,
148.2, 138.1, 133.4, 132.3, 129.8 (2×), 128.5, 128.4, 128.2
(2×), 126.8, 126.7, 124.8, 124.2, 121.2, 120.8, 118.4, 10.2.
(3,5-Dimethylbenzofuran-2-yl)phenylmethanone (5p). 5p
was prepared according to general synthetic procedure from 1e
(450 mg, 3.0 mmol) and 3a (422 mg, 3.1 mmol); Yield=73%
°
(548 mg); White solid; mp=78–80 C (recrystallized from
hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M+H]+ calcd
1
for C17H15O2 251.1072, found 251.1079; H NMR (400 MHz,
CDCl3): δ 8.12–8.09 (m, 2H), 7.62–7.58 (m, 1H), 7.55–7.50 (m,
2H), 7.46 (br t, J=0.8 Hz, 1H), 7.41 (d, J=8.4 Hz, 1H), 7.29
(dd, J=1.6, 8.4 Hz, 1H), 2.63 (s, 3H), 2.49 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3): δ 185.8, 152.7, 148.4, 137.8, 132.8,
132.4, 129.7, 129.6 (2×), 129.2, 128.2 (2×), 126.6, 120.8,
111.6, 21.3, 9.9.
(1-Methylnaphtho[2,1-b]furan-2-yl)phenylmethanone (5u).
5u was prepared according to general synthetic procedure from
1m (558 mg, 3.0 mmol) and 3a (422 mg, 3.1 mmol); Yield=
°
65% (558 mg); White solid; mp=113–115 C (recrystallized
from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M+H]+
calcd for C20H15O2 287.1072, found 287.1078; 1H NMR
(400 MHz, CDCl3): δ 8.49 (d, J=8.4 Hz, 1H), 8.10–8.08 (m,
2H), 7.97 (d, J=8.0 Hz, 1H), 7.87 (d, J=9.2 Hz, 1H), 7.66 (dt,
J=1.2, 8.4 Hz, 1H), 7.63–7.53 (m, 5H), 3.07 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3): δ 185.7, 152.9, 148.0, 138.2, 132.4,
130.8, 130.0, 129.7 (2×), 129.4, 128.7, 128.2 (3×), 127.2,
125.0, 123.2, 122.6, 112.7, 12.7. Single-crystal X-Ray diagram:
crystal of compound 5u was grown by slow diffusion of EtOAc
into a solution of compound 5u in CH2Cl2 to yield colorless
prisms. The compound crystallizes in the triclinic crystal
system, space group P-1, a=10.1806(3) Å, b=14.1372(6) Å,
(5-Methoxy-3-methylbenzofuran-2-yl)phenylmethanone
(5q). 5q was prepared according to general synthetic procedure
from 1f (498 mg, 3.0 mmol) and 3a (422 mg, 3.1 mmol);
Yield=74% (591 mg); Colorless oil; HRMS (ESI-TOF) m/z:
[M+H]+ calcd for C17H15O3 267.1021, found 267.1028; 1H
NMR (400 MHz, CDCl3): δ 8.10–8.07 (m, 2H), 7.61–7.56 (m,
1H), 7.53–7.48 (m, 2H), 7.40 (d, J=9.2 Hz, 1H), 7.09 (dd, J=
2.4, 9.2 Hz, 1H), 7.04 (d, J=2.4 Hz, 1H), 3.87 (s, 3H), 2.61 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3): δ 185.6, 156.2, 149.3,
148.9, 137.8, 132.4, 129.6 (2×), 129.5, 128.2 (2×), 126.7,
118.2, 112.8, 102.0, 55.7, 10.0.
c=19.8189(3) Å, V=2755.52(15) Å3, Z=2, dcalcd =1.380 g/
3
°
cm , F(000)=1200, 2θ range 2.056~27.002 , R indices (all
(6-Methoxy-3-methylbenzofuran-2-yl)phenylmethanone
(5r). 5r was prepared according to general synthetic procedure
from 1h (498 mg, 3.0 mmol) and 3a (422 mg, 3.1 mmol);
Yield=70% (559 mg); Colorless oil; HRMS (ESI-TOF) m/z:
[M+H]+ calcd for C17H15O3 267.1021, found 267.1013; 1H
NMR (400 MHz, CDCl3): δ 8.08–8.05 (m, 2H), 7.61–7.49 (m,
4H), 7.00 (d, J=2.0 Hz, 1H), 6.96 (dd, J=2.0, 8.4 Hz, 1H),
3.87 (s, 3H), 2.61 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ
185.3, 161.2, 155.7, 148.1, 138.1, 132.2, 129.5 (2×), 128.2
(2×), 127.7, 122.6, 121.8, 113.7, 95.4, 55.7, 10.2.
data) R1=0.0861, wR2=0.1931.
