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

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Synthesis of tetracyclic chromenones via platinum(II) chloride catalysed cascade cyclization of enediyne–enones† 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

DOI: 10.1039/c3ob41911h

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.

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reported, which proceeds through two consecutive highly regioselective 6-endo–dig cyclizations in a

Introduction

Results and discussion

Platinum catalysed cascade reaction has proven to be a versatile strategy in organic synthesis due to the formation of structurally complex frameworks from suitable scaffolds.1 Platinum is reported to initiate the cascade reaction by electrophilic activation 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 enediynes is well documented there is scope for catalytic transformation 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 multiple bonds and rearrangement occurred.6 By the cascade cyclization 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 coupling 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-( prop2-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 halopalladation 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: [email protected]; 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

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Scheme 1

Concept of enediyne–enone cyclization.

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Organic & Biomolecular Chemistry

Scheme 2

Table 1

Paper

Synthesis of required precursors.

Optimization of reaction conditions for 4a

Catalyst, additives Entry (equiv.)

Solvent

Conditions

Yielda of 4a/4a′ (%)

1 2 3 4 5 6 7 8 9 10 11 12 13

THF THF THF CH3CN Toluene CH3CN CH3CN Toluene Toluene Toluene Toluene Toluene Toluene

80 °C, 1 h 80 °C, 1 h 80 °C, 2 h 80 °C, 6 h 110 °C, 2 h 80 °C, 8 h 80 °C, 24 h 110 °C, 3 h 110 °C, 3 h 110 °C, 3 h 110 °C, 24 h 110 °C, 24 h 110 °C, 4 h

—b —b —c —c —c 52 (4a′/4a = 1 : 2) 43 (4a) 86 (4a) 88 (4a) 72 (4a) — 30 (4a′)d 32 (4a)

PdCl2 (0.1), CuCl2 (2) PdCl2 (0.1), CuBr2 (2) CuBr2 (2) FeCl3 (10) 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)

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.

mixture (Table 1, entries 1 and 2). When the reaction was performed 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 catalysed 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 dialkyne 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


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 cyclohexane1,3-dione (Table 2, entry 1) gave a better yield compared to the starting material derived from 5,5-dimethylcyclohexane-1,3dione (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 difficulties 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 techniques (Fig. 1). 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 chromenone 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

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Table 2

Organic & Biomolecular Chemistry Substrate scope of the reactiona

Entry

3 (R1; R2; R3)

Entry

3 (R1; R2; R3)

1

3a (H; Ph; H)

9

3i (H; 1-naphthyl; H)

2

3b (Me; Ph; H)

10

3j (H; C4H9; H)

3

3c (H; p-MeC6H4; H)

11

3k (H; C6H13; H)

4

3d (H; m-MeC6H4; H)

12

3l (H; p-MeC6H4; Me)

5

3e (H; p-MeOC6H4; H)

13

3m (H; p-MeC6H4; Cl)

6

3f (H; p-BrC6H4; H)

14

3n (H; p-MeC6H4; NO2)

7

3g (H; p-CO2MeC6H4; H)

15

3o (H; TMS; H)

8

3h (H; p-COMeC6H4; H)

16

3p (H; 2-thienyl; H)

a

Product (time, yield%)

Product (time, yield%)

Isolated yield. b Complex reaction mixture.

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Fig. 1

Paper

ORTEP diagram of compound 4p.

Scheme 4 reaction.

Proposed

mechanism

for

enediyne–enone

cascade

Experimental section General methods

Scheme 3

An attempt to cyclize triyne system.

cyclized product 4a′ and then finally to the dialkyne cyclized product 4a, which supports the proposed mechanism of enediyne–enone cascade reaction.

Purification of crude compounds was done by column chromatography 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 reported in ppm downfield from TMS (δ = 0) for 1H 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 General procedure for synthesis of compounds 1a–1o

Conclusions In conclusion, a PtCl2 catalysed facile cascade enediyne–enone cyclization pathway for the synthesis of tetracyclic chromenone was achieved. This method involves easy preparation of starting materials, high atom economy, low catalyst loading, and tolerates a wide scope of substrates to afford good to excellent yield, which allows the construction of tetracyclic chromenones in a single step through two consecutive highly regioselective 6-endo-dig cyclizations. Further evidence for the reaction mechanism was confirmed by the isolation of intermediate 4a′. Further transformations of this diyne–enone scaffold under iodine are underway.


To a solution of p-TsOH·H2O (3 equiv.) in MeCN was added 2-(2-phenylethynyl)benzenamine (1 equiv.). The resulting suspension of amine salt was cooled to 10–15 °C and to this was added gradually a solution of NaNO2 (2 equiv.) and KI (2.5 equiv.) in H2O. The reaction mixture was stirred for 10 min then allowed to come to 20 °C and stirred for 2 h. To the reaction mixture was then added saturated NaHCO3 (until pH = 9–10) and saturated Na2S2O3 solution. Then it was extracted with EtOAc and dried over Na2SO4. The crude product was purified by column chromatography ( pet. ether– EtOAc, 9 : 1) to afford the product. The products 1a–1d, 1f, 1h, 1j, and 1k, were spectroscopically identical to previously 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 procedure above. After purification by column chromatography (PE–EtOAc 9 : 1) the desired compound was isolated as a brownish orange viscous fluid. IR (Neat) νmax: 517, 645, 691, 758, 767, 817, 854, 964, 1016, 1024, 1109, 1177, 1278, 1307, 1359, 1406, 1431, 1457, 1509, 1553, 1577, 1603, 1715, 1727, 1811, 1927, 2219, 2948 cm−1; 1H NMR (500 MHz, CDCl3): δ = 3.93 (s, 3H), 7.04 (td, J = 7.7, 1.6 Hz, 1H), 7.34 (td, J = 7.7, 1.1 Hz, 1H), 7.54 (dd, J = 7.7, 1.6 Hz, 1H), 7.65 (d, J = 8.4 Hz, 2H), 7.88 (dd, J = 8.4, 1.2 Hz, 1H), 8.03 (d, J = 8.4 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ = 52.4, 92.2, 94.5, 101.4, 127.7, 128.0, 129.7, 130.0, 131.6, 132.7, 138.9, 166.6. Compound 1i. Compound 1i was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 9 : 1) the desired compound was isolated as a brownish orange viscous fluid. IR (Neat) νmax: 565, 644, 751, 772, 798, 863, 1014, 1396, 1429, 1455, 1468, 1507, 1585, 2209, 3055 cm−1; 1H NMR (500 MHz, CDCl3): δ = 7.04 (td, J = 7.7, 1.6 Hz, 1H), 7.37 (t, J = 7.4 Hz, 1H), 7.45–7.50 (m, 1H), 7.54 (t, J = 7.4 Hz, 1H), 7.61 (t, J = 7.4 Hz, 1H), 7.65 (dd, J = 7.7, 1.6 Hz, 1H), 7.84 (d, J = 7.1 Hz, 1H), 7.87 (dd, J = 8.2, 2.7 Hz, 2H), 7.92 (d, J = 8.1 Hz, 1H), 8.64 (d, J = 8.1 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 139.0, 133.4, 133.3, 133.0, 130.9, 130.2, 129.6, 129.3, 128.4, 128.0, 127.0, 126.8, 126.7, 125.4, 120.7, 100.9, 96.2, 91.5. Compound 1l. Compound 1l was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 9 : 1) the desired compound was isolated as a brownish orange viscous fluid. IR (Neat) νmax: 448, 523, 574, 585, 746, 814, 880, 1016, 1116, 1179, 1205, 1389, 1453, 1510, 1585, 1902, 2210, 2919, 3028 cm−1; 1H NMR (500 MHz, CDCl3): δ = 2.29 (s, 3H), 2.37 (s, 3H), 6.82 (dd, J = 8.2, 2.1 Hz, 1H), 7.17 (d, J = 7.8 Hz, 2H), 7.35 (d, J = 2.1 Hz, 1H), 7.48 (d, J = 8.1 Hz, 2H), 7.72 (d, J = 8.1 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 21.0, 21.7, 91.2, 93.0, 97.2, 120.0, 129.3, 129.7, 130.6, 131.6, 133.2, 138.0, 138.5, 138.9. Compound 1m. Compound 1m was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 9 : 1) the desired compound was isolated as a white solid. IR (KBr) νmax: 507, 524, 560, 577, 654, 680, 710, 811, 878, 944, 1016, 1091, 1116, 1151, 1180, 1210, 1243, 1300, 1379, 1448, 1540, 1570, 1591, 1645, 1752, 1791, 1902, 2186, 2218, 2866, 2993, 3029, 3054 cm−1; 1H NMR (500 MHz, CDCl3): δ = 2.38 (s, 3H), 6.98 (dd, J = 8.5, 2.5 Hz, 1H), 7.18 (d, J = 8.0 Hz, 2H), 7.46–7.51 (m, 3H), 7.76 (d, J = 8.5 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 21.8, 90.1, 94.7, 98.4, 119.4, 129.4, 129.6, 131.7, 131.7, 132.1, 134.2, 139.4, 139.8. Compound 1n. Compound 1n was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 9 : 1) the desired compound was isolated as a yellow solid. IR (KBr) νmax: 488, 522, 581, 670, 704, 734, 812, 831, 925, 1017, 1123, 1149, 1240, 1278, 1343, 1519, 1557, 1603, 1894, 2208, 2231, 2850, 2916, 3023, 3096, 3128 cm−1; 1H NMR (500 MHz, CDCl3): δ = 2.39 (s, 3H), 7.20 (d, J = 7.6 Hz, 2H), 7.50 (d, J = 7.6 Hz, 2H), 7.79 (d, J = 8.7 Hz, 1H), 8.04 (d, J = 8.7 Hz, 1H), 8.29 (s, 1H); 13C NMR (125 MHz, CDCl3): δ = 21.8, 89.5,

