Synthesis of tetracyclic chromenones via platinum(ii) chloride catalysed cascade cyclization of enediyne-enones

Article abstract of DOI:10.1039/c3ob41911h

PtCl₂ catalysed cascade cyclization of an enediyne-enone system to afford a tetracyclic chromenone is reported, which proceeds through two consecutive highly regioselective 6-endo-dig cyclizations in a single step with the formation of two new C-C bonds and two new rings in excellent yield. A mechanism for this transformation is proposed based on the isolated intermediates.

Full text of DOI:10.1039/c3ob41911h

Organic &
Biomolecular Chemistry
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PAPER
Synthesis of tetracyclic chromenones via
platinum(II) chloride catalysed cascade cyclization
of enediyne–enones†
Cite this: Org. Biomol. Chem., 2014,
12, 1318
Mahalingam Sivaraman and Paramasivan T. Perumal*
Received 20th September 2013,
Accepted 27th November 2013
PtCl2 catalysed cascade cyclization of an enediyne–enone system to afford a tetracyclic chromenone is
reported, which proceeds through two consecutive highly regioselective 6-endo–dig cyclizations in a
single step with the formation of two new C–C bonds and two new rings in excellent yield. A mechanism
for this transformation is proposed based on the isolated intermediates.
DOI: 10.1039/c3ob41911h
www.rsc.org/obc
Introduction
Results and discussion
Platinum catalysed cascade reaction has proven to be a versa-
tile strategy in organic synthesis due to the formation of struc-
turally complex frameworks from suitable scaffolds.1 Platinum
is reported to initiate the cascade reaction by electrophilic acti-
vation of C–C multiple bonds and subsequent cyclization,
which does not generally require rigorously inert conditions.2
Enediynes with internal nucleophile groups undergo cascade
cyclization by the catalytic activation of the alkyne to give
indole, benzofuran, indene, or benzothiophene scaffolds
(Scheme 1, eqn (1) and (2)).3 Even though the chemistry of ene-
diynes is well documented there is scope for catalytic trans-
formation to new scaffolds.4 As part of our ongoing research
studies on cascade cyclization reactions,5 recently we have
reported iodocyclization of a cyclohexenone tethered alkyne
leading to an acridinone moiety, in which formation of mul-
tiple bonds and rearrangement occurred.6 By the cascade cycli-
zation of propargyl tethered enones, benzofuran, pyridine, or
indole derivatives are formed by the catalytic activation of the
triple bond followed by cyclization with the electron rich C2
enone carbon and further rearrangement (Scheme 1, eqn (3)).7
In our continuing efforts to explore cyclohexenone tethered
alkyne reactions, we planned cascade cyclization of 3 by coup-
ling the enediyne and propargyl oxyenone moieties to afford
tetracyclic chromenone scaffolds (Scheme 1, eqn (4)). The
resulting chromenone scaffold is present in the core structure
of numerous natural products.8
To check the feasibility of this hypothesis, we began with 3a as
a model substrate bearing both enediyne and enone moieties.
It is easily synthesised by Sonogashira coupling of 3-(prop-
2-ynyloxy)cyclohex-2-enone 2 and 1-iodo-2-(2-phenylethynyl)-
benzene 1a (Scheme 2). The palladium catalyst chosen for this
transformation was available from the interesting halopallada-
tion reported by Ming-Jung Wu et al.9 When reaction of 3a was
carried out in the presence of PdCl2 (0.1 equiv.) and CuCl2 or
CuBr2 (2 equiv.) in THF at 80 °C we got a complex reaction
Organic Chemistry Division, CSIR – Central Leather Research Institute, Adyar,
Chennai, 600020 Tamilnadu, India. E-mail: ptperumal@gmail.com;
Fax: +91-044-24911589
†Electronic supplementary information (ESI) available: Experimental procedures
and characterization data of 3p and 5. 1H NMR and 13C NMR spectra for all new
compounds. CCDC 948676. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c3ob41911h
Scheme 1 Concept of enediyne–enone cyclization.
1318 | Org. Biomol. Chem., 2014, 12, 1318–1327
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as the sole product (Table 1, entry 9) whereas PtCl4 gave a
reduced yield of 72% (Table 1, entry 10) and Pt(Ph3P)4 was
ineffective for this cascade transformation (Table 1, entry 11).
On continuing the optimization of the reaction conditions
with AuCl3, the monoalkyne cyclized product 4a′ was obtained
in 30% isolated yield (Table 1, entry 12), and with (Ph3P)AuCl/
AgBF4, 32% of dialkyne cyclized product 4a was obtained
(Table 1, entry 13) (for complete optimization table see ESI†).
Finally we achieved PtCl2 catalysed cascade cyclization of
the enediyne–enone system (3a) to give a naphthalene fused
chromenone (4a) in excellent yield. After confirmation of the
product and the optimum reaction conditions (Table 1, entry
9) were in hand, we examined the scope of this transformation
and the results are documented in Table 2. On changing the
substituent R1, the starting material derived from cyclohexane-
1,3-dione (Table 2, entry 1) gave a better yield compared to the
starting material derived from 5,5-dimethylcyclohexane-1,3-
dione (Table 2, entry 2). The electron donating aryl groups R2
(Table 2, entries 3, 4 and 5) gave better results compared to the
electron withdrawing aryl groups (Table 2, entries 6, 7 and 8).
When R2 was naphthyl, the reaction proceeded with moderate
yield (Table 2, entry 9). When R2 was an alkyl group (Table 2,
entries 10 and 11), the reaction proceeded without any difficul-
ties to give good yields. When R2 was p-tolyl, neither the
methyl or nitro substituent at R3 shows any effect on this
cascade transformation and both give good yields (Table 2,
entries 12 and 14). A chloro substituent gave an excellent yield
(Table 2, entry 13). When R2 was TMS, the reaction proceeded
to give a complex reaction mixture (Table 2, entry 15) and no
trace of product was isolated even on further optimization. To
explore the synthetic potential of the PtCl2 catalysed cascade
transformation further, we planned to synthesise a polycyclic
framework with the heteroaromatic system 4p. Enediyne–
enone cascade reaction of 3p under the standard conditions
gave 4p in 76% yield (Table 2, entry 16). The product 4p is
unequivocally confirmed by NMR and single crystal XRD tech-
niques (Fig. 1).
Scheme 2 Synthesis of required precursors.
Table 1 Optimization of reaction conditions for 4a
Catalyst, additives
Entry (equiv.)
Yielda of
Solvent Conditions 4a/4a′ (%)
b
1
2
3
PdCl2 (0.1), CuCl2 (2) THF
PdCl2 (0.1), CuBr2 (2) THF
80 °C, 1 h
80 °C, 1 h
80 °C, 2 h
—
—
—
—
—
b
c
c
c
CuBr2 (2)
THF
4
5
6
7
8
9
10
11
12
13
FeCl3 (10)
CH3CN 80 °C, 6 h
Toluene 110 °C, 2 h
CH3CN 80 °C, 8 h
CH3CN 80 °C, 24 h 43 (4a)
Toluene 110 °C, 3 h 86 (4a)
Toluene 110 °C, 3 h 88 (4a)
Toluene 110 °C, 3 h 72 (4a)
In(OTf)3 (0.1)
PtCl2 (0.05)
PtCl2 (0.05)
PtCl2 (0.05)
PtCl2 (0.02)
PtCl4 (0.02)
Pt(Ph3P)4 (0.05)
AuCl3 (0.05)
(Ph3P)AuCl (0.05),
AgBF4 (0.1)
52 (4a′/4a = 1 : 2)
Toluene 110 °C, 24 h
—
Toluene 110 °C, 24 h 30 (4a′)d
Toluene 110 °C, 4 h 32 (4a)
a Isolated yield. b Complex reaction mixture. c Ether link cleavage lead
to 3-(2-(2-phenylethynyl)phenyl)prop-2-yn-1-ol. d 50% of 3a is
recovered.
