Lewis acid promoted dual bond formation: Facile synthesis of dihydrocoumarins and spiro-tetracyclic dihydrocoumarins

Article abstract of DOI:10.1039/c4ob00490f

Lewis acid (FeCl₃) mediated dual bond (C-C and C-O) formation for synthesis of 3,4-dihydrocoumarins is presented. This method has successfully delivered a number of dihydrocoumarins containing dense functionalities on the aromatic ring. Significantly, the present method enabled achieving dihydrocoumarins with tertiary as well as quaternary carbon atoms at the benzylic position. Gratifyingly, the novel spiro-tetracyclic lactones have also been dextrously prepared using this process. the Partner Organisations 2014.

Full text of DOI:10.1039/c4ob00490f

Organic &
Biomolecular Chemistry
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Lewis acid promoted dual bond formation:
facile synthesis of dihydrocoumarins and
spiro-tetracyclic dihydrocoumarins†
Cite this: Org. Biomol. Chem., 2014,
12, 4347
Pedireddi Niharika, Bokka Venkat Ramulu and Gedu Satyanarayana*
Lewis acid (FeCl3) mediated dual bond (C–C and C–O) formation for synthesis of 3,4-dihydrocoumarins
is presented. This method has successfully delivered a number of dihydrocoumarins containing dense
functionalities on the aromatic ring. Significantly, the present method enabled achieving dihydro-
coumarins with tertiary as well as quaternary carbon atoms at the benzylic position. Gratifyingly, the novel
spiro-tetracyclic lactones have also been dextrously prepared using this process.
Received 4th March 2014,
Accepted 24th April 2014
DOI: 10.1039/c4ob00490f
www.rsc.org/obc
Introduction
Coumarins are widely prevalent in nature, and show a broad
range of biological activities1 such as anti-inflammatory, anti-
aging, anti-oxidative and anti-cancer activities.2 The coumarin
derivatives, with the core carbon skeleton of 4-aryl-3,4-dihydro-
coumarin, are present in several classes of plants (neoflava-
noids) exhibiting some interesting biological activities such as
antiherpetic activity,3 aldose reductase inhibition,4 protein
kinase inhibition,5 and they are also important synthetic inter-
mediates for pharmaceutical compounds. Some tannins pos-
sessing this dihydrocoumarin unit are known to have been
used in the treatment of infections and diseases.6 Some of the
synthetically prepared dihydrocoumarins have gained popular-
ity for their biological advantages. For example, compound 1
is a key intermediate in the synthesis of an endothelin anta-
gonist7 as well as the drug tolterodine,8 which is an antagonist
formulated to treat overactive bladder (Fig. 1),9 whereas the
dihydrocoumarin 2 acts as a bactericide with the in vitro
activity against members of the Tripanosoma family (Fig. 1).10
Some of the naturally occurring dihydrocoumarins like 3 11
and 4 11 (Fig. 1), obtained from Aloe vera2,12 and Gnetum cleis-
tostachyum,1,13 respectively, show anti-inflammatory and anti-
oxidant activities.14 They are also notably known for their
ability to protect low-density lipoproteins from oxidative
attack15 and recent studies have also revealed their ability to
control the chronic heart and colon-rectal cancer.
Fig. 1 Examples of unnatural and natural dihydrocoumarins of biologi-
cal relevance.
Owing to the diverse advantages of the aryl-dihydrocoumar-
ins, development of various methodologies for their synthesis
has received tremendous attention. There have been a reasonable
number of reports on the synthesis of these dihydrocoumarins.
A few to be mentioned include the transition-metal-mediated
catalytic hydrogenation,16 protic acid induced hydroarylation of
the cinnamic acids with phenols,17 Lewis acid mediated cycliza-
tion between highly activated phenols and arylonitriles,18 the use
of oxidants on acids,19 synthesis from ionic liquids, solid state
catalysts, the use of molecular iodine as a catalyst, 5-alkylidene
Meldrum’s acids,20 Baeyer–Villiger oxidation of 1-indanones,21
and microwave assisted synthesis from phenols and cinnamoyl
chloride in the presence of the montmorillonite K-10 catalyst.22
Department of Chemistry, Indian Institute of Technology (IIT) Hyderabad, Ordnance
Factory Estate Campus, Yeddumailaram – 502 205, Medak District, Andhra Pradesh,
India. E-mail: gvsatya@iith.ac.in; Fax: +91 (40) 2301 6032
†Electronic supplementary information (ESI) available: 1H-NMR data of the
known compounds and the copies of 1H and 13C-NMR spectra are provided.
See DOI: 10.1039/c4ob00490f
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In this regard, we recently reported superacid mediated
Table 1 Screening conditions for synthesis of dihydrocoumarin 7a
under Lewis acidic conditions
dual C–C bond formation, for the efficient synthesis of inda-
nones.23 Herein we report an efficient and practical method
for the facile synthesis of the dihydrocoumarins promoted by a
Lewis acid (FeCl3) upon treatment of simple cinnamate esters
with phenols. Notably, the approach has some significant
advantages compared to those reported earlier. For example,
the present method, using a Lewis acid (FeCl3), describes the
direct treatment of cinnamate esters with phenols. Particularly,
the other striking facet is the facile formation of a stereogenic
quaternary carbon atom at the benzylic position and to the
best of our knowledge there is no report on dihydrocoumarins
with a quaternary carbon atom in such mild acidic transform-
ations. Significantly, this method is applicable to accomplish
the novel spiro-tetracyclic lactones which are quite difficult to
achieve starting from cyclohexanone derivatives, since self-
aromatization is a serious problem either under strong acidic
or basic conditions. Moreover, the present study is broadly
applied to check the scope and limitations of the method by
Yieldb (%)
Solvent
(mL)
Temp
(°C)
Entrya
Lewis acid
7a
8a
1c
2
3
4
5
FeCl3 (10 mol%)
FeCl3 (20 mol%)
FeCl3 (60 mol%)
FeCl3 (3 equiv.)
FeCl3 (5 equiv.)
FeCl3 (3 equiv.)
AlCl3 (3 equiv.)
FeCl3 (3 equiv.)
FeCl3 (3 equiv.)
AuCl3 (10 mol%)
Sc(OTf)3 (10 mol%)
Cu(OTf)2 (10 mol%)
TfOH
DCE (2)
DCE (2)
DCE (2)
DCE (2)
DCE (2)
DCM (2)
DCE (2)
DCE (2)
Benzene (2)
DCE (2)
DCE (2)
DCE (2)
DCE (2)
80
80
80
80
80
rt
80
rt
80
80
80
80
80
0
0
0
60
55
20
0
20
0
0
0
0
50
0
10
30
20
0
0
0
0
35
0
0
0
6
7d
8
9
employing on different cinnamates with varying functional- 10c
11c
ities on the aromatic rings.
12c
13
0
a All reactions were carried out on a 0.5 mmol scale of 5a and
1.5 equiv. of 6a, in solvent DCE (2 mL). b Isolated yields of
chromatographically pure products. c Only the starting material was
recovered. d Neither the product (7a) nor the starting material was
isolated.
Results and discussion
To begin with, the required cinnamate esters 5 were prepared
from the corresponding benzaldehydes/acetophenones using
the standard Wittig–Horner–Wadsworth–Emmons reaction. In
order to determine the best optimized reaction conditions,
initially, the simple ethyl cinnamate 5a was chosen as the
model to study the reaction with phenol under various con-
ditions as described in Table 1. The initial trials with catalytic
amounts of a Lewis acid (FeCl3) did not facilitate the product
7a formation, rather furnished the Michael addition product
8a along with the recovery of the starting material (Table 1,
entries 1 to 3). Though the precise mechanism cannot be
given at this stage, the regioselective formation of the Michael
addition product 8a, under catalytic loading of a Lewis acid
would be explained due to selective activation of the enoate
double bond by the Lewis acid that may facilitate the para-
attack by the phenol. Gratifyingly, increasing the Lewis acid
concentration (3 equiv.) at 80 °C in 1,2-dichloroethane resulted
in the formation of lactone 7a in fair yields along with the
Michael addition product 8a (Table 1, entry 4). An increase of
FeCl3 from 3 equiv. to 5 equiv. exclusively gave the final
product 7a albeit in moderate yields (Table 1, entry 5). The use
of dichloromethane as a solvent was found to be inferior
(Table 1, entry 6), while in benzene it better facilitated 8a. The
predominant formation of the cyclic product 7a, in a stoichio-
metric amount of the Lewis acid, may be justified based on
simultaneous activation of the enoate double bond, the carbo-
nyl group of the ester as well as the phenol by the Lewis acid
that might facilitate the Michael addition/condensation to give
the lactone product 7a. The use of AlCl3 neither gave the
lactone product nor allowed the recovery of the starting
material (Table 1, entry 7). Also, it is concluded that the temp-
erature played an important role, as when the reaction was
conducted at ambient temperature, the reaction slowed down
(Table 1, entry 8). The use of the other Lewis acid catalysts, like
Sc(OTf)3, Cu(OTf)2 and AuCl3, in the catalytic amounts was
found to be futile and led to the starting material recovery
(Table 1, entries 10 to 12). In the presence of a superacid
(TfOH) also the product 7a was formed, however, in moderate
yields (Table 1, entry 13).
Among all the screened conditions, conditions of entry 4 of
Table 1 were found to be the best with regard to the formation
of 7a. Therefore, to check the scope and generality of the
method, these conditions were applied to different cinnamates
5a–5c containing various functional groups on the aromatic
rings with phenols 6a–6c. Gratifyingly, the method was found
amenable and gave dihydrocoumarins 7a–7e containing a ter-
tiary carbon atom, as summarized in Table 2. Disappointingly,
in the case of electron rich cinnamate esters 5d–5f it could not
be amenable under standard conditions, however at the
ambient temperature it furnished the clean lactone products
7f–7l (Table 2).
Furthermore, to check the feasibility of the method, β-alkyl
(methyl/ethyl) ethyl cinnamates 5g–5j were explored. Interest-
ingly, it was noted that the reaction is temperature and system
dependent. For example, when β-methyl cinnamate ester 5g,
derived from the corresponding acetophenone, was treated
with the phenol 6a using the above optimized reaction con-
ditions at 80 °C (Table 1, entry 4), it was not clean. However,
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Table 2 Lewis acid (FeCl3) mediated synthesis of dihydrocoumarins 7a–7l starting from cinnamates 5a–5fa,b,c,d
a All reactions were carried out on a 0.5 mmol scale of 5 and 1.5 equiv. of 6, in solvent DCE (2 mL). b Isolated yields of chromatographically pure
products 7. c For compounds 7a–7e, the reaction was carried out at 80 °C for 24 h. d For compounds 7f–7l, the reaction was carried out at room
temperature for 16 h.
the reaction was quite successful at room temperature and ment/cleavage of either X or Y intermediates, as shown in
furnished the desired product 9a (Table 3). This would be Scheme 1.
justified owing to the slightly increased reactivity of 5g that
Furthermore, to study the regiochemical preference (i.e. the
may be due to the presence of the β-methyl substituent which effect of the ortho-substituent on the Friedel–Crafts alkylation),
would facilitate the polarization of the enoate double bond by 2-phenylphenol 6g was used as an external phenol on the cin-
the Lewis acid. After optimizing the reaction conditions for the namate esters 5g–5h. However, the cyclized products 11a–11b
ester 5g at room temperature, the generality of the reaction were formed, albeit, in poor yields, while the Michael addition
was established by employing the reaction between β-alkyl adducts 12a–12b were formed as the by-products, in moderate
cinnamate esters 5h–5j and the phenols 6a–6f. In general, yields. This can be attributed to the steric crowding of
the method was smooth and furnished the dihydrocoumarins 2-phenylphenol 6g that prefers para-attack on the Michael
9b–9q (Table 3).
acceptor ethyl cinnamates 5g–5h (Scheme 2).
However, when attempting to apply the present method on
Upon accomplishing the dihydrocoumarins (7, 9 and 11) in
β-methyl ethyl cinnamates 5k–5l, it did not furnish the a wide generality, we envisioned to use this method in a more
expected dihydrocoumarins, rather gave coumarins 10a–10c applicable facet by performing the reaction with the cinnamate
(Table 4).
ester 5m obtained from the tetralone. Nevertheless, one could
This can be rationalized based on the more reactive nature easily realize that such systems derived from six membered
of the electron rich aromatic ring derived from the cinnamates ketones would pose a serious problem of self-aromatization
5k–5l, with suitably positioned electron donating groups. either under strong acidic or basic reaction conditions. As
Though, the precise reaction mechanism cannot be given at expected, the reaction of cinnamate ester 5m under standard
this stage, however their formation is believed to be via the for- conditions at 80 °C was unclear, whereas at room temperature,
mation of the usual dihydrocoumarin product 9 followed by it gave only the self-aromatized product 14 (Table 5, entries 1
ipso type of aromatic substitution through internal rearrange- and 2). This made us to realize that the phenol is not
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Table 3 Lewis acid (FeCl3) mediated synthesis of dihydrocoumarins 9 starting from cinnamates 5
sufficient enough to compete with usual self-aromatization. promote the reaction, because phenol could also chelate with
Therefore, performing the reaction with 5 equiv. of the phenol the Lewis acid and decrease its reactivity.