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96.2, 109.4, 118.9, 123.1, 126.4, 129.4, 131.9, 132.0, 139.9, 140.0, 148.0. General procedure for synthesis of compounds 3a–3o and 5 Iodo compound 1 (1.0 equiv.), PdCl2(PPh3)2 (0.03 equiv.) and CuI (0.04 equiv.) were suspended in triethylamine under a nitrogen atmosphere. The reaction mixture was stirred at 30 °C for 30 minutes. After the addition of 2 (1.5 equiv.) the suspension was stirred for 3 hours at 30 °C. The reaction mixture was filtered through a celite pad and purified by column chromatography furnished the desired products. Compound 3a. Compound 3a was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 6 : 4) the desired compound was isolated as a brownish orange viscous fluid. IR (Neat) νmax: 493, 527, 613, 691, 735, 758, 824, 861, 913, 955, 1000, 1135, 1179, 1213, 1241, 1328, 1358, 1385, 1428, 1443, 1475, 1494, 1607, 1652, 2217, 2949, 3061 cm−1; 1H NMR (500 MHz, CDCl3): δ = 1.95 (quint, J = 6.3 Hz, 2H), 2.33 (t, J = 6.3 Hz, 2H), 2.43 (t, J = 6.3 Hz, 2H), 4.84 (s, 2H), 5.54 (s, 1H), 7.26–7.38 (m, 5H), 7.48 (dd, J = 7.6, 1.5 Hz, 1H), 7.52–7.58 (m, 3H); 13C NMR (125 MHz, CDCl3): δ = 21.2, 28.9, 36.7, 57.1, 85.8, 87.0, 87.8, 93.7, 103.7, 123.1, 124.3, 126.1, 128.1, 128.5, 128.7, 128.8, 131.8, 131.9, 132.2, 176.7, 199.7. Compound 3b. Compound 3b was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 6 : 4) the desired compound was isolated as a brownish orange viscous fluid. IR (Neat) νmax: 611, 689, 758, 824, 983, 1010, 1078, 1142, 1160, 1198, 1211, 1263, 1320, 1354, 1378, 1440, 1471, 1493, 1609, 1655, 1729, 2870, 2928, 2957, 3060 cm−1; 1H NMR (500 MHz, CDCl3): δ = 1.05 (s, 6H), 2.20 (s, 2H), 2.29 (s, 2H), 4.84 (s, 2H), 5.52 (s, 1H), 7.26–7.34 (m, 2H), 7.34–7.38 (m, 3H), 7.48 (dd, J = 7.6, 1.5 Hz, 1H), 7.51–7.60 (m, 3H); 13C NMR (125 MHz, CDCl3) δ 28.3, 32.7, 42.7, 50.8, 57.2, 85.8, 87.0, 87.9, 93.7, 102.5, 123.2, 124.4, 126.1, 128.1, 128.5, 128.7, 128.8, 131.9, 132.2, 175.0, 199.5. Compound 3c. Compound 3c was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 6 : 4) the desired compound was isolated as a brownish orange solid with mp 93–95 °C. IR (KBr) νmax: 527, 759, 817, 954, 999, 1135, 1179, 1213, 1241, 1327, 1357, 1384, 1445, 1479, 1511, 1606, 1654, 2215, 2870, 2947, 3029, 3059 cm−1; 1H NMR (500 MHz, CDCl3): δ = 1.97 (quint, J = 6.5 Hz, 2H), 2.34 (t, J = 6.5 Hz, 2H), 2.38 (s, 3H), 2.44 (t, J = 6.5 Hz, 2H), 4.84 (s, 2H), 5.54 (s, 1H), 7.17 (d, J = 8.0 Hz, 2H), 7.24–7.30 (m, 1H), 7.32 (td, J = 7.5, 1.3 Hz, 1H), 7.39–7.50 (m, 3H), 7.52 (d, J = 7.7 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 21.2, 21.7, 28.9, 36.8, 57.2, 85.7, 87.1, 87.3, 94.0, 103.7, 120.1, 124.3, 126.4, 127.9, 128.8, 129.3, 131.8, 131.9, 132.3, 138.9, 176.7, 199.7; MS (ESI+): m/z = 341 [M + H]+. Compound 3d. Compound 3d was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 6 : 4) the desired compound was isolated as a brownish orange viscous fluid. IR (Neat) νmax: 494, 527, 690, 759, 785, 824, 861, 910, 954, 1000, 1038, 1099, 1135, 1179, 1213, 1241, 1327, 1357, 1385, 1428, 1444, 1489, 1607, 1654,