Next we planned to extend this diyne cyclization towards
triynes to synthesis chrysene derivative 7 (Scheme 3). Cascade
cyclization of the triyne 5 was performed under the standard
conditions, which gave dicyclized naphthalene fused chrome-
none 6 and not the tricyclized chrysene fused chromenone 7
(Scheme 3). On increasing the catalyst load a complex reaction
mixture resulted and further screening did not improve the
result.
The proposed mechanism for the enediyne–enone cascade
cyclization is shown in Scheme 4. Initial coordination of the
catalyst with the central triple bond of 3a gave intermediate A,
in which 6-endo-dig cyclization of the electron rich C2 enone
carbon led to the intermediate B. Protodemetallation of B led
to 4a′, where the triple bond of 4a′ is activated by coordination
with the catalyst, to give intermediate C. 6-endo-dig cyclization
of the electron rich C5 pyran carbon with the activated alkyne
gave intermediate D. On protodemetallation D gave the
product 4a. From Table 1 (entries 6 and 7) we found that the
starting material 3a first converted into the monoalkyne
mixture (Table 1, entries 1 and 2). When the reaction was per-
formed with only CuBr2, ether link cleavage occurred to give 3-
(2-(2-phenylethynyl)phenyl)prop-2-yn-1-ol (Table 1, entry 3).10
Similarly other Pd sources also failed to make the cascade
halopalladation proceed (see ESI†). FeCl3 and In(OTf)3 cata-
lysed reaction also led to ether link cleavage (Table 1, entries 4
and 5). From the literature review we found that platinum and
gold catalysts would facilitate C–C bond forming reactions by
the activation of alkyne and subsequent cyclization.11
Pleasingly PtCl2 (0.05 equiv.) as the catalyst with acetonitrile
solvent at 80 °C for 8 h led to the mixture of mono and di-
alkyne cyclized products 4a′ and 4a with isolated yield 52% in
1 : 2 ratio (Table 1, entry 6). The above reaction was carried out
under identical conditions for 24 h resulting in 4a as sole
product with an isolated yield of 43% (Table 1, entry 7). On
further optimization with PtCl2, we found that only 0.02 equiv.
of catalyst and toluene at 110 °C is enough to yield 88% of 4a
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Table 2 Substrate scope of the reactiona
Entry
1
3 (R1; R2; R3)
3a (H; Ph; H)
Product (time, yield%)
Entry
9
3 (R1; R2; R3)
3i (H; 1-naphthyl; H)
Product (time, yield%)
2
3
3b (Me; Ph; H)
10
11
3j (H; C4H9; H)
3c (H; p-MeC6H4; H)
3k (H; C6H13; H)
4
5
6
3d (H; m-MeC6H4; H)
3e (H; p-MeOC6H4; H)
3f (H; p-BrC6H4; H)
12
13
14
3l (H; p-MeC6H4; Me)
3m (H; p-MeC6H4; Cl)
3n (H; p-MeC6H4; NO2)
7
8
3g (H; p-CO2MeC6H4; H)
15
16
3o (H; TMS; H)
3h (H; p-COMeC6H4; H)
3p (H; 2-thienyl; H)
a Isolated yield. b Complex reaction mixture.
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Fig. 1 ORTEP diagram of compound 4p.
Scheme 4 Proposed mechanism for enediyne–enone cascade
reaction.
Experimental section
General methods
Purification of crude compounds was done by column chrom-
atography using silica gel (100–200 mesh, Himedia). Melting
points were determined in capillary tubes and are uncorrected.
FTIR spectra were recorded on a Perkin-Elmer spectrometer
Spectrum Two and absorbences are reported in cm−1. NMR
spectra were recorded at 500 MHz on a JEOL spectrometer and
400 MHz on a Bruker spectrometer. The chemical shifts are
Scheme 3 An attempt to cyclize triyne system.
1
reported in ppm downfield from TMS (δ = 0) for H NMR and
relative to the central CDCl3 resonance (δ = 77.0) for 13C NMR.
The coupling constants J are given in Hz. ESI mass spectra
were recorded on an LCQ Fleet, Thermo Fisher Instruments
Limited, US mass spectrometer. All solvents and commercially
available chemicals were used as received. The compound 2
was prepared according to the literature procedure.12
cyclized product 4a′ and then finally to the dialkyne cyclized
product 4a, which supports the proposed mechanism of
enediyne–enone cascade reaction.
General procedure for synthesis of compounds 1a–1o
To a solution of p-TsOH·H2O (3 equiv.) in MeCN was added
2-(2-phenylethynyl)benzenamine (1 equiv.). The resulting sus-
Conclusions
In conclusion, a PtCl2 catalysed facile cascade enediyne–enone pension of amine salt was cooled to 10–15 °C and to this was
cyclization pathway for the synthesis of tetracyclic chromenone added gradually a solution of NaNO2 (2 equiv.) and KI
was achieved. This method involves easy preparation of start- (2.5 equiv.) in H2O. The reaction mixture was stirred for
ing materials, high atom economy, low catalyst loading, and 10 min then allowed to come to 20 °C and stirred for 2 h. To
tolerates a wide scope of substrates to afford good to excellent the reaction mixture was then added saturated NaHCO3
yield, which allows the construction of tetracyclic chrome- (until pH = 9–10) and saturated Na2S2O3 solution. Then it was
nones in a single step through two consecutive highly regio- extracted with EtOAc and dried over Na2SO4. The crude
selective 6-endo-dig cyclizations. Further evidence for the reac- product was purified by column chromatography (pet. ether–
tion mechanism was confirmed by the isolation of intermedi- EtOAc, 9 : 1) to afford the product. The products 1a–1d, 1f, 1h,
ate 4a′. Further transformations of this diyne–enone scaffold 1j, and 1k, were spectroscopically identical to previously
under iodine are underway.
reported samples.13,14 For the synthesis of 1e, see ref. 14.
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Compound 1g. Compound 1g was prepared by the general 96.2, 109.4, 118.9, 123.1, 126.4, 129.4, 131.9, 132.0, 139.9,
procedure above. After purification by column chromatography 140.0, 148.0.
(PE–EtOAc 9 : 1) the desired compound was isolated as a
brownish orange viscous fluid. IR (Neat) νmax: 517, 645, 691,
General procedure for synthesis of compounds 3a–3o and 5
758, 767, 817, 854, 964, 1016, 1024, 1109, 1177, 1278, 1307, Iodo compound 1 (1.0 equiv.), PdCl2(PPh3)2 (0.03 equiv.) and
1359, 1406, 1431, 1457, 1509, 1553, 1577, 1603, 1715, 1727, CuI (0.04 equiv.) were suspended in triethylamine under a
1
1811, 1927, 2219, 2948 cm−1; H NMR (500 MHz, CDCl3): δ = nitrogen atmosphere. The reaction mixture was stirred at 30 °C
3.93 (s, 3H), 7.04 (td, J = 7.7, 1.6 Hz, 1H), 7.34 (td, J = 7.7, for 30 minutes. After the addition of 2 (1.5 equiv.) the suspen-
1.1 Hz, 1H), 7.54 (dd, J = 7.7, 1.6 Hz, 1H), 7.65 (d, J = 8.4 Hz, sion was stirred for 3 hours at 30 °C. The reaction mixture was
2H), 7.88 (dd, J = 8.4, 1.2 Hz, 1H), 8.03 (d, J = 8.4 Hz, 2H); 13C filtered through a celite pad and purified by column chromato-
NMR (125 MHz, CDCl3): δ = 52.4, 92.2, 94.5, 101.4, 127.7, graphy furnished the desired products.
128.0, 129.7, 130.0, 131.6, 132.7, 138.9, 166.6.