6a led to the formation of the novel tetracyclic lactone 13a, in
Among the screened conditions, conditions with either 5 or
33% yield along with the aromatized product 14 (Table 5, entry 10 equiv. of phenol 6a in benzene (Table 5, entries 5 and 6)
3). On the other hand, interestingly, benzene was identified as were found to be the best with respect to the formation of 13a.
the good solvent, hence it gave the product 13a, albeit, in poor Therefore, these conditions were used to generate different
yield, even with 1.5 equiv. of phenol 6a (Table 5, entry 4). Grati- tetracyclic lactones 13. Gratifyingly, the method conveniently
fyingly, with the increased amount of phenol 6a (5 equiv.), the furnished the novel tetracyclic lactones 13b–13f, as summar-
product 13a was furnished in moderate yields along with the ized in Table 6.
aromatized product 14 (Table 5, entry 5). However, a further
increase of phenol 6a quantity (10 equiv.) could not improve
the yield of the product drastically (Table 5, entry 6). It is note-
worthy that the amount of the Lewis acid is slightly increased
Conclusions
to 4 equiv. from 3 equiv. wherever more amount of phenol has
been used in order to maintain the reasonable reactivity to
In summary, we have developed a simple and practical method
for the synthesis of dihydrocoumarins, a ubiquitous system
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Table 4 Lewis acid (FeCl3) mediated synthesis of coumarins
10 starting from cinnamates 5
Scheme 2 Regioselective Michael addition of 2-phenylphenol 6g onto
the cinnamate esters 5g–5h.
Table 5 Screening conditions for synthesis of spiro-dihydrocoumarins
13a under Lewis acidic conditions
Yieldb (%)
FeCl3
(equiv.)
Phenol
(equiv.)
Solvent
(mL)
Temp
(°C)
Entrya
13a
14
1
2
3
4
5
6
3
3
4
3
4
4
1.5
1.5
5
1.5
5
DCE (2)
DCE (2)
DCE (2)
Benzene
Benzene
Benzene
80
rt
rt
rt
rt
rt
0
0
33
15
40
42
0
38
10
40
23
20
10
a All reactions were carried out on a 0.5 mmol scale of 5m. b Isolated
yields of chromatographically pure products.
Experimental section
General
IR spectra were recorded on a Bruker Tensor 37 (FTIR) spectro-
photometer. 1H NMR spectra were recorded on a Bruker
Avance 400 (400 MHz) spectrometer at 295 K in CDCl3; chemi-
cal shifts (δ ppm) and coupling constants (J in Hz) are
reported in a standard fashion with reference to either internal
standard tetramethylsilane (TMS) (δH = 0.00 ppm) or CHCl3
(δH = 7.25 ppm). 13C NMR spectra were recorded on a Bruker
Avance 400 (100 MHz) spectrometer at RT in CDCl3; chemical
Scheme 1 Plausible mechanism for the formation of 10.
present in many natural products. It was also extended to syn-
thesize the novel spiro-tetracyclic lactones. The strategy is
efficient and successful for the synthesis of a number of
analogues. Moreover, this method availed the creation of the
quaternary centre.
shifts (δ in ppm) are reported relative to CHCl3 [δC
=
77.00 ppm (central line of triplet)]. In the 13C NMR, the nature
of carbons (C, CH, CH2 and CH3) was determined 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)
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Table 6 Synthesis of spiro-dihydrocoumarins 13 from cinnamates 5a,b
6 (70–81 mg, 0.75 mmol) and anhydrous FeCl3 (324.0 mg,
2 mmol) followed by DCE (2 mL). The resulting reaction
mixture was stirred at 80 °C for 5a–5c for 24 h (for other esters
5d–5j, the reaction was carried out at room temperature, for
6 to 16 h). Progress of the reaction was monitored by TLC until
the reaction was completed. The reaction mixture was
quenched by the addition of aqueous NaHCO3 and extracted
in ethyl acetate (3 × 20 mL). The combined organic layers were
dried (Na2SO4) and concentrated in vacuo. Purification of the
residue on a silica gel column using petroleum ether–ethyl
acetate as the eluent furnished lactones 7 (35–67%) and 9
(54–90%) as viscous liquids/solids.
General procedure (GP-2) for spiro-cyclization
Into an oven dried Schlenk tube under a nitrogen atmosphere
were added cinnamate ester 5 (88–133 mg, 0.5 mmol), phenol
6 (235–360 mg, 2.5 mmol) and anhydrous FeCl3 (324.0 mg,
2 mmol) followed by benzene (2.5 mL). The resulting reaction
mixture was stirred at rt for 2 h. Progress of the reaction was
monitored by TLC until the reaction was completed. The reac-
tion mixture was quenched by the addition of aqueous
NaHCO3 and extracted in ethyl acetate (3 × 20 mL). The com-
bined organic layers were dried (Na2SO4) and concentrated
in vacuo. Purification of the residue on a silica gel column
using petroleum ether–ethyl acetate as the eluent furnished
spiro-lactones 13 (39–62%) as viscous liquids/solids.
4-(3-Methoxyphenyl)-6-methylchroman-2-one (7e). GP-1 was
carried out on the ester 5c (103 mg, 0.5 mmol), para-cresol 6c
(81.0 mg, 0.75 mmol), anhydrous FeCl3 (243.3 mg, 1.5 mmol)
and DCE (2 mL). The resulting reaction mixture was stirred at
80 °C for 24 h [TLC control Rf(5c) = 0.83, Rf(7e) = 0.66 (pet-
roleum ether–ethyl acetate 88 : 12, UV detection)]. Purification
of the residue on a silica gel column (petroleum ether–ethyl
acetate 96 : 4 to 85 : 15 as the eluent) furnished the lactone
a All reactions were carried out on a 0.5 mmol scale of 5 and 5 equiv. of
6, in solvent benzene (2 mL). b Isolated yields of chromatographically
pure products 13.
and q = quartet (for CH3). In the 1H-NMR, the following
abbreviations were used throughout: s = singlet, d = doublet,
t = triplet, q = quartet, qui = quintet, m = multiplet and br.
s = broad singlet. The assignment of signals was confirmed from
1H, 13C CPD and DEPT spectra. High-resolution mass spectra
(HR-MS) were recorded on an Agilent 6538 UHD Q-TOF using a
multimode source. All small scale dry reactions were carried
out using the standard syringe-septum technique. Regarding
the Horner–Wadsworth–Emmons reaction, TEPA from Avra
Synthesis with a purity of 98%, NaH from Sigma–Aldrich (60%
immersion in mineral oil), and benzaldehydes/acetophenones
from Sisco Research Laboratories having 97–98% purity were
used. Solvent THF was dried over sodium metal. Similarly, for
cyclization reaction anhydrous FeCl3 from Merck Chemicals
and phenols from Sisco Research Laboratories were used. DCE
was dried over calcium hydride and used. Reactions were
monitored by TLC on silica gel using a mixture of petroleum
ether and ethyl acetate as eluents. Reactions were generally
run under an argon or nitrogen atmosphere. Solvents were dis-
tilled prior to use; petroleum ether with a boiling range of
60 to 80 °C was used. Acme’s silica gel (60–120 mesh) was
used for column chromatography (approximately 20 g per
gram of crude material).
7e (66 mg, 51%) as
a viscous liquid. IR (MIR-ATR,
4000–600 cm−1): νmax = 2924, 1765, 1511, 1493, 1462, 1245,
1199, 1179, 1145, 1033, 820 cm−1. H NMR (CDCl3, 400 MHz):
1
δ = 7.26 (dd, 1H, J = 7.8 and 7.8 Hz, ArH), 7.08 (dd, 1H, J = 8.3
and 2.0 Hz, ArH), 7.01 (d, 1H, J = 7.8 Hz, ArH), 6.81 (dd, 1H, J =
8.3 and 2.0 Hz, ArH), 6.79 (s, 1H, ArH), 6.73 (d, 1H, J = 7.8 Hz,
ArH), 6.68 (dd, 1H, J = 2.0 and 2.0 Hz, ArH), 4.25 (dd, 1H, J =
7.8 and 6.4 Hz, ArCHCH2CO), 3.77 (s, 3H, ArOCH3), 3.03 (dd,
1H, J = 16.1 and 6.4 Hz, ArCHCHaHbCO), 2.98 (dd, 1H, J = 16.1
and 7.8 Hz, ArCHCHaHbCO), 2.25 (s, 3H, ArCH3) ppm. 13C
NMR (CDCl3, 100 MHz): δ = 167.8 (s, O–CvO), 160.0 (s, ArC),
149.6 (s, ArC), 142.1 (s, ArC), 134.3 (s, ArC), 130.1 (d, ArCH),
129.3 (d, ArCH), 128.6 (d, ArCH), 125.1 (s, ArC), 119.7 (d,
ArCH), 116.8 (d, ArCH), 113.6 (d, ArCH), 112.5 (d, ArCH), 55.2
(q, ArOCH3), 40.7 (d, ArCHCH2CO), 37.0 (t, CH2CO), 20.7 (q,
ArCH3) ppm. HR-MS (ESI+) m/z calculated for [C17H16NaO3]+ =
[M + Na]+: 291.0992; found 291.0991.
4-(3,4-Dimethoxyphenyl)-7-methylchroman-2-one (7i). GP-1
was carried out on the ester 5e (118.0 mg, 0.50 mmol), meta-
cresol 6b (81.0 mg, 0.75 mmol), anhydrous FeCl3 (243.3 mg,
General procedure (GP-1) for cyclization
Into an oven dried Schlenk tube under a nitrogen atmosphere 1.5 mmol) and DCE (2 mL). The resulting reaction mixture was
were added cinnamate ester 5 (88–133 mg, 0.5 mmol), phenol stirred at room temperature for 16 h [TLC control Rf(5e) = 0.75,
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Rf(7i) = 0.50 (petroleum ether–ethyl acetate 80 : 20, UV detec- δ = 6.93 (s, 1H, ArH), 6.90 (d, 1H, J = 7.8 Hz, ArH), 6.88 (d, 1H,
tion)]. Purification of the residue on a silica gel column (pet- J = 7.8 Hz, ArH), 6.34 (s, 2H, ArH), 4.22 (dd, 1H, J = 7.8 and
roleum ether–ethyl acetate 95 : 5 to 75 : 25 as the eluent) 6.4 Hz, ArCHCH2CO), 3.82 (s, 3H, ArOCH3), 3.79 (s, 6H, 2 ×
furnished the lactone 7i (79.0 mg, 53%) as a liquid. IR ArOCH3), 3.03 (dd, 1H, J = 16.1 and 6.4 Hz, ArCHCHaHbCO),
(MIR-ATR, 4000–600 cm−1): νmax = 2922, 2852, 1762, 1591, 2.98 (dd, 1H, J = 16.1 and 7.8 Hz, ArCHCHaHbCO), 2.35 (s, 3H,
1
1516, 1463, 1419, 1253, 1219, 1142, 1025, 817 cm−1. H NMR ArCH3) ppm. 13C NMR (CDCl3, 100 MHz): δ = 167.8 (s,
(CDCl3, 400 MHz): δ = 6.93 (s, 1H, ArH), 6.89 (d, 1H, J = 8.3 Hz, O–CvO), 153.6 (s, 2C, 2 × ArC), 151.5 (s, ArC), 139.2 (s, ArC),
ArH), 6.85 (d, 1H, J = 7.8 Hz, ArH), 6.81 (d, 1H, J = 7.8 Hz, 136.2 (s, ArC), 128.0 (d, ArCH), 125.4 (d, ArCH), 122.5 (s, ArC),
ArH), 6.67 (dd, 1H, J = 8.3 and 1.9 Hz, ArH), 6.65 (d, 1H, J = 117.5 (d, ArCH), 104.5 (d, 2C, 2 × ArCH), 60.8 (q, ArOCH3), 56.1
1.9 Hz, ArH), 4.23 (dd, 1H, J = 7.8 and 6.4 Hz, ArCHCH2CO), (q, 2C, 2 × ArOCH3), 40.7 (d, ArCHCH2CO), 37.2 (t, CH2CO),
3.85 (s, 3H, ArOCH3), 3.81 (s, 3H, ArOCH3), 3.03 (dd, 1H, J = 21.1 (q, ArCH3) ppm. HR-MS (ESI+) m/z calculated for
16.1 and 6.4 Hz, ArCHCHaHbCO), 2.96 (dd, 1H, J = 16.1 and [C19H20NaO5]+ = [M + Na]+: 351.1203; found 351.1206.