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2207, 2242, 2949, 3060 cm−1; 1H NMR (500 MHz, CDCl3): δ = 1.95 (quint, J = 6.3 Hz, 2H), 2.29–2.34 (m, 2H), 2.36 (s, 3H), 2.42 (t, J = 6.3 Hz, 2H), 4.84 (s, 2H), 5.53 (s, 1H), 7.16 (d, J = 7.9 Hz, 1H), 7.21–7.40 (m, 5H), 7.47 (dd, J = 7.6, 1.4 Hz, 1H), 7.52 (dd, J = 7.6, 1.4 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 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, 132.3, 138.1, 176.7, 199.6; MS (ESI+): m/z = 341 [M + H]+. Compound 3e. Compound 3e was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 6 : 4) the desired compound was isolated as a brownish viscous fluid. IR (Neat) νmax: 535, 759, 832, 954, 1000, 1028, 1136, 1179, 1249, 1288, 1358, 1327, 1385, 1444, 1511, 1606, 1652, 2214, 2952 cm−1; 1H NMR (400 MHz, CDCl3): δ = 1.92–2.01 (m, 2H), 2.34 (t, J = 6.4 Hz, 2H), 2.44 (t, J = 6.1 Hz, 2H), 3.83 (s, 3H), 4.84 (s, 2H), 5.54 (s, 1H), 6.89 (d, J = 7.6 Hz, 2H), 7.23–7.28 (t, J = 7.6 Hz, 1H), 7.31 (t, J = 7.6 Hz, 1H), 7.49 (m, 4H); 13C NMR (100 MHz, CDCl3): δ = 21.2, 28.9, 36.6, 55.4, 57.1, 85.6, 86.6, 87.1, 93.9, 103.67, 114.1, 115.2, 124.1, 126.5, 127.7, 128.8, 131.7, 132.2, 133.3, 159.9, 176.8, 199.7; MS (ESI+): m/z = 357 [M + H]+. Compound 3f. Compound 3f was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 6 : 4) the desired compound was isolated as a brownish orange viscous fluid. IR (Neat) νmax: 495, 523, 612, 759, 823, 861, 911, 954, 1009, 1038, 1069, 1096, 1135, 1179, 1213, 1241, 1327, 1357, 1392, 1434, 1490, 1606, 1653, 2221, 2948, 3063 cm−1; 1H NMR (500 MHz, CDCl3): δ = 1.97 (quint, J = 6.5 Hz, 2H), 2.34 (t, J = 6.5 Hz, 2H), 2.43 (t, J = 6.3 Hz, 2H), 4.84 (s, 2H), 5.54 (s, 1H), 7.26–7.36 (m, 2H), 7.42 (d, J = 7.7 Hz, 2H), 7.48–7.53 (m, 4H); 13C NMR (125 MHz, CDCl3): δ = 21.2, 28.9, 36.8, 57.1, 85.9, 86.9, 89.0, 92.6, 103.8, 122.1, 122.9, 124.4, 125.8, 128.4, 128.9, 131.8, 131.9, 132.4, 133.3, 176.6, 199.6; MS (ESI+): m/z = 405 [M + H]+. Compound 3g. Compound 3g was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 6 : 4) the desired compound was isolated as a brown solid with mp 135–137 °C. IR (KBr) νmax: 695, 768, 821, 859, 956, 998, 1107, 1136, 1178, 1213, 1276, 1358, 1435, 1606, 1656, 1722, 2951 cm−1; 1H NMR (500 MHz, CDCl3): δ = 1.97 (quint, J = 6.3 Hz, 2H), 2.30–2.39 (m, 2H), 2.44 (t, J = 6.3 Hz, 2H), 3.94 (s, 3H), 4.85 (s, 2H), 5.55 (s, 1H), 7.29–7.38 (m, 2H), 7.49–7.51 (m, 1H), 7.53–7.57 (m, 1H), 7.58–7.65 (m, 2H), 8.01–8.07 (m, 2H); 13C NMR (125 MHz, CDCl3): δ = 21.2, 28.9, 36.8, 52.4, 57.1, 86.1, 86.8, 90.8, 92.8, 103.8, 124.6, 125.5, 127.9, 128.6, 128.9, 129.6, 129.8, 131.8, 132.1, 132.4, 166.6, 176.6, 199.6; MS (ESI+): m/z = 385 [M + H]+. Compound 3h. Compound 3h was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 6 : 4) the desired compound was isolated as a brown solid. IR (KBr) νmax: 459, 592, 612, 638, 760, 829, 861, 912, 957, 1000, 1038, 1136, 1180, 1214, 1264, 1328, 1359, 1403, 1478, 1556, 1606, 1651, 1658, 1682, 2219, 2950, 3065 cm−1; 1H NMR (400 MHz, CDCl3): δ = 1.91–2.02 (m, 2H), 2.34 (t, J = 6.5 Hz, 2H), 2.44 (t, J = 6.2 Hz, 2H), 2.62 (s, 3H), 4.85 (s, 2H), 5.55 (s, 1H), 7.27–7.38 (m, 2H), 7.50 (d, J = 7.3 Hz, 1H), 7.55


