Palladium-Catalyzed Copper-Free Sonogashira Coupling of 2-Bromoarylcarbonyls: Synthesis of Isobenzofurans via One-Pot Reductive Cyclization

Article abstract of DOI:10.1055/s-0036-1588513

Palladium-catalyzed copper-free Sonogashira coupling of 2-bromocarbonyls is presented. This method afforded the 2-alkynylaryl carbonyls, useful synthons for the accomplishment of many carbocyclic and heterocyclic motifs. Significantly, the strategy was extended to the one-pot synthesis of isobenzofurans via reduction followed by intramolecular 5- exo -dig cyclization.

Full text of DOI:10.1055/s-0036-1588513

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–J
paper
A
en
A. G. Krishna Reddy, G. Satyanarayana
Paper
Synthesis
Palladium-Catalyzed Copper-Free Sonogashira Coupling of
2-Bromoarylcarbonyls: Synthesis of Isobenzofurans via One-Pot
Reductive Cyclization
R3
Alavala Gopi Krishna Reddy
Gedu Satyanarayana*
R2
O
R1 = COR3
copper-free
Ph
exo-dig
Department of Chemistry, Indian Institute of Technology,
Hyderabad, Kandi – 502 285, Sangareddy, Telangana, India
gvsatya@iith.ac.in
H
(2 equiv)
14 examples
yields up to 79%
R3 = H, Me, Et, 2-thienyl
R1
R1
Br
Pd(OAc)2 (4 mol%)
xantphos (8 mol%)
NaBH4
R2
R2
K3PO4 (4 equiv)
toluene
(7 equiv)
120 °C, 2–6 h
Ar
O
R1 = CH2CH2COAr
16 examples
yields up to 91%
R
1 = COR3, CH2CH2COAr
endo-dig
R2 = NO2, F, H, Me, OMe, OCH2O
R3 = H, Me, Et, 2-thienyl
Ar = Ph, 3,4,5-(MeO)3C6H2
2 examples
yields up to 54%
Ar = Ph, 3,4,5-(MeO)3C6H2
Received: 27.06.2017
Accepted after revision: 29.06.2017
Published online: 02.08.2017
sirable diacetylene by-products from acetylenes (Glaser
products).19 Based on such drawbacks, few copper-free
Sonogashira couplings have also been developed using sole-
ly palladium catalyst or palladium catalyst with some sup-
port or with preparation of [Pd]-precatalyst.20 However, we
realized that there is no copper-free general method re-
ported for the preparation of wide range of 2-alkynyl carbo-
nyls. In continuation to our focus on transition metal catal-
ysis and one-pot transformations,21 very recently, we have
described a domino one-pot synthesis of isobenzofurans
via copper-catalyzed Sonogashira coupling followed by 5-
exo-dig cyclization of 2-bromobenzyl tertiary alcohols.22
However, this copper-catalyzed protocol was unsuccessful
with 2-bromobenzyl primary/secondary alcohols. Mostly, it
furnished undesired simple oxidized products such as 2-
bromoaryl aldehydes/ketones, which is a quite reasonable
transformation in the presence of a copper catalyst.23 Here-
in, we demonstrate a copper-free Sonogashira coupling of
2-bromoaryl carbonyl compounds for the synthesis of 2-
alkynylaryl aldehydes/ketones using a simple palladium
catalytic system. Moreover, isobenzofurans were achieved
starting from 2-alkynylaryl aldehydes/ketones, using one-
pot reduction followed by intramolecular 5-exo-dig cycliza-
tion.
DOI: 10.1055/s-0036-1588513; Art ID: ss-2017-n0152-op
Abstract Palladium-catalyzed copper-free Sonogashira coupling of 2-
bromocarbonyls is presented. This method afforded the 2-alkynylaryl
carbonyls, useful synthons for the accomplishment of many carbocyclic
and heterocyclic motifs. Significantly, the strategy was extended to the
one-pot synthesis of isobenzofurans via reduction followed by intramo-
lecular 5-exo-dig cyclization.
Key words carbonyls, alkynes, Sonogashira coupling, isobenzofurans,
benzoxocines
2-Alkynylaryl carbonyl compounds are indispensable
synthons for the synthesis of various carbocyclic and het-
erocyclic compounds of natural and unnatural interest.
Some of the notable examples include the preparation of
indenones,1 polycyclic indoles,2 fused pyrrole systems,3 3-
benzazepines,4 fused pyrazoles,5 trifluoromethylated
phthalans,6 isochromenes,7 isoquinolines,8 oxazolo-fused
pyrroloquinolines,9 naphthalenes,10 chrysene derivatives,11
fluorenes,12 benzothiophenes,13 triazolo-heterocyclics,14
spiro systems,15 and complex bridged molecules.16 Conse-
quently, there were reports on the synthesis of 2-alkyny-
laryl carbonyls via Sonogashira coupling.17 Most of them
were promoted by a dual catalytic systems (palladium cata-
lyst in combination with copper co-catalyst). The use of a
copper co-catalyst, rather than being beneficial, sometimes
may reduce or completely inhibit the catalytic activity.18 On
the other hand, although copper(I) catalyst alone could pro-
mote the Sonogashira coupling, quite often, it affords unde-
The synthetic study was initiated with the ketone 1k
and phenylacetylene. Initially, the reaction was performed
using well established conditions [i.e., CuI (10 mol%), 1,10-
phenanthroline (20 mol%), Cs2CO3 (2 equiv) in toluene (0.5
mL) at 110 °C for 24 h].22 However, no product was formed
(Table 1, entry 1) except the formation of undesired diacet-
ylene product. Also, the reaction failed to furnish the prod-
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B
A. G. Krishna Reddy, G. Satyanarayana
Paper
Synthesis
uct in the presence of bases NaHMDS/Cs2CO3, different sol-
vents, and at altered temperatures with 10 mol% of CuI (en-
tries 2–8). Interestingly, switching the reaction conditions
to Pd(OAc)2 (5 mol%), ligand PPh3 (10 mol%), base Cs2CO3 (4
equiv) in DMF at 80 °C for 4 hours, gave the product 2k, in
fair yield (entry 9). Use of xantphos ligand, under slightly
lowered loading of palladium catalyst, improved the yield of
2k (entry 10). The reaction at relatively high temperature
(120 °C) in DMF, suppressed the yield (entry 11), whereas
in toluene the yield of product 2k was increased to 82% (en-
try 12). Among Cs2CO3, K2CO3, Na2CO3, and K3PO4, the base
K3PO4 was found to be more effective (entries 12–15). Grat-
ifyingly, the reaction in toluene at 120 °C for 2 hours using
Pd(OAc)2 (4 mol%), xantphos (8 mol%), and K3PO4 (4 equiv)
was found to be the best and afforded the 2-alkynyl ketone
2k, in excellent yield (entry 16).
withdrawing and -donating functionalities on the aromatic
ring. Interestingly, the reaction was amenable and fur-
nished the products 2a–n, in very good to excellent yields
(Scheme 1). Notably, the reaction was also successful with
electron-withdrawing nitro group (2j) and with a het-
eroaryl moiety (2n).