Compound 3a. Compound 3a was prepared by the general
Compound 1i. Compound 1i was prepared by the general procedure above. After purification by column chromatography
procedure above. After purification by column chromatography (PE–EtOAc 6 : 4) the desired compound was isolated as a
(PE–EtOAc 9 : 1) the desired compound was isolated as a brownish orange viscous fluid. IR (Neat) νmax: 493, 527, 613,
brownish orange viscous fluid. IR (Neat) νmax: 565, 644, 751, 691, 735, 758, 824, 861, 913, 955, 1000, 1135, 1179, 1213, 1241,
772, 798, 863, 1014, 1396, 1429, 1455, 1468, 1507, 1585, 2209, 1328, 1358, 1385, 1428, 1443, 1475, 1494, 1607, 1652, 2217,
1
3055 cm−1
;
1H NMR (500 MHz, CDCl3): δ = 7.04 (td, J = 7.7, 2949, 3061 cm−1; H NMR (500 MHz, CDCl3): δ = 1.95 (quint,
1.6 Hz, 1H), 7.37 (t, J = 7.4 Hz, 1H), 7.45–7.50 (m, 1H), 7.54 (t, J = 6.3 Hz, 2H), 2.33 (t, J = 6.3 Hz, 2H), 2.43 (t, J = 6.3 Hz, 2H),
J = 7.4 Hz, 1H), 7.61 (t, J = 7.4 Hz, 1H), 7.65 (dd, J = 7.7, 1.6 Hz, 4.84 (s, 2H), 5.54 (s, 1H), 7.26–7.38 (m, 5H), 7.48 (dd, J =
1H), 7.84 (d, J = 7.1 Hz, 1H), 7.87 (dd, J = 8.2, 2.7 Hz, 2H), 7.92 7.6, 1.5 Hz, 1H), 7.52–7.58 (m, 3H); 13C NMR (125 MHz,
(d, J = 8.1 Hz, 1H), 8.64 (d, J = 8.1 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 21.2, 28.9, 36.7, 57.1, 85.8, 87.0, 87.8, 93.7, 103.7,
CDCl3): δ = 139.0, 133.4, 133.3, 133.0, 130.9, 130.2, 129.6, 123.1, 124.3, 126.1, 128.1, 128.5, 128.7, 128.8, 131.8, 131.9,
129.3, 128.4, 128.0, 127.0, 126.8, 126.7, 125.4, 120.7, 100.9, 132.2, 176.7, 199.7.
96.2, 91.5.
Compound 3b. Compound 3b was prepared by the general
Compound 1l. Compound 1l was prepared by the general procedure above. After purification by column chromatography
procedure above. After purification by column chromatography (PE–EtOAc 6 : 4) the desired compound was isolated as a
(PE–EtOAc 9 : 1) the desired compound was isolated as a brownish orange viscous fluid. IR (Neat) νmax: 611, 689, 758,
brownish orange viscous fluid. IR (Neat) νmax: 448, 523, 574, 824, 983, 1010, 1078, 1142, 1160, 1198, 1211, 1263, 1320, 1354,
585, 746, 814, 880, 1016, 1116, 1179, 1205, 1389, 1453, 1510, 1378, 1440, 1471, 1493, 1609, 1655, 1729, 2870, 2928, 2957,
1585, 1902, 2210, 2919, 3028 cm−1; 1H NMR (500 MHz, CDCl3): 3060 cm−1; 1H NMR (500 MHz, CDCl3): δ = 1.05 (s, 6H), 2.20 (s,
δ = 2.29 (s, 3H), 2.37 (s, 3H), 6.82 (dd, J = 8.2, 2.1 Hz, 1H), 7.17 2H), 2.29 (s, 2H), 4.84 (s, 2H), 5.52 (s, 1H), 7.26–7.34 (m, 2H),
(d, J = 7.8 Hz, 2H), 7.35 (d, J = 2.1 Hz, 1H), 7.48 (d, J = 8.1 Hz, 7.34–7.38 (m, 3H), 7.48 (dd, J = 7.6, 1.5 Hz, 1H), 7.51–7.60 (m,
2H), 7.72 (d, J = 8.1 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 3H); 13C NMR (125 MHz, CDCl3) δ 28.3, 32.7, 42.7, 50.8, 57.2,
21.0, 21.7, 91.2, 93.0, 97.2, 120.0, 129.3, 129.7, 130.6, 131.6, 85.8, 87.0, 87.9, 93.7, 102.5, 123.2, 124.4, 126.1, 128.1, 128.5,
133.2, 138.0, 138.5, 138.9.
128.7, 128.8, 131.9, 132.2, 175.0, 199.5.
Compound 1m. Compound 1m was prepared by the general
Compound 3c. Compound 3c was prepared by the general
procedure above. After purification by column chromatography procedure above. After purification by column chromatography
(PE–EtOAc 9 : 1) the desired compound was isolated as a white (PE–EtOAc 6 : 4) the desired compound was isolated as a
solid. IR (KBr) νmax: 507, 524, 560, 577, 654, 680, 710, 811, 878, brownish orange solid with mp 93–95 °C. IR (KBr) νmax: 527,
944, 1016, 1091, 1116, 1151, 1180, 1210, 1243, 1300, 1379, 759, 817, 954, 999, 1135, 1179, 1213, 1241, 1327, 1357, 1384,
1448, 1540, 1570, 1591, 1645, 1752, 1791, 1902, 2186, 2218, 1445, 1479, 1511, 1606, 1654, 2215, 2870, 2947, 3029,
1
2866, 2993, 3029, 3054 cm−1; H NMR (500 MHz, CDCl3): δ = 3059 cm−1
;
1H NMR (500 MHz, CDCl3): δ = 1.97 (quint, J =
2.38 (s, 3H), 6.98 (dd, J = 8.5, 2.5 Hz, 1H), 7.18 (d, J = 8.0 Hz, 6.5 Hz, 2H), 2.34 (t, J = 6.5 Hz, 2H), 2.38 (s, 3H), 2.44 (t, J =
2H), 7.46–7.51 (m, 3H), 7.76 (d, J = 8.5 Hz, 1H); 13C NMR 6.5 Hz, 2H), 4.84 (s, 2H), 5.54 (s, 1H), 7.17 (d, J = 8.0 Hz, 2H),
(125 MHz, CDCl3): δ = 21.8, 90.1, 94.7, 98.4, 119.4, 129.4, 7.24–7.30 (m, 1H), 7.32 (td, J = 7.5, 1.3 Hz, 1H), 7.39–7.50
129.6, 131.7, 131.7, 132.1, 134.2, 139.4, 139.8.
(m, 3H), 7.52 (d, J = 7.7 Hz, 1H); 13C NMR (125 MHz, CDCl3):
Compound 1n. Compound 1n was prepared by the general δ = 21.2, 21.7, 28.9, 36.8, 57.2, 85.7, 87.1, 87.3, 94.0, 103.7,
procedure above. After purification by column chromatography 120.1, 124.3, 126.4, 127.9, 128.8, 129.3, 131.8, 131.9, 132.3,
(PE–EtOAc 9 : 1) the desired compound was isolated as a yellow 138.9, 176.7, 199.7; MS (ESI+): m/z = 341 [M + H]+.
solid. IR (KBr) νmax: 488, 522, 581, 670, 704, 734, 812, 831, 925,
1017, 1123, 1149, 1240, 1278, 1343, 1519, 1557, 1603, 1894, procedure above. After purification by column chromatography
2208, 2231, 2850, 2916, 3023, 3096, 3128 cm−1 1H NMR (PE–EtOAc 6 : 4) the desired compound was isolated as a
Compound 3d. Compound 3d was prepared by the general
;
(500 MHz, CDCl3): δ = 2.39 (s, 3H), 7.20 (d, J = 7.6 Hz, 2H), 7.50 brownish orange viscous fluid. IR (Neat) νmax: 494, 527, 690,
(d, J = 7.6 Hz, 2H), 7.79 (d, J = 8.7 Hz, 1H), 8.04 (d, J = 8.7 Hz, 759, 785, 824, 861, 910, 954, 1000, 1038, 1099, 1135, 1179,
1H), 8.29 (s, 1H); 13C NMR (125 MHz, CDCl3): δ = 21.8, 89.5, 1213, 1241, 1327, 1357, 1385, 1428, 1444, 1489, 1607, 1654,
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1
2207, 2242, 2949, 3060 cm−1; H NMR (500 MHz, CDCl3): δ = (d, J = 7.2 Hz, 1H), 7.64 (d, J = 8.1 Hz, 2H), 7.95 (d, J = 8.1 Hz,
1.95 (quint, J = 6.3 Hz, 2H), 2.29–2.34 (m, 2H), 2.36 (s, 3H), 2H); 13C NMR (100 MHz, CDCl3): δ = 21.1, 26.7, 28.9, 36.7,
2.42 (t, J = 6.3 Hz, 2H), 4.84 (s, 2H), 5.53 (s, 1H), 7.16 (d, J = 57.0, 86.1, 86.7, 91.0, 92.7, 103.7, 124.5, 125.4, 127.9, 128.3,
7.9 Hz, 1H), 7.21–7.40 (m, 5H), 7.47 (dd, J = 7.6, 1.4 Hz, 1H), 128.6, 128.9, 131.9, 132.0, 132.4, 136.4, 176.6, 197.4, 199.5; MS
7.52 (dd, J = 7.6, 1.4 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = (ESI+): m/z = 369 [M + H]+.
