Catalyst-free one-pot domino reactions for selective synthesis of functionalized 2,8-oxazabicyclo[3.3.1]-nonanes and 5H-indeno[1,2-b]pyridin-5-ones

Abstract

A simple and efficient method for one-pot synthesis of new functionalized 2,8-oxazabicyclo-[3.3.1]nonanes from easily accessible 2-hydroxychalcones, 4-hydroxycoumarin/1,3-cyclohexandiones and aqueous ammonia under catalyst-free conditions is described. This reaction was probably achieved via an intermolecular Michael addition/amination/intramolecular bicyclization domino process. Hydroxy-containing 5H-indeno[1,2-b]pyridin-5-ones were obtained when five-membered 1,3-indandione was employed in this reaction.

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Introduction

Much attention has been paid to the functionalized oxygen- and nitrogen-containing heterobicyclo[3.3.1]nonanes in recent years due to their unique cleft-shaped structure.¹ They have been widely employed in host-guest chemistry and asymmetric catalysis.^2,3 The development of efficient synthetic routes to this type of rigid molecules has become more significant and challenging.^4–9 In a recent study, we demonstrated a stereoselective synthesis of 2,8-dioxabicyclo [3.3.1]nonanes by the reactions of 2-hydroxychalcones with 4-hydroxycoumarin (or its analogues) and naphthols/substituted phenols.¹⁰ 2,8-Oxazabicyclo[3.3.1]nonanes, as another kind of important hetero-bicyclic system, are frequently encountered in a variety of natural products and biologically active molecules. For example, alkaloids Larutensine, Naucleamide E and Calycinumine B show excellent antiproliferative, anti-inflammatory and cytotoxic activity against tumor cell lines (Fig. 1).^11–13 In addition, coumarin chemistry has captured the continuous attention of chemists and pharmacists for their biological activities.¹⁴ It is well known that many synthetic drugs, such as warfarin, phenprocoumon, brodifacoum, and arisugacin A are coumarin derivatives.¹⁵ However, only several synthetic methods have thus far been reported for the construction of 2,8-oxazabicyclo[3.3.1]nonane skeleton,^16–18 and coumarin-derived [3.3.1]hetero-bicyclic system is rarely involved. Recently, Yang reported the synthesis of coumarin-fused 2,8-oxazabicyclo[3.3.1]nonane as photochromic colorants by a one-pot multicomponent reaction of p-anisidine, o-nitrobenzaldehyde and isobutyraldehyde in the presence of p-TsOH to form tetrahydroquinoline, followed by treating with 4-hydroxycoumarin.¹⁹ Zhang also reported a fluorous benzaldehyde-based green synthesis of biaryl-substituted oxazabicyclo[3.3.1]nonanes by a multi-step synthesis to form oxazabicycles, then introducing the biaryl group via Suzuki coupling reaction.²⁰ It should be noted that nitrogen-atom is connected to the aromatic ring in these reported coumarin-fused oxazabicyclo[3.3.1]nonanes. In continuation of our efforts to develop new synthetic protocols for constructing rigid bicyclic frameworks,²¹ we herein described a clean synthesis of coumarin-fused 2,8-oxazabicyclo[3.3.1]nonanes from easily accessible 2-hydroxychalcones, 4-hydroxycoumarin and aqueous ammonia in a one-pot domino procedure. Nitrogen-atom is connected to the coumarin ring in these molecules. 1,3-Cyclohexanedione and its derivatives were also suitable for this reaction. Nevertheless, five-membered substrate 1,3-indandione delivered the corresponding 5H-indeno[1,2-b]pyridin-5-ones.

Fig. 1 Examples of natural products.

Results and discussion

We initiated our studies on the synthesis of coumarin-fused oxazabicycle 8-phenyl-7,8-dihydro-8,14-methanobenzo[g]chromeno[4,3-d][1,3]oxazocin-1(14H)-one (3a). As outlined in Table 1, various nitrogen sources, solvents and temperature were examined. When 2-hydroxychalcone (1a, 0.5 mmol), 4-hydroxycoumarin (2, 0.5 mmol) and ammonium acetate (10 mmol) were heated in ethanol under reflux for 12 h, the desired product 3a was isolated in 20% yield (Table 1, entry 1). The structure was confirmed by means of ¹H NMR, ¹³C NMR, HRMS and IR spectra. It was found that 30% mass concentration of aqueous ammonia was more effective for this reaction, affording the product in 38% yield (Table 1, entry 2). This transformation was also attempted in other solvents, such as MeOH, t-BuOH, i-PrOH and n-PrOH, and we found that the higher boiling point solvent gave rise to the higher yield (n-PrOH, 72%, Table 1, entries 3–6). The pale yellow solid 3a crystallized spontaneously when the reaction mixture was cooled to room temperature overnight. Increasing or decreasing the amount of aqueous ammonia both resulted in a low yield (Table 1, entries 7 and 8). None of the expected product was formed in THF (Table 1, entry 9). In addition, the reactions were also examined in DMSO, DMF, toluene, benzene, MeCN and 1,2-dichloroethane (DCE), 3a was isolated in 18–41% yield (Table 1, entries 10–15). 3a was only obtained in 40% yield when no other solvent was used (Table 1, entry 16).

Table 1 Optimization of the reaction conditions for the synthesis of 3a

Entry^a	Nitrogen source^b	Solvent	Temp. (°C)	Yield^c (%)
a All reactions were performed with 2-hydroxychalcone (1a, 0.5 mmol), 4-hydroxycoumarin (2, 0.5 mmol) and nitrogen source (10 mmol) in an appropriate solvent (5 mL) for 12 h.b Aqueous ammonia with a 30% (w/w) concentration.c Isolated yield.d 15 mmol NH3·H2O was used.e 5 mmol NH3·H2O was used.f None of the expected product was observed.g 3 mL NH3·H2O was used.
1	NH4OAc	EtOH	Reflux	20
2	NH3·H2O	EtOH	Reflux	38
3	NH3·H2O	MeOH	Reflux	25
4	NH3·H2O	t-BuOH	Reflux	44
5	NH3·H2O	i-PrOH	Reflux	42
6	NH3·H2O	n-PrOH	Reflux	72
7	NH3·H2O	n-PrOH	Reflux	63^d
8	NH3·H2O	n-PrOH	Reflux	50^e
9	NH3·H2O	THF	Reflux	—^f
10	NH3·H2O	DMSO	100	36
11	NH3·H2O	DMF	100	41
12	NH3·H2O	Toluene	Reflux	38
13	NH3·H2O	Benzene	Reflux	18
14	NH3·H2O	MeCN	Reflux	35
15	NH3·H2O	DCE	Reflux	23
16	NH3·H2O	None	100	40^g