After the successful preparation of alkynes 2, we aimed
to extend our strategy for the synthesis of isobenzofurans
via a one-pot reduction followed by 5-exo-dig cyclization of
2. Interestingly, isobenzofuran skeleton comprises preva-
lent structural motif in small molecules possessing inter-
esting biological and fluorescent properties (Figure 1). For
example, n-butylphthalide (3) is an antiplatelet drug.24a The
natural product 3-deoxyisochracinic acid (4) was isolated
from the species of Cladosporium that exhibits antibacterial
activity by the inhibition of Bacillus subtilis growth.24b The
cyclic ether pestacin (5) was isolated from microorganism
Pestalotipsis microspore, which displays antimycotic, anti-
fungal, and antioxidant activities.24c Compound 6 acts as
fluorophore with very good light-absorbing efficiency.24d
Among the optimized reaction conditions, the condi-
tions of Table 1, entry 16 were the best, therefore, these
conditions were applied for other 2-bromoaryl aldehydes
1a–j and 2-bromoaryl ketones 1k–n bearing electron-
Table 1 Optimization of Reaction Conditions for Sonogashira Coupling of 1k
O
O
Ph
H (2 equiv)
catalyst, ligand
Me
Me
base, solvent
temperature, time
Br
Ph
1k
2k
Entry
Ligand (mol%)
Base (equiv)
Solvent
Temp (°C)
Time (h)
Yield (%)a of 2k
c
1b
2b
1,10-phenanthroline (20)
1,10-phenanthroline (20)
–
Cs2CO3 (2)
NaHMDS (4)
NaHMDS (4)
Cs2CO3 (3)
Cs2CO3 (4)
Cs2CO3 (4)
Cs2CO3 (4)
Cs2CO3 (4)
Cs2CO3 (4)
Cs2CO3 (4)
Cs2CO3 (4)
Cs2CO3 (4)
K2CO3 (4)
toluene
toluene
toluene
1,4-dioxane
toluene
DMF
110
80
24
12
12
12
12
12
0.5
1
–
c
–
c
3b
80
–
c
4b
1,10-phenanthroline (20)
1,10-phenanthroline (20)
1,10-phenanthroline (20)
1,10-phenanthroline (20)
1,10-phenanthroline (20)
PPh3 (10)
120
120
150
160
110
80
–
c
5b
–
c
6b
–
c,d
7b
DMSO
MeCN
DMF
–
c,d
8b
–
9e
2
61
78
70
82
76
30
81
91
10f
11f
12f
13f
14f
15f
16f
xantphos (8)
DMF
80
2
xantphos (8)
DMF
120
120
120
120
120
120
2
xantphos (8)
toluene
toluene
DMF
2
xantphos (8)
4
xantphos (8)
Na2CO3 (4)
K3PO4 (4)
2
xantphos (8)
DMF
0.75
2
xantphos (8)
K3PO4(4)
toluene
a Isolated yields of chromatographically pure products.
b CuI (10 mol%) was used as catalyst.
c No significant spot was seen on TLC.
d Reaction was performed under microwave conditions.
e Pd(OAc)2 (5 mol%) was used as the catalyst.
f Pd(OAc)2 (4 mol%) was used as the catalyst.
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A. G. Krishna Reddy, G. Satyanarayana
Paper
Synthesis
Ph
H (2 equiv)
O
Me
O
OH
Pd(OAc)2 (4 mol%)
xantphos (8 mol%)
R2
R2
R1
R1
O
K3PO4 (4 equiv)
toluene
O
Br
Ph
H
CO2H
120 °C, 2 to 6 h
O
1
2
3 n-butylphthalide (NBP)
4 3-deoxyisochracinic
acid
O
O
H
O
Me
BnO
H
N
Me
Me
O
Me
Ph
Ph
Ph
OH
O
OH
HO
2a (89%)
2b (86%)
2c (82%)
O
O
O
MeO
BnO
MeO
O
O
H
H
H
5 pestacin
6
Figure 1 Representative examples of important isobenzofurans
Ph
Ph
Ph
2d (84%)
2e (86%)
2f (91%)
peratures (Table 2). To our delight, the reaction with excess
sodium borohydride in DMF as a solvent at 110 °C for 24
hours afforded the isobenzofuran 7k as a single isomer, in
very good yield. Further, its structure and stereochemistry
were unambiguously confirmed from the reported data.
O
O
O
MeO
MeO
MeO
MeO
H
H
H
F
Ph
OMe
Ph
Ph
2g (79%)
2h (89%)
2i (81%)
O
O
O
Table 2 Optimization of Reaction Conditions for One-Pot Reductive
Cyclization
O2N
BnO
H
Me
Me
O
Me
NaBH4 (equiv)
Ph
Ph
Ph
solvent (0.5 mL)
Me
2j (72%)
2k (91%)
2l (83%)
O
O
O
temperature, time
MeO
MeO
S
Ph
Ph
Et
2k
7k
MeO
Ph
Ph
Entry
NaBH4
(equiv)
Solventc
Temp
(°C)
Time
(h)
Yield (%)a
of 7k
2m (88%)
2n (89%)
Scheme 1 Scope and generality of the Sonogashira coupling of 2-alky-
nylaryl aldehydes/ketones 1. Reagents and conditions: Unless otherwise
mentioned, all the reactions were carried out by using 2-bromoarylcar-
bonyl 1 (0.54 mmol), alkyne (1.08 mmol), Pd(OAc)2 (4 mol%), xantphos
(8 mol%), and K3PO4 (2.16 mmol) followed by toluene (1.0 mL). Yields in
parentheses are the isolated yields of chromatographically pure prod-
ucts.
b
1
2
3
4
5
2
2
5
7
7
DMF
DMF
DMF
DMF
MeOH
80
110
110
110
70
24
–
b
24
24
24
24
–
40
78
b
–
a Isolated yields of chromatographically pure products.
b No product formation, only the reduced alcohol was observed on TLC.
c Reduction in toluene was found to be very slow even at 115 °C.
Isobenzofurans are also important building blocks for the
synthesis of complex molecules and natural product syn-
thesis.25
Due to the above salient features, the synthesis of iso-
benzofurans has received much attention26 and we targeted
a one-pot preparation of isobenzofurans. Sodium borohy-
dride was chosen as the medium by the assumption that it
could promote both reduction as well as intramolecular 5-
exo-dig cyclization in one pot. Thus, the reaction was per-
formed under different solvents and also at various tem-
The scope of the one-pot reduction and intramolecular
5-exo-dig cyclization was further explored on different 2-
alkynylbenzaldehydes/arylketones 2 bearing various func-
tionalities on aromatic ring. Delightfully, the one-pot proto-
col was quite successful and delivered the isobenzofurans 7,
in fair to good yields (Scheme 2). However, the reaction was
unsuccessful with 2j (neither the starting material nor the
product was isolated), maybe due to the more reactive na-
ture of the nitro group.
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A. G. Krishna Reddy, G. Satyanarayana
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Synthesis
O
R2
O
NaBH4 (7 equiv)
1. [Pd]
R2
DMF
R1
R1
O
O
2. NaBH4
r.t., 1 h; then
110 °C, 12–48 h
Br
Ph
O
Ph
2
7
BnO
10
8
O
O
Me
Scheme 3 Retrosynthetic approach for the synthesis of 2-benzoxepine
Ph
O
Ph
10
Ph
7a (78%)
7b (73%)
7e (74%)
7c (60%)
MeO
BnO
MeO
O
O
O
O
O
oxepine 10 was observed only in minute quantities. The
structure of 3-benzoxocine was confirmed by the X-ray
crystal data of 11a.28 The formation of benzoxocine 11, as a
major product, may be due to the flexibility of side chain of
9, for the endo-dig cyclization. It seems that this protocol
for the synthesis of benzoxocine 11 has some limitations, as
it was not successful with other systems that were explored
under these standard conditions.