21.2, 21.4, 28.9, 36.7, 57.1, 85.7, 87.0, 87.5, 93.9, 103.7, 123.0,
124.3, 126.2, 128.0, 128.3, 128.8, 129.0, 129.6, 131.9, 132.2, procedure above. After purification by column chromatography
132.3, 138.1, 176.7, 199.6; MS (ESI+): m/z = 341 [M + H]+.
(PE–EtOAc 6 : 4) the desired compound was isolated as a
Compound 3i. Compound 3i was prepared by the general
Compound 3e. Compound 3e was prepared by the general brownish orange viscous fluid. IR (Neat) νmax: 567, 759, 773,
procedure above. After purification by column chromatography 801, 823, 861, 954, 999, 1135, 1178, 1213, 1240, 1327, 1357,
(PE–EtOAc 6 : 4) the desired compound was isolated as a 1385, 1444, 1482, 1507, 1606, 1652, 2212, 2238, 2875, 2948,
brownish viscous fluid. IR (Neat) νmax: 535, 759, 832, 954, 3058 cm−1 1H NMR (500 MHz, CDCl3): δ = 1.89 (quint, J =
;
1000, 1028, 1136, 1179, 1249, 1288, 1358, 1327, 1385, 1444, 6.3 Hz, 2H), 2.28–2.33 (m, 4H), 4.85 (s, 2H), 5.52 (s, 1H), 7.31
1511, 1606, 1652, 2214, 2952 cm−1; 1H NMR (400 MHz, CDCl3): (t, J = 7.6 Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H), 7.47 (t, J = 7.6 Hz,
δ = 1.92–2.01 (m, 2H), 2.34 (t, J = 6.4 Hz, 2H), 2.44 (t, J = 1H), 7.51–7.58 (m, 3H), 7.63 (d, J = 7.6 Hz, 1H), 7.79 (d, J =
6.1 Hz, 2H), 3.83 (s, 3H), 4.84 (s, 2H), 5.54 (s, 1H), 6.89 (d, J = 7.6 Hz, 1H), 7.83–7.90 (m, 2H), 8.58 (d, J = 8.0 Hz, 1H); 13C
7.6 Hz, 2H), 7.23–7.28 (t, J = 7.6 Hz, 1H), 7.31 (t, J = 7.6 Hz, NMR (125 MHz, CDCl3): δ = 21.2, 28.8, 36.8, 57.1, 85.9, 87.4,
1H), 7.49 (m, 4H); 13C NMR (100 MHz, CDCl3): δ = 21.2, 28.9, 91.9, 92.7, 103.7, 120.8, 124.3, 125.4, 126.4, 126.4, 126.6, 126.8,
36.6, 55.4, 57.1, 85.6, 86.6, 87.1, 93.9, 103.67, 114.1, 115.2, 128.2, 128.5, 129.0, 129.2, 130.8, 132.0, 132.5, 133.3, 133.4,
124.1, 126.5, 127.7, 128.8, 131.7, 132.2, 133.3, 159.9, 176.8, 176.7, 199.6; MS (ESI+): m/z = 377 [M + H]+.
199.7; MS (ESI+): m/z = 357 [M + H]+.
Compound 3j. Compound 3j was prepared by the general
Compound 3f. Compound 3f was prepared by the general procedure above. After purification by column chromatography
procedure above. After purification by column chromatography (PE–EtOAc 6 : 4) the desired compound was isolated as a
(PE–EtOAc 6 : 4) the desired compound was isolated as a brownish orange viscous fluid. IR (Neat) νmax: 528, 613, 760,
brownish orange viscous fluid. IR (Neat) νmax: 495, 523, 612, 825, 861, 954, 1000, 1057, 1135, 1176, 1213, 1240, 1327, 1356,
759, 823, 861, 911, 954, 1009, 1038, 1069, 1096, 1135, 1179, 1384, 1444, 1480, 1607, 1657, 2232, 2870, 2955, 3064 cm−1
;
1213, 1241, 1327, 1357, 1392, 1434, 1490, 1606, 1653, 2221, 1H NMR (400 MHz, CDCl3): δ = 0.95 (t, J = 7.2 Hz, 3H),
1
2948, 3063 cm−1; H NMR (500 MHz, CDCl3): δ = 1.97 (quint, 1.47–1.65 (m, 4H), 1.98–2.06 m, 2H), 2.37 (t, J = 6.6 Hz, 2H),
J = 6.5 Hz, 2H), 2.34 (t, J = 6.5 Hz, 2H), 2.43 (t, J = 6.3 Hz, 2H), 2.48 (q, J = 6.3 Hz, 4H), 4.81 (s, 2H), 5.54 (s, 1H), 7.17–7.31
4.84 (s, 2H), 5.54 (s, 1H), 7.26–7.36 (m, 2H), 7.42 (d, J = 7.7 Hz, (m, 2H), 7.39–7.44 (m, 2H); 13C NMR (100 MHz, CDCl3): δ =
2H), 7.48–7.53 (m, 4H); 13C NMR (125 MHz, CDCl3): δ = 21.2, 13.8, 19.4, 21.3, 22.0, 29.0, 30.8, 36.8, 57.2, 79.1, 85.0, 87.3,
28.9, 36.8, 57.1, 85.9, 86.9, 89.0, 92.6, 103.8, 122.1, 122.9, 95.3, 103.7, 124.1, 127.1, 127.3, 128.8, 132.0, 132.4, 176.7,
124.4, 125.8, 128.4, 128.9, 131.8, 131.9, 132.4, 133.3, 176.6, 199.6; MS (ESI+): m/z = 307 [M + H]+.
199.6; MS (ESI+): m/z = 405 [M + H]+.
Compound 3k. Compound 3k was prepared by the general
Compound 3g. Compound 3g was prepared by the general procedure above. After purification by column chromatography
procedure above. After purification by column chromatography (PE–EtOAc 6 : 4) the desired compound was isolated as a
(PE–EtOAc 6 : 4) the desired compound was isolated as a brownish orange viscous fluid. IR (Neat) νmax: 759, 821, 861,
brown solid with mp 135–137 °C. IR (KBr) νmax: 695, 768, 821, 954, 1001, 1135, 1177, 1212, 1239, 1255, 1327, 1356, 1383,
859, 956, 998, 1107, 1136, 1178, 1213, 1276, 1358, 1435, 1606, 1442, 1456, 1480, 1608, 1659, 2228, 2860, 2930, 3064 cm−1
;
1656, 1722, 2951 cm−1 1H NMR (500 MHz, CDCl3): δ = 1.97 1H NMR (500 MHz, CDCl3): δ = 0.84–0.95 (m, 3H), 1.30–1.33
;
(quint, J = 6.3 Hz, 2H), 2.30–2.39 (m, 2H), 2.44 (t, J = 6.3 Hz, (m, 4H), 1.46–1.52 (m, 2H), 1.56–1.67 (m, 2H), 2.01 (quint, J =
2H), 3.94 (s, 3H), 4.85 (s, 2H), 5.55 (s, 1H), 7.29–7.38 (m, 2H), 6.5 Hz, 2H), 2.35–2.40 (m, 2H), 2.44–2.50 (m, 4H), 4.81 (s, 2H),
7.49–7.51 (m, 1H), 7.53–7.57 (m, 1H), 7.58–7.65 (m, 2H), 5.54 (s, 1H), 7.21 (td, J = 7.6, 1.5 Hz, 1H), 7.24–7.29 (m, 1H),
8.01–8.07 (m, 2H); 13C NMR (125 MHz, CDCl3): δ = 21.2, 28.9, 7.40 (dd, J = 7.6, 1.5 Hz, 1H), 7.43 (dd, J = 7.6, 1.5 Hz, 1H);
36.8, 52.4, 57.1, 86.1, 86.8, 90.8, 92.8, 103.8, 124.6, 125.5, 13C NMR (125 MHz, CDCl3): δ = 14.3, 19.7, 21.3, 22.7, 28.7,
127.9, 128.6, 128.9, 129.6, 129.8, 131.8, 132.1, 132.4, 166.6, 28.8, 29.0, 31.5, 36.9, 57.2, 79.1, 85.0, 87.3, 95.4, 103.7, 124.1,
176.6, 199.6; MS (ESI+): m/z = 385 [M + H]+.