7.8 Hz, ArCHCHaHbCO), 2.34 (s, 3H, ArCH3) ppm. 13C NMR
6-Methyl-4-(3,4,5-trimethoxyphenyl)chroman-2-one (7l). GP-1
(CDCl3, 100 MHz): δ = 168.0 (s, O–CvO), 151.5 (s, ArC), 149.3 was carried out on the ester 5f (133.0 mg, 0.50 mmol), para-
(s, ArC), 148.4 (s, ArC), 139.0 (s, ArC), 132.9 (s, ArC), 127.9 (d, cresol 6c (81.0 mg, 0.75 mmol), anhydrous FeCl3 (243.3 mg,
ArCH), 125.4 (d, ArCH), 122.9 (s, ArC), 119.7 (d, ArCH), 117.4 1.5 mmol) and DCE (2 mL). The resulting reaction mixture was
(d, ArCH), 111.5 (d, ArCH), 110.5 (d, ArCH), 55.9 (q, 2C, 2 × stirred at room temperature for 16 h [TLC control Rf(5f) = 0.80,
ArOCH3), 40.0 (d, ArCHCH2CO), 37.3 (t, CH2CO), 21.0 (q, Rf(7l) = 0.60 (petroleum ether–ethyl acetate 85 : 15, UV detec-
ArCH3) ppm. HR-MS (ESI+) m/z calculated for [C18H18NaO4]+ = tion)]. Purification of the residue on a silica gel column
[M + Na]+: 321.1097; found 321.1098.
(petroleum ether–ethyl acetate 95 : 5 to 80 : 15 as the eluent)
4-(3,4-Dimethoxyphenyl)-6-methylchroman-2-one (7j). GP-1 furnished the lactone 7l (67.2 mg, 41%) as a liquid. IR
was carried out on the ester 5e (118.0 mg, 0.50 mmol), para- (MIR-ATR, 4000–600 cm−1): νmax = 2921, 2850, 1764, 1591,
1
cresol 6c (81.0 mg, 0.75 mmol), anhydrous FeCl3 (243.3 mg, 1460, 1243, 1124, 1006, 815 cm−1. H NMR (CDCl3, 400 MHz):
1.5 mmol) and DCE (2 mL). The resulting reaction mixture was δ = 7.08 (dd, 1H, J = 8.3 and 1.9 Hz, ArH), 7.01 (d, 1H, J =
stirred at room temperature for 16 h [TLC control Rf(5e) = 0.75, 8.3 Hz, ArH), 6.81 (d, 1H, J = 1.9 Hz, ArH), 6.34 (s, 2H, 2 ×
Rf(7j) = 0.57 (petroleum ether–ethyl acetate 80 : 20, UV detec- ArH), 4.21 (dd, 1H, J = 7.8 and 6.3 Hz, ArCHCH2CO), 3.83 (s,
tion)]. Purification of the residue on a silica gel column (pet- 3H, ArOCH3), 3.79 (s, 6H, 2 × ArOCH3), 3.04 (dd, 1H, J = 16.1
roleum ether–ethyl acetate 95 : 5 to 75 : 25 as the eluent) and 6.3 Hz, ArCHCHaHbCO), 2.96 (dd, 1H, J = 16.1 and 7.8 Hz,
furnished the lactone 7j (99.8 mg, 67%) as a liquid. IR ArCHCHaHbCO), 2.27 (s, 3H, ArCH3) ppm. 13C NMR (CDCl3,
(MIR-ATR, 4000–600 cm−1): νmax = 2924, 2852, 1762, 1592, 100 MHz): δ = 167.8 (s, O–CvO), 153.6 (s, 2C, 2 × ArC), 149.5
1493, 1420, 1243, 1137, 1025, 813 cm−1 1H NMR (CDCl3, (s, ArC), 137.3 (s, ArC), 136.2 (s, ArC), 134.4 (s, ArC), 129.4 (d,
.
400 MHz): δ = 7.07 (dd, 1H, J = 8.3 and 1.9 Hz, ArH), 7.00 (d, ArCH), 128.6 (d, ArCH), 125.2 (s, ArC), 116.8 (s, ArC), 104.5 (d,
1H, J = 8.3 Hz, ArH), 6.82 (d, 1H, J = 7.8 Hz, ArH), 6.78 (d, 1H, 2C, 2 × ArCH), 60.8 (q, ArOCH3), 56.1 (q, 2C, 2 × ArOCH3), 41.1
J = 1.9 Hz, ArH), 6.67 (dd, 1H, J = 7.8 and 1.9 Hz, ArH), 6.66 (s, (d, ArCHCH2CO), 37.2 (t, CH2CO), 20.7 (q, ArCH3) ppm.
1H, ArH), 4.23 (dd, 1H, J = 7.8 and 6.4 Hz, ArCHCH2CO), 3.85 HR-MS (ESI+) m/z calculated for [C19H20NaO5]+ = [M + Na]+:
(s, 3H, ArOCH3), 3.82 (s, 3H, ArOCH3), 3.03 (dd, 1H, J = 16.1 351.1203; found 351.1204.
and 6.4 Hz, ArCHCHaHbCO), 2.96 (dd, 1H, J = 16.1 and 7.8 Hz,
4-Methyl-4-phenylchroman-2-one (9a). GP-1 was carried out
ArCHCHaHbCO), 2.25 (s, 3H, ArCH3) ppm. 13C NMR (CDCl3, on the ester 5g (95.1 mg, 0.5 mmol), phenol 6a (69.8 mg,
100 MHz): δ = 168.0 (s, O–CvO), 149.5 (s, ArC), 149.3 (s, ArC), 0.75 mmol), and anhydrous FeCl3 (243.3 mg, 1.5 mmol)
148.4 (s, ArC), 134.3 (s, ArC), 132.9 (s, ArC), 129.2 (d, ArCH), followed by addition of DCE (2 mL). The resulting reaction
128.5 (d, ArCH), 125.6 (s, ArC), 119.7 (d, ArCH), 116.8 (d, mixture was stirred at room temperature for 6 h [TLC control
ArCH), 111.5 (d, ArCH), 110.5 (d, ArCH), 55.9 (q, 2C, 2 × Rf(5g) = 0.60, Rf(9a) = 0.45 (petroleum ether–ethyl acetate
ArOCH3), 40.4 (d, ArCHCH2CO), 37.3 (t, CH2CO), 20.7 (q, 94 : 6, UV detection)]. Purification of the residue on a silica gel
ArCH3) ppm. HR-MS (ESI+) m/z calculated for [C18H18NaO4]+ = column (petroleum ether–ethyl acetate 96 : 4 to 94 : 6 as the
[M + Na]+: 321.1097; found 321.1100.
eluent) furnished the lactone 9a (76 mg, 64%) as a colorless
7-Methyl-4-(3,4,5-trimethoxyphenyl)chroman-2-one (7k). GP-1 viscous liquid. IR (MIR-ATR, 4000–600 cm−1): νmax = 2922,
was carried out on the ester 5f (133.0 mg, 0.50 mmol), meta- 1774, 1586, 1487, 1448, 1283, 1202, 1135, 1051, 910, 758,
cresol 6b (81.0 mg, 0.75 mmol), anhydrous FeCl3 (243.3 mg, 700 cm−1 1H NMR (CDCl3, 400 MHz): δ = 7.34 (dd, 1H, J =
.
1.5 mmol) and DCE (2 mL). The resulting reaction mixture was 7.8 and 1.5 Hz, ArH), 7.30 (dd, 2H, J = 7.8 and 1.5 Hz, ArH),
stirred at room temperature for 16 h [TLC control Rf(5f) = 0.80, 7.27–7.21 (m, 2H, ArH), 7.21–7.16 (m, 3H, ArH), 7.11 (dd, 1H,
Rf(7k) = 0.55 (petroleum ether–ethyl acetate 85 : 15, UV detec- J = 8.3 and 1.5 Hz, ArH), 3.29 (d, 1H, J = 15.6 Hz, CHaHbCO),
tion)]. Purification of the residue on a silica gel column 2.84 (d, 1H, J = 15.6 Hz, CHaHbCO), 1.76 [s, 3H, ArC(CH2CO)-
(petroleum ether–ethyl acetate 95 : 5 to 85 : 15 as the eluent) CH3] ppm. 13C NMR (CDCl3, 100 MHz): δ = 167.4 (s, O–CvO),
furnished the lactone 7k (57.4 mg, 35%) as a semi-solid. IR 151.2 (s, ArC), 143.9 (s, ArC), 130.8 (s, ArC), 128.7 (d, 3C, 3 ×
(MIR-ATR, 4000–600 cm−1): νmax = 2923, 2852, 1767, 1508, ArCH), 127.1 (d, ArCH), 126.6 (d, ArCH), 126.1 (d, 2C, 2 ×
1
1461, 1235, 1126, 1008, 818 cm−1. H NMR (CDCl3, 400 MHz): ArCH), 124.7 (d, ArCH), 117.3 (d, ArCH), 43.7 (t, CH2CO), 41.1
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[s, ArC(CH2CO)CH3], 27.5 [q, ArC(CH2CO)CH3] ppm. HR-MS reaction mixture was stirred at room temperature for 6 h [TLC
(ESI+) m/z calculated for [C16H15O2]+ = [M + H]+: 239.1067; control Rf(5g) = 0.65, Rf(9d) = 0.50 (petroleum ether–ethyl
found: 239.1067.
acetate 94 : 6, UV detection)]. Purification of the residue on a
4,7-Dimethyl-4-phenylchroman-2-one (9b). GP-1 was carried silica gel column chromatography (petroleum ether–ethyl
out on the ester 5g (95.1 mg, 0.5 mmol), meta-cresol 6b acetate 98 : 2 to 94 : 6 as the eluent) furnished the lactone 9d
(69.8 mg, 0.75 mmol), and anhydrous FeCl3 (243.3 mg, (81.9 mg, 65%) as colorless viscous liquid. IR (MIR-ATR,
1.5 mmol) followed by addition of DCE (2 mL). The resulting 4000–600 cm−1): νmax = 2967, 2921, 1765, 1463, 1445, 1266,
reaction mixture was stirred at room temperature for 6 h [TLC 1192, 1101, 915, 751, 699 cm−1. 1H NMR (CDCl3, 400 MHz): δ =
control Rf(5g) = 0.60, Rf(9b) = 0.45 (petroleum ether–ethyl 7.29 (ddd, 2H, J = 8.8, 7.3 and 1.5 Hz, ArH), 7.23 (dd, 1H, J =
acetate 94 : 6, UV detection)]. Purification of the residue on a 8.3 and 1.5 Hz, ArH), 7.21–7.15 (m, 3H, ArH), 7.07 (d, 2H, J =
silica gel column (petroleum ether–ethyl acetate 96 : 4 to 94 : 6 4.9 Hz, ArH), 3.28 (d, 1H, J = 15.6 Hz, CHaHbCO), 2.81 (d, 1H,
as the eluent) furnished the lactone 9b (107.5 mg, 85%) as a J = 15.6 Hz, CHaHbCO), 2.32 (s, 3H, ArCH3), 1.73 [s, 3H, ArC-
colorless viscous liquid. IR (MIR-ATR, 4000–600 cm−1): νmax
=
(CH2CO)CH3] ppm. 13C NMR (CDCl3, 100 MHz): δ = 167.7 (s,
2972, 2926, 1763, 1623, 1578, 1445, 1413, 1215, 1199, 1164, O–CvO), 149.4 (s, ArC), 144.0 (s, ArC), 130.5 (s, ArC), 130.2 (d,
1150, 1047, 820, 764, 699 cm−1. 1H NMR (CDCl3, 400 MHz): δ = ArCH), 128.6 (d, 3C, 3 × ArCH), 127.1 (d, ArCH), 126.6 (s, ArC),
7.29 (ddd, 2H, J = 7.8, 7.3 and 1.9 Hz, ArH), 7.22 (t, 1H, J = 126.1 (d, 2C, 2 × ArCH), 124.1 (d, ArCH), 43.6 (t, CH2CO), 41.1
7.3 Hz, ArH), 7.17 (dd, 2H, J = 7.8 and 1.9 Hz, ArH), 7.11 (d, [s, ArC(CH2CO)CH3], 27.7 [q, ArC(CH2CO)CH3], 15.9 (q, ArCH3)
1H, J = 7.8 Hz, ArH), 6.98 (dd, 1H, J = 7.8 and 1.0 Hz, ArH), ppm. HR-MS m/z calculated for [C17H17O2]+ = [M + H]+:
6.92 (d, 1H, J = 1.0 Hz, ArH), 3.26 (d, 1H, J = 15.6 Hz, 253.1223; found: 253.1210.