Ph
Ph
Ph
7d (74%)
7f (71%)
7i (53%)
MeO
MeO
MeO
MeO
O
O
F
Ph
Ph
Ph
OMe
7g (73%)
7h (79%)
Me
Me
O
O2N
BnO
O
O
Ph
Ph
Ph
7j –
7k (78%)
7l (62%)
S
Et
MeO
MeO
MeO
O
O
Ph
Ph
7m (74%)
7n (71%)
Scheme 2 Scope and generality of the one-pot reductive cyclization to
isobenzofurans 7. Reagents and conditions: Unless otherwise mentioned,
all the reactions were carried out by using 2-alkynylarylcarbonyls 2
(0.48 mmol), anhyd DMF (0.5 mL) followed by NaBH4 (3.4 mmol). Iso-
lated yields of chromatographically pure products. In the case of 7j, the
reaction was not clean and no significant spot on TLC was noted.
After the synthesis of isobenzofurans, we envisioned
that the benzoxepine 10 could be obtained from the
bromoketone 8 (Scheme 3). The benzoxepine is an import-
ant core unit present in antibacterial natural products.27 We
thought that benzoxepine 10 can be attained using
Sonogashira coupling, reduction and exo-dig cyclization of
ketone 8. The ketone 8 could be easily synthesized by em-
ploying Jeffery–Heck reaction of the corresponding allylic
alcohol and 2-bromoiodo derivatives.21u
Thus, Sonogashira coupling of ketones 8a and 8b, gave
the alkynes 9a and 9b, in very good yields, respectively.
However, the one-pot reduction and cyclization, to our sur-
prise, resulted in the 3-benzoxocines 11a and 11b as the
major product, respectively, via 8-endo-dig cyclization, in
poor to moderate yield (Scheme 4). The expected 2-benz-
Scheme 4 Synthesis of 3-benzoxocines 11 via Sonogashira coupling
followed by one-pot reductive cyclization
Furthermore, we intended to apply the successful con-
ditions of Sonogashira coupling on 2-bromobenzyl 1°/2°/3°
alcohols 12 for a possible direct synthesis of isobenzofurans
7/13. However, this approach was quite successful only
with 2-bromobenzyl 3° alcohol 12c and furnished corre-
sponding isobenzofuran 13c (Scheme 5). This is in analogy
to our previous report on copper-catalyzed one-pot synthe-
sis of isobenzofurans starting from 2-bromobenzyl 3° alco-
hols.23 In the case of primary and secondary alcohols 12a
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E
A. G. Krishna Reddy, G. Satyanarayana
Paper
Synthesis
and 12b, the reaction resulted in the usual oxidation prod-
ucts 1521d,i along with poor to moderate amounts of
Sonogashira coupled products 14 (Scheme 5).
O
R1
Ar-X
Ar
Ar
PdL2(0)
R2
2
Ph
(II) Ar
Pd
(a)
Ph
H (2 equiv)
L
2
Pd(OAc)2 (4 mol%)
xantphos (8 mol%)
CHO
Ar
(II)
L
L
OH
OH
Pd
+
L
Ar
X
NaBH4
B
Br
K3PO4 (4 equiv)
toluene
120 °C, 12 h
A
Ph
12a
14a (15%)
15a (30%)
R1
K2HPO4
KX +
Ph
H
O
Ph
H (2 equiv)
(b)
R2
Me
Br
Me
+
R1
O
Pd(OAc)2 (4 mol%)
xantphos (8 mol%)
K3PO4
MeO
MeO
OH
OH
Ph
R2
K3PO4 (4 equiv)
toluene
C
Ph
120 °C, 12 h
12b
14b (53%)
O
7
+
MeO
Scheme 6 Mechanism for copper-free Sonogashira coupling and one-
Me
pot reductive cyclization
15b (15%)
(c)
Ph
H (2 equiv)
Me
Me
OH
Me
Pd(OAc)2 (4 mol%)
xantphos (8 mol%)
IR spectra were recorded on a Bruker Tensor 37 (FTIR) spectropho-
tometer. 1H NMR spectra were recorded on Bruker Avance 400 (400
MHz) spectrometer at 295 K in CDCl3; chemical shifts (δ ppm) and
coupling constants (Hz) are reported in standard fashion with refer-
ence to either internal standard TMS (δH = 0.00) or residual CHCl3
(δH = 7.25). 13C NMR spectra were recorded on Bruker Avance 400
(100 MHz) spectrometer at r.t. in CDCl3; chemical shifts (δ ppm) are
reported relative to residual CHCl3 [δC = 77.00 (central line of triplet)].
In the 13C NMR, the nature of carbons (C, CH, CH2, and CH3) was deter-
mined by recording the DEPT-135 spectra, and is given in parentheses
and noted as s = singlet (for C), d = doublet (for CH), t = triplet (for CH2)
and q = quartet (for CH3). In the 1H NMR, standard abbreviations were
Me
MeO
MeO
MeO
O
K3PO4 (4 equiv)
toluene
MeO
Br
Ph
120 °C, 12 h
12c
13c (79%)
Scheme 5 Scope of the direct Sonogashira coupling of 2-bromobenzyl
alcohols 12 in the formation of isobenzofurans 7/13
A plausible mechanism for the copper-free Sonogashira
coupling and reductive cyclization is outlined in Scheme 6.
Initially, the Pd(0) species, is expected to be generated in si-
tu, which would undergo an oxidative addition by insertion
of Pd(0) species into the Ar–X (X = Br) bond of 2-bromo-
aldehyde/ketone and form the aryl Pd(II) intermediate A.
Subsequent C(sp)–H activation of acetylene via the co-ordi-
nation by the displacement of halide in the presence of base
would furnish alkynylpalladium(II) species B.29 Further, the
intermediate B upon reductive elimination would produce
the Sonogashira coupled product 2 and regenerate Pd(0) to
repeat the catalytic cycle. Additionally, 2 upon reaction
with NaBH4 is expected to lead to the one-pot reductive
exo-dig cyclization via the formation of alkoxide intermedi-
ate C to generate the isobenzofuran 7. Similarly, reductive
cyclization would lead to benzoxocine 11 from the corre-
sponding precursor 8 in an endo-dig manner.
used throughout. The assignment of signals was confirmed by 1H, 13
C
CPD, and DEPT spectra. High-resolution mass spectra (HRMS) were
recorded on an Agilent 6538 UHD Q-TOF electron spray ionization
(ESI) mode and atmospheric pressure chemical ionization (APCI)
modes. All small scale dry reactions were carried out using Schlenk
tubes under inert atmosphere. Reactions were monitored by TLC on
silica gel using a combination of hexane and EtOAc as eluents. Reac-
tions were generally run under argon or N2 atmosphere. Solvents
were distilled prior to use; petroleum ether (PE) with a boiling range
of 60 to 80 °C was used. Toluene was dried over sodium metal and
DMF was dried over CaH2. NaBH4 was purchased from local sources
(SRL Pvt. Ltd.,) and used as received. Acme silica gel (60–120 mesh)
was used for column chromatography (approximately 20 g silica gel/g
crude material).
The alkynes 2a,b,d,f–k and compounds 7a,b,d,f,g,h,i,k and 13c are
known in the literature.
Alkynes 2 and 9; General Procedure 1 (GP 1)
To conclude, we have disclosed a simple palladium-cata-
lyzed copper-free Sonogashira coupling of 2-alkynylaryl
carbonyl compounds from readily available 2-bromoaryl
derivatives. Significantly, the strategy was extended for the
one-pot synthesis of isobenzofurans through reduction fol-
lowed by intramolecular 5-exo-dig cyclization.
