Pd-catalyzed tandem homocoupling–aldol–dehydration of ortho-acylphenyl iodides

Abstract

A Pd-catalyzed cascade Ullmann coupling–aldol–dehydration reaction of ortho-acylphenyl iodides has been explored. This transformation provides a concise access to colchino analogues in moderate to good yields with wide functional group tolerance.

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Introduction

Transition-metal catalyzed homocoupling of aryl halides, as a powerful tool to construct aryl carbon (sp²)–aryl carbon (sp²) bonds, provides an efficient route to biaryl motifs which are frequently encountered in the fields of optical materials,¹ molecular devices² and natural products.³ Since the Ullmann coupling was first reported one century ago,⁴ much significant progress on various transition-metal catalyzed homocoupling reactions of aryl halides has already been achieved.⁵ In contrast, there have been rare reports about the transition-metal catalyzed cascade Ullmann coupling reaction of aryl halides, which possibly provides a concise approach to construct complex organic compounds.⁶

On the other hand, rapid assembly of dibenzo-seven-memebered-ring system has attracted growing interesting in synthetic and medicinal field due to that this macrocyclic system belongs to an important core structure of many biologically active molecules such colchicine derivatives.⁷ Therefore, various methodologies including the ring expansion of phenanthrene derivatives,⁸ Diels–Alder reactions,⁹ direct arylations¹⁰ and Nicholas reactions,¹¹ Suzuki–Miyaura coupling–aldol condensation reaction¹² were successively developed to make these compounds. Nevertheless, the number and range of examples disclosed in the above-mentioned methods to date is still limited. Moreover, Leonard ever reported an elegant synthetic process to construct dibenzo-cycloheptenone core via a six-step protocol including Ullmann coupling and aldol condensation, etc.¹³ However, this procedure suffered from tedious reaction steps and harsh reaction conditions. Considering that colchicine derivatives possesses potent anti-tumour properties, the development of a concise approach to these compounds therefore is desirable. In order to further richen the colchinol library, herein we described a Pd-catalyzed tandem Ullmann homocoupling–aldol–dehydration of ortho-acylphenyl iodides¹⁴ to rapidly construct colchinol analogues.

Results and discussion

The Pd(OAc)₂-catalyzed cascade cyclization of ortho-bromoacetophenone 1b (0.20 mmol) in the presence of NaHCO₃ (1.5 equiv.) and PPh₃ (10 mol%) was first investigated in DMF (1.0 mL) at 150 °C for 3 h (Table 1, entry 1), and we quickly found that this transformation could provide us the 7-membered-ring product 2a (23% yield) and the by product 3a (16% yield) which was derived from the further C–H functionalization reaction of 2a, and the chemical structure of 3a was also unambiguously confirmed by its single crystal X-ray analysis (see Fig. 1 and ESI† for more details).

Fig. 1 Single crystal structure of 3a.

Table 1 Optimisation of the Pd-catalyzed cascade cyclization of ortho-haloacetophenone^a

Entry	X	Pd salts	L	Base	2a/3a yield^b (%)
a Unless otherwise noted, ortho-haloacetophenone (0.20 mmol) was treated with Pd catalyst (5 mol%) in the presence of ligand (L) (10 mol%) and base (1.5 equiv.) in DMF (1.0 mL) at 150 °C for 3 h under Ar condition in a sealed tube, followed by flash chromatography on SiO2.b Isolated yield.c The reaction temperature was 140 °C.d 2.5 mol% of PdCl2 was used.
1	Br	Pd(OAc)2	L1	NaHCO3	23/16
2	Br	Pd(OAc)2	L1	K2CO3	32/32
3	Br	Pd(OAc)2	L1	Cs2CO3	14/10
4	Br	Pd(OAc)2	L1	NEt3	0/16
5	Br	Pd(TFA)2	L1	K2CO3	28/37
6	Br	Pd(MeCN)2Cl2	L1	K2CO3	32/32
7	Br	PdCl2	L1	K2CO3	41/37
8	Br	PdCl2	L2	K2CO3	41/42
9	Br	PdCl2	L3	K2CO3	42/39
10	Br	PdCl2	L4	K2CO3	32/18
11	Br	PdCl2	L5	K2CO3	0/22
12	Br	PdCl2	L6	K2CO3	0/0
13	Br	PdCl2	L7	K2CO3	0/0
14	Cl	PdCl2	L3	K2CO3	0/0
15	I	PdCl2	L1	K2CO3	14/28
16	I	PdCl2	L2	K2CO3	60/4
17	I	PdCl2	L3	K2CO3	80/<5
18	I	PdCl2	L4	K2CO3	46/18
19	I	PdCl2	L3	K2CO3	71/4^c
20	I	PdCl2	L3	K2CO3	68/<5^d