1-(3-Methylbenzofuran-2-yl)ethanone (5v). 5v was prepared
according to general synthetic procedure from 1a (408 mg,
3.0 mmol) and 3m (229 mg, 3.1 mmol); Yield=66% (345 mg);
Colorless oil; HRMS (ESI-TOF) m/z: [M+H]+ calcd for
C11H11O2 175.0759, found 175.0763; 1H NMR (400 MHz,
CDCl3): δ 7.62 (dt, J=0.4, 8.0 Hz, 1H), 7.50–7.43 (m, 2H),
7.29 (dt, J=1.6, 8.0 Hz, 1H), 2.60 (s, 3H), 2.58 (s, 3H); 13C
{1H} NMR (100 MHz, CDCl3): δ 191.2, 153.9, 148.1, 129.3,
128.0, 124.0, 123.1, 121.4, 112.0, 27.7, 9.38.
(5,7-Difluoro-3-methylbenzofuran-2-yl)phenylmethanone
(5s). 5s was prepared according to general synthetic procedure
from 1k (516 mg, 3.0 mmol) and 3a (422 mg, 3.1 mmol);
(2-Acetylphenoxy)acetic acid ethyl ester (5w–1). 5w–1 was
prepared according to general synthetic procedure from 1a
(408 mg, 3.0 mmol) and 3n (323 mg, 3.1 mmol); Yield=16%
°
Yield=70% (571 mg); White solid; mp=117–119 C (recrys-
tallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M
+H]+ calcd for C16H11F2O2 273.0727, found 273.0733; 1H
NMR (400 MHz, CDCl3): δ 8.13 (m, 2H), 7.63 (tt, J=1.2,
8.4 Hz, 1H), 7.56–7.52 (m, 2H), 7.15 (ddd, J=0.8, 2.4, 7.6 Hz,
1H), 7.02 (ddt, J=2.4, 9.2, 10.4 Hz, 1H), 2.61 (s, 3H); 13C{1H}
°
(107 mg); White solid; mp=43–45 C (recrystallized from
hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M+H]+ calcd
1
for C12H15O4 223.0970, found 223.0975; H NMR (400 MHz,
CDCl3): δ 7.72 (dd, J=1.6, 7.6 Hz, 1H), 7.40 (dt, J=2.0,
7.6 Hz, 1H), 7.00 (dt, J=0.8, 7.6 Hz, 1H), 6.80 (d, J=8.4 Hz,
1H), 4.69 (s, 2H), 4.24 (q, J=7.2 Hz, 2H), 2.68 (s, 3H), 1.26 (t,
J=7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 199.5,
168.0, 156.8, 133.4, 130.5, 128.6, 121.5, 112.1, 65.4, 61.4, 31.9,
14.0.
NMR (100 MHz, CDCl3):
δ 185.2, 158.6 (dd, J=9.1,
242.6 Hz), 150.2, 147.7 (dd, J=13.7, 253.2 Hz), 137.1, 133.0,
132.2 (d, J=3.8 Hz), 132.1 (d, J=3.7 Hz), 139.8 (2×), 128.4
(2×), 126.6 (dd, J=3.0, 5.3 Hz), 103.8 (dd, J=19.7, 30.3 Hz),
102.3 (dd, J=4.5, 24.3 Hz), 10.0. Single-crystal X-Ray dia-
gram: crystal of compound 5s was grown by slow diffusion of
EtOAc into a solution of compound 5s in CH2Cl2 to yield
colorless prisms. The compound crystallizes in the orthorhom-
bic crystal system, space group Pbcn, a=18.2388(5) Å, b=
10.0383(2) Å, c=13.2457(3) Å, V=2425.11(10) Å3, Z=8,
General synthetic procedure of skeleton 6is as follows:
Bi(OTf)3 (400 mg, 20 mol%) was added to a stirred solution of
°
2v, 2w (3.0 mmol) in MeNO2 (4 mL) at 25 C. The reaction
°
mixture was stirred at 25 C for 10 min. 3a (422 mg, 3.1 mmol)
°
in MeNO2 (1 mL) was added to the reaction mixture at 25 C.