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(d, J = 7.2 Hz, 1H), 7.64 (d, J = 8.1 Hz, 2H), 7.95 (d, J = 8.1 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ = 21.1, 26.7, 28.9, 36.7, 57.0, 86.1, 86.7, 91.0, 92.7, 103.7, 124.5, 125.4, 127.9, 128.3, 128.6, 128.9, 131.9, 132.0, 132.4, 136.4, 176.6, 197.4, 199.5; MS (ESI+): m/z = 369 [M + H]+. Compound 3i. Compound 3i was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 6 : 4) the desired compound was isolated as a brownish orange viscous fluid. IR (Neat) νmax: 567, 759, 773, 801, 823, 861, 954, 999, 1135, 1178, 1213, 1240, 1327, 1357, 1385, 1444, 1482, 1507, 1606, 1652, 2212, 2238, 2875, 2948, 3058 cm−1; 1H NMR (500 MHz, CDCl3): δ = 1.89 (quint, J = 6.3 Hz, 2H), 2.28–2.33 (m, 4H), 4.85 (s, 2H), 5.52 (s, 1H), 7.31 (t, J = 7.6 Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H), 7.47 (t, J = 7.6 Hz, 1H), 7.51–7.58 (m, 3H), 7.63 (d, J = 7.6 Hz, 1H), 7.79 (d, J = 7.6 Hz, 1H), 7.83–7.90 (m, 2H), 8.58 (d, J = 8.0 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 21.2, 28.8, 36.8, 57.1, 85.9, 87.4, 91.9, 92.7, 103.7, 120.8, 124.3, 125.4, 126.4, 126.4, 126.6, 126.8, 128.2, 128.5, 129.0, 129.2, 130.8, 132.0, 132.5, 133.3, 133.4, 176.7, 199.6; MS (ESI+): m/z = 377 [M + H]+. Compound 3j. Compound 3j was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 6 : 4) the desired compound was isolated as a brownish orange viscous fluid. IR (Neat) νmax: 528, 613, 760, 825, 861, 954, 1000, 1057, 1135, 1176, 1213, 1240, 1327, 1356, 1384, 1444, 1480, 1607, 1657, 2232, 2870, 2955, 3064 cm−1; 1 H NMR (400 MHz, CDCl3): δ = 0.95 (t, J = 7.2 Hz, 3H), 1.47–1.65 (m, 4H), 1.98–2.06 m, 2H), 2.37 (t, J = 6.6 Hz, 2H), 2.48 (q, J = 6.3 Hz, 4H), 4.81 (s, 2H), 5.54 (s, 1H), 7.17–7.31 (m, 2H), 7.39–7.44 (m, 2H); 13C NMR (100 MHz, CDCl3): δ = 13.8, 19.4, 21.3, 22.0, 29.0, 30.8, 36.8, 57.2, 79.1, 85.0, 87.3, 95.3, 103.7, 124.1, 127.1, 127.3, 128.8, 132.0, 132.4, 176.7, 199.6; MS (ESI+): m/z = 307 [M + H]+. Compound 3k. Compound 3k was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 6 : 4) the desired compound was isolated as a brownish orange viscous fluid. IR (Neat) νmax: 759, 821, 861, 954, 1001, 1135, 1177, 1212, 1239, 1255, 1327, 1356, 1383, 1442, 1456, 1480, 1608, 1659, 2228, 2860, 2930, 3064 cm−1; 1 H NMR (500 MHz, CDCl3): δ = 0.84–0.95 (m, 3H), 1.30–1.33 (m, 4H), 1.46–1.52 (m, 2H), 1.56–1.67 (m, 2H), 2.01 (quint, J = 6.5 Hz, 2H), 2.35–2.40 (m, 2H), 2.44–2.50 (m, 4H), 4.81 (s, 2H), 5.54 (s, 1H), 7.21 (td, J = 7.6, 1.5 Hz, 1H), 7.24–7.29 (m, 1H), 7.40 (dd, J = 7.6, 1.5 Hz, 1H), 7.43 (dd, J = 7.6, 1.5 Hz, 1H); 13 C NMR (125 MHz, CDCl3): δ = 14.3, 19.7, 21.3, 22.7, 28.7, 28.8, 29.0, 31.5, 36.9, 57.2, 79.1, 85.0, 87.3, 95.4, 103.7, 124.1, 127.1, 127.3, 128.8, 132.1, 132.4, 176.7, 199.7; MS (ESI+): m/z = 335 [M + H]+. Compound 3l. Compound 3l was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 6 : 4) the desired compound was isolated as a light yellow semi solid. IR (Neat) νmax: 497, 526, 579, 600, 761, 819, 867, 959, 982, 1140, 1181, 1218, 1330, 1361, 1453, 1488, 1511, 1602, 1651, 1910, 2210, 2848, 2917, 2953, 3029 cm−1; 1H NMR (500 MHz, CDCl3): δ = 1.97 (quint, J = 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, J = 7.8 Hz, 2H), 7.33–7.39 (m, 2H), 7.44 (d, J = 8.1 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ = 21.2, 21.4, 21.7, 28.9, 36.8, 57.3, 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 = 355 [M + H]+. Compound 3m. Compound 3m was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 6 : 4) the desired compound was isolated as a light yellow solid. IR (KBr) νmax: 526, 817, 889, 956, 980, 1110, 1138, 1181, 1218, 1329, 1350, 1453, 1475, 1508, 1604, 1650, 2216 cm−1; 1H NMR (400 MHz, CDCl3): δ = 1.97 (quint, J = 6.1 Hz, 2H), 2.25–2.41 (m, 5H), 2.44 (t, J = 6.1 Hz, 2H), 4.82 (s, 2H), 5.52 (s, 1H), 7.18 (d, J = 7.3 Hz, 2H), 7.25 (t, J = 7.3 Hz, 1H), 7.39 (d, J = 8.3 Hz, 1H), 7.44 (d, J = 7.7 Hz, 2H), 7.50 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 21.2, 21.7, 28.9, 36.8, 57.0, 86.1, 86.2, 86.6, 95.2, 103.7, 119.6, 122.7, 127.9, 128.2, 129.3, 131.6, 131.8, 133.3, 134.8, 139.3, 176.6, 199.6; MS (ESI+): m/z = 375 [M + H]+. Compound 3n. Compound 3n was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 6 : 4) the desired compound was isolated as a light yellow solid with mp 119–121 °C. IR (KBr) νmax: 495, 529, 604, 723, 741, 763, 790, 865, 903, 959, 984, 996, 1077, 1138, 1182, 1219, 1343, 1363, 1452, 1478, 1524, 1572, 1603, 1648, 1739, 1913, 2204, 2867, 2934 cm−1; 1H NMR (400 MHz, CDCl3): δ = 1.92–2.02 (m, 2H), 2.32–2.37 (m, 2H), 2.40 (s, 3H), 2.45 (t, J = 5.4 Hz, 2H), 4.87 (s, 2H), 5.53 (s, 1H), 7.20 (d, J = 7.1 Hz, 2H), 7.46 (d, J = 7.1 Hz, 2H), 7.61 (d, J = 8.2 Hz, 1H), 8.10 (d, J = 8.2 Hz, 1H), 8.36 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 21.2, 21.8, 28.8, 36.8, 56.8, 85.4, 85.5, 90.7, 96.6, 103.8, 119.1, 122.4, 126.6, 127.9, 129.4, 130.3, 131.9, 133.0, 139.9, 147.3, 176.5, 199.6; MS (ESI+): m/z = 386 [M + H]+. Compound 3p. For experimental procedure see ESI.† IR (Neat) νmax: 443, 498, 528, 612, 705, 759, 825, 853, 911, 954, 1000, 1034, 1058, 1094, 1135, 1179, 1213, 1241, 1255, 1327, 1357, 1385, 1421, 1446, 1478, 1520, 1606, 1651, 1718, 1959, 2204, 2871, 2948, 3072 cm−1; 1H NMR (400 MHz, CDCl3): δ = 1.97 (quint, J = 6.3 Hz, 2H), 2.30–2.38 (m, 2H), 2.45 (t, J = 6.3 Hz, 2H), 4.85 (s, 2H), 5.54 (s, 1H), 7.03 (dd, J = 5.1, 3.7 Hz, 1H), 7.25–7.36 (m, 4H), 7.46–7.52 (m, 2H); 13C NMR (100 MHz, CDCl3): δ = 21.2, 28.9, 36.8, 57.1, 86.0, 86.8, 87.0, 91.6, 103.7, 123.1, 124.2, 125.9, 127.3, 127.9, 128.2, 128.9, 131.6, 132.3, 132.4, 176.8, 199.7; MS (ESI+): m/z = 355 [M + Na+]. Compound 5. Compound 5 was prepared by the general procedure above; for further details see ESI.† After purification by column chromatography (PE–EtOAc 6 : 4) the desired compound was isolated as a brownish orange viscous fluid. IR (Neat) νmax: 494, 585, 611, 690, 756, 823, 860, 954, 999, 1135, 1178, 1212, 1240, 1327, 1356, 1384, 1428, 1446, 1494, 1606, 1654, 2216, 2948, 3056 cm−1; 1H NMR (400 MHz, CDCl3): δ = 1.91 (quint, J = 6.1 Hz, 2H), 2.27–2.35 (m, 4H), 4.60 (s, 2H), 5.38 (s, 1H), 7.28–7.34 (m, 7H), 7.50 (d, J = 7.0 Hz, 1H), 7.55–7.61 (m, 5H); 13C NMR (100 MHz, CDCl3): δ = 21.2, 28.8, 36.8, 57.1, 86.1, 86.8, 88.4, 91.8, 92.4, 93.7, 103.6, 123.3, 124.4,