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Although the competitive C–H arylation led to lower yield of the desired dibenzo-cycloheptenone 2a, this positive result still encouraged us to conduct further optimization of the reaction conditions for achieving excellent selectivity. Then, we found the PdCl₂/PPh₃/K₂CO₃ system could afford 2a and 3a in 78% overall yield, but the reaction specification is still very poor (2a/3a ≈ 1, entry 7). Subsequently, we had to switch our focus to the substrate and ligand screening for improving the reaction selectivity (entries 8–17). To our delight, ortho-iodo-substituted acetophenone (1c) could high-specifically give the desired product 2a in 80% yield using 1,3-bis (diphenylphosphino) propane (DPPP) (L₃) as ligand, and only trace amounts of 3a (<5% yield) was observed (entry 17). Notably, the Pd-catalyzed cascade cyclization of ortho-chloro-substituted acetophenone (1a) could not furnish 2a or 3a under PdCl₂/L₃/K₂CO₃ conditions, and the starting material 1a was recovered completely (entry 14). Further optimization of this reaction conditions demonstrated that lowering the reaction temperature or reducing the Pd catalyst loading led to poorer yield of 2a (compare entries 17 with 19 and 20) (see ESI for more details†).

Having established an efficient reaction protocol that enables the smooth cascade homocoupling cyclization of ortho-iodoacetophenone, we next investigated the effect of substituents on this tandem reaction. As shown in Table 2, although the various functional group-substituted phenylketones (1) could smoothly homocouple and cyclize to furnish dibenzo-cycloheptenone 2 under the optimized conditions, the substituted group on the benzene ring showed significant electronic effects. The electron donating group including 5-MeO, 5-Me, 5-NH₂, 5-NHAc, 5-aryl, 5-alkynyl, 4-Me, 4-MeO, 4-NH₂ and 4-AcNH on the phenyl ring afforded the dibenzo-7-membered-ring compounds in moderate to excellent yields (48–80%) (entries 1–5, 10–19).¹⁵ On the contrary, the electron withdrawing group such as 5-Cl and 5-CO₂Et on the phenyl ring gave the desired product in poorer yields (30–46%) (entries 6 and 9). It is worth noting that the 5-bromo-substituted phenylketone 1i led to the formation of 3-acetylphenanthrene instead of 7-membered ring product (entry 7). Moreover, no cascade homocoupling/cyclization product from the electon-poor 5-nitro-substituted phenylketone 1j was observed (entry 8). To further explore the substrate scope, we also investigated the effect of the acyl substituent (R₁CH₂CO–) on this cascade reaction, and found the ortho-propionyl phenyl iodide (1v) and ortho-phenyl acetyl phenyl iodide (1w) could also provide the expected polysubstituted dibenzo-cycloheptenone 2t and 2u (entries 20 and 21). Unfortunately, ortho-bromoactyl phenyl iodide (1x) only led to the formation of 2a in which bromo group was reductively removed. In addition, we tried to use the 1-(2-iodo-3-methyl-phenyl)-ethanone (1y) as a substrate, but no desired product 2v was obtained possibly due to the “ortho-substitutent” effect (entry 23).