CHaHbCO), 2.80 (d, 1H, J = 15.6 Hz, CHaHbCO), 2.36 (s, 3H,
4-Methyl-4-phenyl-3,4-dihydro-2H-benzo[h]chromen-2-one
ArCH3), 1.72 [s, 3H, ArC(CH2CO)CH3] ppm. 13C NMR (CDCl3, (9e). GP-1 was carried out on the ester 5g (95.1 mg, 0.5 mmol),
100 MHz): δ = 167.7 (s, O–CvO), 151.0 (s, ArC), 144.1 (s, ArC), 1-naphthol 6e (108.0 mg, 0.75 mmol), and anhydrous FeCl3
139.0 (s, ArC), 128.6 (d, 2C, 2 × ArCH), 127.6 (s, ArC), 127.0 (d, (243.3 mg, 1.5 mmol) followed by addition of DCE (2 mL). The
ArCH), 126.3 (d, ArCH), 126.1 (d, 2C, 2 × ArCH), 125.4 (d, resulting reaction mixture was stirred at room temperature for
ArCH), 117.7 (d, ArCH), 43.9 (t, CH2CO), 40.8 [s, ArC(CH2CO)- 6 h [TLC control Rf(5g) = 0.60, Rf(9e) = 0.50 (petroleum ether–
CH3], 27.6 [q, ArC(CH2CO)CH3], 21.0 (q, ArCH3) ppm. HR-MS ethyl acetate 94 : 6, UV detection)]. Purification of the residue
(ESI+) m/z calculated for [C17H16NaO2]+ = [M + Na]+: 275.1043; on a silica gel column (petroleum ether–ethyl acetate 98 : 2 to
found 275.1048.
94 : 6 as the eluent) furnished the lactone 9e (84.9 mg, 59%) as
4,6-Dimethyl-4-phenylchroman-2-one (9c). GP-1 was carried a white solid, recrystallized the solid with dichloromethane/
on the ester 5g (95.1 mg, 0.5 mmol), para-cresol 6c (69.8 mg, hexane, m. p. 144–146 °C. IR (MIR-ATR, 4000–600 cm−1): νmax
0.75 mmol), and anhydrous FeCl3 (243.3 mg, 1.5 mmol) fol- = 2970, 2928, 1769, 1494, 1468, 1190, 1150, 1068, 816, 750,
lowed by addition of DCE (2 mL). The resulting reaction 700, 625 cm−1. 1H NMR (CDCl3, 400 MHz): δ = 8.29 (dd, 1H, J =
mixture was stirred at room temperature for 6 h [TLC control 8.8, and 2.0 Hz, ArH), 7.84 (dd, 1H, J = 7.3 and 2.0 Hz, ArH),
Rf(5g) = 0.60, Rf(9c) = 0.45 (petroleum ether–ethyl acetate 7.64 (d, 1H, J = 8.8 Hz, ArH), 7.59–7.51 (m, 2H, ArH), 7.34–7.18
94 : 6, UV detection)]. Purification of the residue on a silica gel (m, 6H, ArH), 3.34 (d, 1H, J = 15.6 Hz, CHaHbCO), 2.93 (d, 1H,
column (petroleum ether–ethyl acetate 96 : 4 to 94 : 6 as the J = 15.6 Hz, CHaHbCO), 1.82 [s, 3H, ArC(CH2CO)CH3] ppm.
eluent) furnished the lactone 9c (107.5 mg, 85%) as a colorless 13C NMR (CDCl3, 100 MHz): δ = 167.3 (s, O–CvO), 146.1 (s,
viscous liquid. IR (MIR-ATR, 4000–600 cm−1): νmax = 2974, ArC), 144.2 (s, ArC), 133.6 (s, ArC), 128.7 (d, 2C, 2 × ArCH),
2921, 1763, 1598, 1493, 1266, 1202, 1124, 1049, 913, 824, 732, 127.4 (d, ArCH), 127.2 (d, ArCH), 126.8 (d, ArCH), 126.7 (d,
1
698 cm−1. H NMR (CDCl3, 400 MHz): δ = 7.30 (ddd, 2H, J = ArCH), 126.3 (d, 2C, 2 × ArCH), 125.1 (s, ArC), 124.2 (d, ArCH),
7.8, 7.3 and 2.0 Hz, ArH), 7.23 (t, 1H, J = 7.3 Hz, ArH), 7.18 (dd, 123.7 (s, ArC), 123.6 (d, ArCH), 121.5 (d, ArCH), 44.2 (t,
2H, J = 7.8 and 2.0 Hz, ArH), 7.11 (dd, 1H, J = 8.3 and 2.0 Hz, CH2CO), 41.4 [s, ArC(CH2CO)CH3], 27.4 [q, ArC(CH2CO)CH3]
ArH), 7.02 (d, 1H, J = 2.0 Hz, ArH), 6.99 (d, 1H, J = 8.3 Hz, ppm. HR-MS (ESI+) m/z calculated for [C20H17O2]+ = [M + H]+:
ArH), 3.25 (d, 1H, J = 15.6 Hz, CHaHbCO), 2.80 (d, 1H, J = 289.1223; found 289.1221.
15.6 Hz, CHaHbCO), 2.34 (s, 3H, ArCH3), 1.73 [s, 3H, ArC-
1-Methyl-1-phenyl-1,2-dihydro-3H-benzo[f]chromen-3-one
(CH2CO)CH3] ppm. 13C NMR (CDCl3, 100 MHz): δ = 167.7 (s, (9f). GP-1 was carried out on the ester 5g (95.1 mg, 0.5 mmol),
O–CvO), 149.1 (s, ArC), 144.0 (s, ArC), 134.3 (s, ArC), 130.3 (s, β-naphthol 6f (108.1 mg, 0.75 mmol), anhydrous FeCl3
ArC), 129.2 (d, ArCH), 128.6 (d, 2C, 2 × ArCH), 127.1 (d, ArCH), (243.3 mg, 1.5 mmol) and DCE (2 mL). The resulting reaction
126.9 (d, ArCH), 126.1 (d, 2C, 2 × ArCH), 117.0 (d, ArCH), 43.8 mixture was stirred at room temperature for 6 h [TLC control
(t, CH2CO), 41.0 [s, ArC(CH2CO)CH3], 27.5 [q, ArC(CH2CO)- Rf(5g) = 0.65, Rf(9f) = 0.50 (petroleum ether–ethyl acetate
CH3], 20.9 (q, ArCH3) ppm. HR-MS (ESI+) m/z calculated for 94 : 6, UV detection)]. Purification of the residue on a silica gel
[C17H16NaO2]+ = [M + Na]+: 275.1048; found 275.1042.
column (petroleum ether–ethyl acetate 96 : 4 to 94 : 6 as the
4,8-Dimethyl-4-phenylchroman-2-one (9d). GP-1 was carried eluent) furnished the lactone 9f (81 mg, 56%) as a colorless
out with the ester 5g (95.1 mg, 0.5 mmol), ortho-cresol 6d viscous liquid. IR (MIR-ATR, 4000–600 cm−1): νmax = 2920,
(81.0 mg, 0.75 mmol), and anhydrous FeCl3 (243.3 mg, 2851, 1775, 1599, 1512, 1494, 1459, 1336, 1210, 1163, 1019,
1
1.5 mmol) followed by addition of DCE (2 mL). The resulting 982, 912, 814, 733, 701 cm−1. H NMR (CDCl3, 400 MHz): δ =
4354 | Org. Biomol. Chem., 2014, 12, 4347–4360
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7.79 (dd, 2H, J = 8.8 and 7.3 Hz, ArH), 7.40–7.19 (m, 7H, ArH), [s, ArC(CH2CO)CH3], 27.6 [q, ArC(CH2CO)CH3], 21.0 (q, ArCH3)
7.13 (d, 1H, J = 8.3 Hz, ArH), 7.08 (ddd, 1H, J = 8.8, 7.8 and ppm. HR-MS (ESI+) m/z calculated for [C17H15ClNaO2]+ = [M +
1.4 Hz, ArH), 3.07 (d, 1H, J = 15.6 Hz, CHaHbCO), 2.86 (d, 1H, Na]+: 309.0658; found 309.0656.
J = 15.6 Hz, CHaHbCO), 1.94 [s, 3H, ArC(CH2CO)CH3] ppm. 13
C
4-(4-Chlorophenyl)-4,6-dimethylchroman-2-one
(9i). GP-1
NMR (CDCl3, 100 MHz): δ = 166.5 (s, O–CvO), 149.9 (s, ArC), was carried out on the ester 5h (112 mg, 0.5 mmol), para-
147.0 (s, ArC), 131.9 (s, ArC), 130.4 (s, ArC), 130.1 (s, ArC), cresol 6c (81.7 mg, 0.75 mmol), anhydrous FeCl3 (243.3 mg,
129.0 (d, 2C, 2 × ArCH), 128.8 (d, ArCH), 127.0 (d, ArCH), 126.0 1.5 mmol) and DCE (2 mL). The resulting reaction mixture was
(d, 2C, 2 × ArCH), 125.9 (d, ArCH), 125.8 (d, ArCH), 124.4 (d, stirred at room temperature for 6 h [TLC control Rf(5h) = 0.60,
ArCH), 122.8 (s, ArC), 117.8 (d, ArCH), 48.0 (t, CH2CO), 42.9 [s, Rf(9i) = 0.45 (petroleum ether–ethyl acetate 94 : 6, UV detec-
ArC(CH2CO)CH3], 24.7 [q, ArC(CH2CO)CH3] ppm. HR-MS tion)]. Purification of the residue on a silica gel column (pet-
(ESI+) m/z calculated for [C20H16NaO2]+ = [M + Na]+: 311.1048; roleum ether–ethyl acetate 96 : 4 to 94 : 6 as the eluent)
found 311.1042.
furnished the lactone 9i (99 mg, 69%) as a colorless viscous
4-(4-Chlorophenyl)-4-methylchroman-2-one (9g). GP-1 was liquid. IR (MIR-ATR, 4000–600 cm−1): νmax = 2972, 2924, 1761,
carried out on the ester 5h (112 mg, 0.5 mmol), phenol 6a 1592, 1491, 1413, 1278, 1199, 1124, 1095, 1012, 914, 824, 717,
(69.8 mg, 0.75 mmol), anhydrous FeCl3 (243.3 mg, 1.5 mmol) 671 cm−1 1H NMR (CDCl3, 400 MHz): δ = 7.26 (d, 2H, J =
.
and DCE (2 mL). The resulting reaction mixture was stirred at 8.8 Hz, ArH), 7.12 (dd, 1H, J = 8.3 and 1.4 Hz, ArH), 7.10 (d,
room temperature for 6 h [TLC control Rf(5h) = 0.60, Rf(9g) = 2H, J = 8.8 Hz, ArH), 7.01 (d, 1H, J = 1.4 Hz, ArH), 6.99 (d, 1H,
0.35 (petroleum ether–ethyl acetate 94 : 6, UV detection)]. Puri- J = 8.3 Hz, ArH), 3.20 (d, 1H, J = 15.6 Hz, CHaHbCO), 2.80 (d,
fication of the residue on a silica gel column (petroleum 1H, J = 15.6 Hz, CHaHbCO), 2.35 (s, 3H, ArCH3), 1.72 [s, 3H,
ether–ethyl acetate 96 : 4 to 94 : 6 as the eluent) furnished the ArC(CH2CO)CH3] ppm. 13C NMR (CDCl3, 100 MHz): δ = 167.4
lactone 9g (90 mg, 66%) as a colorless viscous liquid. IR (s, O–CvO), 149.1 (s, ArC), 142.6 (s, ArC), 134.5 (s, ArC), 133.1
(MIR-ATR, 4000–600 cm−1): νmax = 2973, 2925, 1763, 1586, (s, ArC), 129.8 (s, ArC), 129.5 (d, ArCH), 128.8 (d, 2C, 2 ×
1487, 1449, 1279, 1232, 1198, 1134, 1095, 1012, 910, 828, 756, ArCH), 127.7 (d, 2C, 2 × ArCH), 126.7 (d, ArCH), 117.2 (d,
1
683 cm−1. H NMR (CDCl3, 400 MHz): δ = 7.32 (ddd, 1H, J = ArCH), 43.8 (t, CH2CO), 40.8 [s, ArC(CH2CO)CH3], 27.5 [q, ArC-
8.3, 7.3 and 2.0 Hz, ArH), 7.25 (d, 2H, J = 8.3 Hz, ArH), 7.22 (CH2CO)CH3], 21.0 (q, ArCH3) ppm. HR-MS (ESI+) m/z
(dd, 1H, J = 7.8 and 2.0 Hz, ArH), 7.18 (ddd, 1H, J = 8.3, 7.8 calculated for [C17H15ClNaO2]+ = [M + Na]+: 309.0658; found
and 2.0 Hz, ArH), 7.10 (dd, 1H, J = 7.3 and 2.0 Hz, ArH), 7.09 309.0650.