1324 | Org. Biomol. Chem., 2014, 12, 1318–1327


125.7, 125.9, 126.2, 128.1, 128.3, 128.4, 128.5, 128.6, 128.8, 131.9, 132.0, 132.2, 132.3, 132.4, 176.7, 199.6. General procedure for synthesis of compounds 4a–4p and 6 A solution of 3 (1.0 equiv.) and PtCl2 (0.02 equiv.) in toluene was stirred at 110 °C under nitrogen atmosphere. After completion of the reaction as monitored by TLC, the solvent was evaporated and the residue was purified by column chromatography to afford 4. Compound 4a. Compound 4a was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 7 : 3) the desired compound was isolated as a pale yellow solid with mp 114–116 °C. IR (KBr) νmax: 424, 454, 486, 531, 551, 570, 593, 625, 647, 704, 733, 766, 785, 867, 910, 954, 994, 1036, 1075, 1143, 1185, 1221, 1262, 1284, 1312, 1335, 1395, 1453, 1494, 1581, 1593, 1654, 1728, 1954, 2246, 2855, 2929, 3055 cm−1; 1H NMR (500 MHz, DMSO-d6): δ = 2.02 (quint, J = 6.4 Hz, 2H), 2.57 (t, J = 6.4 Hz, 2H), 2.66 (t, J = 6.0 Hz, 2H), 5.15 (s, 2H), 7.42–7.49 (m, 4H), 7.50–7.54 (m, 3H), 7.69 (d, J = 8.0 Hz, 1H), 7.88 (s, 1H), 7.95 (d, J = 8.0 Hz, 1H); 13 C NMR (125 MHz, DMSO-d6): δ = 18.8, 28.0, 37.2, 68.5, 116.9, 125.0, 125.4, 125.9, 126.2, 126.7, 127.3, 127.8, 128.1, 128.2, 128.6, 129.2, 133.1, 136.3, 138.8, 177.3, 193.8; HRMS (EI/[M]+) calcd for C23H18O2, 326.1307, found 326.1307. Compound 4b. Compound 4b was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 7 : 3) the desired compound was isolated as a pale yellow viscous fluid. IR (Neat) νmax: 545, 576, 635, 703, 732, 765, 888, 908, 1005, 1030, 1066, 1164, 1222, 1260, 1341, 1368, 1397, 1451, 1495, 1584, 1595, 1656, 1709, 2252, 2853, 2870, 2927, 2958, 3056 cm−1; 1H NMR (500 MHz, DMSO-d6): δ = 1.18 (s, 6H), 2.51 (s, 2H), 2.60 (s, 2H), 5.14 (s, 2H), 7.43–7.48 (m, 4H), 7.50–7.54 (m, 3H), 7.64 (d, J = 8.3 Hz, 1H), 7.88 (s, 1H), 7.96 (d, J = 8.3 Hz, 1H); 13C NMR (125 MHz, DMSO-d6): δ = 27.8, 41.1, 50.9, 54.9, 68.5, 116.1, 125.1, 125.2, 126.0, 126.2, 126.8, 127.1, 127.8, 128.1, 128.3, 128.7, 129.2, 133.2, 136.4, 138.8, 175.5, 193.9; HRMS (EI/[M]+) calcd for C25H22O2, 354.1620, found 354.1620. Compound 4c. Compound 4c was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 7 : 3) the desired compound was isolated as a light yellow solid with mp 207–209 °C. IR (KBr) νmax: 545, 576, 635, 703, 732, 765, 888, 908, 1005, 1030, 1066, 1164, 1222, 1260, 1341, 1368, 1397, 1451, 1495, 1584, 1595, 1656, 1709, 2252, 2853, 2870, 2927, 2958, 3056 cm−1; 1H NMR (400 MHz, DMSO-d6): δ = 2.02 (quint, J = 6.3 Hz, 2H), 2.39 (s, 3H), 2.56 (t, J = 6.4 Hz, 2H), 2.66 (t, J = 6.0 Hz, 2H), 5.15 (s, 2H), 7.32 (s, 4H), 7.42 (t, J = 7.2 Hz, 1H), 7.50 (t, J = 7.2 Hz, 1H), 7.67 (d, J = 8.5 Hz, 1H), 7.84 (s, 1H), 7.93 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz, DMSO-d6): δ = 18.8, 20.8, 28.0, 37.2, 68.5, 116.9, 124.9, 125.4, 125.9, 126.3, 126.6, 127.3, 128.0, 128.1, 129.1, 129.2, 133.1, 135.9, 136.3, 137.1, 177.3, 193.8; HRMS (ESI/[M + H]+) calcd for C24H21O2, 341.15415, found 341.15253. Compound 4d. Compound 4d was prepared by the general procedure above. After purification by column chromatography


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(PE–EtOAc 7 : 3) the desired compound was isolated as a yellow solid with mp 153–155 °C. IR (KBr) νmax: 470, 499, 539, 553, 574, 598, 631, 647, 711, 731, 785, 887, 909, 957, 990, 1023, 1037, 1075, 1135, 1180, 1191, 1225, 1262, 1288, 1333, 1394, 1453, 1499, 1585, 1654, 2245, 2863, 2923, 2947, 3051 cm−1; 1H NMR (400 MHz, DMSO-d6): δ = 2.02 (quint, J = 6.2 Hz, 2H), 2.39 (s, 3H), 2.56 (t, J = 6.2 Hz, 2H), 2.64 (t, J = 6.2 Hz, 2H), 5.14 (s, 2H), 7.21 (d, J = 7.5 Hz, 1H), 7.26–7.28 (m, 2H), 7.35–7.42 (m, 1H), 7.44 (d, J = 6.9 Hz, 1H), 7.50 (t, J = 7.5 Hz, 1H), 7.69 (d, J = 8.3 Hz, 1H), 7.85 (s, 1H), 7.94 (d, J = 8.3 Hz, 1H); 13C NMR (100 MHz, DMSO-d6): δ = 18.8, 21.1, 28.0, 37.2, 68.5, 116.9, 125.0, 125.4, 125.9, 126.3, 126.3, 126.7, 127.3, 128.0, 128.1, 128.4, 128.5, 129.8, 133.1, 136.4, 137.9, 138.7, 177.3, 193.8; HRMS (ESI/[M + H]+) calcd for C24H21O2, 341.15415, found 341. 15225. Compound 4e. Compound 4e was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 7 : 3) the desired compound was isolated as a yellow solid. IR (KBr) νmax: 418, 536, 595, 745, 783, 837, 982, 1035, 1072, 1176, 1245, 1286, 1333, 1397, 1452, 1511, 1580, 1645, 2838, 2928 cm−1; 1H NMR (400 MHz, CDCl3): δ = 2.08–2.17 (m, 2H), 2.63–2.71 (m, 4H), 5.14 (s, 2H), 3.88 (s, 3H), 7.00 (d, J = 8.0 Hz, 2H), 7.23–7.30 (m, 2H), 7.41–7.52 (m, 2H), 7.73 (d, J = 5.1 Hz, 2H), 7.82 (d, J = 7.7 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 19.4, 28.8, 37.7, 55.5, 69.3, 114.1, 117.9, 125.3, 125.4, 126.2, 126.7, 127.1, 127.1, 128.4, 128.9, 130.5, 132.1, 133.8, 136.4, 159.3, 177.2, 195.0; HRMS (ESI/[M + H]+) calcd for C24H21O3, 357.1491, found 357. 1487. Compound 4f. Compound 4f was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 7 : 3) the desired compound was isolated as a pale white solid with mp 235–237 °C. IR (KBr) νmax: 426, 491, 531, 550, 592, 619, 658, 708, 744, 760, 782, 817, 836, 887, 870, 907, 948, 981, 1009, 1021, 1034, 1068, 1101, 1135, 1181, 1220, 1260, 1283, 1325, 1400, 1449, 1487, 1586, 1647, 2864, 2916 cm−1; 1H NMR (500 MHz, CDCl3): δ = 2.13 (quint, J = 6.3 Hz, 2H), 2.64–2.71 (m, 4H), 5.10 (s, 2H), 7.21 (d, J = 8.3 Hz, 2H), 7.43–7.54 (m, 2H), 7.59 (d, J = 8.3 Hz, 2H), 7.69–7.78 (m, 2H), 7.82 (d, J = 7.3 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 19.3, 28.8, 37.7, 69.1, 117.8, 122.1, 125.6, 125.8, 126.0, 126.4, 127.2, 127.3, 128.4, 128.9, 130.9, 131.8, 133.7, 135.4, 138.6, 177.3, 195.0; MS (ESI+): m/z = 405 [M + H]+. Compound 4g. Compound 4g was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 7 : 3) the desired compound was isolated as a light yellow solid with mp 187–189 °C. IR (KBr) νmax: 532, 550, 592, 620, 646, 711, 731, 775, 786, 812, 872, 911, 955, 985, 1020, 1036, 1074, 1103, 1143, 1181, 1282, 1311, 1333, 1395, 1435, 1498, 1594, 1654, 1719, 1941, 2247, 2886, 2950, 2996, 3052 cm−1; 1H NMR (500 MHz, CDCl3): δ = 2.13 (quint, J = 6.1 Hz, 2H), 2.65 (t, J = 6.1 Hz, 2H), 2.70 (t, J = 6.1 Hz, 2H), 3.97 (s, 3H), 5.11 (s, 2H), 7.41 (d, J = 8.2 Hz, 2H), 7.45–7.53 (m, 2H), 7.75 (d, J = 2.1 Hz, 1H), 7.77 (s, 1H), 7.80–7.86 (m, 1H), 8.14 (d, J = 8.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ = 19.3, 28.8, 37.7, 52.4, 69.1, 117.8, 125.7, 125.9, 126.5, 127.2, 127.5, 128.5, 129.0, 129.4, 129.4, 129.9, 133.7, 135.6, 144.3, 166.9, 177.3,