Compound 3h. Compound 3h was prepared by the general 335 [M + H]+.
127.1, 127.3, 128.8, 132.1, 132.4, 176.7, 199.7; MS (ESI+): m/z =
procedure above. After purification by column chromatography
Compound 3l. Compound 3l was prepared by the general
(PE–EtOAc 6 : 4) the desired compound was isolated as a procedure above. After purification by column chromatography
brown solid. IR (KBr) νmax: 459, 592, 612, 638, 760, 829, 861, (PE–EtOAc 6 : 4) the desired compound was isolated as a
912, 957, 1000, 1038, 1136, 1180, 1214, 1264, 1328, 1359, 1403, light yellow semi solid. IR (Neat) νmax: 497, 526, 579, 600,
1
1478, 1556, 1606, 1651, 1658, 1682, 2219, 2950, 3065 cm−1; H 761, 819, 867, 959, 982, 1140, 1181, 1218, 1330, 1361, 1453,
NMR (400 MHz, CDCl3): δ = 1.91–2.02 (m, 2H), 2.34 (t, J = 1488, 1511, 1602, 1651, 1910, 2210, 2848, 2917, 2953,
6.5 Hz, 2H), 2.44 (t, J = 6.2 Hz, 2H), 2.62 (s, 3H), 4.85 (s, 2H), 3029 cm−1 1H NMR (500 MHz, CDCl3): δ = 1.97 (quint, J =
;
5.55 (s, 1H), 7.27–7.38 (m, 2H), 7.50 (d, J = 7.3 Hz, 1H), 7.55 6.3 Hz, 2H), 2.32–2.36 (m, 5H), 2.38 (s, 3H), 2.44 (t, J = 6.3 Hz,
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2H), 4.83 (s, 2H), 5.53 (s, 1H), 7.08 (d, J = 7.8 Hz, 1H), 7.17 (d, 125.7, 125.9, 126.2, 128.1, 128.3, 128.4, 128.5, 128.6, 128.8,
J = 7.8 Hz, 2H), 7.33–7.39 (m, 2H), 7.44 (d, J = 8.1 Hz, 2H); 13C 131.9, 132.0, 132.2, 132.3, 132.4, 176.7, 199.6.
NMR (125 MHz, CDCl3): δ = 21.2, 21.4, 21.7, 28.9, 36.8, 57.3,
General procedure for synthesis of compounds 4a–4p and 6
84.9, 87.2, 87.4, 93.6, 103.7, 120.2, 121.3, 126.2, 129.0, 129.2,
131.8, 132.2, 132.4, 138.8, 139.1, 176.8, 199.7; MS (ESI+): m/z = A solution of 3 (1.0 equiv.) and PtCl2 (0.02 equiv.) in toluene
355 [M + H]+.
was stirred at 110 °C under nitrogen atmosphere. After com-
Compound 3m. Compound 3m was prepared by the general pletion of the reaction as monitored by TLC, the solvent was
procedure above. After purification by column chromatography evaporated and the residue was purified by column chromato-
(PE–EtOAc 6 : 4) the desired compound was isolated as a graphy to afford 4.
light yellow solid. IR (KBr) νmax: 526, 817, 889, 956, 980,
Compound 4a. Compound 4a was prepared by the general
1110, 1138, 1181, 1218, 1329, 1350, 1453, 1475, 1508, 1604, procedure above. After purification by column chromatography
1
1650, 2216 cm−1; H NMR (400 MHz, CDCl3): δ = 1.97 (quint, (PE–EtOAc 7 : 3) the desired compound was isolated as a pale
J = 6.1 Hz, 2H), 2.25–2.41 (m, 5H), 2.44 (t, J = 6.1 Hz, 2H), 4.82 yellow solid with mp 114–116 °C. IR (KBr) νmax: 424, 454, 486,
(s, 2H), 5.52 (s, 1H), 7.18 (d, J = 7.3 Hz, 2H), 7.25 (t, J = 7.3 Hz, 531, 551, 570, 593, 625, 647, 704, 733, 766, 785, 867, 910, 954,
1H), 7.39 (d, J = 8.3 Hz, 1H), 7.44 (d, J = 7.7 Hz, 2H), 7.50 (s, 994, 1036, 1075, 1143, 1185, 1221, 1262, 1284, 1312, 1335,
1H); 13C NMR (100 MHz, CDCl3): δ = 21.2, 21.7, 28.9, 36.8, 1395, 1453, 1494, 1581, 1593, 1654, 1728, 1954, 2246, 2855,
57.0, 86.1, 86.2, 86.6, 95.2, 103.7, 119.6, 122.7, 127.9, 128.2, 2929, 3055 cm−1 1H NMR (500 MHz, DMSO-d6): δ = 2.02
;
129.3, 131.6, 131.8, 133.3, 134.8, 139.3, 176.6, 199.6; MS (ESI+): (quint, J = 6.4 Hz, 2H), 2.57 (t, J = 6.4 Hz, 2H), 2.66 (t, J =
m/z = 375 [M + H]+.
6.0 Hz, 2H), 5.15 (s, 2H), 7.42–7.49 (m, 4H), 7.50–7.54 (m, 3H),
Compound 3n. Compound 3n was prepared by the general 7.69 (d, J = 8.0 Hz, 1H), 7.88 (s, 1H), 7.95 (d, J = 8.0 Hz, 1H);
procedure above. After purification by column chromatography 13C NMR (125 MHz, DMSO-d6): δ = 18.8, 28.0, 37.2, 68.5, 116.9,
(PE–EtOAc 6 : 4) the desired compound was isolated as a 125.0, 125.4, 125.9, 126.2, 126.7, 127.3, 127.8, 128.1, 128.2,
light yellow solid with mp 119–121 °C. IR (KBr) νmax: 495, 128.6, 129.2, 133.1, 136.3, 138.8, 177.3, 193.8; HRMS (EI/[M]+)
529, 604, 723, 741, 763, 790, 865, 903, 959, 984, 996, calcd for C23H18O2, 326.1307, found 326.1307.