(d, 2H, J = 8.3 Hz, ArH), 3.22 (d, 1H, J = 15.6 Hz, CHaHbCO),
4-(4-Chlorophenyl)-4,8-dimethylchroman-2-one
(9j). GP-1
2.82 (d, 1H, J = 15.6 Hz, CHaHbCO), 1.72 [s, 3H, ArC(CH2CO)- was carried out on the ester 5h (112.3 mg, 0.5 mmol), ortho-
CH3] ppm. 13C NMR (CDCl3, 100 MHz): δ = 167.2 (s, O–CvO), cresol 6d (81.0 mg, 0.75 mmol), and anhydrous FeCl3
151.1 (s, ArC), 142.5 (s, ArC), 133.1 (s, ArC), 130.2 (s, ArC), (243.0 mg, 1.5 mmol) followed by addition of DCE (2 mL). The
129.0 (d, ArCH), 128.8 (d, 2C, 2 × ArCH), 127.6 (d, 2C, 2 × resulting reaction mixture was stirred at room temperature for
ArCH), 126.4 (d, ArCH), 124.8 (d, ArCH), 117.4 (d, ArCH), 43.6 6 h [TLC control Rf(5h) = 0.65, Rf(9j) = 0.56 (petroleum ether–
(t, CH2CO), 40.8 [s, ArC(CH2CO)CH3], 27.5 [q, ArC(CH2CO)- ethyl acetate 94 : 6, UV detection)]. Purification of the residue
CH3] ppm. HR-MS (ESI+) m/z calculated for [C16H13ClNaO2]+ = on a silica gel column (petroleum ether–ethyl acetate 96 : 4 to
[M + Na]+: 295.0502; found 295.0500.
94 : 6 as the eluent) furnished the lactone 9j (85.8 mg, 60%) as
4-(4-Chlorophenyl)-4,7-dimethylchroman-2-one (9h). GP-1 a colorless viscous liquid. IR (MIR-ATR, 4000–600 cm−1):
was carried out on the ester 5h (112 mg, 0.5 mmol), meta- νmax = 2965, 2923, 1770, 1493, 1465, 1195, 1098, 1012, 828,
cresol 6b (81.7 mg, 0.75 mmol), anhydrous FeCl3 (243.3 mg, 787, 754 cm−1. 1H NMR (CDCl3, 400 MHz): δ = 7.26 (dd, 2H, J =
1.5 mmol) and DCE (2 mL). The resulting reaction mixture was 8.8, and 2.4 Hz, ArH), 7.18 (dd, 1H, J = 7.3 and 2.4 Hz, ArH),
stirred at room temperature for 6 h [TLC control Rf(5h) = 0.60, 7.10 (dd, 2H, J = 8.8 and 2.4 Hz, ArH), 7.06 (dd, 2H, J = 8.8 and
Rf(9h) = 0.40 (petroleum ether–ethyl acetate 94 : 6, UV detec- 2.4 Hz, ArH), 3.22 (d, 1H, J = 15.6 Hz, CHaHbCO), 2.80 (d, 1H,
tion)]. Purification of the residue on a silica gel column J = 15.7 Hz, CHaHbCO), 2.31 (s, 3H, ArCH3), 1.70 [s, 3H, ArC-
(petroleum ether–ethyl acetate 96 : 4 to 94 : 6 as the eluent) (CH2CO)CH3] ppm. 13C NMR (CDCl3, 100 MHz): δ = 167.3 (s,
furnished the lactone 9h (103 mg, 72%) as a colorless viscous O–CvO), 149.4 (s, ArC), 142.7 (s, ArC), 133.0 (s, ArC), 130.5 (d,
liquid. IR (MIR-ATR, 4000–600 cm−1): νmax = 2964, 2925, 1766, ArCH), 130.0 (s, ArC), 128.6 (d, 2C, 2 × ArCH), 127.7 (d, 2C, 2 ×
1579, 1494, 1413, 1257, 1213, 1162, 1096, 1048, 1012, 820, ArCH), 126.8 (s, ArC), 124.3 (d, ArCH), 123.9 (d, ArCH), 43.5 (t,
1
736 cm−1. H NMR (CDCl3, 400 MHz): δ = 7.24 (d, 2H, J = 8.8 CH2CO), 40.9 [s, ArC(CH2CO)CH3], 27.7 [q, ArC(CH2CO)CH3],
Hz, ArH), 7.09 (d, 2H, J = 8.8 Hz, ArH), 7.08 (d, 1H, J = 7.8 Hz, 15.9 (q, ArCH3) ppm. HR-MS (APCI+) m/z calculated for
ArH), 6.98 (d, 1H, J = 7.8 Hz, ArH), 6.91 (s, 1H, ArH), 3.20 (d, [C17H16ClO2]+ = [M + H]+: 287.0833; found: 287.0824.
1H, J = 15.6 Hz, CHaHbCO), 2.79 (d, 1H, J = 15.6 Hz,
4-(4-Chlorophenyl)-4-methyl-3,4-dihydro-2H-benzo[h]chromen-
CHaHbCO), 2.36 (s, 3H, ArCH3), 1.69 [s, 3H, ArC(CH2CO)CH3] 2-one (9k). GP-1 was carried out on the ester 5h (112.3 mg,
ppm. 13C NMR (CDCl3, 100 MHz): δ = 167.4 (s, O–CvO), 151.0 0.5 mmol), 1-naphthol 6e (108.0 mg, 0.75 mmol), and an-
(s, ArC), 142.8 (s, ArC), 139.4 (s, ArC), 133.0 (s, ArC), 128.8 (d, hydrous FeCl3 (243.3 mg, 1.5 mmol) followed by addition of
2C, 2 × ArCH), 127.6 (d, 2C, 2 × ArCH), 127.1 (s, ArC), 126.1 (d, DCE (2 mL). The resulting reaction mixture was stirred at room
ArCH), 125.6 (d, ArCH), 117.8 (d, ArCH), 43.8 (t, CH2CO), 40.6 temperature for 6 h [TLC control Rf(5h) = 0.60, Rf(9k) = 0.50
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(petroleum ether–ethyl acetate 94 : 6, UV detection)]. Purifi- 1250, 1201, 1136, 1125, 1052, 915, 813 cm−1. H NMR (CDCl3,
cation of the residue on a silica gel column (petroleum ether– 400 MHz): δ = 7.31 (ddd, 1H, J = 7.8, 7.8 and 1.5 Hz, ArH), 7.21
ethyl acetate 96 : 2 to 94 : 6 as the eluent) furnished the lactone (dd, 1H, J = 7.8 and 1.5 Hz, ArH), 7.16 (ddd, 1H, J = 7.8, 7.8
9k (77.8 mg, 56%) as a white solid, and the solid was recrystal- and 1.5 Hz, ArH), 7.13–7.07 (m, 3H, ArH), 7.05 (d, 2H, J =
lized with dichloromethane/hexane, m. p. 152–154 °C. IR 8.3 Hz, ArH), 3.26 [d, 1H, J = 15.6 Hz, ArC(CH3)CHaHbCO], 2.80
(MIR-ATR, 4000–600 cm−1): νmax = 2958, 2921, 2851, 1767, [d, 1H, J = 15.6 Hz, ArC(CH3)CHaHbCO], 2.30 (s, 3H, ArCH3),
1493, 1463, 1374, 1247, 1191, 1151, 1068, 1012, 816, 751, 699, 1.72 [s, 3H, ArC(CH3)CH2CO] ppm. 13C NMR (CDCl3,
1
660 cm−1. H NMR (CDCl3, 400 MHz): δ = 8.28 (dd, 1H, J = 6.8 100 MHz): δ = 167.7 (s, O–CvO), 151.1 (s, ArC), 140.9 (s, ArC),
and 2.4 Hz, ArH), 7.84 (dd, 1H, J = 6.8 and 2.4 Hz, ArH), 7.66 136.8 (s, ArC), 131.0 (s, ArC), 129.4 (d, 2C, 2 × ArCH), 128.6 (d,
(d, 1H, J = 8.8 Hz, ArH), 7.60–7.52 (m, 2H, ArH), 7.25 (dd, 3H, ArCH), 126.6 (d, ArCH), 126.0 (d, 2C, 2 × ArCH), 124.7 (d,
J = 8.8 and 2.0 Hz, ArH), 7.15 (dd, 2H, J = 8.8 and 2.0 Hz, ArH), ArCH), 117.3 (d, ArCH), 43.8 (t, CH2CO), 40.8 [s, ArC(CH3)-
3.29 (d, 1H, J = 15.6 Hz, CHaHbCO), 2.94 (d, 1H, J = 15.6 Hz, CH2CO], 27.5 [q, ArC(CH3)CH2CO], 20.8 (q, ArCH3) ppm.
CHaHbCO), 1.81 [s, 3H, ArC(CH2CO)CH3] ppm. 13C NMR HR-MS (ESI+) m/z calculated for [C17H17O2]+ = [M]+: 253.1223;
(CDCl3, 100 MHz): δ = 167.0 (s, O–CvO), 146.2 (s, ArC), 142.8 found 253.1223.
(s, ArC), 133.7 (s, ArC), 133.2 (s, ArC), 128.9 (d, 2C, 2 × ArCH),
4,7-Dimethyl-4-(4-methylphenyl)chroman-2-one (9n). GP-1
127.8 (d, 2C, 2 × ArCH), 127.5 (d, ArCH), 127.0 (d, ArCH), 126.9 was carried out on the ester 5i (97.0 mg, 0.50 mmol), meta-
(d, ArCH), 124.5 (s, ArC), 124.5 (d, ArCH), 123.7 (s, ArC), 123.2 cresol 6b (81.0 mg, 0.75 mmol), anhydrous FeCl3 (243.3 mg,
(d, ArCH), 121.6 (d, ArCH), 44.2 (t, CH2CO), 41.1 [s, ArC- 1.5 mmol) and DCE (2 mL). The resulting reaction mixture was
(CH2CO)CH3], 27.4 [q, ArC(CH2CO)CH3] ppm. HR-MS (APCI+) stirred at room temperature for 6 h [TLC control Rf(5i) = 0.70,
m/z calculated for [C20H16O2Cl]+ = [M + H]+: 323.0833; found: Rf(9n) = 0.50 (petroleum ether–ethyl acetate 95 : 5, UV detec-
323.0822.
tion)]. Purification of the residue on a silica gel column (pet-
1-(4-Chlorophenyl)-1-methyl-1,2-dihydro-3H-benzo[ f ]chromen- roleum ether–ethyl acetate 100 : 0 to 94 : 6 as the eluent)
3-one (9l). GP-1 was carried out on the ester 5h (112 mg, furnished the lactone 9n (90.4 mg, 68%) as a yellow viscous
0.5 mmol), β-naphthol 6f (108.1 mg, 0.75 mmol), anhydrous liquid. IR (MIR-ATR, 4000–600 cm−1): νmax = 2922, 1766, 1578,
1
FeCl3 (243.3 mg, 1.5 mmol) and DCE (2 mL). The resulting 1506, 1449, 1414, 1253, 1200, 1164, 1124, 1048, 815 cm−1. H
reaction mixture was stirred at room temperature for 6 h [TLC NMR (CDCl3, 400 MHz): δ = 7.11 (d, 1H, J = 7.8 Hz, ArH), 7.10
control Rf(5h) = 0.60, Rf(9l) = 0.50 (petroleum ether–ethyl (d, 2H, J = 8.3 Hz, ArH), 7.05 (d, 2H, J = 8.3 Hz, ArH), 6.98 (d,
acetate 94 : 6, UV detection)]. Purification of the residue on a 1H, J = 7.8 Hz, ArH), 6.91 (s, 1H, ArH), 3.24 [d, 1H, J = 15.6 Hz,
silica gel column (petroleum ether–ethyl acetate 96 : 4 to 94 : 6 ArC(CH3)CHaHbCO], 2.78 [d, 1H, J = 15.6 Hz, ArC(CH3)-
as the eluent) furnished the lactone 9l (110 mg, 68%) as a col- CHaHbCO], 2.36 (s, 3H, ArCH3), 2.30 (s, 3H, ArCH3), 1.70 [s,
orless viscous liquid. IR (MIR-ATR, 4000–600 cm−1): νmax
=
3H, ArC(CH3)CH2CO] ppm. 13C NMR (CDCl3, 100 MHz): δ =
2964, 2925, 1777, 1600, 1513, 1492, 1458, 1336, 1212, 1096, 167.8 (s, O–CvO), 150.9 (s, ArC), 141.1 (s, ArC), 138.8 (s, ArC),
1
1012, 913, 814, 748 cm−1. H NMR (CDCl3, 400 MHz): δ = 7.80 136.6 (s, ArC), 129.3 (d, 2C, 2 × ArCH), 127.8 (s, ArC), 126.2 (d,
(dd, 2H, J = 8.8 and 7.3 Hz, ArH), 7.36–7.30 (m, 2H, ArH), 7.28 ArCH), 126.0 (d, 2C, 2 × ArCH), 125.3 (d, ArCH), 117.6 (d,
(d, 2H, J = 8.3 Hz, ArH), 7.20 (d, 2H, J = 8.3 Hz, ArH), 7.14 ArCH), 43.9 (t, CH2CO), 40.4 [s, ArC(CH3)CH2CO], 27.5 [q, ArC
(ddd, 1H, J = 8.8, 8.8 and 1.5 Hz, ArH), 7.11 (d, 1H, J = 8.8 Hz, (CH3)CH2CO], 20.9 (q, ArCH3), 20.8 (q, ArCH3) ppm. HR-MS
ArH), 3.00 (d, 1H, J = 15.6 Hz, CHaHbCO), 2.84 (d, 1H, J = 15.6 (ESI+) m/z calculated for [C18H18NaO2]+ = [M + Na]+: 289.1199;
Hz, CHaHbCO), 1.93 [s, 3H, ArC(CH2CO)CH3] ppm. 13C NMR found 289.1197.