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With the optimum reaction conditions in hand, a variety of substituted 2-hydroxychalcones (1) was subsequently investigated, and the results were summarized in Scheme 1. It was observed that substrates in which R¹ = H and R² was a phenyl ring bearing electron-donating substituents (–OCH₃) or electron-withdrawing substituent (–Br, –Cl and –F) gave the corresponding products 3b–3e in 61–71% yields. The substrates for R² were naphthalene, furan, and thiophene rings, delivering 3f–3h in 60–65% yields. Moreover, an alkyl group (–CH₃) substrate was also suitable for this transformation with isolation of the product 3i in 62% yield. To our delight, 5-chloro- and 5-bromo-substituted (R¹) 2-hydroxychalcone also furnished 3j and 3k in 69% and 70% yields respectively.

Scheme 1 Scope of 2-hydroxychalcone derivatives. Reaction conditions: 2-hydroxychalcones (1, 0.5 mmol), 4-hydroxycoumarin (2, 0.5 mmol) and aqueous ammonia (10 mmol) in n-propanol (5 mL) under reflux for 12 h. Isolated yield.

Next, we further extended the substrates to 1,3-cyclohexandione (4a, R³ = R⁴ = H) for the preparation of the structurally diverse and functionalized 2,8-oxazabicyclo[3.3.1]nonane library (Scheme 2). It was found that the expected products 5a–5d were obtained in 60–71% yields. In addition, substrates 5,5-dimethyl-1.3-cyclohexanedione (4b, R³ = R⁴ = CH₃) also gave the corresponding products 5e–5j in satisfactory yields (63–72%). The steric configuration of 5e was further clarified by X-ray single-crystal diffraction analysis (Fig. 2).²² When 5-methyl-1,3-cyclohexanedione (4c, R³ = CH₃, R⁴ = H) was employed in this reaction, cyclohexanedione-fused 2,8-oxazabicyclo[3.3.1]nonanes 5k–5n were obtained in 65–71% yields with an approximate diastereometric ratio of 1 : 1 according to NMR spectrum analysis.

Scheme 2 Scope of 1,3-diones. Reaction conditions: 2-hydroxychalcones (1, 0.5 mmol), 1,3-cyclohexandiones (4a–4c, 0.5 mmol) and aqueous ammonia (10 mmol) in n-propanol (5 mL) under reflux for 12 h. Isolated yield.

Fig. 2 X-ray structure of 5e.†

Next, five-membered substrate 1,3-indandione (6) was also used to react with 2-hydroxychalcones in the presence of aqueous ammonia, as shown in Scheme 3. It was found that the expected oxazabicyclo[3.3.1]nonane did not form, and the reaction gave 4-(2-hydroxyphenyl)-2-phenyl-5H-indeno[1,2-b]pyridin-5-one (7a) in 63% yield. The 2-position hydroxyl group of 1a did not participate in the reaction, probably due to the effect of the ring strain of 1,3-indandione. Moreover, we use the substrates in which R¹ = H and R² was a phenyl ring bearing electron-donating substituent (–OCH₃) or electron-withdrawing substituent (–F) also smoothly furnished the corresponding products 7b and 7c in 62% and 75% yields respectively.

Scheme 3 Reaction conditions: 2-hydroxychalcones (1, 0.5 mmol), 1,3-indandione (6, 0.5 mmol) and aqueous ammonia (10 mmol) in n-propanol (5 mL) under reflux for 12 h. Isolated yield.

A possible domino reaction mechanism was proposed as shown in Scheme 4. First, intermediate I was formed through Michael addition reaction between 2-hydroxychalcone (1a) and 1,3-cyclohexanedione (4a).^10a,23 One possible pathway was that intermediate I was reacted with ammonia to form intermediate III by amination substitution reaction of the hydroxyl group (–OH),²⁴ which was converted to intermediate IV via an intramolecular cyclization process after loss of water. Finally, 5a was formed by a spontaneous addition intramolecular cyclization process.²⁵ However, we were failed to isolate the intermediates during the reaction process. In order to further confirm this reaction process, 2-hydroxychalcone and 3-aminocyclohex-2-enone (8) was heated in refluxing n-PrOH for 12 h, and it was found the expected product 5a was not formed. The unexpected 4-substituted 4H-chromene (9) was obtained in 78% isolated yield (Scheme 5). Obviously, intermediate III was formed during the reaction, but the hydroxyl group was first attacked the carbonyl group (C=O) to deliver the dehydration product 9. Therefore, we believe that product 5a was formed without involving the intermediate III. The other possible pathway was that intermediate I was directly converted to imine intermediate II-A, which could be isomerized to II-B. The latter gave the corresponding dehydration cyclization intermediate IV, sequentially delivering the target molecule 5a. Similarly, when 1,3-indandione (6) was employed, the reaction afforded the corresponding intermediate VI by subsequent intermolecular Michael addition–amination–dehydration cyclization process, which could be easily oxidized to more thermodynamic stable π-conjugated structure 5H-indeno[1,2-b]pyridin-5-one 7a in the presence of air.²⁶

Scheme 4 The possible reaction mechanism.

Scheme 5

Conclusions

In summary, we have described a simple and efficient method for the stereoselective synthesis of new coumarin- and cyclohexandione-fused 2,8-oxazabicyclo[3.3.1]nonane derivatives from 2-hydroxychalcones, 4-hydroxy coumarin/1,3-cyclohexandiones and aqueous ammonia. This reaction was probably achieved via an intermolecular Michael addition/amination/intramolecular bicyclization domino process. Functionalized hydroxy-containing 5H-indeno[1,2-b]pyridin-5-ones were obtained when five-membered 1,3-indandione was employed in this reaction. The hydroxyl group of substrate 1 did not participate in the reaction probably due to the effect of the ring strain. All these reported compounds were unknown and characterized by means of ¹H NMR, ¹³C NMR, HRMS and IR spectra. The structure and steric configuration of 5e were further clarified by X-ray single-crystal diffraction analysis. The prominent advantages of this approach are easily available starting materials, a wide scope of substrates, mild reaction conditions, ease of purification and catalyst-free conditions. Further investigations on the applications of this transformation to other bicyclic systems are currently underway in our laboratory.