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194.9; HRMS (ESI/[M + H]+) calcd for C25H21O4, 385.14398, found 385.14236. Compound 4h. Compound 4h was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 7 : 3) the desired compound was isolated as a brown solid. IR (KBr) νmax: 619, 733, 840, 910, 956, 985, 1036, 1075, 1144, 1186, 1266, 1359, 1396, 1455, 1497, 1602, 1652, 1682, 2247, 2854, 2925 cm−1; 1H NMR (400 MHz, CDCl3): δ = 2.09–2.19 (m, 2H), 2.63–2.77 (m, 7H), 5.12 (s, 2H), 7.45 (d, J = 7.5 Hz, 2H), 7.48–7.55 (m, 2H), 7.76 (d, J = 9.7 Hz, 2H), 7.84 (d, J = 7.5 Hz, 1H), 8.07 (d, J = 7.5 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ = 19.3, 26.8, 28.8, 37.7, 69.1, 117.9, 125.8, 125.9, 126.0, 126.5, 127.3, 127.5, 128.6, 128.7, 129.1, 129.7, 133.7, 135.6, 136.4, 144.6, 177.3, 194.9, 197.9; HRMS (ESI/[M + H]+) calcd for C25H21O3, 369.1491, found 369. 1499. Compound 4i. Compound 4i was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 7 : 3) the desired compound was isolated as a yellow solid with mp 215–217 °C. IR (KBr) νmax: 470, 503, 539, 592, 619, 646, 731, 781, 804, 872, 908, 949, 990, 1036, 1075, 1146, 1177, 1190, 1247, 1284, 1331, 1395, 1451, 1499, 1579, 1654, 2244, 2857, 2931, 2946, 3053 cm−1; 1H NMR (500 MHz, CDCl3): δ = 2.11 (quint, J = 6.3 Hz, 2H), 2.60 (t, J = 6.3 Hz, 2H), 2.70 (q, J = 6.3 Hz, 2H), 4.77 (s, 2H), 7.33–7.44 (m, 2H), 7.46–7.59 (m, 5H), 7.77–7.87 (m, 3H), 7.93 (dd, J = 8.3, 4.0 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ = 19.3, 28.9, 37.8, 69.2, 117.8, 125.1, 125.5, 125.6, 126.0, 126.2, 126.3, 126.7, 127.3, 127.4, 127.4, 127.5, 128.4, 128.5, 128.5, 129.8, 132.4, 133.6, 133.9, 134.5, 137.3, 177.4, 195.0; HRMS (ESI/[M + H]+) calcd for C27H21O2, 377.15415, found 377.15247. Compound 4j. Compound 4j was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 7 : 3) the desired compound was isolated as a yellow solid with mp 115–117 °C. IR (KBr) νmax: 551, 613, 710, 745, 878, 989, 1034, 1075, 1176, 1242, 1339, 1395, 1454, 1503, 1583, 1656, 2868, 2930 cm−1; 1H NMR (400 MHz, CDCl3): δ = 0.95 (t, J = 7.3 Hz, 3H), 1.41 (h, J = 7.5 Hz, 2H), 1.57 (quint, J = 6.8 Hz, 2H), 2.11 ( p, J = 6.3 Hz, 2H), 2.65–2.68 (m, 4H), 2.73 (t, J = 7.8 Hz, 2H), 5.20 (s, 2H), 7.40 (dt, J = 18.4, 7.1 Hz, 2H), 7.59 (s, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.73 (d, J = 7.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 14.1, 19.4, 22.6, 28.8, 32.9, 33.3, 37.8, 68.1, 117.8, 124.7, 124.9, 125.8, 126.6, 127.1, 127.2, 127.8, 128.1, 134.0, 135.1, 176.7, 194.8; MS (ESI+): m/z = 307 [M + H]+. Compound 4k. Compound 4k was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 7 : 3) the desired compound was isolated as a light yellow solid with mp 101–103 °C. IR (KBr) νmax: 512, 550, 614, 642, 710, 745, 763, 785, 844, 883, 934, 962, 989, 1035, 1075, 1107, 1150, 1176, 1190, 1207, 1243, 1261, 1309, 1339, 1396, 1419, 1454, 1503, 1583, 1597, 1658, 1729, 1828, 1923, 1945, 2855, 2951, 2927, 3052, 3290 cm−1; 1H NMR (400 MHz, CDCl3): δ = 0.86–0.91 (m, 3H), 1.28–1.43 (m, 6H), 1.57 (quint, J = 7.6 Hz, 2H), 2.12 ( p, J = 6.3 Hz, 2H), 2.65–2.68 (m, 4H), 2.73 (t, J = 7.6 Hz, 2H), 5.20 (s, 2H), 7.36–7.44 (m, 2H), 7.59 (s, 1H), 7.66 (d, J = 8.2 Hz, 1H), 7.73 (d, J = 8.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 14.2, 19.4, 22.8, 28.8, 29.2, 31.1, 31.8,