Table 2 Pd-catalyzed cascade cyclization of ortho-acylphenyl iodides^a

Entry	Substrate	Product	Yield^b (%)
a Unless otherwise noted, ortho-acylphenyl iodides 1 (0.20 mmol) was treated with PdCl2 (5 mol%) in the presence of ligand (DPPP) (10 mol%) and K2CO3 (1.5 equiv.) in DMF (1.0 mL) at 150 °C for 3 h under Ar condition in a sealed tube, followed by flash chromatography on SiO2.b Isolated yield.
1			80
2			72
3			80
4			64
5			72
6			35
7			30
8			0
9			46
10			62
11			66
12			80
13			61
14			48
15			74
16			75
17			72
18			68
19			78
20			34
21			40
22			48
23			0

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To further investigate the reaction mechanism, we conducted the Pd(II)-catalyzed cascade cyclization of ortho-iodoacetophone (1c) at lower reaction temperature (130 °C) in order to trap some possible byproducts and intermediates (Scheme 1a). After the reaction was carried out for 0.5 h, we observed the formation of alcohol intermediate 3b (18% isolated yield) which could be further converted into the desired product 2a in 82% yield under our standard conditions (Scheme 1b). Considering that aryl halides (1c) could easily convert to symmetric biaryl ketone (3c) using palladium catalysts via a Ullmann process,^5d,16 and the alcohol intermediate 3b is also possibly derived from the ketone 3c via an intramolecular aldol reaction (Scheme 1c), we tried to use 3c as a substrate under our standard conditions. As expected, we also obtained the 7-membered-ring product 2a in 81% yield (Scheme 1d).

Scheme 1 Control reactions.

Although the exact reaction mechanism about Pd-catalyzed homocoupling of aryl halides is not still clear,¹⁷ on the basis of the above-mentioned control experimental results, we proposed two plausible reaction pathways (see Fig. 2). At first, the organic phosphine ligand (DPPP) or DMF¹⁸ reduces Pd(II) to Pd(0), followed by the oxidative addition with Ar–I (1c) to form Pd(II) intermediate A.¹⁵ Then the second oxidative addition of Pd(II) intermediate A with another ortho-iodoacetophenone molecule (1c) via Pathway I leads to the formation of the Pd(IV) intermediate B,^15,19 and subsequent reductive elimination affords homocoupling product 3c which can further lead to the formation of the final dibenzo-cycloheptenone 2a via cascade intramolecular aldol–dehydration process;²⁰ in addition to Pathway I, an alternative reaction Pathway II can not be ruled out in the absence of strong oxidizing agents, in which the disproportionation between two Ar–Pd(II)–I (A) molecules can lead to Ar–Pd(II)–Ar (C) and Pd(II)I₂.²¹ The resulting bisarylpalladium(II) C will be subjected to reductive elimination to afford the corresponding coupling product 3c and Pd(0).

Fig. 2 The proposed reaction mechanism.

Conclusions

In summary, we have developed an efficient Pd-catalyzed cascade homocoupling–aldol–dehydration reaction of ortho-acylphenyl iodides to rapidly construct colchinol analogues in moderate to good yields, and the further biological activity evaluation for these compounds is currently underway in our laboratory.