Experimental

General information

All the chemicals were commercially available and used without further purification. All the organic solvents were dried and freshly distilled before use. ¹H and ¹³C NMR spectra were recorded using Bruker AV 300 MHz spectrometers with CDCl₃ or DMSO-d₆ as the solvent. Chemical shifts are reported relative to TMS (internal standard). High resolution mass spectra were recorded using a Waters GCT Premier (ESI) or a Bruker ultrafleXtreme MALDI-TOF/TOF (HCCA matrix). IR spectra were obtained as KBr pellet samples using a Nicolet 5700 FTIR spectrometer. Melting points were determined using an uncorrected X-4 apparatus. The X-ray crystal structure determination was performed using a Bruker SMART APEX CCD system.

General one-pot procedure for the synthesis of 3 and 5

A mixture of 2-hydroxychalcones (1, 0.5 mmol), 4-hydroxycoumarin (2, 0.5 mmol)/substituted 1,3-cyclohexandiones (4, 0.5 mmol) and 30% aqueous ammonia (10 mmol, w/w) was heated in n-propanol (5 mL) under reflux. After the reaction was completed (12 h, monitored by thin layer chromatography), the mixture was slowly cooled to room temperature overnight. Then crystals precipitated, which were filtrated and washed with a small amount of anhydrous ethanol to give the products 3 and 5 respectively.

8-Phenyl-7,8-dihydro-8,14-methanobenzo[g]chromeno [4,3-d][1,3]oxazocin-1(14H)-one (3a). White solid, 132 mg, yield 72%; mp 286–288 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.80–7.76 (m, 2H), 7.58–7.45 (m, 5H), 7.30–7.27 (m, 1H), 7.23–7.11 (m, 3H), 6.95–6.90 (m, 2H), 6.09 (s, 1H), 4.51 (t, J = 3.0 Hz, 1H), 2.43–2.29 (m, 2H); ¹³C NMR (75 MHz, CDCl₃) δ 161.1, 152.5, 151.6, 146.0, 141.5, 131.5, 129.1, 128.9, 128.8, 127.8, 126.0, 125.7, 123.6, 121.3, 119.7, 117.7, 116.5, 113.3, 101.1, 83.6, 33.7, 28.6; IR (KBr) ν 3435, 2026, 1660, 1614, 1524, 1475, 1390, 1104, 885, 751, 621 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₄H₁₈NO₃ [M + H]⁺ 368.1281, found 368.1278.

8-(4-Methoxyphenyl)-7,8-dihydro-8,14-methanobenzo[g]chromeno[4,3-d][1,3]oxazocin-1(14H)-one (3b). White solid, 121 mg, yield 61%; mp 274–276 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.71–7.66 (m, 2H), 7.50–7.45 (m, 1H), 7.30–7.27 (m, 1H), 7.24–7.11 (m, 3H), 7.04–6.99 (m, 2H), 6.95–6.90 (m, 2H), 6.08 (s, 1H), 4.50 (t, J = 2.9 Hz, 1H), 3.88 (s, 1H), 2.40–2.26 (m, 2H); ¹³C NMR (75 MHz, CDCl₃) δ 161.1, 160.1, 152.5, 151.7, 146.0, 133.6, 131.5, 128.8, 127.8, 127.0, 126.1, 123.6, 121.2, 119.7, 117.7, 116.5, 114.1, 113.4, 101.0, 83.4, 55.4, 33.7, 28.7; IR (KBr) ν 3437, 2027, 1664, 1614, 1521, 1470, 1390, 1104, 886, 824, 754, 621 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₅H₂₀NO₄ [M + H]⁺ 398.1387, found 398.1398.

8-(4-Bromophenyl)-7,8-dihydro-8,14-methanobenzo[g]chromeno[4,3-d][1,3]oxazocin-1(14H)-one (3c). White solid, 147 mg, yield 66%; mp 290–291 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.68–7.61 (m, 4H), 7.56–7.48 (m, 2H), 7.33–7.29 (m, 2H), 7.25–7.13 (m, 2H), 6.99–6.91 (m, 2H), 6.02 (s, 1H), 4.51 (s, 1H), 2.41–2.27 (m, 2H); ¹³C NMR (75 MHz, CDCl₃) δ 161.0, 152.6, 151.4, 145.9, 140.6, 132.0, 131.7, 128.8, 127.9, 127.6, 125.8, 123.7, 123.4, 121.5, 119.7, 117.8, 116.5, 113.3, 101.4, 83.3, 33.6, 28.5; IR (KBr) ν 3433, 3294, 2026, 1667, 1616, 1530, 1475, 1391, 1105, 997, 890, 823, 755, 622 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₄H₁₇BrNO₃ [M + H]⁺ 446.0386, found 446.0397.

8-(4-Chlorophenyl)-7,8-dihydro-8,14-methanobenzo[g]chromeno[4,3-d][1,3]oxazocin-1(14H)-one (3d). White solid, 140 mg, yield 70%; mp 291–292 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.74–7.71 (m, 2H), 7.57–7.46 (m, 4H), 7.32–7.28 (m, 2H), 7.24–7.12 (m, 2H), 6.98–6.91 (m, 2H), 6.06 (s, 1H), 4.51 (t, J = 3.0 Hz, 1H), 2.40–2.27 (m, 2H); ¹³C NMR (75 MHz, CDCl₃) δ 161.0, 152.6, 151.4, 145.9, 140.1, 135.2, 131.7, 129.0, 128.8, 127.9, 127.3, 125.9, 123.7, 121.5, 119.7, 117.8, 116.5, 113.3, 101.4, 83.3, 33.7, 28.5; IR (KBr) ν 3433, 2026, 1666, 1616, 1529, 1477, 1391, 1104, 757, 621 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₄H₁₇ClNO₃ [M + H]⁺ 402.0891, found 402.0897.