1077, 1138, 1182, 1219, 1343, 1363, 1452, 1478, 1524, 1572,
Compound 4b. Compound 4b was prepared by the general
1603, 1648, 1739, 1913, 2204, 2867, 2934 cm−1 1H NMR procedure above. After purification by column chromatography
;
(400 MHz, CDCl3): δ = 1.92–2.02 (m, 2H), 2.32–2.37 (m, 2H), (PE–EtOAc 7 : 3) the desired compound was isolated as a pale
2.40 (s, 3H), 2.45 (t, J = 5.4 Hz, 2H), 4.87 (s, 2H), 5.53 (s, 1H), yellow viscous fluid. IR (Neat) νmax: 545, 576, 635, 703, 732,
7.20 (d, J = 7.1 Hz, 2H), 7.46 (d, J = 7.1 Hz, 2H), 7.61 (d, J = 765, 888, 908, 1005, 1030, 1066, 1164, 1222, 1260, 1341, 1368,
8.2 Hz, 1H), 8.10 (d, J = 8.2 Hz, 1H), 8.36 (s, 1H); 13C NMR 1397, 1451, 1495, 1584, 1595, 1656, 1709, 2252, 2853, 2870,
(100 MHz, CDCl3): δ = 21.2, 21.8, 28.8, 36.8, 56.8, 85.4, 2927, 2958, 3056 cm−1; 1H NMR (500 MHz, DMSO-d6): δ = 1.18
85.5, 90.7, 96.6, 103.8, 119.1, 122.4, 126.6, 127.9, 129.4, 130.3, (s, 6H), 2.51 (s, 2H), 2.60 (s, 2H), 5.14 (s, 2H), 7.43–7.48 (m,
131.9, 133.0, 139.9, 147.3, 176.5, 199.6; MS (ESI+): m/z = 386 4H), 7.50–7.54 (m, 3H), 7.64 (d, J = 8.3 Hz, 1H), 7.88 (s, 1H),
[M + H]+.
7.96 (d, J = 8.3 Hz, 1H); 13C NMR (125 MHz, DMSO-d6): δ =
Compound 3p. For experimental procedure see ESI.† IR 27.8, 41.1, 50.9, 54.9, 68.5, 116.1, 125.1, 125.2, 126.0, 126.2,
(Neat) νmax: 443, 498, 528, 612, 705, 759, 825, 853, 911, 954, 126.8, 127.1, 127.8, 128.1, 128.3, 128.7, 129.2, 133.2, 136.4,
1000, 1034, 1058, 1094, 1135, 1179, 1213, 1241, 1255, 1327, 138.8, 175.5, 193.9; HRMS (EI/[M]+) calcd for C25H22O2,
1357, 1385, 1421, 1446, 1478, 1520, 1606, 1651, 1718, 1959, 354.1620, found 354.1620.
1
2204, 2871, 2948, 3072 cm−1; H NMR (400 MHz, CDCl3): δ =
Compound 4c. Compound 4c was prepared by the general
1.97 (quint, J = 6.3 Hz, 2H), 2.30–2.38 (m, 2H), 2.45 (t, J = procedure above. After purification by column chromatography
6.3 Hz, 2H), 4.85 (s, 2H), 5.54 (s, 1H), 7.03 (dd, J = 5.1, 3.7 Hz, (PE–EtOAc 7 : 3) the desired compound was isolated as a
1H), 7.25–7.36 (m, 4H), 7.46–7.52 (m, 2H); 13C NMR (100 MHz, light yellow solid with mp 207–209 °C. IR (KBr) νmax: 545,
CDCl3): δ = 21.2, 28.9, 36.8, 57.1, 86.0, 86.8, 87.0, 91.6, 103.7, 576, 635, 703, 732, 765, 888, 908, 1005, 1030, 1066, 1164, 1222,
123.1, 124.2, 125.9, 127.3, 127.9, 128.2, 128.9, 131.6, 132.3, 1260, 1341, 1368, 1397, 1451, 1495, 1584, 1595, 1656, 1709,
1
132.4, 176.8, 199.7; MS (ESI+): m/z = 355 [M + Na+].
2252, 2853, 2870, 2927, 2958, 3056 cm−1; H NMR (400 MHz,
Compound 5. Compound 5 was prepared by the general DMSO-d6): δ = 2.02 (quint, J = 6.3 Hz, 2H), 2.39 (s, 3H), 2.56
procedure above; for further details see ESI.† After purification (t, J = 6.4 Hz, 2H), 2.66 (t, J = 6.0 Hz, 2H), 5.15 (s, 2H), 7.32
by column chromatography (PE–EtOAc 6 : 4) the desired com- (s, 4H), 7.42 (t, J = 7.2 Hz, 1H), 7.50 (t, J = 7.2 Hz, 1H), 7.67 (d,
pound was isolated as a brownish orange viscous fluid. IR J = 8.5 Hz, 1H), 7.84 (s, 1H), 7.93 (d, J = 8.0 Hz, 1H); 13C
(Neat) νmax: 494, 585, 611, 690, 756, 823, 860, 954, 999, 1135, NMR (100 MHz, DMSO-d6):
δ = 18.8, 20.8, 28.0, 37.2,
1178, 1212, 1240, 1327, 1356, 1384, 1428, 1446, 1494, 1606, 68.5, 116.9, 124.9, 125.4, 125.9, 126.3, 126.6, 127.3, 128.0,
1
1654, 2216, 2948, 3056 cm−1; H NMR (400 MHz, CDCl3): δ = 128.1, 129.1, 129.2, 133.1, 135.9, 136.3, 137.1, 177.3, 193.8;
1.91 (quint, J = 6.1 Hz, 2H), 2.27–2.35 (m, 4H), 4.60 (s, 2H), HRMS (ESI/[M + H]+) calcd for C24H21O2, 341.15415, found
5.38 (s, 1H), 7.28–7.34 (m, 7H), 7.50 (d, J = 7.0 Hz, 1H), 341.15253.
7.55–7.61 (m, 5H); 13C NMR (100 MHz, CDCl3): δ = 21.2, 28.8,
Compound 4d. Compound 4d was prepared by the general
36.8, 57.1, 86.1, 86.8, 88.4, 91.8, 92.4, 93.7, 103.6, 123.3, 124.4, procedure above. After purification by column chromatography
1324 | Org. Biomol. Chem., 2014, 12, 1318–1327
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(PE–EtOAc 7 : 3) the desired compound was isolated as a yellow 194.9; HRMS (ESI/[M + H]+) calcd for C25H21O4, 385.14398,
solid with mp 153–155 °C. IR (KBr) νmax: 470, 499, 539, 553, found 385.14236.
574, 598, 631, 647, 711, 731, 785, 887, 909, 957, 990, 1023,
Compound 4h. Compound 4h was prepared by the general
1037, 1075, 1135, 1180, 1191, 1225, 1262, 1288, 1333, 1394, procedure above. After purification by column chromatography
1
1453, 1499, 1585, 1654, 2245, 2863, 2923, 2947, 3051 cm−1; H (PE–EtOAc 7 : 3) the desired compound was isolated as a
NMR (400 MHz, DMSO-d6): δ = 2.02 (quint, J = 6.2 Hz, 2H), brown solid. IR (KBr) νmax: 619, 733, 840, 910, 956, 985, 1036,
2.39 (s, 3H), 2.56 (t, J = 6.2 Hz, 2H), 2.64 (t, J = 6.2 Hz, 2H), 1075, 1144, 1186, 1266, 1359, 1396, 1455, 1497, 1602, 1652,
1
5.14 (s, 2H), 7.21 (d, J = 7.5 Hz, 1H), 7.26–7.28 (m, 2H), 1682, 2247, 2854, 2925 cm−1; H NMR (400 MHz, CDCl3): δ =
7.35–7.42 (m, 1H), 7.44 (d, J = 6.9 Hz, 1H), 7.50 (t, J = 7.5 Hz, 2.09–2.19 (m, 2H), 2.63–2.77 (m, 7H), 5.12 (s, 2H), 7.45 (d, J =
1H), 7.69 (d, J = 8.3 Hz, 1H), 7.85 (s, 1H), 7.94 (d, J = 8.3 Hz, 7.5 Hz, 2H), 7.48–7.55 (m, 2H), 7.76 (d, J = 9.7 Hz, 2H), 7.84 (d,
1H); 13C NMR (100 MHz, DMSO-d6): δ = 18.8, 21.1, 28.0, 37.2, J = 7.5 Hz, 1H), 8.07 (d, J = 7.5 Hz, 2H); 13C NMR (100 MHz,
68.5, 116.9, 125.0, 125.4, 125.9, 126.3, 126.3, 126.7, 127.3, CDCl3): δ = 19.3, 26.8, 28.8, 37.7, 69.1, 117.9, 125.8, 125.9,
128.0, 128.1, 128.4, 128.5, 129.8, 133.1, 136.4, 137.9, 138.7, 126.0, 126.5, 127.3, 127.5, 128.6, 128.7, 129.1, 129.7, 133.7,
177.3, 193.8; HRMS (ESI/[M + H]+) calcd for C24H21O2, 135.6, 136.4, 144.6, 177.3, 194.9, 197.9; HRMS (ESI/[M + H]+)
341.15415, found 341. 15225.
calcd for C25H21O3, 369.1491, found 369. 1499.