In an oven-dried Schlenk tube were added bromoarylcarbonyl 1/8
(100.0–204.8 mg, 0.54 mmol), phenylacetylene (110.2 mg, 1.08
mmol), Pd(OAc)2 (4.8 mg, 4 mol%), xantphos (25 mg, 8 mol%), and
K3PO4 (458 mg, 2.16 mmol) followed by anhyd toluene (1.0 mL) at r.t.
under N2 atmosphere and the reaction mixture was allowed to stir at
120 °C for 2–6 h. Progress of the alkyne 2 and 9 formation was moni-
tored by TLC until the reaction was complete. Then, the mixture was
filtered through Celite and washed with CH2Cl2. Evaporation of the
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A. G. Krishna Reddy, G. Satyanarayana
Paper
Synthesis
solvent under reduced pressure and purification of the crude material
by silica gel column chromatography (PE/EtOAc) furnished the alkyne
2 and 9 (72–91%), respectively, as viscous liquid/semi-solid.
13C NMR (CDCl3, 100 MHz): δ = 190.2 (d, CHO), 154.1 (s, Ar-C), 148.8
(s, Ar-C), 135.9 (s, Ar-C), 131.5 (d, 2 C, 2 × Ar-CH), 130.0 (s, Ar-C),
128.8 (d, Ar-CH), 128.6 (d, 2 C, 2 × Ar-CH), 128.4 (d, 2 C, 2 × Ar-CH),
128.1 (d, Ar-CH), 127.5 (d, 2 C, 2 × Ar-CH), 122.4 (s, Ar-C), 121.6
(s, Ar-C), 114.5 (d, Ar-CH), 110.1 (d, Ar-CH), 94.9 (s, Ar-C≡C), 84.8 (s,
Ar-C≡C), 70.7 (t, OCH2Ph), 56.2 (q, Ar-OCH3).
Isobenzofurans 7 and Benzoxocines 11; General Procedure 2 (GP-
2)
HRMS (ESI+): m/z [M + H]+ calcd for [C23H19O3]+: 343.1329; found:
343.1330.
To an ice cold, magnetically stirred solution of alkyne 2/9 (100–192
mg, 0.48 mmol) in anhyd DMF (1 mL), was added NaBH4 (127 mg,
3.36 mmol). Then the reaction mixture was allowed to attain r.t. and
stirred for 1 h, then at 110 °C for 12–96 h. Progress of the isobenzofu-
ran 7 and benzoxocine 11 formation was monitored by TLC until the
reaction was complete. The reaction mixture was cooled to r.t., treat-
ed with ice cold aq NH4Cl and then extracted with CH2Cl2 (3 × 10 mL).
The combined organic layers were washed with brine, dried (Na2SO4),
and filtered. Evaporation of the filtrate under reduced pressure and
purification of the crude material by silica gel column chromatogra-
phy (PE/EtOAc) furnished the isobenzofuran 7 and benzoxocine 11
(26–79%), respectively. Note: H2 gas was liberated during the reaction.
1-[5-(Benzyloxy)-2-(phenylethynyl)phenyl]ethanone (2l)
GP-1 was carried out with ketone 1l (164.8 mg, 0.54 mmol), phenyl-
acetylene (110.2 mg, 1.08 mmol), Pd(OAc)2 (4.8 mg, 4 mol%), xant-
phos (25 mg, 8 mol%), and K3PO4 (458 mg, 2.16 mmol) followed by
anhyd toluene (1.0 mL) for alkyne 2l formation at 120 °C for 3 h. Puri-
fication of the crude material by silica gel column chromatography
(PE/EtOAc, 98:2 to 95:5) furnished the alkyne 2l (146.3 mg, 83%) as a
pale yellow viscous liquid; Rf (1l) = 0.60, Rf (2l) = 0.50 (PE/EtOAc,
90:10) [UV detection].
IR (MIR-ATR): 3062, 2925, 1679, 1593, 1495, 1322, 1283, 1221, 1206,
5-(Benzyloxy)-2-(phenylethynyl)benzaldehyde (2c)
1023, 754, 691 cm–1
.
GP-1 was carried out with benzaldehyde 1c (157 mg, 0.54 mmol),
phenylacetylene (110 mg, 1.08 mmol), Pd(OAc)2 (5 mg, 4 mol%), xant-
phos (25 mg, 8 mol%), and K3PO4 (458 mg, 2.16 mmol) followed by
anhyd toluene (1.0 mL) for alkyne 2c formation at 120 °C for 3 h. Puri-
fication of the crude material by silica gel column chromatography
(PE/EtOAc, 98:2 to 95:5) furnished the alkyne 2c (138.5 mg, 82%) as a
pale yellow viscous liquid; Rf (1c) = 0.60, Rf (2c) = 0.50 (PE/EtOAc,
90:10) [UV detection].
1H NMR (CDCl3, 400 MHz): δ = 7.56 (d, 1 H, J = 8.3 Hz, Ar-H), 7.55–
7.49 (m, 2 H, Ar-H), 7.47–7.30 (m, 9 H, Ar-H), 7.08 (dd, 1 H, J = 8.3, 2.4
Hz, Ar-H), 5.11 (s, 2 H, OCH2Ph), 2.81 (s, 3 H, CH3).
13C NMR (CDCl3, 100 MHz): δ = 200.1 (s, C=O), 158.6 (s, Ar-C), 142.1 (s,
Ar-C), 136.1 (s, Ar-C), 135.3 (d, Ar-CH), 131.3 (d, 2 C, 2 × Ar-CH), 128.6
(d, 2 C, 2 × Ar-CH), 128.4 (d, Ar-CH), 128.4 (d, 2 C, 2 × Ar-CH), 128.2 (d,
Ar-CH), 127.5 (d, 2 C, 2 × Ar-CH), 123.1 (s, Ar-C), 118.6 (d, Ar-CH),
114.2 (s, Ar-C), 114.1 (d, Ar-CH), 93.8 (s, Ar-C≡C), 88.4 (s, Ar-C≡C),
70.2 (t, OCH2Ph), 30.1 (q, CH3).
IR (MIR-ATR): 3062, 2841, 1688, 1594, 1497, 1454, 1386, 1273, 1163,
1083, 1024, 832 cm–1
.
HRMS (ESI+): m/z [M + H]+ calcd for [C23H19O2]+: 327.1380; found:
327.1384.
1H NMR (CDCl3, 400 MHz): δ = 10.62 (s, 1 H, CHO), 7.62–7.50 (m, 4 H,
ArH), 7.47–7.30 (m, 8 H, ArH), 7.20 (dd, 1 H, J = 8.8, 2.9 Hz, ArH), 5.12
(s, 2 H, OCH2Ph).
13C NMR (CDCl3, 100 MHz): δ = 191.4 (d, CHO), 158.8 (s, Ar-C), 137.1
(s, Ar-C), 135.9 (s, Ar-C), 135.6 (d, Ar-CH), 131.5 (d, 2 C, 2 × Ar-CH),
128.7 (d, Ar-CH), 128.6 (d, 2 C, 2 × Ar-CH), 128.4 (d, 2 C, 2 × Ar-CH),
128.2 (d, Ar-CH), 127.5 (d, 2 C, 2 × Ar-CH), 122.3 (s, Ar-C), 122.2 (d,
Ar-CH), 119.7 (s, Ar-C), 110.9 (d, Ar-CH), 94.9 (s, Ar-C≡C), 84.8 (s,
Ar-C≡C), 70.2 (t, OCH2Ph).
1-[5-Methoxy-2-(phenylethynyl)phenyl]propan-1-one (2m)
GP-1 was carried out with ketone 1m (131.3 mg, 0.54 mmol), phenyl-
acetylene (110.2 mg, 1.08 mmol), Pd(OAc)2 (4.8 mg, 4 mol%), xant-
phos (25 mg, 8 mol%), and K3PO4 (458 mg, 2.16 mmol) followed by
anhyd toluene (1.0 mL) for alkyne 2m formation at 120 °C for 2 h. Pu-
rification of the crude material by silica gel column chromatography
(PE/EtOAc, 98:2 to 95:5) furnished the alkyne 2m (125.6 mg, 88%) as
a pale yellow viscous liquid; Rf (1m) = 0.60, Rf (2m) = 0.50 (PE/EtOAc,
90:10) [UV detection].