(CDCl3, 100 MHz): δ = 166.2 (s, O–CvO), 149.8 (s, ArC), 145.5
4,6-Dimethyl-4-(4-methylphenyl)chroman-2-one (9o). GP-1
(s, ArC), 132.8 (s, ArC), 131.9 (s, ArC), 130.3 (d, ArCH), 130.1 (s, was carried out on the ester 5i (97.0 mg, 0.5 mmol), para-
ArC), 129.2 (d, 2C, 2 × ArCH), 129.0 (d, ArCH), 127.4 (d, 2C, 2 × cresol 6c (81.0 mg, 0.75 mmol), anhydrous FeCl3 (243.3 mg,
ArCH), 126.0 (d, ArCH), 125.7 (d, ArCH), 124.6 (d, ArCH), 122.0 1.5 mmol) and DCE (2 mL). The resulting reaction mixture was
(s, ArC), 117.8 (d, ArCH), 47.8 (t, CH2CO), 42.6 [s, ArC(CH2CO)- stirred at room temperature for 6 h [TLC control Rf(5i) = 0.70,
CH3], 24.7 [q, ArC(CH2CO)CH3] ppm. HR-MS (ESI+) m/z Rf(9o) = 0.48 (petroleum ether–ethyl acetate 95 : 5, UV detec-
calculated for [C20H15ClNaO2]+ = [M + Na]+: 345.0658; found tion)]. Purification of the residue on a silica gel column
345.0655.
4-Methyl-4-(4-methylphenyl)chroman-2-one (9m). GP-1 was as the eluent) furnished the lactone 9o (107.7 mg, 81%) as a
carried out on the ester 5i (97.0 mg, 0.50 mmol), phenol 6a yellow viscous liquid. IR (MIR-ATR, 4000–600 cm−1): νmax
chromatography (petroleum ether–ethyl acetate 100 : 0 to 94 : 6
=
(70.5 mg, 0.75 mmol), anhydrous FeCl3 (243.3 mg, 1.5 mmol) 2921, 1763, 1594, 1493, 1416, 1279, 1199, 1134, 1123, 1051,
1
and DCE (2 mL). The resulting reaction mixture was stirred at 913, 814 cm−1. H NMR (CDCl3, 400 MHz): δ = 7.15–7.08 (m,
room temperature for 6 h [TLC control Rf(5i) = 0.70, Rf(9m) = 3H, ArH), 7.06 (d, 2H, J = 8.3 Hz, ArH), 7.01 (d, 1H, J = 1.5 Hz,
0.50 (petroleum ether–ethyl acetate 95 : 5, UV detection)]. Puri- ArH), 6.98 (d, 1H, J = 8.3 Hz, ArH), 3.33 [d, 1H, J = 15.6 Hz, ArC-
fication of the residue on a silica gel column (petroleum (CH3)CHaHbCO], 2.78 [d, 1H, J = 15.6 Hz, ArC(CH3)CHaHbCO],
ether–ethyl acetate 100 : 0 to 94 : 6 as the eluent) furnished 2.33 (s, 3H, ArCH3), 2.30 (s, 3H, ArCH3), 1.71 [s, 3H, ArC(CH3)-
the lactone 9m (68.1 mg, 54%) as a liquid. IR (MIR-ATR, CH2CO] ppm. 13C NMR (CDCl3, 100 MHz): δ = 167.9 (s,
4000–600 cm−1): νmax = 2924, 1761, 1596, 1494, 1418, 1281, O–CvO), 149.1 (s, ArC), 141.0 (s, ArC), 136.7 (s, ArC), 134.2 (s,
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ArC), 130.6 (s, ArC), 129.3 (d, 2C, 2 × ArCH), 129.1 (d, ArCH), resulting reaction mixture was stirred at room temperature for
126.9 (d, ArCH), 126.0 (d, 2C, 2 × ArCH), 117.0 (d, ArCH), 43.9 20 h [TLC control Rf(5g) = 0.60, Rf(11a) = 0.50 (petroleum
(t, CH2CO), 40.7 [s, ArC(CH3)CH2CO], 27.5 [q, ArC(CH3)- ether–ethyl acetate 94 : 6, UV detection)]. Purification of the
CH2CO], 20.9 (q, ArCH3), 20.8 (q, ArCH3) ppm. HR-MS (ESI+) residue on a silica gel column (petroleum ether–ethyl acetate
m/z calculated for [C18H18NaO2]+ = [M + Na]+: 289.1199; found 96 : 4 to 94 : 6 as the eluent) furnished the lactone 11a
289.1199.
4-Ethyl-7-methyl-4-phenylchroman-2-one (9p). GP-1 was 4000–600 cm−1): νmax = 3342, 2922, 2852, 1770, 1680, 1640,
carried out on the ester 5j (95.1 mg, 0.5 mmol), meta-cresol 6b 1454, 1426, 1256, 1198, 1120, 1068, 1023, 762, 699, 653 cm−1
(54.9 mg, 35%) as a colorless viscous liquid. IR (MIR-ATR,
.
(69.8 mg, 0.75 mmol), anhydrous FeCl3 (243.3 mg, 1.5 mmol) 1H NMR (CDCl3, 400 MHz): δ = 7.52 (dd, 2H, J = 8.3 and
and DCE (2 mL). The resulting reaction mixture was stirred at 1.5 Hz, ArH), 7.42 (dd, 2H, J = 7.8 and 7.3 Hz, ArH), 7.37 (dd,
room temperature for 6 h [TLC control Rf(5j) = 0.60, Rf(9p) = 2H, J = 6.4 and 2.4 Hz, ArH), 7.32 (dd, 2H, J = 7.8 and 1.5 Hz,
0.45 (petroleum ether–ethyl acetate 94 : 6, UV detection)]. Puri- ArH), 7.24 (ddd, 5H, J = 7.8, 6.4 and 1.5 Hz, ArH), 3.32 (d, 1H,
fication of the residue on a silica gel column (petroleum J = 15.6 Hz, CHaHbCO), 2.86 (d, 1H, J = 15.6 Hz, CHaHbCO),
ether–ethyl acetate 96 : 4 to 94 : 6 as the eluent) furnished the 1.78 [s, 3H, ArC(CH2CO)CH3] ppm. 13C NMR (CDCl3,
lactone 9p (107.5 mg, 85%) as a colorless viscous liquid. IR 100 MHz): δ = 167.2 (s, O–CvO), 148.0 (s, ArC), 144.0 (s, ArC),
(MIR-ATR, 4000–600 cm−1): νmax = 2970, 2924, 1762, 1623, 136.6 (s, ArC), 131.5 (s, ArC), 130.8 (s, ArC), 130.4 (d, ArCH),
1577, 1446, 1412, 1208, 1192, 1161, 1150, 1061, 814, 759, 129.6 (d, 2C, 2 × ArCH), 128.8 (d, 2C, 2 × ArCH), 128.3 (d, 2C,
698 cm−1. H NMR (CDCl3, 400 MHz): δ = 7.27 (dd, 2H, J = 7.3 2 × ArCH), 127.6 (d, ArCH), 127.2 (d, ArCH), 126.3 (d, 2C, 2 ×
1
and 7.3 Hz, ArH), 7.22–7.10 (m, 4H, ArH), 6.99 (dd, 1H, J = 7.8 ArCH), 125.9 (s, ArCH), 124.6 (d, ArCH), 43.5 (t, CH2CO), 41.4
and 1.0 Hz, ArH), 6.88 (d, 1H, J = 1.0 Hz, ArH), 3.25 (d, 1H, J = [s, ArC(CH2CO)CH3], 27.8 [q, ArC(CH2CO)CH3] ppm. HR-MS
15.6 Hz, CHaHbCO), 2.81 (d, 1H, J = 15.6 Hz, CHaHbCO), 2.34 (APCI+) m/z calculated for [C22H19O2]+ = [M + H]+: 315.1380;
(s, 3H, Ar–CH3), 2.25–2.00 (m, 2H, CH2CH3), 0.88 (t, 3H, J = 7.3 found: 315.1372.
Hz, CH2CH3) ppm. 13C NMR (CDCl3, 100 MHz): δ = 168.3 (s,
4-(4-Chlorophenyl)-4-methyl-8-phenylchroman-2-one (11b).
O–CvO), 151.4 (s, ArC), 143.1 (s, ArC), 138.8 (s, ArC), 128.5 (d, GP-1 was carried out on the ester 5h (112.3 mg, 0.5 mmol),
2C, 2 × ArCH), 126.8 (d, ArCH), 126.7 (d, ArCH), 126.6 (d, 2C, 2 2-phenylphenol 6g (127.5 mg, 0.75 mmol), and anhydrous
× ArCH), 126.0 (s, ArC), 125.0 (d, ArCH), 117.9 (d, ArCH), 44.5 FeCl3 (243.3 mg, 1.5 mmol) followed by addition of DCE
[s, ArC(CH2CO)Et], 39.8 (t, CH2CO), 32.1 (t, CH2CH3), 20.9 (q, (2 mL). The resulting reaction mixture was stirred at room
ArCH3), 8.8 (q, CH2CH3), ppm. HR-MS (ESI+) m/z calculated temperature for 6 h [TLC control Rf(5h) = 0.60, Rf(11b) = 0.50
for [C18H18NaO2]+ = [M + Na]+: 289.1199; found 289.1200.
(petroleum ether–ethyl acetate 94 : 6, UV detection)]. Purifi-
4-Ethyl-6-methyl-4-phenylchroman-2-one (9q). GP-1 was cation of the residue on a silica gel column (petroleum ether–
carried out on the ester 5j (95.1 mg, 0.5 mmol), para-cresol 6c ethyl acetate 96 : 4 to 94 : 6 as the eluent) furnished the lactone
(69.8 mg, 0.75 mmol), anhydrous FeCl3 (243.3 mg, 1.5 mmol) 11b (64.5 mg, 37%) as a white solid, and the solid was recrys-
and DCE (2 mL). The resulting reaction mixture was stirred at tallized with dichloromethane/hexane, m. p. 172–174 °C. IR
room temperature for 6 h [TLC control Rf(5j) = 0.60, Rf(9q) = (MIR-ATR, 4000–600 cm−1): νmax = 3342, 2922, 2852, 1770,
0.45 (petroleum ether–ethyl acetate 94 : 6, UV detection)]. Puri- 1680, 1640, 1454, 1426, 1256, 1198, 1120, 1068, 1023, 762, 699,
1
fication of the residue on a silica gel column (petroleum 653 cm−1. H NMR (CDCl3, 400 MHz): δ = 7.50 (ddd, 2H, J =
ether–ethyl acetate 96 : 4 to 94 : 6 as the eluent) furnished the 9.8, 8.8 and 1.5 Hz, ArH), 7.41 (dd, 2H, J = 7.3 and 1.5 Hz,
lactone 9q (107.5 mg, 85%) as a colorless viscous liquid. IR ArH), 7.36 (dd, 2H, J = 6.4 and 2.9 Hz, ArH), 7.31 (dd, 2H, J =
(MIR-ATR, 4000–600 cm−1): νmax = 2970, 2924, 1764, 1598, 7.8 and 1.5 Hz, ArH), 7.22 (dd, 5H, J = 8.3 and 2.0 Hz, ArH),
1491, 1259, 1197, 1124, 1060, 922, 823, 734, 698 cm−1 1H 3.31 (d, 1H, J = 15.6 Hz, CHaHbCO), 2.85 (d, 1H, J = 15.6 Hz,
.