Experimental

General information

Unless otherwise noted, all reagents including 1a, 1b and 1c were purchased from commercial suppliers and used without purification, and all reactions were carried out under argon atmosphere in flame-dried sealed tubes with magnetic stirring. Solvents were treated with 4 Å molecular sieves or sodium and distilled prior to use. Flash chromatography was performed on silica gel (40–63 mm) by standard technique. ¹H and ¹³C NMR spectra were recorded on a 400 MHz spectrometer at room temperature with tetramethylsilane (TMS) as internal standard. Chemical shifts are reported in parts per million (ppm) and coupling constants are reported as Hertz (Hz). Splitting patterns are designated as singlet (s), doublet (d), triplet (t), quartet (q). Splitting patterns that could not be interpreted or easily visualized are designated as multiple (m). High resolution exact mass measurements (HR-MS) were performed on a TOF spectrometer (Micromass). Infrared spectra (IR) were reported as wavelength numbers (cm⁻¹). Infrared spectra were recorded by preparing a KBr pellet containing the title compound. Crystal data were obtained by employing graphite monochromated Mo-Kα radiation (λ = 0.71073 Å) at 293(2) K and operating in the φ–ω scan mode. The structure was solved by direct methods SHELXS-97; 1-(2-amino-5-methylphenyl)ethanone,²⁰ 1-(2-amino-5-chlorophenyl)ethanone,²² 2-amino-5-nitroacetophenone,²³ 1-(2-amino-5-bromophenyl)ethanone,²⁴ 1-(4-amino-[1,1′-biphenyl]-3-yl)ethanone,²⁴ 1-(2-amino-5-(thiophen-3-yl)phenyl)ethanone,²⁴ 1-(2-amino-5-(furan-2-yl)phenyl)ethanone,²⁴ 1-(2-amino-5-(phenylethynyl)phenyl)ethanone,²⁴ ethyl-3-acetyl-4-aminobenzoate,²⁵ 1-(2-amino-4,5-dimethylphenyl)ethanone,²⁶ 1-(2-amino-3-methylphenyl)ethanone²⁷ and 1,1′-([1,1′-biphenyl]-2,2′-diyl)diethanone,²⁸ 1-(2-iodo-5-methoxyphenyl)ethanone (1e),²⁹ 1-(2-iodo-4-methylphenyl)ethanone (1q),³⁰ 1-(2-iodo-4-methoxyphenyl)ethanone (1r),³⁰ 1-(2-iodophenyl)propan-1-one (1v),²⁹ 1-(2-iodophenyl)-2-phenyl-1-ethanone (1w),³¹ 2-bromo-1-(2-iodophenyl)ethanone (1x)³² and 2-iodo-3-methylacetophenone (1y)³³ were prepared using the previous reported procedure. Procedures for the preparation of ortho-acylphenyl iodides.

Procedure A: general procedure for the preparation of 1d, 1f, 1h–1p and 1u

To a stirred solution of p-toluenesulfonic acid monohydrate (3.8 g, 20.1 mol) in acetonitrile (24 mL) was added corresponding 4- or 5-substituted-2-acyl-anilines (6.7 mmol). The resulting suspension of protonated amine was cooled to 10 °C. To this mixture was carefully added an aqueous solution (4 mL) of potassium iodide (2.78 g, 16.75 mmol) and sodium nitrite (0.92 g, 13.4 mmol). The resulting brown solution was warmed to room temperature after N₂ gas evolution ceased. After 4.5 hours, 55 mL of water was added, the mixture was brought to pH = 9 by saturated sodium bicarbonate solution and adding 6 mL of a saturated aqueous solution of sodium thiosulfate. The resulting light yellow solution was extracted with ether (3 × 50 mL) and washed with brine, dried over anhydrous magnesium sulphate, and concentrated under reduced pressure to afford the aryl iodides after purification via flash column chromatography.

1-(2-Iodo-5-methylphenyl)ethanone (1d). Yellow oil; 48% yield; ¹H NMR (400 MHz, CDCl₃) δ 7.76 (dd, J = 7.9, 3.2 Hz, 1H), 7.26 (s, 1H), 6.93 (d, J = 7.9 Hz, 1H), 2.59 (s, 3H), 2.33 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 202.0, 143.9, 140.5, 138.2, 132.8, 129.1, 86.8, 29.5, 20.9; IR (KBr): 3680, 2979, 2924, 1699, 1562, 1467, 1268, 1175, 1120, 1014, 756 cm⁻¹; HRMS (EI) calcd for [M]⁺: C₉H₉IO 259.9693, found 259.9692.