HRMS (ESI+): m/z [M + H]+ calcd for [C22H17O2]+: 313.1229; found:
313.1226.
IR (MIR-ATR): 2937, 2837, 1688, 1594, 1496, 1416, 1293, 1276, 1196,
5-(Benzyloxy)-4-methoxy-2-(phenylethynyl)benzaldehyde (2e)
1173, 1025, 823, 755, 691 cm–1
.
GP-1 was carried out with benzaldehyde 1e (173 mg, 0.54 mmol),
phenylacetylene (110.2 mg, 1.08 mmol), Pd(OAc)2 (4.8 mg, 4 mol%),
xantphos (25 mg, 8 mol%), and K3PO4 (458 mg, 2.16 mmol) followed
by anhyd toluene (1.0 mL) for alkyne 2e formation at 120 °C for 3 h.
Purification of the crude material by silica gel column chromatogra-
phy (PE/EtOAc, 98:2 to 95:5) furnished the alkyne 2e (159.2 mg, 86%)
as a pale yellow viscous liquid; Rf (1e) = 0.60, Rf (2e) = 0.50 (PE/EtOAc,
90:10) [UV detection].
1H NMR (CDCl3, 400 MHz): δ = 7.53 (d, 1 H, J = 8.8 Hz, Ar-H), 7.53–
7.46 (m, 2 H, Ar-H), 7.39–7.30 (m, 3 H, Ar-H), 7.18 (d, 1 H, J = 2.9 Hz,
Ar-H), 6.98 (dd, 1 H, J = 8.8, 2.9 Hz, Ar-H), 3.84 (s, 3 H, ArOCH3), 3.20
(q, 2 H, J = 7.3 Hz, CH2CH3), 1.24 (t, 3 H, J = 7.3 Hz, CH2CH3).
13C NMR (CDCl3, 100 MHz): δ = 204.0 (s, C=O), 159.4 (s, Ar-C), 142.7 (s,
Ar-C), 135.1 (d, Ar-CH), 131.3 (d, 2 C, 2 × Ar-CH), 128.4 (d, 2 C, 2 × Ar-
CH), 128.3 (d, Ar-CH), 123.2 (s, Ar-C), 117.2 (d, Ar-CH), 113.3 (s, Ar-C),
112.8 (d, Ar-CH), 93.1 (s, Ar-C≡C), 88.2 (s, Ar-C≡C), 55.5 (q, ArOCH3),
35.4 (t, CH2CH3), 8.5 (q, CH2CH3).
IR (MIR-ATR): 3061, 2937, 2839, 1679, 1587, 1503, 1442, 1396, 1350,
1297, 1249, 1162, 1089, 1025, 992, 910, 871, 733 cm–1
.
HRMS (ESI+): m/z [M + H]+ calcd for [C18H17O2]+: 265.1223; found:
265.1231.
1H NMR (CDCl3, 400 MHz): δ = 10.48 (s, 1 H, CHO), 7.60–7.52 (m, 2 H,
Ar-H), 7.48 (s, 1 H, Ar-H), 7.46 (d, 2 H, J = 8.3 Hz, Ar-H), 7.42–7.27 (m,
6 H, Ar-H), 7.06 (s, 1 H, Ar-H), 5.18 (s, 2 H, OCH2Ph), 3.95 (s, 3 H,
Ar-OCH3).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

G
A. G. Krishna Reddy, G. Satyanarayana
Paper
Synthesis
[4,5-Dimethoxy-2-(phenylethynyl)phenyl](thien-2-yl)methanone
(2n)
IR (MIR-ATR): 2928, 1655, 1596, 1500, 1453, 1345, 1287, 1225, 1129
cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 7.70 (dd, 2 H, J = 8.3, 1.0 Hz, Ar-H), 7.44
(dd, 2 H, J = 8.3, 1.5 Hz, Ar-H), 7.38 (ddd, 2 H, J = 8.3, 7.3, 1.5 Hz, Ar-H),
7.31 (dd, 2 H, J = 8.3, 7.3 Hz, Ar-H), 7.11 (t, 1 H, J = 7.3 Hz, Ar-H), 7.03
(s, 1 H, Ar-H), 6.81 (s, 1 H, Ar-H), 5.77 (s, 1 H, C=CH), 5.38 (s, 2 H,
OCH2Ar), 5.18 (s, 2 H, OCH2Ph), 3.96 (s, 3 H, ArOCH3).
13C NMR (CDCl3, 100 MHz): δ = 156.8 (s, C=CH), 150.4 (s, Ar-C), 149.8
(s, Ar-C), 136.6 (s, Ar-C), 136.5 (s, Ar-C), 131.9 (d, Ar-CH), 128.6 (d, 2
C, 2 × Ar-CH), 128.3 (d, 2 C, 2 × Ar-CH), 128.0 (d, Ar-CH), 127.5 (s, Ar-
C), 127.4 (d, 2 C, 2 × Ar-CH), 127.2 (d, 2 C, 2 × Ar-CH), 124.9 (d, Ar-CH),
106.1 (d, Ar-CH), 102.6 (d, Ar-CH), 94.5 (d, C=CH), 74.7 (t, OCH2Ar),
71.2 (t, OCH2Ph), 56.2 (q, ArOCH3).
GP-1 was carried out with ketone 1n (176.7 mg, 0.54 mmol), phenyl-
acetylene (110.2 mg, 1.08 mmol), Pd(OAc)2 (4.8 mg, 4 mol%), xant-
phos (25 mg, 8 mol%), and K3PO4 (458 mg, 2.16 mmol) followed by
anhyd toluene (1.0 mL) for alkyne 2n formation at 120 °C for 2 h. Puri-
fication of the crude material by silica gel column chromatography
(PE/EtOAc, 98:2 to 95:5) furnished the alkyne 2n (167.5 mg, 89%) as a
pale brown viscous liquid; Rf (1n) = 0.60, Rf (2n) = 0.50 (PE/EtOAc,
90:10) [UV detection].
IR (MIR-ATR): 2933, 2848, 1637, 1593, 1508, 1462, 1411, 1352, 1251,
1211, 1178, 1088, 1029, 728 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 7.70 (dd, 1 H, J = 4.9, 1.0 Hz, Ar-H), 7.60
(dd, 1 H, J = 3.9, 1.0 Hz, Ar-H), 7.25–7.18 (m, 3 H, Ar-H), 7.17–7.12 (m,
2 H, Ar-H), 7.09 (dd, 1 H, J = 4.9, 3.9 Hz, Ar-H), 7.08 (s, 1 H, Ar-H), 7.07
(s, 1 H, Ar-H), 3.95 (s, 3 H, ArOCH3), 3.91 (s, 3 H, ArOCH3).
HRMS (ESI+): m/z [M + H]+ calcd for [C23H21O3]+: 345.1485; found:
345.1470.
13C NMR (CDCl3, 100 MHz): δ = 188.1 (s, C=O), 150.4 (s, Ar-C), 148.9 (s,
Ar-C), 144.1 (s, Ar-C), 135.6 (d, Ar-CH), 134.6 (s, Ar-C), 134.3 (d, Ar-
CH), 131.2 (d, 2 C, 2 × Ar-CH), 128.2 (d, Ar-CH), 128.1 (d, 2 C, 2 × Ar-
CH), 128.0 (d, Ar-CH), 122.8 (s, Ar-C), 114.7 (s, Ar-C), 114.6 (d, Ar-CH),
111.4 (d, Ar-CH), 93.6 (s, Ar-C≡C), 87.5 (s, Ar-C≡C), 56.1 (q, ArOCH3),
56.0 (q, ArOCH3).