NMR (CDCl3, 400 MHz): δ = 7.29 (dd, 2H, J = 7.8 and 7.3 Hz, CHaHbCO), 1.77 [s, 3H, ArC(CH2CO)CH3] ppm. 13C NMR
ArH), 7.23–7.14 (m, 3H, ArH), 7.12–7.05 (m, 2H, ArH), 6.96 (d, (CDCl3, 100 MHz): δ = 167.2 (s, O–CvO), 147.9 (s, ArC), 143.9
1H, J = 8.8 Hz, ArH), 3.25 (d, 1H, J = 15.6 Hz, CHaHbCO), 2.81 (s, ArC), 136.5 (s, ArC), 131.5 (s, ArC), 130.5 (s, ArC), 130.3 (d,
(d, 1H, J = 15.6 Hz, CHaHbCO), 2.36 (s, 3H, Ar–CH3), 2.21–2.02 ArCH), 129.6 (d, 2C, 2 × ArCH), 128.7 (d, 2C, 2 × ArCH), 128.2
(m, 2H, CH2CH3), 0.90 (t, 3H, J = 7.3 Hz, CH2CH3) ppm. (d, 2C, 2 × ArCH), 127.5 (d, ArCH), 127.2 (d, ArCH), 126.2 (d,
13C NMR (CDCl3, 100 MHz): δ = 168.4 (s, O–CvO), 149.5 (s, 2C, 2 × ArCH), 125.8 (d, ArCH), 124.5 (d, ArCH), 120.7 (s, ArC),
ArC), 143.0 (s, ArC), 133.9 (s, ArC), 129.0 (d, ArCH), 128.8 (s, 115.8 (s, ArC), 43.4 (t, CH2CO), 41.4 [s, ArC(CH2CO)CH3], 27.5
ArC), 128.6 (d, 2C, 2 × ArCH), 127.3 (d, ArCH), 126.9 (d, ArCH), [q, ArC(CH2CO)CH3] ppm.
126.7 (d, 2C, 2 × ArCH), 117.2 (d, ArCH), 44.7 [s, ArC(CH2CO)-
Ethyl
3-(6-hydroxy-1,1′-biphenyl-3-yl)-3-phenylbutanoate
Et], 39.7 (t, CH2CO), 32.1 (t, CH2CH3), 21.0 (q, Ar–CH3), 8.8 (q, (12a). GP-1 was carried out on the ester 5g (95.1 mg,
CH2CH3) ppm. HR-MS (ESI+) m/z calculated for [C18H18NaO2]+ 0.5 mmol), 2-phenylphenol 6g (127.6 mg, 0.75 mmol), and
= [M + Na]+: 289.1199; found 289.1198.
anhydrous FeCl3 (243.3 mg, 1.5 mmol) followed by addition of
4-Methyl-4,8-diphenylchroman-2-one
(11a). GP-1
was DCE (2 mL). The resulting reaction mixture was stirred at room
carried out on the ester 5g (95.1 mg, 0.5 mmol), 2-phenyl- temperature for 12 h [TLC control Rf(5g) = 0.60, Rf(12a) = 0.30
phenol 6g (127.5 mg, 0.75 mmol), and anhydrous FeCl3 (petroleum ether–ethyl acetate 92 : 8, UV detection)]. Purifi-
(243.3 mg, 1.5 mmol) followed by addition of DCE (2 mL). The cation of the residue on a silica gel column (petroleum ether–
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ethyl acetate 96 : 4 to 94 : 6 as the eluent) furnished the 1774, 1484, 1449, 1252, 1197, 1068, 920 cm−1. 1H NMR (CDCl3,
Michael addition ester 12a (94.0 mg, 52%) as a colorless 400 MHz): δ = 7.30–7.12 (m, 4H, ArH), 7.10 (dd, 1H, J = 8.3 and
viscous liquid. IR (MIR-ATR, 4000–600 cm−1): νmax = 3412, 1.0 Hz, ArH), 7.05 (d, 1H, J = 7.8 Hz, ArH), 6.98 (ddd, 1H, J =
2978, 2926, 1712, 1507, 1490, 1406, 1369, 1322, 1273, 1222, 7.8, 7.3 and 1.5 Hz, ArH), 6.64 (dd, 1H, J = 7.8 and 1.5 Hz,
1157, 1095, 1012, 829, 700 cm−1. 1H NMR (CDCl3, 400 MHz): δ ArH), 3.20 (d, 1H, J = 15.6 Hz, CHaHbCO), 2.95 (d, 1H, J =
= 7.50–7.40 (m, 3H, ArH), 7.36 (t, 1H, J = 7.3 Hz, ArH), 15.6 Hz, CHaHbCO), 2.88 (dd, 2H, J = 7.8 and 5.4 Hz,
7.30–7.13 (m, 6H, ArH), 7.08 (d, 1H, J = 2.4 Hz, ArH), 7.04 (dd, ArCH2CH2CH2), 1.95 (dd, 2H,
J = 5.9 and 5.4 Hz,
1H, J = 8.3 and 2.4 Hz, ArH), 6.86 (d, 1H, J = 8.3 Hz, ArH), 5.28 ArCH2CH2CH2), 1.87–1.65 (m, 2H, ArCH2CH2CH2) ppm. 13C
(s, 1H, ArOH), 3.88 (q, 2H, J = 7.3 Hz, OCH2CH3), 3.11 (s, 2H, NMR (CDCl3, 100 MHz): δ = 167.8 (s, O–CvO), 150.8 (s, ArC),
CH2COOEt), 1.86 [s, 3H, ArC(CH2CO)CH3], 0.97 (t, 3H, J = 138.4 (s, ArC), 137.9 (s, ArC), 132.4 (s, ArC), 129.6 (d, ArCH),
7.3 Hz, OCH2CH3) ppm. 13C NMR (CDCl3, 100 MHz): δ = 171.4 128.6 (d, ArCH), 128.3 (d, ArCH), 128.1 (d, ArCH), 127.1 (d,
(s, O–CvO), 150.6 (s, ArC), 148.5 (s, ArC), 140.5 (s, ArC), 137.4 ArCH), 126.5 (d, ArCH), 124.3 (d, ArCH), 117.0 (d, ArCH), 43.4
(s, ArC), 129.1 (d, 2C, 2 × ArCH), 129.0 (d, 2C, 2 × ArCH), 128.9 (t, CH2CO), 41.2 (s, ArCCH2CO), 36.0 (t, CH2), 30.0 (t, CH2),
(d, ArCH), 128.0 (d, ArCH), 127.9 (d, 2C, 2 × ArCH), 127.7 (d, 18.6 (t, CH2) ppm. HR-MS (ESI+) m/z calculated for [C18H17O2]+
ArCH), 127.4 (s, ArC), 127.0 (d, 2C, 2 × ArCH), 126.0 (d, ArCH), = [M + H]+: 265.1223; found 265.1216.
115.3 (d, ArCH), 60.0 (t, OCH2CH3), 46.8 (t, CH2COOEt),
7-Methyl-3′,4′-dihydro-2′H-spiro[chromene-4,1′-naphthalen]-
45.0 (s, ArCCH2COOEt), 28.5 [q, ArC(CH2COOEt)CH3], 13.9 2(3H)-one (13b). GP-2 was carried out on the ester 5m
(q, OCH2CH3) ppm. HR-MS (ESI+) m/z calculated for (108.0 mg, 0.50 mmol), meta-cresol 6b (270.0 mg, 2.5 mmol),
[C24H24NaO3]+ = [M + Na]+: 383.1618; found 383.1620.
Ethyl
anhydrous FeCl3 (243.3 mg, 1.5 mmol) and benzene (2 mL).
3-(4-chlorophenyl)-3-(6-hydroxy-1,1′-biphenyl-3-yl)- The resulting reaction mixture was stirred at room temperature
butanoate (12b). GP-1 was carried on the ester 5h (112 mg, for 2 h [TLC control Rf(5m) = 0.75, Rf(13b) = 0.55 (petroleum
0.5 mmol), 2-phenyl phenol 6g (127.6 mg, 0.75 mmol), and ether–ethyl acetate 95 : 5, UV detection)]. Purification of the
anhydrous FeCl3 (243.3 mg, 1.5 mmol) followed by addition of residue on a silica gel column (petroleum ether–ethyl acetate
DCE (2 mL). The resulting reaction mixture was stirred at room 97 : 3 to 95 : 5 as the eluent) furnished the lactone 13b
temperature for 12 h [TLC control Rf(5h) = 0.60, Rf(12b) = 0.30 (86.2 mg, 62%) as a liquid. IR (MIR-ATR, 4000–600 cm−1): νmax
(petroleum ether–ethyl acetate 92 : 8, UV detection)]. Purifi- = 2920, 2851, 1769, 1578, 1490, 1448, 1163, 1065, 759 cm−1. 1H
cation of the residue on a silica gel column (petroleum ether– NMR (CDCl3, 400 MHz): δ = 7.25–7.09 (m, 3H, ArH), 7.05 (d,
ethyl acetate 96 : 4 to 94 : 6 as the eluent) furnished 1H, J = 7.8 Hz, ArH), 6.91 (d, 1H, J = 1.0 Hz, ArH), 6.80 (dd, 1H,
the Michael addition ester 12b (80.0 mg, 54%) as a colorless J = 7.8 and 1.0 Hz, ArH), 6.52 (d, 1H, J = 7.8 Hz, ArH), 3.17 (d,
viscous liquid. IR (MIR-ATR, 4000–600 cm−1): νmax = 3429, 1H, J = 15.6 Hz, CHaHbCO), 2.93 (d, 1H, J = 15.6 Hz,
2978, 2922, 1712, 1507, 1490, 1464, 1406, 1369, 1273, 1222, CHaHbCO), 2.87 (dd, 2H, J = 7.8 and 5.4 Hz, ArCH2CH2CH2),
1157, 1095, 1012, 829, 700 cm−1. 1H NMR (CDCl3, 400 MHz): δ 2.32 (s, 3H, ArCH3), 1.92 (dd, 2H, J = 6.4 and 5.4 Hz,
= 7.52–7.30 (m, 5H, ArH), 7.22 (d, 2H, J = 8.8 Hz, ArH), 7.15 (d, ArCH2CH2CH2), 1.85–1.65 (m, 2H, ArCH2CH2CH2) ppm. 13C
2H, J = 8.8 Hz, ArH), 7.03 (d, 1H, J = 2.4 Hz, ArH), 7.00 (dd, 1H, NMR (CDCl3, 100 MHz): δ = 168.0 (s, O–CvO), 150.7 (s, ArC),
J = 8.8 and 2.4 Hz, ArH), 6.84 (d, 1H, J = 8.8 Hz, ArH), 5.38 (br. 138.5 (s, ArC), 138.4 (s, ArC), 138.1 (s, ArC), 129.5 (d, ArCH),
s, 1H, ArOH), 3.88 (q, 2H, J = 7.3 Hz, OCH2CH3), 3.07 (s, 2H, 129.3 (s, ArC), 128.3 (d, ArCH), 128.1 (d, ArCH), 127.0 (d,
CH2COOEt), 1.83 [s, 3H, ArC(CH2COOEt)CH3], 0.98 (t, 3H, J = ArCH), 126.4 (d, ArCH), 125.0 (d, ArCH), 117.4 (d, ArCH), 43.5
7.3 Hz, OCH2CH3) ppm. 13C NMR (CDCl3, 100 MHz): δ = 171.2 (t, CH2CO), 40.9 (s, ArCCH2CO), 36.1 (t, CH2), 30.0 (t, CH2),
(s, O–CvO), 150.8 (s, ArC), 146.9 (s, ArC), 140.1 (s, ArC), 137.2 20.9 (q, ArCH3), 18.6 (t, CH2) ppm. HR-MS (ESI+) m/z calcu-
(s, ArC), 131.8 (s, ArC), 129.1 (d, 2C, 2 × ArCH), 129.0 (d, 2C, lated for [C19H19O2]+ = [M + H]+: 279.1380; found 279.1371.