1-(5-Amino-2-iodophenyl)ethanone (1f). Yellow solid; 52% yield; mp 276–278 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.60 (d, J = 8.4 Hz, 1H), 6.75 (d, J = 2.5 Hz, 1H), 6.48 (dd, J = 8.4, 2.5 Hz, 1H), 3.86 (s, 2H), 2.57 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 202.4, 146.6, 145.0, 141.0, 118.6, 114.7, 75.3, 29.5; IR (KBr): 3541, 2955, 1631, 1528, 1484, 1242, 1125, 1010, 754, 536 cm⁻¹. HRMS (EI) calcd for [M]⁺: C₈H₈INO 260.9645, found 260.9646.

Procedure B: general procedure for the preparation of 1g and 1t

A solution of 1-(5-amino-2-iodophenyl)ethanone (1f) or 1-(4-amino-2-iodophenyl)ethanone (1s) (3.7 mmol) in dichloromethane (15 mL) at room temperature was treated with triethylamine (4 mmol) and acetyl chloride (4.5 mmol). The reaction mixture was stirred at room temperature for 3 h. The reaction mixture was diluted with EtOAc and washed with water. The aqueous layer was extracted with ethyl acetate. The combined extracts were washed with brine, dried over MgSO₄, and concentrated to provide the desired product 1g or 1t after purification via flash column chromatography.

N-(3-Acetyl-4-iodophenyl)acetamide (1g). Yellow solid; 82% yield; mp 223–225 °C; 1H NMR (400 MHz, CDCl₃) δ 8.11 (d, J = 18.9 Hz, 1H), 7.84–7.76 (m, 2H), 7.27 (d, J = 9.2 Hz, 1H), 2.60 (s, 3H), 2.18 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 202.6, 169.6, 144.2, 140.9, 138.7, 123.2, 119.7, 83.4, 29.6, 24.4; IR (KBr): 3601, 2999, 1718, 1588, 1268, 1115, 1024, 755, 561 cm⁻¹; HRMS (EI) calcd for [M + Na]⁺: C₁₀H₁₀INO₂Na 325.9648, found 325.9655.

1-(5-Chloro-2-iodophenyl)ethanone (1h). Yellow oil; 40% yield; ¹H NMR (400 MHz, CDCl₃) δ 7.83 (d, J = 8.4 Hz, 1H), 7.41 (d, J = 2.4 Hz, 1H), 7.11 (dd, J = 8.4, 2.4 Hz, 1H), 2.60 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 200.3, 145.4, 141.9, 134.7, 131.8, 128.3, 88.0, 29.4; IR (KBr): 3618, 2936, 1700, 1548, 1447, 1270, 1229, 1011, 814, 754, 670 cm⁻¹. HRMS (EI) calcd for [M]⁺: C₈H₆IClO 279.9146, found 279.9147.

1-(5-Bromo-2-iodophenyl)ethanone (1i). Yellow oil; 53% yield; ¹H NMR (400 MHz, CDCl₃) δ 7.77 (d, J = 8.4 Hz, 1H), 7.55 (d, J = 2.3 Hz, 1H), 7.25 (dd, J = 8.4, 2.4 Hz, 1H), 2.60 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 200.2, 145.6, 142.1, 134.8, 131.2, 122.5, 88.9, 29.4; IR (KBr): 3542, 2987, 1695, 1447, 1338, 1142, 1019, 754, 548 cm⁻¹; HRMS (EI) calcd for [M]⁺: C₈H₆IBrO 323.8641, found 323.8640.

1-(2-Iodo-5-nitrophenyl)ethanone (1j). Yellow solid; 36% yield; mp 145–147 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.27 (d, J = 2.4 Hz, 1H), 8.17 (d, J = 8.6 Hz, 1H), 7.96 (dd, J = 8.6, 2.5 Hz, 1H), 2.69 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 199.5, 147.8, 145.0, 142.3, 125.6, 122.6, 99.3, 29.3; IR (KBr): 3779, 3538, 3082, 2916, 1704, 1567, 1415, 1264, 1113, 1014, 752, 494 cm⁻¹; HRMS (EI) calcd for [M]⁺: C₈H₆INO₃ 290.9387, found 290.9388.