Compound 4e. Compound 4e was prepared by the general
Compound 4i. Compound 4i was prepared by the general
procedure above. After purification by column chromatography procedure above. After purification by column chromatography
(PE–EtOAc 7 : 3) the desired compound was isolated as a yellow (PE–EtOAc 7 : 3) the desired compound was isolated as a yellow
solid. IR (KBr) νmax: 418, 536, 595, 745, 783, 837, 982, 1035, solid with mp 215–217 °C. IR (KBr) νmax: 470, 503, 539, 592,
1072, 1176, 1245, 1286, 1333, 1397, 1452, 1511, 1580, 1645, 619, 646, 731, 781, 804, 872, 908, 949, 990, 1036, 1075, 1146,
2838, 2928 cm−1; 1H NMR (400 MHz, CDCl3): δ = 2.08–2.17 (m, 1177, 1190, 1247, 1284, 1331, 1395, 1451, 1499, 1579, 1654,
2H), 2.63–2.71 (m, 4H), 5.14 (s, 2H), 3.88 (s, 3H), 7.00 (d, J = 2244, 2857, 2931, 2946, 3053 cm−1; 1H NMR (500 MHz, CDCl3):
8.0 Hz, 2H), 7.23–7.30 (m, 2H), 7.41–7.52 (m, 2H), 7.73 (d, J = δ = 2.11 (quint, J = 6.3 Hz, 2H), 2.60 (t, J = 6.3 Hz, 2H), 2.70 (q,
5.1 Hz, 2H), 7.82 (d, J = 7.7 Hz, 1H); 13C NMR (100 MHz, J = 6.3 Hz, 2H), 4.77 (s, 2H), 7.33–7.44 (m, 2H), 7.46–7.59 (m,
CDCl3): δ = 19.4, 28.8, 37.7, 55.5, 69.3, 114.1, 117.9, 125.3, 5H), 7.77–7.87 (m, 3H), 7.93 (dd, J = 8.3, 4.0 Hz, 2H); 13C NMR
125.4, 126.2, 126.7, 127.1, 127.1, 128.4, 128.9, 130.5, 132.1, (125 MHz, CDCl3): δ = 19.3, 28.9, 37.8, 69.2, 117.8, 125.1,
133.8, 136.4, 159.3, 177.2, 195.0; HRMS (ESI/[M + H]+) calcd 125.5, 125.6, 126.0, 126.2, 126.3, 126.7, 127.3, 127.4, 127.4,
for C24H21O3, 357.1491, found 357. 1487.
127.5, 128.4, 128.5, 128.5, 129.8, 132.4, 133.6, 133.9, 134.5,
Compound 4f. Compound 4f was prepared by the general 137.3, 177.4, 195.0; HRMS (ESI/[M + H]+) calcd for C27H21O2,
procedure above. After purification by column chromatography 377.15415, found 377.15247.
(PE–EtOAc 7 : 3) the desired compound was isolated as a pale
Compound 4j. Compound 4j was prepared by the general
white solid with mp 235–237 °C. IR (KBr) νmax: 426, 491, 531, procedure above. After purification by column chromatography
550, 592, 619, 658, 708, 744, 760, 782, 817, 836, 887, 870, 907, (PE–EtOAc 7 : 3) the desired compound was isolated as a yellow
948, 981, 1009, 1021, 1034, 1068, 1101, 1135, 1181, 1220, 1260, solid with mp 115–117 °C. IR (KBr) νmax: 551, 613, 710, 745,
1
1283, 1325, 1400, 1449, 1487, 1586, 1647, 2864, 2916 cm−1; H 878, 989, 1034, 1075, 1176, 1242, 1339, 1395, 1454, 1503, 1583,
1
NMR (500 MHz, CDCl3): δ = 2.13 (quint, J = 6.3 Hz, 2H), 1656, 2868, 2930 cm−1; H NMR (400 MHz, CDCl3): δ = 0.95 (t,
2.64–2.71 (m, 4H), 5.10 (s, 2H), 7.21 (d, J = 8.3 Hz, 2H), J = 7.3 Hz, 3H), 1.41 (h, J = 7.5 Hz, 2H), 1.57 (quint, J = 6.8 Hz,
7.43–7.54 (m, 2H), 7.59 (d, J = 8.3 Hz, 2H), 7.69–7.78 (m, 2H), 2H), 2.11 (p, J = 6.3 Hz, 2H), 2.65–2.68 (m, 4H), 2.73 (t, J = 7.8
7.82 (d, J = 7.3 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 19.3, Hz, 2H), 5.20 (s, 2H), 7.40 (dt, J = 18.4, 7.1 Hz, 2H), 7.59 (s,
28.8, 37.7, 69.1, 117.8, 122.1, 125.6, 125.8, 126.0, 126.4, 127.2, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.73 (d, J = 7.9 Hz, 1H); 13C NMR
127.3, 128.4, 128.9, 130.9, 131.8, 133.7, 135.4, 138.6, 177.3, (100 MHz, CDCl3): δ = 14.1, 19.4, 22.6, 28.8, 32.9, 33.3, 37.8,
195.0; MS (ESI+): m/z = 405 [M + H]+.
Compound 4g. Compound 4g was prepared by the general 128.1, 134.0, 135.1, 176.7, 194.8; MS (ESI+): m/z = 307 [M + H]+.
procedure above. After purification by column chromatography Compound 4k. Compound 4k was prepared by the general
68.1, 117.8, 124.7, 124.9, 125.8, 126.6, 127.1, 127.2, 127.8,
(PE–EtOAc 7 : 3) the desired compound was isolated as a procedure above. After purification by column chromatography
light yellow solid with mp 187–189 °C. IR (KBr) νmax: 532, (PE–EtOAc 7 : 3) the desired compound was isolated as a
550, 592, 620, 646, 711, 731, 775, 786, 812, 872, 911, 955, 985, light yellow solid with mp 101–103 °C. IR (KBr) νmax: 512,
1020, 1036, 1074, 1103, 1143, 1181, 1282, 1311, 1333, 1395, 550, 614, 642, 710, 745, 763, 785, 844, 883, 934, 962, 989, 1035,
1435, 1498, 1594, 1654, 1719, 1941, 2247, 2886, 2950, 2996, 1075, 1107, 1150, 1176, 1190, 1207, 1243, 1261, 1309, 1339,
3052 cm−1
;
1H NMR (500 MHz, CDCl3): δ = 2.13 (quint, J = 1396, 1419, 1454, 1503, 1583, 1597, 1658, 1729, 1828, 1923,
6.1 Hz, 2H), 2.65 (t, J = 6.1 Hz, 2H), 2.70 (t, J = 6.1 Hz, 2H), 3.97 1945, 2855, 2951, 2927, 3052, 3290 cm−1; H NMR (400 MHz,
(s, 3H), 5.11 (s, 2H), 7.41 (d, J = 8.2 Hz, 2H), 7.45–7.53 (m, 2H), CDCl3): δ = 0.86–0.91 (m, 3H), 1.28–1.43 (m, 6H), 1.57 (quint, J
7.75 (d, J = 2.1 Hz, 1H), 7.77 (s, 1H), 7.80–7.86 (m, 1H), 8.14 (d, = 7.6 Hz, 2H), 2.12 (p, J = 6.3 Hz, 2H), 2.65–2.68 (m, 4H), 2.73
J = 8.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ = 19.3, 28.8, (t, J = 7.6 Hz, 2H), 5.20 (s, 2H), 7.36–7.44 (m, 2H), 7.59 (s, 1H),
37.7, 52.4, 69.1, 117.8, 125.7, 125.9, 126.5, 127.2, 127.5, 128.5, 7.66 (d, J = 8.2 Hz, 1H), 7.73 (d, J = 8.2 Hz, 1H); 13C NMR
129.0, 129.4, 129.4, 129.9, 133.7, 135.6, 144.3, 166.9, 177.3, (100 MHz, CDCl3): δ = 14.2, 19.4, 22.8, 28.8, 29.2, 31.1, 31.8,
1
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33.2, 37.8, 68.1, 117.8, 124.7, 124.9, 125.8, 126.6, 127.1, 127.2, 1H), 7.40 (d, J = 5.1 Hz, 1H), 7.43–7.51 (m, 2H), 7.72 (d, J = 7.4
127.8, 128.1, 134.0, 135.2, 176.7, 194.9; HRMS (ESI/[M + H]+) Hz, 1H), 7.81 (d, J = 7.4 Hz, 1H), 7.88 (s, 1H); 13C NMR
calcd for C23H27O2, 335.20111, found 335.19919.