2 × ArCH), 128.8 (d, ArCH), 128.5 (d, 2C, 2 × ArCH), 128.1 (d,
6-Methyl-3′,4′-dihydro-2′H-spiro[chromene-4,1′-naphthalen]-
2C, 2 × ArCH), 127.8 (d, 2C, ArCH), 127.6 (s, ArC), 115.5 (d, 2(3H)-one (13c). GP-2 was carried out on the ester 5m
ArCH), 60.2 (t, OCH2CH3), 46.6 (t, CH2COOEt), 44.7 [s, ArC- (108.0 mg, 0.50 mmol), para-cresol 6c (270.0 mg, 2.5 mmol),
(CH2COOEt)CH3], 28.5 [q, ArC(CH2COOEt)CH3], 13.9 (q, anhydrous FeCl3 (243.0 mg, 1.5 mmol) and benzene (2 mL).
OCH2CH3) ppm. HR-MS (ESI+) m/z calculated for The resulting reaction mixture was stirred at room temperature
[C24H23ClNaO3]+ = [M + Na]+: 417.1228; found 417.1229.
for 2 h [TLC control Rf(5e) = 0.73, Rf(7j) = 0.58 (petroleum
3′,4′-Dihydro-2′H-spiro[chromene-4,1′-naphthalen]-2(3H)-one ether–ethyl acetate 95 : 5, UV detection)]. Purification of the
(13a). GP-2 was carried out on the ester 5m (108.0 mg, residue on a silica gel column (petroleum ether–ethyl acetate
0.50 mmol), phenol 6a (235.0 mg, 2.5 mmol), anhydrous FeCl3 97 : 3 to 95 : 5 as the eluent) furnished the lactone 13c
(243.3 mg, 1.5 mmol) and benzene (2 mL). The resulting reac- (61.2 mg, 44%) as a liquid. IR (MIR-ATR, 4000–600 cm−1): νmax
1
tion mixture was stirred at room temperature for 2 h [TLC = 2921, 2851, 1766, 1578, 1446, 1202, 1162, 962, 729 cm−1. H
control Rf(5m) = 0.73, Rf(13a) = 0.56 (petroleum ether–ethyl NMR (CDCl3, 400 MHz): δ = 7.25–7.10 (m, 3H, ArH), 7.05 (d,
acetate 95 : 05, UV detection)]. Purification of the residue on a 1H, J = 7.3 Hz, ArH), 7.03 (dd, 1H, J = 8.3 and 1.5 Hz, ArH),
silica gel column (petroleum ether–ethyl acetate 97 : 3 to 95 : 5 6.98 (d, 1H, J = 8.3 Hz, ArH), 6.43 (d, 1H, J = 1.5 Hz, ArH), 3.15
as the eluent) furnished the spiro-lactone 13a (52.8 mg, 40%) (d, 1H, J = 15.6 Hz, CHaHbCO), 2.92 (d, 1H, J = 15.6 Hz,
as a liquid. IR (MIR-ATR, 4000–600 cm−1): νmax = 2923, 2852, CHaHbCO), 2.91–2.80 (m, 2H, ArCH2CH2CH2), 2.18 (s, 3H,
4358 | Org. Biomol. Chem., 2014, 12, 4347–4360
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ArCH3), 1.93 (dd, 2H, J = 5.9 and 5.4 Hz, ArCH2CH2CH2), 130.0 (s, ArC), 129.5 (d, ArCH), 128.9 (d, ArCH), 128.3 (d,
1.87–1.65 (m, 2H, ArCH2CH2CH2) ppm. 13C NMR (CDCl3, ArCH), 126.9 (d, ArCH), 126.7 (d, ArCH), 125.8 (d, ArCH), 125.6
100 MHz): δ = 167.9 (s, O–CvO), 148.9 (s, ArC), 138.4 (s, ArC), (d, ArCH), 124.3 (d, ArCH), 123.5 (s, ArC), 117.7 (d, ArCH), 44.5
138.1 (s, ArC), 133.9 (s, ArC), 132.1 (s, ArC), 129.6 (d, ArCH), (t, CH2CO), 42.4 (s, ArCCH2CO), 33.4 (t, CH2), 29.8 (t, CH2),
128.8 (d, ArCH), 128.7 (d, ArCH), 128.2 (d, ArCH), 127.0 (d, 18.8 (t, CH2) ppm. HR-MS (ESI+) m/z calculated for [C22H19O2]+
ArCH), 126.5 (d, ArCH), 116.8 (d, ArCH), 43.6 (t, CH2CO), 41.3 = [M + H]+: 315.1380; found 315.1369.
(s, ArCCH2CO), 36.1 (t, CH2), 30.0 (t, CH2), 20.8 (q, ArCH3),
18.7 (t, CH2) ppm. HR-MS (ESI+) m/z calculated for [C19H19O2]+ len]-2(3H)-one (13f). GP-2 was carried out on the ester 5n
= [M + H]+: 279.1380; found 279.1369.
(115.0 mg, 0.50 mmol), meta-cresol 6b (270.0 mg, 2.5 mmol),
7,7′-Dimethyl-3′,4′-dihydro-2′H-spiro[chromene-4,1′-naphtha-
8-Methyl-3′,4′-dihydro-2′H-spiro[chromene-4,1′-naphthalen]- anhydrous FeCl3 (243.0 mg, 1.5 mmol) and benzene (2 mL).
2(3H)-one (13d). GP-2 was carried out on the ester 5m The resulting reaction mixture was stirred at room temperature
(108.0 mg, 0.50 mmol), ortho-cresol 6d (270.0 mg, 2.5 mmol), for 2 h [TLC control Rf(5n) = 0.73, Rf(13f) = 0.55 (petroleum
anhydrous FeCl3 (243 mg, 1.5 mmol) and benzene (2 mL). The ether–ethyl acetate 95 : 5, UV detection)]. Purification of the
resulting reaction mixture was stirred at room temperature for residue on a silica gel column (petroleum ether–ethyl acetate
2 h [TLC control Rf(5e) = 0.73, Rf(7j) = 0.58 (petroleum ether– 97 : 3 to 95 : 5 as the eluent) furnished the lactone 13f
ethyl acetate 95 : 5, UV detection)]. Purification of the residue (62.8 mg, 43%) as a liquid. IR (MIR-ATR, 4000–600 cm−1): νmax
on a silica gel column (petroleum ether–ethyl acetate 97 : 3 to = 2924, 2853, 1773, 1621, 1503, 1452, 1416, 1212, 1167, 963,
1
95 : 5 as the eluent) furnished the lactone 13d (54.2 mg, 39%) 814 cm−1. H NMR (CDCl3, 400 MHz): δ = 7.07 (d, 1H, J = 7.8
as a liquid. IR (MIR-ATR, 4000–600 cm−1): νmax = 2921, 2851, Hz, ArH), 7.01 (dd, 1H, J = 7.8 and 1.0 Hz, ArH), 6.91 (d, 1H, J =
1773, 1462, 1243, 1192, 1085, 920 cm−1 1H NMR (CDCl3, 1.0 Hz, ArH), 6.85 (s, 1H, ArH), 6.80 (d, 1H, J = 7.8 Hz, ArH),
.
400 MHz): δ = 7.25–7.12 (m, 3H, ArH), 7.08 (d, 1H, J = 7.3 Hz, 6.52 (d, 1H, J = 7.8 Hz, ArH), 3.18 (d, 1H, J = 15.6 Hz,
ArH), 7.05 (d, 1H, J = 7.8 Hz, ArH), 6.87 (dd, 1H, J = 7.8 and 7.3 CHaHbCO), 2.91 (d, 1H, J = 15.6 Hz, CHaHbCO), 2.82 (dd, 2H,
Hz, ArH), 6.45 (d, 1H, J = 7.8 Hz, ArH), 3.20 (d, 1H, J = 15.6 Hz, J = 5.9 and 5.4 Hz, ArCH2CH2CH2), 2.32 (s, 3H, ArCH3), 2.23 (s,
CHaHbCO), 2.92 (d, 1H, J = 15.6 Hz, CHaHbCO), 2.87 (dd, 2H, 3H, ArCH3), 1.89 (dd, 2H, J = 6.3 and 5.4 Hz, ArCH2CH2CH2),
J = 7.3 and 5.9 Hz, ArCH2CH2CH2), 2.35 (s, 3H, ArCH3), 1.84–1.62 (m, 2H, ArCH2CH2CH2) ppm. 13C NMR (CDCl3,
2.05–1.90 (m, 2H, ArCH2CH2CH2), 1.85–1.65 (m, 2H, 100 MHz): δ = 168.1 (s, O–CvO), 150.7 (s, ArC), 138.5 (s, ArC),
ArCH2CH2CH2) ppm. 13C NMR (CDCl3, 100 MHz): δ = 167.9 (s, 137.8 (s, ArC), 135.9 (s, ArC), 135.3 (s, ArC), 129.5 (s, ArC),
O–CvO), 149.1 (s, ArC), 138.4 (s, ArC), 138.2 (s, ArC), 132.2 (s, 129.4 (d, ArCH), 128.4 (d, ArCH), 128.3 (d, ArCH), 128.0 (d,
ArC), 129.8 (d, ArCH), 129.6 (d, ArCH), 128.1 (d, ArCH), 127.0 ArCH), 125.0 (d, ArCH), 117.3 (d, ArCH), 43.5 (t, CH2CO), 40.9
(d, ArCH), 126.4 (d, ArCH), 126.2 (1s and 1d, 2C, ArC and (s, ArCCH2CO), 36.2 (t, CH2), 29.6 (t, CH2), 21.1 (q, ArCH3),
ArCH), 123.6 (d, ArCH), 43.3 (t, CH2CO), 41.2 (s, ArCCH2CO), 20.9 (q, ArCH3), 18.7 (t, CH2) ppm. HR-MS (ESI+) m/z calcu-
35.8 (t, CH2), 30.0 (t, CH2), 18.6 (t, CH2), 15.9 (q, ArCH3) ppm. lated for [C20H21O2]+ = [M + H]+: 293.1536; found 293.1525.
HR-MS (ESI+) m/z calculated for [C19H19O2]+ = [M + H]+:
279.1380; found 279.1362.
3′,4′,7,10-Tetrahydro-2′H-spiro[benzo[f]chromene-1,1′-naphtha-
len]-3(2H)-one (13e). GP-2 was carried out on the ester 5m
Acknowledgements
(108.0 mg, 0.50 mmol), phenol 6f (360.0 mg, 2.5 mmol), anhy- Financial support by the Council of Scientific and Industrial
drous FeCl3 (243.3 mg, 1.5 mmol) and benzene (2 mL). The Research [(CSIR), 02(0018)/11/EMR-II], New Delhi is gratefully
resulting reaction mixture was stirred at room temperature for acknowledged. P.N thanks CSIR [(CSIR), 02(0018)/11/EMR-II]
2 h [TLC control Rf(5m) = 0.73, Rf(13e) = 0.55 (petroleum New Delhi for the financial support. B.V.R. thanks CSIR for the
ether–ethyl acetate 95 : 5, UV detection)]. Purification of the award of a fellowship.
residue on a silica gel column (petroleum ether–ethyl acetate
97 : 3 to 95 : 5 as the eluent) furnished the lactone 13e
(80.7 mg, 51%) as a liquid. IR (MIR-ATR, 4000–600 cm−1): νmax
Notes and references
= 2917, 2849, 1773, 1600, 1461, 1210, 1174, 1025, 812 cm−1. 1H
NMR (CDCl3, 400 MHz): δ = 7.79 (d, 1H, J = 9.3 Hz, ArH), 7.78
(d, 1H, J = 8.3 Hz, ArH), 7.28 (ddd, 1H, J = 8.3, 7.8 and 1.5 Hz,
ArH), 7.27 (d, 1H, J = 9.3 Hz, ArH), 7.22 (d, 1H, J = 7.8 Hz,
ArH), 7.15 (ddd, 1H, J = 7.8, 7.8 and 1.5 Hz, ArH), 7.08 (ddd,
1H, J = 8.8, 8.3 and 1.5 Hz, ArH), 7.05 (d, 1H, J = 8.8 Hz, ArH),
6.95 (dd, 1H, J = 8.3 and 7.8 Hz, ArH), 6.77 (d, 1H, J = 7.8 Hz,
ArH), 3.31 (d, 1H, J = 15.6 Hz, CHaHbCO), 3.13–2.92 (m, 2H,
ArCH2CH2CH2), 2.98 (d, 1H, J = 15.6 Hz, CHaHbCO), 2.35–2.20
(m, 1H, CHaHb), 2.16–1.90 (m, 3H, CHaHb and CH2) ppm. 13C
NMR (CDCl3, 100 MHz): δ = 166.7 (s, O–CvO), 150.1 (s, ArC),
141.8 (s, ArC), 136.0 (s, ArC), 132.1 (s, ArC), 130.1 (d, ArCH),
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