8-(4-Fluorophenyl)-7,8-dihydro-8,14-methanobenzo[g]chromeno[4,3-d][1,3]oxazocin-1(14H)-one (3e). White solid, 137 mg, yield 71%; mp 286–287 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.80–7.73 (m, 2H), 7.57–7.47 (m, 2H), 7.32–7.29 (m, 2H), 7.23–7.12 (m, 4H), 6.97–6.91 (m, 2H), 6.05 (s, 1H), 4.51 (t, J = 2.9 Hz, 1H), 2.41–2.28 (m, 2H); ¹³C NMR (75 MHz, CDCl₃) δ 163.0 (d, ¹J_C–F = 247.2 Hz), 161.0, 152.5, 151.5, 145.9, 137.4 (d, ⁴J_C–F = 2.9 Hz), 131.6, 128.8, 127.9, 127.8 (d, ³J_C–F = 8.3 Hz), 125.9, 123.7, 121.4, 119.7, 117.8, 116.4, 115.7 (d, ²J_C–F = 21.5 Hz), 113.3, 101.3, 83.3, 33.8, 28.6; IR (KBr) ν 3432, 2026, 1665, 1617, 1525, 1474, 1391, 1104, 755, 621 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₄H₁₇FNO₃ [M + H]⁺ 386.1187, found 386.1182.

8-(Naphthalen-2-yl)-7,8-dihydro-8,14-methanobenzo[g]chromeno[4,3-d][1,3]oxazocin-1(14H)-one (3f). Brown solid, 127 mg, yield 61%; mp 267–268 °C; ¹H NMR (300 MHz, CDCl₃) δ 8.31–8.30 (m, 1H), 7.99–7.91 (m, 3H), 7.81–7.77 (m, 1H), 7.60–7.57 (m, 3H), 7.52–7.47 (m, 1H), 7.32–7.29 (m, 2H), 7.22–7.14 (m, 2H), 7.02–6.92 (m, 2H), 6.22 (s, 1H), 4.55 (t, J = 2.9 Hz, 1H), 2.50–2.38 (m, 2H); ¹³C NMR (75 MHz, CDCl₃) δ 161.1, 152.6, 151.7, 146.0, 138.6, 133.3, 133.0, 131.6, 128.9, 128.8, 128.5, 127.9, 127.7, 127.0, 126.8, 126.1, 125.2, 123.6, 123.2, 121.4, 119.8, 117.7, 116.5, 113.4, 101.2, 83.7, 33.6, 28.6; IR (KBr) ν 3429, 3300, 2026, 1665, 1615, 1528, 1472, 1391, 1105, 889, 815, 751, 620 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₈H₂₀NO₃ [M + H]⁺ 418.1438, found 418.1445.

8-(Furan-2-yl)-7,8-dihydro-8,14-methanobenzo[g]chromeno[4,3-d][1,3]oxazocin-1(14H)-one (3g). White solid, 116 mg, yield 65%; mp 257–258 °C; ¹H NMR (300 MHz, DMSO-d₆) δ 9.09 (s, 1H), 8.19–8.16 (m, 1H), 7.80–7.79 (m, 1H), 7.61–7.55 (m, 1H), 7.35–7.29 (m, 3H), 7.15–7.09 (m, 1H), 6.93–6.85 (m, 2H), 6.81–6.80 (m, 1H), 6.61–6.59 (m, 1H), 4.32 (t, J = 2.9 Hz, 1H), 2.45–2.40 (m, 1H), 2.31–2.26 (m, 1H); ¹³C NMR (75 MHz, DMSO-d₆) δ 160.5, 152.7, 152.4, 151.7, 147.0, 143.7, 132.3, 128.6, 128.1, 126.7, 124.1, 123.5, 121.3, 117.2, 116.8, 113.9, 111.2, 108.7, 100.5, 80.8, 31.0, 27.9; IR (KBr) ν 3434, 3265, 2026, 1664, 1617, 1530, 1474, 1392, 1103, 884, 749, 619 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₂H₁₆NO₄ [M + H]⁺ 358.1074, found 358.1066.

8-(Thiophen-2-yl)-7,8-dihydro-8,14-methanobenzo[g]chromeno[4,3-d][1,3]oxazocin-1(14H)-one (3h). Brown solid, 112 mg, yield 60%; mp 264–265 °C; ¹H NMR (300 MHz, DMSO-d₆) δ 9.21 (s, 1H), 8.19–8.17 (m, 1H), 7.65–7.56 (m, 2H), 7.36–7.28 (m, 4H), 7.15–7.11 (m, 2H), 6.96–6.87 (m, 2H), 4.30 (s, 1H), 2.42–2.31 (m, 2H); ¹³C NMR (75 MHz, DMSO-d₆) δ 160.6, 152.5, 151.9, 147.3, 145.7, 132.4, 128.6, 128.2, 127.8, 127.0, 126.8, 126.3, 124.2, 123.6, 121.5, 117.2, 116.9, 114.0, 100.4, 83.4, 35.1, 28.8; IR (KBr) ν 3433, 2026, 1616, 1525, 1388, 1104, 620 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₂H₁₆NO₃S [M + H]⁺ 374.0845, found 374.0851.

8-Methyl-7,8-dihydro-8,14-methanobenzo[g]chromeno [4,3-d][1,3]oxazocin-1(14H)-one (3i). White solid, 95 mg, yield 62%; mp 317–318 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.52–7.44 (m, 2H), 7.32–7.28 (m, 2H), 7.23–7.17 (m, 1H), 7.11–7.06 (m, 1H), 6.89–6.81 (m, 2H), 5.87 (s, 1H), 4.47 (t, J = 2.9 Hz, 1H), 2.36–2.30 (m, 1H), 2.11–2.06 (m, 1H), 1.95 (s, 1H); ¹³C NMR (75 MHz, CDCl₃) δ 161.1, 152.5, 151.7, 145.7, 131.4, 128.8, 127.7, 126.0, 123.5, 121.0, 119.7, 117.7, 116.1, 113.2, 100.9, 80.9, 31.3, 28.2, 27.6; IR (KBr) ν 3434, 2026, 1655, 1614, 1533, 1390, 1206, 1104, 874, 752, 620 cm⁻¹; HRMS m/z (MALDI) calcd for C₁₉H₁₆NO₃ [M + H]⁺ 306.1125, found 306.1126.