(100 MHz, CDCl3): δ = 19.4, 28.8, 37.7, 69.0, 117.7, 125.7,
Compound 4l. Compound 4l was prepared by the general 125.9, 126.3, 126.4, 126.7, 127.2, 127.3, 127.6, 127.7, 128.5,
procedure above. After purification by column chromatography 128.8, 129.8, 133.6, 140.9, 177.3, 194.8.
(PE–EtOAc 7 : 3) the desired compound was isolated as a
Compound 6. Compound 6 was prepared by the general
light yellow solid with mp 152–154 °C. IR (KBr) νmax: 492, procedure above, in which 3 is replaced by 5. After purification
526, 582, 617, 731, 768, 821, 907, 986, 1032, 1075, 1186, 1336, by column chromatography (PE–EtOAc 7 : 3) the desired com-
1398, 1453, 1500, 1579, 1601, 1654, 2246, 2864, 2923, pound was isolated as a brownish orange viscous fluid. IR
1
3025 cm−1; H NMR (500 MHz, CDCl3): δ = 2.11 (quint, J = 6.0 (Neat) νmax: 545, 594, 624, 691, 758, 953, 983, 1036, 1073, 1122,
Hz, 2H), 2.43 (s, 3H), 2.50 (s, 3H), 2.64 (t, J = 6.0 Hz, 2H), 2.68 1184, 1287, 1334, 1395, 1453, 1493, 1580, 1656, 1725, 2873,
1
(t, J = 6.0 Hz, 2H), 5.12 (s, 2H), 7.22 (d, J = 7.5 Hz, 2H), 2959, 3058 cm−1; H NMR (400 MHz, CDCl3): δ = 2.11 (quint, J
7.24–7.32 (m, 3H), 7.58 (s, 1H), 7.63 (d, J = 8.8 Hz, 1H), 7.66 (s, = 7.3, 6.5 Hz, 2H), 2.54–2.79 (m, 4H), 5.00 (d, J = 12.9 Hz, 1H),
1H); 13C NMR (125 MHz, CDCl3): δ = 19.4, 21.4, 21.7, 28.8, 5.16 (d, J = 12.9 Hz, 1H), 7.04 (d, J = 7.2 Hz, 2H), 7.13–7.21 (m,
37.7, 69.3, 117.9, 125.0, 125.4, 125.6, 126.9, 127.3, 127.7, 128.3, 3H), 7.35–7.56 (m, 5H), 7.66 (d, J = 6.8 Hz, 1H), 7.76–7.89 (m,
129.2, 129.3, 134.1, 135.8, 136.7, 136.9, 137.4, 177.2, 195.1; 3H); 13C NMR (100 MHz, CDCl3): δ = 19.4, 28.8, 37.8, 69.6,
HRMS (ESI/[M + H]+) calcd for C25H23O2, 355.1698, found 88.7, 93.5, 117.9, 122.9, 123.5, 125.0, 125.7, 126.2, 127.2, 127.4,
355.16815.
127.5, 128.0, 128.4, 128.4, 128.6, 128.6, 129.5, 130.1, 131.5,
Compound 4m. Compound 4m was prepared by the general 131.9, 133.7, 135.3, 142.2, 177.4, 194.6; HRMS (ESI/[M + H]+)
procedure above. After purification by column chromatography calcd for C31H23O2, 427.1698, found 427.1679.
(PE–EtOAc 7 : 3) the desired compound was isolated as a yellow
Compound 4a′. Light yellow solid. IR (KBr) νmax: 692, 730,
solid with mp 161–163 °C. IR (KBr) νmax: 491, 527, 571, 610, 758, 919, 992, 1020, 1069, 1121, 1188, 1213, 1246, 1370, 1398,
730, 818, 894, 986, 1031, 1074, 1189, 1261, 1332, 1397, 1452, 1444, 1455, 1493, 1578, 1658, 1742, 2844, 2871, 2948, 3022,
1
1
1490, 1513, 1578, 1618, 1652, 1739, 2244, 2923 cm−1; H NMR 3058 cm−1; H NMR (500 MHz, CDCl3): δ = 1.73 (quint, J = 6.3
(400 MHz, CDCl3): δ = 2.11 (quint, J = 5.7 Hz, 2H), 2.43 (s, 3H), Hz, 2H), 2.25–2.32 (m, 2H), 2.44 (t, J = 6.3 Hz, 2H), 4.83 (d, J =
2.59–2.73 (m, 4H), 5.11 (s, 2H), 7.20 (d, J = 7.5 Hz, 2H), 7.27 (d, 4.1 Hz, 2H), 5.46 (t, J = 4.1 Hz, 1H), 7.22–7.25 (m, 1H),
J = 7.5 Hz, 2H), 7.37 (d, J = 9.2 Hz, 1H), 7.63 (s, 1H), 7.68 (d, J = 7.27–7.29 (m, 1H), 7.30–7.35 (m, 4H), 7.38–7.42 (m, 2H), 7.47
9.2 Hz, 1H), 7.78 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 19.3, (dd, J = 7.5, 1.5 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 19.9,
21.3, 28.8, 37.7, 69.2, 117.5, 125.4, 125.5, 126.1, 126.8, 126.8, 28.6, 37.0, 66.4, 89.3, 92.8, 114.8, 115.7, 121.0, 123.8, 127.0,
127.9, 129.0, 129.1, 129.4, 132.0, 134.5, 136.3, 137.8, 137.9, 128.2, 128.2, 128.5, 128.5, 131.5, 131.8, 135.2, 143.2, 173.5,
177.6, 194.9; HRMS (ESI/[M + H]+) calcd for C24H20ClO2, 194.0; MS (ESI+): m/z = 327 [M + H+].
375.11518, found 375.1136.
Compound 4n. Compound 4n was prepared by the general
procedure above. After purification by column chromatography
(PE–EtOAc 7 : 3) the desired compound was isolated as a
Acknowledgements
light yellow solid with mp 189–191 °C. IR (KBr) νmax: 437,
One of the authors, M.S., thanks the Council of Scientific and
484, 526, 570, 611, 647, 733, 756, 828, 912, 955, 987, 1032,
Industrial Research, New Delhi, India for
fellowship.
a research
1075, 1110, 1147, 1184, 1222, 1262, 1343, 1385, 1402, 1453,
1492, 1524, 1584, 1651, 2250, 2867, 2949 cm−1 1H NMR
;
(400 MHz, CDCl3): δ = 2.15 (quint, J = 6.2 Hz, 2H), 2.45 (s, 3H),
2.68–2.72 (m, 4H), 5.17 (s, 2H), 7.22 (d, J = 7.3 Hz, 2H), 7.31 (d,
J = 7.3 Hz, 2H), 7.86 (d, J = 9.4 Hz, 1H), 7.90 (s, 1H), 8.16 (d, J =
9.4 Hz, 1H), 8.75 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 19.2,
21.4, 28.9, 37.6, 69.1, 117.2, 118.3, 124.8, 126.0, 129.1, 129.3,
129.6, 129.6, 130.5, 130.5, 132.5, 135.5, 138.3, 139.0, 145.5,
178.2, 194.8; HRMS (ESI/[M + H]+) calcd for C24H20NO4,
386.13923, found 386.13705.
Notes and references
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