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33.2, 37.8, 68.1, 117.8, 124.7, 124.9, 125.8, 126.6, 127.1, 127.2, 127.8, 128.1, 134.0, 135.2, 176.7, 194.9; HRMS (ESI/[M + H]+) calcd for C23H27O2, 335.20111, found 335.19919. Compound 4l. Compound 4l was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 7 : 3) the desired compound was isolated as a light yellow solid with mp 152–154 °C. IR (KBr) νmax: 492, 526, 582, 617, 731, 768, 821, 907, 986, 1032, 1075, 1186, 1336, 1398, 1453, 1500, 1579, 1601, 1654, 2246, 2864, 2923, 3025 cm−1; 1H NMR (500 MHz, CDCl3): δ = 2.11 (quint, J = 6.0 Hz, 2H), 2.43 (s, 3H), 2.50 (s, 3H), 2.64 (t, J = 6.0 Hz, 2H), 2.68 (t, J = 6.0 Hz, 2H), 5.12 (s, 2H), 7.22 (d, J = 7.5 Hz, 2H), 7.24–7.32 (m, 3H), 7.58 (s, 1H), 7.63 (d, J = 8.8 Hz, 1H), 7.66 (s, 1H); 13C NMR (125 MHz, CDCl3): δ = 19.4, 21.4, 21.7, 28.8, 37.7, 69.3, 117.9, 125.0, 125.4, 125.6, 126.9, 127.3, 127.7, 128.3, 129.2, 129.3, 134.1, 135.8, 136.7, 136.9, 137.4, 177.2, 195.1; HRMS (ESI/[M + H]+) calcd for C25H23O2, 355.1698, found 355.16815. Compound 4m. Compound 4m was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 7 : 3) the desired compound was isolated as a yellow solid with mp 161–163 °C. IR (KBr) νmax: 491, 527, 571, 610, 730, 818, 894, 986, 1031, 1074, 1189, 1261, 1332, 1397, 1452, 1490, 1513, 1578, 1618, 1652, 1739, 2244, 2923 cm−1; 1H NMR (400 MHz, CDCl3): δ = 2.11 (quint, J = 5.7 Hz, 2H), 2.43 (s, 3H), 2.59–2.73 (m, 4H), 5.11 (s, 2H), 7.20 (d, J = 7.5 Hz, 2H), 7.27 (d, J = 7.5 Hz, 2H), 7.37 (d, J = 9.2 Hz, 1H), 7.63 (s, 1H), 7.68 (d, J = 9.2 Hz, 1H), 7.78 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 19.3, 21.3, 28.8, 37.7, 69.2, 117.5, 125.4, 125.5, 126.1, 126.8, 126.8, 127.9, 129.0, 129.1, 129.4, 132.0, 134.5, 136.3, 137.8, 137.9, 177.6, 194.9; HRMS (ESI/[M + H]+) calcd for C24H20ClO2, 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 light yellow solid with mp 189–191 °C. IR (KBr) νmax: 437, 484, 526, 570, 611, 647, 733, 756, 828, 912, 955, 987, 1032, 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. Compound 4p. Compound 4p was prepared by the general procedure above. After purification by column chromatography (PE–EtOAc 7 : 3) the desired compound was isolated as a brownish orange viscous fluid. IR (Neat) νmax: 429, 487, 526, 548, 578, 597, 644, 708, 730, 784, 850, 868, 886, 909, 946, 990, 1035, 1075, 1124, 1179, 1191, 1248, 1330, 1395, 1452, 1497, 1578, 1594, 1654, 2243, 2852, 2925, 3073 cm−1; 1H NMR (400 MHz, CDCl3): δ = 2.13 (quint, J = 6.2 Hz, 2H), 2.63–2.70 (m, 4H), 5.28 (s, 2H), 6.97 (d, J = 4.1 Hz, 1H), 7.13–7.15 (m,

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1H), 7.40 (d, J = 5.1 Hz, 1H), 7.43–7.51 (m, 2H), 7.72 (d, J = 7.4 Hz, 1H), 7.81 (d, J = 7.4 Hz, 1H), 7.88 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 19.4, 28.8, 37.7, 69.0, 117.7, 125.7, 125.9, 126.3, 126.4, 126.7, 127.2, 127.3, 127.6, 127.7, 128.5, 128.8, 129.8, 133.6, 140.9, 177.3, 194.8. Compound 6. Compound 6 was prepared by the general procedure above, in which 3 is replaced by 5. After purification by column chromatography (PE–EtOAc 7 : 3) the desired compound was isolated as a brownish orange viscous fluid. IR (Neat) νmax: 545, 594, 624, 691, 758, 953, 983, 1036, 1073, 1122, 1184, 1287, 1334, 1395, 1453, 1493, 1580, 1656, 1725, 2873, 2959, 3058 cm−1; 1H NMR (400 MHz, CDCl3): δ = 2.11 (quint, J = 7.3, 6.5 Hz, 2H), 2.54–2.79 (m, 4H), 5.00 (d, J = 12.9 Hz, 1H), 5.16 (d, J = 12.9 Hz, 1H), 7.04 (d, J = 7.2 Hz, 2H), 7.13–7.21 (m, 3H), 7.35–7.56 (m, 5H), 7.66 (d, J = 6.8 Hz, 1H), 7.76–7.89 (m, 3H); 13C NMR (100 MHz, CDCl3): δ = 19.4, 28.8, 37.8, 69.6, 88.7, 93.5, 117.9, 122.9, 123.5, 125.0, 125.7, 126.2, 127.2, 127.4, 127.5, 128.0, 128.4, 128.4, 128.6, 128.6, 129.5, 130.1, 131.5, 131.9, 133.7, 135.3, 142.2, 177.4, 194.6; HRMS (ESI/[M + H]+) calcd for C31H23O2, 427.1698, found 427.1679. Compound 4a′. Light yellow solid. IR (KBr) νmax: 692, 730, 758, 919, 992, 1020, 1069, 1121, 1188, 1213, 1246, 1370, 1398, 1444, 1455, 1493, 1578, 1658, 1742, 2844, 2871, 2948, 3022, 3058 cm−1; 1H NMR (500 MHz, CDCl3): δ = 1.73 (quint, J = 6.3 Hz, 2H), 2.25–2.32 (m, 2H), 2.44 (t, J = 6.3 Hz, 2H), 4.83 (d, J = 4.1 Hz, 2H), 5.46 (t, J = 4.1 Hz, 1H), 7.22–7.25 (m, 1H), 7.27–7.29 (m, 1H), 7.30–7.35 (m, 4H), 7.38–7.42 (m, 2H), 7.47 (dd, J = 7.5, 1.5 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 19.9, 28.6, 37.0, 66.4, 89.3, 92.8, 114.8, 115.7, 121.0, 123.8, 127.0, 128.2, 128.2, 128.5, 128.5, 131.5, 131.8, 135.2, 143.2, 173.5, 194.0; MS (ESI+): m/z = 327 [M + H+].

Acknowledgements One of the authors, M.S., thanks the Council of Scientific and Industrial Research, New Delhi, India for a research fellowship.

Notes and references 1 (a) A. Diéguez-Vázquez, C. Tzschucke, W. Lam and S. Ley, Angew. Chem., Int. Ed., 2008, 47, 209; (b) A. Chianese, S. Lee and M. Gagné, Angew. Chem., Int. Ed., 2007, 46, 4042; (c) A. Fürstner and P. Davies, Angew. Chem., Int. Ed., 2007, 46, 3410; (d) S. Kirsch, J. Binder, C. Liébert and H. Menz, Angew. Chem., Int. Ed., 2006, 45, 5878; (e) J. Barluenga, A. Diéguez, A. Fernández, F. Rodríguez and F. Fañanás, Angew. Chem., Int. Ed., 2006, 45, 2091; (f ) A. Fürstner and C. Aïssa, J. Am. Chem. Soc., 2006, 128, 6306; (g) A. Fürstner, P. Davies and T. Gress, J. Am. Chem. Soc., 2005, 127, 8244; (h) G. Lloyd-Jones, Org. Biomol. Chem., 2003, 1, 215; (i) C. Aubert, O. Buisine and M. Malacria, Chem. Rev., 2002, 102, 813.