12-Chloro-8-phenyl-7,8-dihydro-8,14-methanobenzo[g]chromeno[4,3-d][1,3]oxazocin-1(14H)-one (3j). White solid, 138 mg, yield 69%; mp 297–298 °C; ¹H NMR (300 MHz, DMSO-d₆) δ 9.14 (s, 1H), 8.20–8.18 (m, 1H), 7.76–7.73 (m, 2H), 7.62–7.56 (m, 1H), 7.54–7.43 (m, 3H), 7.36–7.28 (m, 3H), 7.20–7.17 (m, 1H), 7.07–7.04 (m, 1H), 4.28 (t, J = 2.9 Hz, 1H), 2.33–2.19 (m, 2H); ¹³C NMR (75 MHz, DMSO-d₆) δ 160.6, 152.5, 151.4, 148.0, 141.7, 132.5, 129.1, 128.9, 127.8, 127.7, 126.7, 124.5, 124.2, 123.6, 118.8, 117.3, 114.1, 99.3, 84.6, 33.8, 28.7; IR (KBr) ν 3435, 3286, 2026, 1665, 1615, 1527, 1473, 1105, 885, 756, 620 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₄H₁₇ClNO₃ [M + H]⁺ 402.0891, found 402.0878.

12-Bromo-8-phenyl-7,8-dihydro-8,14-methanobenzo[g]chromeno[4,3-d][1,3]oxazocin-1(14H)-one (3k). White solid, 156 mg, yield 70%; mp 293–294 °C; ¹H NMR (300 MHz, DMSO-d₆) δ 9.14 (s, 1H), 8.20–8.18 (m, 1H), 7.75–7.73 (m, 2H), 7.62–7.57 (m, 1H), 7.51–7.44 (m, 4H), 7.37–7.29 (m, 3H), 7.02–6.99 (m, 1H), 4.28 (s, 1H), 2.33–2.19 (m, 2H); ¹³C NMR (75 MHz, DMSO-d₆) δ 160.6, 152.5, 151.8, 147.9, 141.6, 132.4, 130.6, 130.5, 129.6, 129.0, 128.8, 126.6, 124.2, 123.5, 119.2, 117.3, 114.0, 112.2, 99.3, 84.6, 33.7, 28.6; IR (KBr) ν 3434, 3290, 2026, 1664, 1616, 1527, 1474, 1399, 1107, 998, 887, 816, 757, 691, 619 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₄H₁₇BrNO₃ [M + H]⁺ 446.0386, found 446.0393.

6-Phenyl-8,9,10,12-tetrahydro-6H-6,12-methanodibenzo [d,g][1,3]oxazocin-11(7H)-one (5a). White solid, 109 mg, yield 69%; mp 268–269 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.71–7.68 (m, 2H), 7.49–7.39 (m, 4H), 7.14–7.08 (m, 1H), 6.98–6.96 (m, 1H), 6.89–6.84 (m, 1H), 5.44 (s, 1H), 4.40 (t, J = 2.9 Hz, 1H), 2.50–1.83 (m, 8H); ¹³C NMR (75 MHz, CDCl₃) δ 193.4, 156.1, 151.7, 141.8, 128.9, 128.8, 128.7, 127.5, 127.0, 125.5, 120.8, 116.2, 112.3, 83.7, 36.3, 34.0, 28.2, 26.6, 21.4; IR (KBr) ν 3423, 3240, 2940, 2026, 1584, 1510, 1387, 1108, 1031, 914, 757, 696, 619 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₁H₂₀NO₂ [M + H]⁺ 318.1489, found 318.1482.

6-(4-Methoxyphenyl)-8,9,10,12-tetrahydro-6H-6,12-methanodibenzo[d,g][1,3]oxazocin-11(7H)-one (5b). Brown solid, 109 mg, yield 63%; mp 244–245 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.63–7.58 (m, 2H), 7.42–7.39 (m, 1H), 7.13–7.08 (m, 1H), 6.98–6.93 (m, 3H), 6.89–6.83 (m, 1H), 5.37 (s, 1H), 4.39 (s, 1H), 3.85 (s, 3H), 2.48–1.87 (m, 8H); ¹³C NMR (75 MHz, CDCl₃) δ 193.4, 159.8, 156.1, 151.8, 134.0, 128.9, 127.5, 127.0, 126.8, 120.8, 116.1, 113.9, 112.2, 83.6, 55.4, 36.3, 34.1, 28.2, 26.6, 21.4; IR (KBr) ν 3432, 3237, 2956, 2027, 1582, 1508, 1386, 1107, 1035, 928, 829, 759, 697, 617 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₂H₂₂NO₃ [M + H]⁺ 348.1594, found 348.1583.

6-(4-Fluorophenyl)-8,9,10,12-tetrahydro-6H-6,12-meth-anodibenzo[d,g][1,3]oxazocin-11(7H)-one (5c). White solid, 119 mg, yield 71%; mp 266–267 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.72–7.65 (m, 2H), 7.42–7.39 (m, 1H), 7.17–7.09 (m, 3H), 6.98–6.95 (m, 1H), 6.90–6.85 (m, 1H), 5.33 (s, 1H), 4.40 (t, J = 3.0 Hz, 1H), 2.50–1.86 (m, 8H); ¹³C NMR (75 MHz, CDCl₃) δ 193.4, 162.8 (d, ¹J_C–F = 246.5 Hz), 155.9, 151.6, 137.7 (d, ⁴J_C–F = 3.1 Hz), 128.9, 127.5 (d, ³J_C–F = 8.2 Hz), 127.4, 127.1, 121.0, 116.1, 115.5 (d, ²J_C–F = 21.5 Hz), 112.3, 83.4, 36.3, 34.2, 28.2, 26.6, 21.4; IR (KBr) ν 3431, 3243, 2026, 1583, 1504, 1387, 1106, 754, 619 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₁H₁₉FNO₂ [M + H]⁺ 336.1394, found 336.1384.

6-(Thiophen-2-yl)-8,9,10,12-tetrahydro-6H-6,12-meth-anodibenzo[d,g][1,3]oxazocin-11(7H)-one (5d). Brown solid, 97 mg, yield 60%; mp 302–303 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.41–7.35 (m, 2H), 7.24–7.23 (m, 1H), 7.13–7.05 (m, 2H), 6.96–6.85 (m, 2H), 5.47 (s, 1H), 4.42–4.41 (m, 1H), 2.48–1.86 (m, 8H); ¹³C NMR (75 MHz, CDCl₃) δ 193.5, 155.4, 151.4, 145.8, 128.9, 127.2, 127.1, 127.0, 126.1, 124.6, 121.1, 116.2, 112.5, 82.7, 36.3, 34.7, 28.2, 26.6, 21.3; IR (KBr) ν 3439, 3221, 2026, 1586, 1507, 1387, 1103, 620 cm⁻¹; HRMS m/z (MALDI) calcd for C₁₉H₁₈NO₂S [M + H]⁺ 324.1053, found 324.1046.