(1Z)-1-Benzylidene-5-(benzyloxy)-3-methyl-1,3-dihydro-2-ben-
zofuran (7l)
GP-2 was carried out with alkyne 2l (157 mg, 0.48 mmol) and anhyd
DMF (1 mL), followed by NaBH4 (127 mg, 3.36 mmol) for the forma-
tion of isobenzofuran 7l at 110 °C for 24 h. Purification of the crude
material by silica gel column chromatography (PE/EtOAc, 99:1 to
97:3) furnished the isobenzofuran 7l (98.1 mg, 62%) as a pale yellow
viscous liquid; Rf (2l) = 0.50, Rf (7l) = 0.70, (PE/EtOAc, 90:10) [UV de-
tection].
HRMS (ESI+): m/z [M + H]+ calcd for [C21H17O3S]+: 349.0893; found:
349.0887.
(1Z)-1-Benzylidene-5-(benzyloxy)-1,3-dihydro-2-benzofuran (7c)
IR (MIR-ATR): 3050, 1651, 1596, 1493, 1422, 1271, 1230, 1042, 832,
743 cm–1
.
GP-2 was carried out with alkyne 2c (149.9 mg, 0.48 mmol) and an-
hyd DMF (1 mL), followed by NaBH4 (127 mg, 3.36 mmol) for the for-
mation of isobenzofuran 7c at 110 °C for 24 h. Purification of the
crude material by silica gel column chromatography (PE/EtOAc, 99:1
to 97:3) furnished the isobenzofuran 7c (90.6 mg, 60%) as a pale yel-
low viscous liquid; Rf (2c) = 0.50, Rf (7c) = 0.70 (PE/EtOAc, 90:10) [UV
detection].
1H NMR (CDCl3, 400 MHz): δ = 7.73 (d, 2 H, J = 8.3 Hz, Ar-H), 7.50–
7.34 (m, 6 H, Ar-H), 7.33 (dd, 2 H, J = 8.3, 7.3 Hz, Ar-H), 7.12 (t, 1 H, J =
7.3 Hz, Ar-H), 6.99 (dd, 1 H, J = 8.3, 1.9 Hz, Ar-H), 6.83 (d, 1 H, J = 1.9
Hz, Ar-H), 5.78 (s, 1 H, C=CH), 5.69 (q, 1 H, J = 6.4 Hz, CHCH3), 5.10 (s,
2 H, OCH2Ph), 1.62 (q, 3 H, J = 6.4 Hz, CHCH3).
13C NMR (CDCl3, 100 MHz): δ = 159.9 (s, Ar-C), 155.3 (s, C=CH), 145.7
(s, Ar-C), 136.8 (s, Ar-C), 136.5 (s, Ar-C), 128.6 (d, 2 C, 2 × Ar-CH),
128.3 (d, 2 C, 2 × Ar-CH), 128.1 (d, Ar-CH), 127.5 (s, Ar-C), 127.5 (d, 2
C, 2 × Ar-CH), 127.4 (d, 2 C, 2 × Ar-CH), 124.8 (d, Ar-CH), 121.1 (d,
Ar-CH), 115.7 (d, Ar-CH), 106.8 (d, Ar-CH), 94.3 (d, C=CH), 81.9 (d,
CHCH3), 70.4 (t, OCH2Ph), 21.6 (q, CHCH3).
IR (MIR-ATR): 3032, 2871, 1656, 1610, 1593, 1496, 1449, 1371, 1266,
1228, 1040, 805, 741, 695 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 7.69 (d, 2 H, J = 8.3 Hz, Ar-H), 7.47 (d, 1
H, J = 8.3 Hz, Ar-H), 7.45–7.32 (m, 5 H, Ar-H), 7.31 (dd, 2 H, J = 7.8, 7.3
Hz, Ar-H), 7.11 (t, 1 H, J = 7.3 Hz, Ar-H), 6.99 (dd, 1 H, J = 8.3, 2.4 Hz,
Ar-H), 6.90 (s, 1 H, Ar-H), 5.80 (s, 1 H, C=CH), 5.46 (s, 2 H, OCH2Ar),
5.10 (s, 2 H, OCH2Ph).
HRMS (ESI+): m/z [M + H]+ calcd for [C23H21O2]+: 329.1542; found:
329.1545.
13C NMR (CDCl3, 100 MHz): δ = 159.9 (s, Ar-C), 156.2 (s, C=CH), 141.1
(s, Ar-C), 136.6 (s, Ar-C), 136.5 (s, Ar-C), 128.7 (d, 2 C, 2 × Ar-CH),
128.3 (d, 2 C, 2 × Ar-CH), 128.1 (d, Ar-CH), 127.7 (s, Ar-C), 127.4 (2 d,
4 C, 4 × Ar-CH), 124.9 (d, Ar-CH), 121.1 (d, Ar-CH), 116.0 (d, Ar-CH),
106.7 (d, Ar-CH), 94.6 (d, C=CH), 74.6 (t, OCH2Ar), 70.4 (t, OCH2Ph).
HRMS (ESI+): m/z [M + H]+ calcd for [C22H19O2]+: 315.1380; found:
315.1387.
(1Z)-1-Benzylidene-3-ethyl-5-methoxy-1,3-dihydro-2-benzofu-
ran (7m)
GP-2 was carried out with alkyne 2m (127 mg, 0.48 mmol) and anhyd
DMF (1 mL), followed by NaBH4 (127 mg, 3.36 mmol) for the forma-
tion of isobenzofuran 7m at 110 °C for 24 h. Purification of the crude
material by silica gel column chromatography (PE/EtOAc, 99:1 to
97:3) furnished the isobenzofuran 7m (94.5 mg, 74%) as a pale yellow
viscous liquid; Rf (2m) = 0.50, Rf (7m) = 0.70 (PE/EtOAc, 90:10) [UV
detection].
(1Z)-1-Benzylidene-5-(benzyloxy)-6-methoxy-1,3-dihydro-2-ben-
zofuran (7e)
IR (MIR-ATR): 2958, 1654, 1585, 1489, 1426, 1265, 1221, 846, 738
GP-2 was carried out with alkyne 2e (164.3 mg, 0.48 mmol) and an-
hyd DMF (1 mL), followed by NaBH4 (127 mg, 3.36 mmol) for the for-
mation of isobenzofuran 7e at 110 °C for 24 h. Purification of the
crude material by silica gel column chromatography (PE/EtOAc, 99:1
to 97:3) furnished the isobenzofuran 7e (122.4 mg, 74%) as a pale yel-
low viscous liquid; Rf (2e) = 0.50, Rf (7e) = 0.70 (PE/EtOAc, 90:10) [UV
detection].
cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 7.71 (d, 2 H, J = 7.8 Hz, Ar-H), 7.45 (d, 1
H, J = 8.8 Hz, Ar-H), 7.31 (dd, 2 H, J = 7.8, 7.3 Hz, Ar-H), 7.10 (t, 1 H, J =
7.3 Hz, Ar-H), 6.90 (dd, 1 H, J = 8.8, 1.9 Hz, Ar-H), 6.75 (d, 1 H, J = 1.9
Hz, Ar-H), 5.76 (s, 1 H, C=CH), 5.57 (dd, 1 H, J = 7.3, 6.8 Hz,
CHCH-2CH3), 3.85 (s, 3 H, ArOCH3), 2.20–1.95 (m, 1 H, CHCH-aH-bCH3),
1.90–1.70 (m,
1 H, CHCH-aH-bCH3), 1.04 (q, 3 H, J = 7.3 Hz,
CHCH-2CH3).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

H
A. G. Krishna Reddy, G. Satyanarayana
Paper
Synthesis
3C NMR (CDCl3, 100 MHz): δ = 160.7 (s, Ar-C), 155.6 (s, C=CH), 144.3
(s, Ar-C), 136.9 (s, Ar-C), 128.3 (d, 2 C, 2 × Ar-CH), 127.9 (s, Ar-C),
127.4 (d, 2 C, 2 × Ar-CH), 124.7 (d, Ar-CH), 121.1 (d, Ar-CH), 115.0 (d,
Ar-CH), 105.9 (d, Ar-CH), 94.0 (d, C=CH), 86.6 (d, CHCH-2CH3), 55.6 (q,
ArOCH3), 28.8 (t, CHCH-2CH3), 9.0 (t, CHCH-2CH3).