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2 (a) Y. Xiong, S. Schaus and J. Porco, Org. Lett., 2013, 15, 1962; (b) S. Y. Kim, Y. Park, S. Son and Y. K. Chung, Adv. Synth. Catal., 2012, 354, 179; (c) K. Saito, H. Sogou, T. Suga, H. Kusama and N. Iwasawa, J. Am. Chem. Soc., 2011, 133, 689; (d) N. Patil, R. Kavthe, V. Raut and V. Reddy, J. Org. Chem., 2009, 74, 6315; (e) I. Kim, K. Kim and J. Choi, J. Org. Chem., 2009, 74, 8492; (f ) K.-G. Ji, X.-Z. Shu, J. Chen, S.-C. Zhao, Z.-J. Zheng, L. Lu, X.-Y. Liu and Y.-M. Liang, Org. Lett., 2008, 10, 3919. 3 (a) Q. Hou, Z. Zhang, F. Kong, S. Wang, H. Wang and Z.-J. Yao, Chem. Commun., 2013, 49, 695; (b) G. Ferrara, T. Jin, M. Akhtaruzzaman, A. Islam, L. Han, H. Jiang and Y. Yamamoto, Tetrahedron Lett., 2012, 53, 1946; (c) P. Byers, J. Rashid, R. Mohamed and I. Alabugin, Org. Lett., 2012, 14, 6032; (d) C.-C. Chen, S.-C. Yang and M.-J. Wu, J. Org. Chem., 2011, 76, 10269; (e) K. Hirano, Y. Inaba, N. Takahashi, M. Shimano, S. Oishi, N. Fujii and H. Ohno, J. Org. Chem., 2011, 76, 1212; (f ) K. Hirano, Y. Inaba, K. Takasu, S. Oishi, Y. Takemoto, N. Fujii and H. Ohno, J. Org. Chem., 2011, 76, 9068. 4 (a) S. Naoe, Y. Suzuki, K. Hirano, Y. Inaba, S. Oishi, N. Fujii and H. Ohno, J. Org. Chem., 2012, 77, 4907; (b) A. S. K. Hashmi, I. Braun, M. Rudolph and F. Rominger, Organometallics, 2012, 31, 644; (c) P. Byers and I. Alabugin, J. Am. Chem. Soc., 2012, 134, 9609; (d) I. Alabugin, K. Gilmore, S. Patil, M. Manoharan, S. Kovalenko, R. Clark and I. Ghiviriga, J. Am. Chem. Soc., 2008, 130, 11535; (e) H.-K. Chang, Y.-C. Liao and R.-S. Liu, J. Org. Chem., 2007, 72, 8139; (f ) H. Yang, J. L. Petersen and K. K. Wang, Tetrahedron, 2006, 62, 1231; (g) C.-Y. Lo, M. Kumar, H.-K. Chang, S.-F. Lush and R.-S. Liu, J. Org. Chem., 2005, 70, 10482; (h) A. Odedra, C.-J. Wu, T. Pratap, C.-W. Huang, Y.-F. Ran and R.-S. Liu, J. Am. Chem. Soc., 2005, 127, 3406; (i) S. Kovalenko, S. Peabody, M. Manoharan, R. Clark and I. Alabugin, Org. Lett., 2004, 6, 2457; ( j) P. Schreiner, M. Prall and V. Lutz, Angew. Chem., Int. Ed., 2003, 42, 5757; (k) B. König, W. Pitsch, M. Klein, R. Vasold, M. Prall and P. Schreiner, J. Org. Chem., 2001, 66, 1742. 5 (a) M. Sivaraman, D. Muralidharan and P. T. Perumal, Tetrahedron Lett., 2013, 54, 1507; (b) A. Nandakumar and P. T. Perumal, Org. Lett., 2013, 15, 382.


Paper

6 M. Sivaraman, D. Muralidharan and P. T. Perumal, Tetrahedron Lett., 2012, 53, 6039. 7 (a) Z.-B. Zhu and S. Kirsch, Chem. Commun., 2013, 49, 2272; (b) H. Cao, H.-F. Jiang, H.-W. Huang and J.-W. Zhao, Org. Biomol. Chem., 2011, 9, 7313; (c) H. Jiang, W. Yao, H. Cao, H. Huang and D. Cao, J. Org. Chem., 2010, 75, 5347; (d) H. Cao, H. Jiang, R. Mai, S. Zhu and C. Qi, Adv. Synth. Catal., 2010, 352, 143; (e) N. Fei, Q. Hou, S. Wang, H. Wang and Z.-J. Yao, Org. Biomol. Chem., 2010, 8, 4096; (f ) A. Saito, T. Konishi and Y. Hanzawa, Org. Lett., 2010, 12, 372; (g) H. Cao, H. Jiang, W. Yao and X. Liu, Org. Lett., 2009, 11, 1931. 8 (a) C.-S. Wu, Z.-M. Lin, L.-N. Wang, D.-X. Guo, S.-Q. Wang, Y.-Q. Liu, H.-Q. Yuan and H.-X. Lou, Bioorg. Med. Chem. Lett., 2011, 21, 3261; (b) L. Zan, J. Qin, Y. Zhang, Y. Yao, H. Bao and X. Li, Chem. Pharm. Bull., 2011, 59, 770. 9 C.-C. Chen, L.-Y. Chin, S.-C. Yang and M.-J. Wu, Org. Lett., 2010, 12, 5652. 10 N. Fei, H. Yin, S. Wang, H. Wang and Z.-J. Yao, Org. Lett., 2011, 13, 4208. 11 (a) L. Zhang, J. Sun and S. A. Kozmin, Adv. Synth. Catal., 2006, 348, 2271; (b) S. Y. Kim, Y. Park, S. Son and Y. K. Chung, Adv. Synth. Catal., 2012, 354, 179; (c) A. Arcadi, F. Blesi, S. Cacchi, G. Fabrizi, A. Goggiamani and F. Marinelli, Org. Biomol. Chem., 2012, 10, 9700; (d) Z.-B. Zhu and S. F. Kirsch, Chem. Commun., 2013, 49, 2272; (e) J. Storch, M. Bernard, J. Sýkora, J. Karban and J. Čermák, Eur. J. Org. Chem., 2013, 260. 12 B. Banerjee, S. K. Mandal and S. C. Roy, Chem. Lett., 2006, 35, 16. 13 (a) D. J. C. Prasad and G. Sekar, Org. Biomol. Chem., 2013, 11, 1659; (b) T. Hamura, Y. Chuda, Y. Nakatsuji and K. Suzuki, Angew. Chem., Int. Ed., 2012, 51, 3368; (c) A. Orita, H. Taniguchi and J. Otera, Chem.–Asian J., 2006, 1, 430; (d) D. Bruns, H. Miura, K. Vollhardt and A. Stanger, Org. Lett., 2003, 5, 549; (e) M. Wu, L. Chang, L. Wei and C. Lin, Tetrahedron, 1999, 55, 13193; (f) A. Orita, N. Yoshioka, P. Struwe, A. Braier, A. Beckmann and J. Otera, Chem.–Eur. J., 1999, 5, 1355. 14 J. Jin, Y. Luo, C. Zhou, X. Chen, Q. Wen, P. Lu and Y. Wang, J. Org. Chem., 2012, 77, 11368.

Org. Biomol. Chem., 2014, 12, 1318–1327 | 1327

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