9,9-Dimethyl-6-phenyl-8,9,10,12-tetrahydro-6H-6,12-methanodibenzo[d,g][1,3]oxazocin-11(7H)-one (5e). Yellow solid, 121 mg, yield 70%; mp 248–250 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.70–7.67 (m, 2H), 7.49–7.37 (m, 4H), 7.12–7.07 (m, 1H), 6.98–6.95 (m, 1H), 6.88–6.83 (m, 1H), 5.43 (s, 1H), 4.39 (t, J = 2.9 Hz, 1H), 2.31–2.07 (m, 6H), 1.09 (s, 3H), 0.87 (s, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 192.9, 155.0, 151.6, 141.8, 128.7, 128.6, 128.5, 127.4, 126.9, 125.5, 120.8, 116.2, 110.7, 83.8, 50.0, 41.9, 34.1, 32.8, 28.3, 28.1, 26.5; IR (KBr) ν 3434, 3247, 2026, 1596, 1389, 1105, 756, 620 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₃H₂₄NO₂ [M + H]⁺ 346.1802, found 346.1812.

6-(4-Methoxyphenyl)-9,9-dimethyl-8,9,10,12-tetrahydro-6H-6,12-methanodibenzo[d,g][1,3]oxazocin-11(7H)-one (5f). White solid, 120 mg, yield 64%; mp 221–223 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.62–7.57 (m, 2H), 7.41–7.38 (m, 1H), 7.12–7.06 (m, 1H), 6.99–6.94 (m, 3H), 6.88–6.82 (m, 1H), 5.28 (s, 1H), 4.39 (t, J = 2.9 Hz, 1H), 3.85 (s, 3H), 2.29–2.05 (m, 6H), 1.08 (s, 3H), 0.87 (s, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 192.9, 159.8, 154.6, 151.7, 134.0, 128.7, 127.4, 126.9, 126.8, 120.8, 116.2, 113.9, 110.9, 83.7, 55.4, 50.1, 42.1, 34.2, 32.9, 28.4, 28.1, 26.6; IR (KBr) ν 3434, 3246, 2026, 1585, 1510, 1390, 1105, 620 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₄H₂₆NO₃ [M + H]⁺ 376.1907, found 376.1915.

6-(4-Bromophenyl)-9,9-dimethyl-8,9,10,12-tetrahydro-6H-6,12-methanodibenzo[d,g][1,3]oxazocin-11(7H)-one (5g). White solid, 150 mg, yield 71%; mp 278–279 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.60–7.54 (m, 4H), 7.40–7.37 (m, 1H), 7.44–7.36 (m, 3H), 7.13–7.07 (m, 1H), 6.96–6.94 (m, 1H), 6.89–6.83 (m, 1H), 5.31 (s, 1H), 4.38 (t, J = 3.0 Hz, 1H), 2.31–2.05 (m, 6H), 1.08 (s, 3H), 0.87 (s, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 193.0, 154.4, 151.4, 141.0, 131.8, 128.8, 127.4, 127.2, 127.0, 123.0, 121.0, 116.2, 111.1, 83.6, 50.1, 42.0, 34.1, 32.8, 28.4, 28.0, 26.5; IR (KBr) ν 3434, 3243, 2959, 2026, 1585, 1516, 1391, 1105, 825, 760, 620 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₃H₂₃BrNO₂ [M + H]⁺ 424.0907, found 424.0908.

6-(4-Chlorophenyl)-9,9-dimethyl-8,9,10,12-tetrahydro-6H-6,12-methanodibenzo[d,g][1,3]oxazocin-11(7H)-one (5h). White solid, 133 mg, yield 70%; mp 272–273 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.70–7.67 (m, 2H), 7.64–7.60 (m, 2H), 7.44–7.36 (m, 3H), 7.13–7.07 (m, 1H), 6.96–6.94 (m, 1H), 6.89–6.83 (m, 1H), 5.36 (s, 1H), 4.38 (t, J = 3.0 Hz, 1H), 2.31–2.05 (m, 6H), 1.08 (s, 3H), 0.87 (s, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 193.0, 154.5, 151.4, 140.4, 134.8, 128.8, 128.7, 127.2, 127.1, 127.0, 121.0, 116.2, 111.0, 83.6, 50.8, 42.0, 34.2, 32.8, 28.4, 28.0, 26.5; IR (KBr) ν 3430, 3243, 3020, 2957, 2026, 1584, 1517, 1392, 1298, 1257, 1216, 1107, 1023, 974, 911, 827, 759, 719, 621 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₃H₂₃ClNO₂ [M + H]⁺ 380.1412, found 380.1421.

6-(4-Fluorophenyl)-9,9-dimethyl-8,9,10,12-tetrahydro-6H-6,12-methanodibenzo[d,g][1,3]oxazocin-11(7H)-one (5i). White solid, 131 mg, yield 72%; mp 255–256 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.69–7.64 (m, 2H), 7.39–7.36 (m, 1H), 7.16–7.07 (m, 3H), 6.96–6.94 (m, 1H), 6.88–6.83 (m, 1H), 5.39 (s, 1H), 4.38 (t, J = 3.0 Hz, 1H), 2.31–2.04 (m, 6H), 1.08 (s, 3H), 0.87 (s, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 193.0, 162.8 (d, ¹J_C–F = 246.5 Hz), 154.6, 151.5, 137.8 (d, ⁴J_C–F = 3.2 Hz), 128.7, 127.5 (d, ³J_C–F = 8.3 Hz), 127.3, 127.0, 121.0, 116.2, 115.5 (d, ²J_C–F = 21.4 Hz), 110.9, 83.6, 50.1, 42.0, 34.3, 32.8, 28.4, 28.1, 26.5; IR (KBr) ν 3434, 3251, 2958, 2026, 1585, 1510, 1392, 1215, 1107, 911, 834, 759, 620 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₃H₂₃FNO₂ [M + H]⁺ 364.1707, found 364.1707.