HRMS (ESI+): m/z [M + H]+ calcd for [C18H19O2]+ : 267.1385; found:
267.1384.
3-[2-(Phenylethynyl)phenyl]-1-(3,4,5-trimethoxyphenyl)propan-
1-one (9b)
GP-1 was carried out with ketone 8b (204 mg, 0.54 mmol), phenyl-
acetylene (110.2 mg, 1.08 mmol), Pd(OAc)2 (4.8 mg, 4 mol%), xant-
phos (25 mg, 8 mol%), and K3PO4 (458 mg, 2.16 mmol) followed by
anhyd toluene (0.5 mL) for alkyne 9b formation at 120 °C for 2 h. Puri-
fication of the crude material by silica gel column chromatography
(PE/EtOAc, 98:2 to 95:5) furnished the alkyne 9b (170.6 mg, 79%) as a
pale yellow viscous liquid; Rf (8b) = 0.60, Rf (9b) = 0.50 (PE/EtOAc,
90:10) [UV detection].
(1Z)-1-Benzylidene-5,6-dimethoxy-3-thien-3-yl-1,3-dihydro-2-
benzofuran (7n)
IR (MIR-ATR): 2959, 2842, 1686, 1576, 1496, 1465, 1380, 1266, 1161,
GP-2 was carried out with alkyne 2n (167 mg, 0.48 mmol) and anhyd
DMF (1 mL), followed by NaBH4 (127 mg, 3.36 mmol) for the forma-
tion of isobenzofuran 7n at 110 °C for 24 h. Purification of the crude
material by silica gel column chromatography (PE/EtOAc, 99:1 to
97:3) furnished the isobenzofuran 7n (119.4 mg, 71%) as a pale yel-
low viscous liquid; Rf (2n) = 0.50, Rf (7n) = 0.70, (PE/EtOAc 90:10) [UV
detection].
1056, 1028, 832 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 7.53 (dd, 1 H, J = 7.3, 1.0 Hz, Ar-H),
7.49–7.42 (m, 2 H, Ar-H), 7.34–7.25 (m, 5 H, Ar-H), 7.22 (dd, 1 H, J =
7.3, 1.9 Hz, Ar-H), 7.19 (s, 2 H, Ar-H), 3.88 (s, 3 H, ArOCH3), 3.83 (s, 6
H, 2 × ArOCH3), 3.40–3.34 (m, 2 H, CH2), 3.33–3.25 (m, 2 H, CH2).
13C NMR (CDCl3, 100 MHz): δ = 198.3 (s, C=O), 153.0 (s, 2 C, 2 × Ar-C),
143.2 (s, Ar-C), 142.4 (s, Ar-C), 132.3 (d, Ar-CH), 132.2 (s, Ar-C), 131.4
(d, 2 C, 2 × Ar-CH), 129.2 (d, Ar-CH), 128.6 (d, Ar-CH), 128.4 (d, 2 C, 2 ×
Ar-CH), 128.3 (d, Ar-CH), 126.3 (d, Ar-CH), 123.1 (s, Ar-C), 122.6 (s,
Ar-C), 105.5 (d, 2 C, 2 × Ar-CH), 93.5 (s, Ar-C≡C), 87.7 (s, Ar-C≡C), 60.9
(q, ArOCH3), 56.2 (q, 2 C, 2 × ArOCH3), 39.0 (t, CH2), 29.7 (t, CH2).
IR (MIR-ATR): 3010, 2868, 1649, 1593, 1487, 1381, 1246, 1038, 835,
741 cm–1
.
1H NMR (DMSO-d6, 400 MHz): δ = 7.62 (d, 2 H, J = 7.5 Hz, Ar-H), 7.55
(d, 1 H, J = 4.4 Hz, Ar-H), 7.37 (s, 1 H, Ar-H), 7.35–7.22 (m, 3 H, Ar-H),
7.15–7.00 (m, 2 H, Ar-H), 6.95 (s, 1 H, Ar-H), 6.87 (s, 1 H, OCHAr), 6.07
(s, 1 H, C=CH), 3.87 (s, 3 H, ArOCH3), 3.75 (s, 3 H, ArOCH3).
HRMS (ESI+): m/z [M + H]+ calcd for [C26H25O4]+: 401.1747; found:
13C NMR (DMSO-d6, 100 MHz): δ = 154.8 (s, C=CH), 150.7 (s, Ar-C),
150.1 (s, Ar-C), 143.1 (s, Ar-C), 136.4 (s, Ar-C), 134.1 (s, Ar-C), 128.3
(d, 2 C, 2 × Ar-CH), 127.2 (d, 3 C, 3 × Ar-CH), 127.1 (d, Ar-CH), 126.9 (d,
Ar-CH), 125.9 (s, Ar-C), 124.8 (d, Ar-CH), 104.9 (d, Ar-CH), 102.6 (d,
Ar-CH), 94.5 (d, C=CH), 82.2 (d, OCHAr), 55.8 (2 q, 2 C, 2 × ArOCH3).
HRMS (ESI+): m/z [M + H]+ calcd for [C21H19O3S]+: 351.1049; found:
351.1041.
401.1736.
2,4-Diphenyl-5,6-dihydro-4H-3-benzoxocine (11a)
GP-2 was carried out with alkyne 9a (148.8 mg, 0.48 mmol) and an-
hyd DMF (1 mL), followed by NaBH4 (127 mg, 3.36 mmol) for the for-
mation of benzoxocine 11a at 110 °C for 24 h. Purification of the
crude material by silica gel column chromatography (PE/EtOAc, 99:1
to 97:3) furnished the benzoxocine 11a (80.9 mg, 54%) as a pale yel-
low viscous liquid; Rf (9a) = 0.50, Rf (11a) = 0.70 (PE/EtOAc, 90:10)
[UV detection].
1-Phenyl-3-[2-(phenylethynyl)phenyl]propan-1-one (9a)
GP-1 was carried out with ketone 8a (155.5 mg, 0.54 mmol), phenyl-
acetylene (110.2 mg, 1.08 mmol), Pd(OAc)2 (4.8 mg, 4 mol%), xant-
phos (25 mg, 8 mol%), and K3PO4 (458 mg, 2.16 mmol) followed by
anhyd toluene (0.5 mL) for alkyne 9a formation at 120 °C for 2 h. Puri-
fication of the crude material by silica gel column chromatography
(PE/EtOAc, 98:2 to 95:5) furnished the alkyne 9a (140.6 mg, 84%) as a
pale yellow viscous liquid; Rf (8a) = 0.60, Rf (9a) = 0.50 (PE/EtOAc,
90:10) [UV detection].