3
°
°
d
calcd =1.491 g/cm , F(000)=1120, 2θ range 2.233~27.040 , R
The reaction mixture was stirred at 60 C for 12 h. The reaction
mixture was cooled to 25 C and the solvent was concentrated.
The residue was diluted with water (10 mL) and the mixture
°
indices (all data) R1=0.0525, wR2=0.1174.
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was extracted with CH2Cl2 (3×30 mL). The combined organic
layers were washed with brine, dried, filtered and evaporated to
afford crude product under reduced pressure. Purification on
silica gel (hexanes/EtOAc=20/1~8/1) afforded 6.
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°
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in CH2Cl2 to yield colorless prisms. The compound crystallizes
in the orthorhombic crystal system, space group P212121, a=
8.2511(3) Å, b=10.5010(3) Å, c=14.0229(5) Å, V=
1215.01(7) Å3, Z=2, dcalcd =1.303 g/cm3, F(000)=504, 2θ
°
range 4.846~53.884 , R indices (all data) R1=0.0501, wR2=
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Benzofuran-3-one (6b–1). 6b–1 was prepared according to
general synthetic procedure from 2w (483 mg, 3.0 mmol) and
3a (422 mg, 3.1 mmol); Yield=68% (273 mg); White solid;
°
mp=99–101 C (recrystallized from hexanes and EtOAc);
HRMS (ESI-TOF) m/z: [M+H]+ calcd for C8H7O2 135.0446,
1
found 135.0453; H NMR (400 MHz, CDCl3): δ 7.68 (ddd, J=
0.8, 1.2, 7.6 Hz, 1H), 7.62 (dt, J=1.2, 7.6 Hz, 1H), 7.14 (d, J=
8.4 Hz, 1H), 7.09 (dt, J=0.8, 7.6 Hz, 1H), 4.63 (s, 2H); 13C
{1H} NMR (100 MHz, CDCl3): δ 199.9, 174.0, 137.8, 124.1,
122.0, 121.1, 113.6, 74.7.
2-(2-Acetylphenoxy)-1-phenylethanone
(C1)
and
(3-
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°
°
(4 mL) at 25 C. The reaction mixture was stirred at 25 C for
10 min. 3a (422 mg, 3.1 mmol) in MeNO2 (1 mL) was added to
°
the reaction mixture at 25 C. The reaction mixture was stirred
°
°
at 60 C for 1 h. The reaction mixture was cooled to 25 C and
the solvent was concentrated. The residue was diluted with
water (10 mL) and the mixture was extracted with CH2Cl2 (3×
30 mL). The combined organic layers were washed with brine,
dried, filtered and evaporated to afford crude product under
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20/1~10/1) afforded C1 and C2 (ratio >10:1, determined by
NMR sprectum). Yield=95% (724 mg); For major product C1:
1H NMR (400 MHz, CDCl3): δ 7.96–7.92 (m, 2H) 7.72 (dd, J=
2.0, 7.6 Hz, 1H), 7.61–7.57 (m, 1H), 7.48–7.38 (m, 2H), 7.38–
7.34 (m, 1H), 7.30–7.22 (m, 1H), 6.83 (d, J=8.4 Hz, 1H), 5.37
(s, 2H), 2.68 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ
199.7, 193.1, 157.0, 133.9, 133.3, 130.4, 128.74 (2×), 128.69,
128.4, 127.7 (2×), 121.2, 112.3, 70.4, 31.8.
Acknowledgements
The authors would like to thank the Ministry of Science and
Technology of the Republic of China (Taiwan) for financial
support (MOST 109-2113-M-037-014-MY3).
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Bi(OTf)3-Mediated (4+1) Annulation of α-Sulfonyl
o-Hydroxyacetophenones with α-Hydroxy Arylketones to
Access Sulfonyl 2-Aroylbenzofurans
Adv. Synth. Catal. 2021, 363, 1–17
Prof. Dr. M.-Y. Chang*, Dr. K.-T. Chen