9,9-Dimethyl-6-(thiophen-2-yl)-8,9,10,12-tetrahydro-6H-6,12-methanodibenzo[d,g][1,3]oxazocin-11(7H)-one (5j). White solid, 111 mg, yield 63%; mp 251–253 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.40–7.34 (m, 2H), 7.23–7.22 (m, 1H), 7.11–7.04 (m, 2H), 6.94–6.83 (m, 2H), 5.50 (s, 1H), 4.40 (t, J = 2.9 Hz, 1H), 2.41–2.05 (m, 6H), 1.08 (s, 3H), 0.87 (s, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 193.1, 154.0, 151.3, 145.8, 128.7, 127.1, 127.0, 126.9, 126.1, 124.5, 121.0, 116.2, 111.2, 82.8, 50.1, 41.9, 34.7, 32.8, 28.4, 28.1, 26.6; IR (KBr) ν 3435, 3232, 2954, 2026, 1594, 1511, 1388, 1211, 1106, 899, 835, 708, 618 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₁H₂₂NO₂S [M + H]⁺ 352.1366, found 352.1359.

9-Methyl-6-phenyl-8,9,10,12-tetrahydro-6H-6,12-methanodibenzo[d,g][1,3]oxazocin-11(7H)-one (5k). White solid, 114 mg, yield 69%; mp 256–257 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.72–7.66 (m, 2H), 7.49–7.35 (m, 4H), 7.14–7.08 (m, 1H), 6.98–6.96 (m, 1H), 6.89–6.83 (m, 1H), 5.42 (s, 1H), 4.41–4.35 (m, 1H), 2.46–1.93 (m, 7H), 1.08–0.97 (m, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 193.5, 193.4, 155.7, 155.6, 151.7, 151.6, 141.9, 141.8, 128.9, 128.8, 128.7, 128.6, 127.5, 127.4, 127.0, 126.9, 125.5, 125.4, 120.9, 120.8, 116.2, 116.1, 111.8, 111.7, 83.8, 83.7, 44.7, 44.6, 36.6, 36.1, 34.3, 33.8, 29.6, 28.4, 26.7, 26.5, 21.1, 21.0; IR (KBr) ν 3417, 3234, 2026, 1624, 1585, 1515, 1388, 1104, 756, 618 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₂H₂₁NO₂Na [M + Na]⁺ 354.1465, found 354.1458.

6-(4-Methoxyphenyl)-9-methyl-8,9,10,12-tetrahydro-6H-6,12-methanodibenzo[d,g][1,3]oxazocin-11(7H)-one (5l). White solid, 117 mg, yield 65%; mp 242–243 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.64–7.57 (m, 2H), 7.44–7.35 (m, 1H), 7.13–7.07 (m, 1H), 6.97–6.94 (m, 3H), 6.88–6.82 (m, 1H), 5.37 (s, 1H), 4.40–4.34 (m, 1H), 3.85 (s, 1H), 2.45–1.96 (m, 7H), 1.04–0.97 (m, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 193.4, 193.3, 159.8, 155.7, 155.6, 151.8, 151.7, 134.0, 133.9, 128.8, 127.5, 127.4, 127.0, 126.8, 126.7, 120.8, 120.7, 116.2, 116.0, 113.9, 111.8, 111.7, 83.7, 83.6, 55.4, 44.7, 44.6, 36.6, 36.1, 34.4, 33.9, 29.6, 28.4, 26.8, 26.6, 21.1, 21.0; IR (KBr) ν 3419, 3235, 2026, 1622, 1585, 1511, 1389, 1103, 619 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₃H₂₃NO₃Na [M + Na]⁺ 384.1570, found 384.1569.

6-(4-Fluorophenyl)-9-methyl-8,9,10,12-tetrahydro-6H-6,12-methanodibenzo[d,g][1,3]oxazocin-11(7H)-one (5m). White solid, 124 mg, yield 71%; mp 250–251 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.71–7.64 (m, 2H), 7.44–7.35 (m, 1H), 7.16–7.08 (m, 3H), 6.97–6.94 (m, 1H), 6.90–6.84 (m, 1H), 5.33–5.31 (m, 1H), 4.41–4.35 (m, 1H), 2.46–1.94 (m, 7H), 1.04–0.97 (m, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 193.5, 193.4, 162.8 (d, ¹J_C–F = 246.6 Hz), 155.6, 155.5, 151.6, 151.5, 137.8 (d, ⁴J_C–F = 3.1 Hz), 137.7 (d, ⁴J_C–F = 2.9 Hz), 128.8, 127.6 (d, ³J_C–F = 8.2 Hz), 127.5 (d, ³J_C–F = 8.2 Hz), 127.4, 127.3, 127.1, 127.0, 121.0, 120.9, 116.2, 116.0, 115.5 (d, ²J_C–F = 21.4 Hz), 111.9, 111.8, 83.5, 83.4, 44.7, 44.6, 36.6, 36.1, 34.5, 34.0, 29.6, 28.4, 26.7, 26.5, 21.1, 21.0; IR (KBr) ν 3437, 3245, 2026, 1584, 1509, 1391, 1212, 1103, 619 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₂H₂₁FNO₂ [M + H]⁺ 350.1551, found 350.1550.

9-Methyl-6-(thiophen-2-yl)-8,9,10,12-tetrahydro-6H-6,12-methanodibenzo[d,g][1,3]oxazocin-11(7H)-one (5n). Brown solid, 110 mg, yield 65%; mp 253–254 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.44–7.34 (m, 2H), 7.25–7.21 (m, 1H), 7.13–7.04 (m, 2H), 6.95–6.92 (m, 1H), 6.89–6.83 (m, 1H), 5.48 (s, 1H), 4.42–4.37 (m, 1H), 2.46–1.94 (m, 7H), 1.04–0.99 (m, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 193.6, 193.5, 155.1, 155.0, 151.4, 151.3, 145.9, 145.8, 128.8, 127.3, 127.2, 127.1, 127.0, 126.1, 124.6, 124.5, 121.1, 121.0, 116.3, 116.1, 112.1, 112.0, 82.8, 82.7, 44.7, 44.6, 36.5, 36.0, 34.9, 34.5, 29.6, 28.4, 26.8, 26.5, 21.1, 21.0; IR (KBr) ν 3439, 3226, 3013, 2025, 1584, 1513, 1389, 1253, 1213, 1105, 711, 618 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₀H₂₀NO₂S [M + H]⁺ 338.1209, found 338.1209.