IR (MIR-ATR): 3051, 2926, 1652, 1583, 1494, 1453, 1378, 1260, 1030,
836, 741 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 7.68–7.60 (m, 2 H, Ar-H), 7.40–7.25
(m, 8 H, Ar-H), 7.25–7.10 (m, 4 H, Ar-H), 6.02 (s, 1 H, C=CH), 5.41 (dd,
1 H, J = 11.7, 2.9 Hz, CHCH2CH2), 3.33 (ddd, 1 H, J = 13.2, 13.2, 3.9 Hz,
CHCH2CHaHb), 2.83 (ddd, 1 H, J = 13.2, 4.4, 2.9 Hz, CHCH2CHaHb), 2.35–
2.15 (m, 1 H, CHCHaHbCH2), 1.82 (m, 1 H, CHCHaHbCH2).
13C NMR (CDCl3, 100 MHz): δ = 155.3 (s, C=CH), 142.3 (s, Ar-C), 138.3
(s, Ar-C), 137.5 (s, Ar-C), 136.8 (s, Ar-C), 129.5 (2 d, 2 C, 2 × Ar-CH),
128.5 (d, Ar-CH), 128.3 (d, 2 C, 2 × Ar-CH), 128.1 (d, 2 C, 2 × Ar-CH),
127.5 (d, Ar-CH), 126.9 (d, Ar-CH), 126.5 (d, 2 C, 2 × Ar-CH), 126.3 (d,
Ar-CH), 125.9 (d, 2 C, 2 × Ar-CH), 102.1 (d, C=CH), 78.5 (d, OCHAr),
35.7 (t, CH2), 31.6 (t, CH2).
IR (MIR-ATR): 3060, 2839, 1685, 1590, 1514, 1455, 1378, 1276, 1160,
1086, 1020, 830 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 7.97 (dd, 2 H, J = 8.3, 1.0 Hz, Ar-H), 7.54
(dd, 1 H, J = 7.3, 1.0 Hz, Ar-H), 7.53–7.45 (m, 3 H, Ar-H), 7.38 (dd, 2 H,
J = 7.8, 7.3 Hz, Ar-H), 7.35–7.30 (m, 4 H, Ar-H), 7.28 (ddd, 1 H, J = 7.8,
7.3, 1.5 Hz, Ar-H), 7.22 (ddd, 1 H, J = 7.3, 7.3, 1.9 Hz, Ar-H), 3.44–3.36
(m, 2 H, CH2), 3.35–3.26 (m, 2 H, CH2).
HRMS (ESI+): m/z [M + H]+ calcd for [C23H21O]+: 313.1587; found:
13C NMR (CDCl3, 100 MHz): δ = 199.4 (s, C=O), 143.3 (s, Ar-C), 136.8 (s,
Ar-C), 133.0 (d, Ar-CH), 132.3 (d, Ar-CH), 131.5 (d, 2 C, 2 × Ar-CH),
129.2 (d, Ar-CH), 128.6 (d, Ar-CH), 128.5 (d, 2 C, 2 × Ar-CH), 128.4 (d,
2 C, 2 × Ar-CH), 128.3 (d, Ar-CH), 128.1 (d, 2 C, 2 × Ar-CH), 126.3 (d,
Ar-CH), 123.2 (s, Ar-C), 122.6 (s, Ar-C), 93.4 (s, Ar-C≡C), 87.8 (s, Ar-
C≡C), 39.5 (t, CH2), 29.7 (t, CH2).
313.1594.
2,4-Diphenyl-5,6-dihydro-4H-3-benzoxocine (11b)
GP-2 was carried out with alkyne 9b (192 mg, 0.48 mmol) and anhyd
DMF (1 mL), followed by NaBH4 (127 mg, 3.36 mmol) for the forma-
tion of benzoxocine 11b at 110 °C for 24 h. Purification of the crude
material by silica gel column chromatography (PE/EtOAc, 99:1 to
97:3) furnished the benzoxocine 11b (50.3 mg, 26%) as a pale yellow
viscous liquid; Rf (9b) = 0.50, Rf (11b) = 0.70 (PE/EtOAc, 90:10) [UV
detection].
HRMS (ESI+): m/z [M + H]+ calcd for [C23H19O]+: 311.1430; found:
311.1425.
IR (MIR-ATR): 3045, 2920, 1654, 1588, 1495, 1456, 1380, 1321, 1265,
1036, 841, 739 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

I
A. G. Krishna Reddy, G. Satyanarayana
Paper
Synthesis
1H NMR (CDCl3, 400 MHz): δ = 7.70–7.60 (m, 2 H, Ar-H), 7.40–7.30
(m, 3 H, Ar-H), 7.25–7.15 (m, 4 H, Ar-H), 6.58 (s, 2 H, Ar-H), 6.02 (s, 1
H, C=CH), 5.31 (dd, 1 H, J = 11.7, 2.4 Hz, CHCH2CH2), 3.84 (s, 3 H,
ArOCH3), 3.84 (s, 6 H, 2 × ArOCH3), 3.33 (ddd, 1 H, J = 13.2, 13.2, 3.9 Hz,
CHCH2CHaHb), 2.90–2.80 (m, 1 H, CHCH2CHaHb), 2.30–2.18 (m, 1 H,
CHCHaHbCH2), 1.90–1.75 (m, 1 H, CHCHaHbCH2).
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138.3 (s, Ar-C), 138.0 (s, Ar-C), 137.6 (s, Ar-C), 137.1 (s, Ar-C), 136.7
(s, Ar-C), 129.7 (2 × d, 2 C, 2 × Ar-CH), 128.6 (d, Ar-CH), 128.2 (d, 2 C, 2
× Ar-CH), 127.0 (d, Ar-CH), 126.6 (d, 2 C, 2 × Ar-CH), 126.3 (d, Ar-CH),
102.9 (d, 2 C, 2 × Ar-CH), 102.5 (d, C=CH), 78.7 (d, OCHAr), 60.8 (q,
ArOCH3), 56.1 (q, 2 C, 2 × ArOCH3), 35.7 (t, CH2), 31.6 (t, CH2).
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403.1901.
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L.; Satyanarayana, G. Synlett 2012, 23, 375. (c) Reddy, A. G. K.;
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Reddy, A. G. K.; Satyanarayana, G. Adv. Synth. Catal. 2015, 357,
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80, 7089. (n) Krishna, J.; Niharika, P.; Satyanarayana, G. RSC Adv.
2015, 5, 26749. (o) Das, A.; Reddy, A. G. K.; Krishna, J.;
Satyanarayana, G. RSC Adv. 2014, 4, 26662. (p) Ramulu, B. V.;
Satyanarayana, G. RSC Adv. 2015, 5, 70972. (q) Niharika, P.;
Satyanarayana, G. RSC Adv. 2016, 6, 837. (r) Niharika, P.;
Ramulu, B. V.; Satyanarayana, G. Org. Biomol. Chem. 2014, 12,
4347. (s) Ramulu, B. V.; Niharika, P.; Satyanarayana, G. Synthesis
2015, 47, 1255. (t) Kumar, D. R.; Satyanarayana, G. Org. Lett.
2015, 17, 5894. (u) Suchand, B.; Krishna, J.; Ramulu, B. V.;
Dibyendu, D.; Reddy, A. G. K.; Mahendar, L.; Satyanarayana, G.
Tetrahedron Lett. 2012, 53, 3861. (v) Reddy, A. G. K.;
Satyanarayana, G. J. Org. Chem. 2016, 81, 12212. (w) Reddy, A. G.
K.; Krishna, J.; Satyanarayana, G. ChemistrySelect 2016, 1, 1151.
(22) Mahendar, L.; Reddy, A. G. K.; Krishna, J.; Satyanarayana, G.
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Funding Information
We are grateful to the Council of Scientific and Industrial Research
(CSIR), New Delhi, for the financial support [Sanction No.
02(0262)/16/EMR-11].
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The
Cambridge
Crystallographic
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J