General one-pot procedure for the synthesis of 7

A mixture of 2-hydroxychalcones (1, 0.5 mmol), 1,3-indandione (6, 0.5 mmol) and 30% aqueous ammonia (10 mmol, w/w) was heated in n-propanol (5 mL) under reflux. After the reaction was completed (12 h, monitored by thin layer chromatography), the mixture was slowly cooled to room temperature and purified by column chromatography using petroleum ether–ethyl acetate (10 : 1, v/v) to deliver the product 7 as the yellow solids.

4-(2-Hydroxyphenyl)-2-phenyl-5H-indeno[1,2-b]pyridin-5-one (7a). Yellow solid, 110 mg, yield 63%; mp 197–199 °C; ¹H NMR (300 MHz, DMSO-d₆) δ 9.75 (s, 1H), 8.29–8.26 (m, 2H), 7.99–7.97 (m, 1H), 7.80–7.71 (m, 2H), 7.65–7.63 (m, 1H), 7.57–7.52 (m, 4H), 7.39–7.28 (m, 2H), 6.98–6.89 (m, 2H); ¹³C NMR (75 MHz, DMSO-d₆) δ 190.4, 165.3, 160.1, 155.4, 146.5, 142.8, 138.1, 135.7, 135.5, 131.9, 131.0, 130.9, 130.7, 129.4, 127.8, 124.1, 123.8, 123.2, 122.6, 121.1, 119.2, 116.1; IR (KBr) ν 3362, 3055, 2922, 1691, 1583, 1541, 1459, 1364, 1271, 1246, 742, 686 cm⁻¹; HRMS m/z (ESI) calcd for C₂₄H₁₅NO₂Na [M + Na]⁺ 372.0995, found 372.0998.

4-(2-Hydroxyphenyl)-2-(4-methoxyphenyl)-5H-indeno [1,2-b]pyridin-5-one (7b). Yellow solid, 118 mg, yield 62%; mp 239–241 °C; ¹H NMR (300 MHz, DMSO-d₆) δ 9.71 (s, 1H), 8.32–8.24 (m, 2H), 7.97–7.95 (m, 1H), 7.74–7.70 (m, 2H), 7.63–7.61 (m, 1H), 7.56–7.51 (m, 1H), 7.37–7.28 (m, 2H), 7.11–7.08 (m, 2H), 6.97–6.89 (m, 2H), 3.85 (s, 3H); ¹³C NMR (75 MHz, DMSO-d₆) δ 190.4, 165.3, 161.6, 159.9, 155.4, 146.4, 142.8, 135.6, 135.5, 131.8, 131.0, 130.8, 130.5, 129.4, 123.7, 123.4, 123.3, 121.4, 121.0, 119.2, 116.1, 114.8, 55.8; IR (KBr) ν 3421, 2948, 2835, 1718, 1604, 1553, 1460, 1368, 1238, 1177, 1034, 758 cm⁻¹; HRMS m/z (ESI) calcd for C₂₅H₁₇NO₃Na [M + Na]⁺ 402.1101, found 402.1102.

4-(2-Hydroxyphenyl)-2-(4-methoxyphenyl)-5H-indeno [1,2-b]pyridin-5-one (7c). Yellow solid, 138 mg, yield 75%; mp 256–255 °C; ¹H NMR (300 MHz, DMSO-d₆) δ 9.76 (s, 1H), 8.38–8.33 (m, 2H), 7.99–7.96 (m, 1H), 7.80 (s, 1H), 7.76–7.71 (m, 1H), 7.65–7.63 (m, 1H), 7.57–7.52 (m, 1H), 7.41–7.28 (m, 4H), 6.98–6.89 (m, 2H); ¹³C NMR (75 MHz, DMSO-d₆) δ 190.4, 165.4 (d, ¹J_C–F = 246.6 Hz), 165.2, 159.0, 155.4, 146.6, 142.7, 135.8, 135.5, 134.6 (d, ⁴J_C–F = 2.8 Hz), 131.9, 131.0, 130.9, 130.1 (d, ³J_C–F = 8.6 Hz), 124.0, 123.9, 123.2, 122.4, 121.2, 119.2, 116.3 (d, ²J_C–F = 21.4 Hz), 116.1; IR (KBr) ν 3369, 1705, 1594, 1550, 1357, 1223, 1159, 748 cm⁻¹; HRMS m/z (ESI) calcd for C₂₄H₁₄FNO₂Na [M + Na]⁺ 390.0908, found 390.0904.

Synthesis of 3-amino-2-(2-phenyl-4H-chromen-4-yl)-cyclohex-2-enone (9)

A mixture of 2-hydroxychalcone (1a, 112 mg, 0.5 mmol), 3-aminocyclohex-2-enone (8, 56 mg, 0.5 mmol) was heated in n-propanol (5 mL) under reflux. After the reaction was completed (12 h, monitored by thin layer chromatography), the mixture was slowly cooled to room temperature and purified by column chromatography using petroleum ether–ethyl acetate (4 : 1, v/v) to deliver the product 9 (124 mg, 78%) as a white solid. mp 210–211 °C; ¹H NMR (300 MHz, DMSO-d₆) δ 7.71–7.68 (m, 2H), 7.42–7.31 (m, 3H), 7.20–7.14 (m, 1H), 7.06–6.97 (m, 3H), 5.62–5.61 (m, 1H), 5.43–5.42 (m, 1H), 4.62 (br, 2H), 2.49–2.28 (m, 4H), 2.05–1.94 (m, 2H); ¹³C NMR (75 MHz, DMSO-d₆) δ 194.9, 161.1, 151.3, 148.6, 133.7, 128.8, 128.5, 128.4, 127.6, 124.4, 124.0, 122.7, 116.1, 113.8, 100.5, 36.4, 30.9, 27.9, 21.3; IR (KBr) ν 3454, 3304, 3177, 2920, 1648, 1540, 1488, 1409, 1317, 1218, 943, 758 cm⁻¹; HRMS m/z (MALDI) calcd for C₂₁H₂₀NO₂ [M + H]⁺ 318.1489, found 318.1488.

Acknowledgements

We gratefully acknowledge support from the Educational Commission of Hubei Province (D20142501) and the National Natural Science Foundation of China (21102042).

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: Copies of ¹H NMR, ¹³C NMR spectra for all new products 3, 5, 7, 9 and CIF file of 5e. CCDC 1023466. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4ra13166e

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