Ethyl-3-acetyl-4-iodobenzoate (1k). Yellow oil; 54% yield; ¹H NMR (400 MHz, CDCl₃) δ 8.11 (d, J = 2.0 Hz, 1H), 8.05 (d, J = 8.2 Hz, 1H), 7.76 (dd, J = 8.2, 2.0 Hz, 1H), 4.42 (q, J = 7.1 Hz, 2H), 2.67 (s, 3H), 1.42 (t, J = 7.1 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 200.9, 165.3, 144.0, 141.3, 132.1, 130.6, 128.9, 97.0, 61.6, 29.4, 14.2; IR (KBr): 3782, 3542, 1695, 1447, 1338, 1142, 1019, 754, 548 cm⁻¹; HRMS (EI) calcd for [M]⁺: C₁₁H₁₁IO₃ 317.9747, found 317.9749.

1-(6-Iodobenzo[d][1,3]dioxol-5-yl)ethanone (1l). Yellow solid; 65% yield; mp 93–94 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.37 (s, 1H), 7.06 (s, 1H), 6.05 (s, 2H), 2.58 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 199.5, 150.3, 148.2, 136.6, 120.6, 109.1, 102.3, 81.3, 29.2; IR (KBr): 2992, 2906, 1690, 1607, 1482, 1375, 1239, 1128, 1034, 930, 863, 754 cm⁻¹; HRMS (EI) calcd for [M]⁺: C₉H₇IO₃ 289.9434, found 289.9435.

1-(4-Iodo-[1,1′-biphenyl]-3-yl)ethanone (1m). Yellow solid; 61% yield; mp 87–89 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.96 (d, J = 8.2 Hz, 1H), 7.62 (d, J = 2.1 Hz, 1H), 7.57–7.52 (m, 2H), 7.45 (t, J = 7.4 Hz, 2H), 7.38 (t, J = 7.2 Hz, 1H), 7.32 (dd, J = 8.2, 2.0 Hz, 1H), 2.65 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 201.9, 144.7, 141.4, 141.2, 139.1, 130.4, 129.1, 128.2, 126.9, 126.9, 89.5, 29.6; IR (KBr): 3120, 2920, 2767, 1692, 1452, 1355, 1224, 1010, 755, 690 cm⁻¹; HRMS (EI) calcd for [M]⁺: C₁₄H₁₁IO 321.9849, found 321.9848.

1-(2-Iodo-5-(thiophen-3-yl)phenyl)ethanone (1n). Yellow solid; 57% yield; mp 67–68 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.92 (d, J = 8.2 Hz, 1H), 7.62 (d, J = 1.9 Hz, 1H), 7.49 (d, J = 1.4 Hz, 1H), 7.42 (dd, J = 4.7, 3.1 Hz, 1H), 7.33 (dd, J = 12.1, 3.7 Hz, 2H), 2.65 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 202.0, 144.9, 141.1, 140.2, 136.0, 129.5, 127.0, 126.1, 125.9, 121.4, 88.7, 29.6; IR (KBr): 3463, 2922, 2889, 1701, 1625, 1458, 1352, 1256, 1014, 780, 691 cm⁻¹; HRMS (EI) calcd for [M]⁺: C₁₂H₉IOS 327.9413, found 327.9412.

1-(5-(Furan-2-yl)-2-iodophenyl)ethanone (1o). Yellow solid; 52% yield; mp 94–96 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.90 (d, J = 8.3 Hz, 1H), 7.72 (d, J = 2.0 Hz, 1H), 7.48 (d, J = 8.2 Hz, 1H), 7.37 (dd, J = 8.3, 2.0 Hz, 1H), 6.71 (d, J = 3.3 Hz, 1H), 6.49 (dd, J = 3.3, 1.7 Hz, 1H), 2.65 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 201.7, 151.9, 144.5, 142.9, 141.1, 130.9, 126.6, 123.3, 112.0, 106.6, 88.7, 29.5; IR (KBr): 3119, 2922, 2855, 1766, 1695, 1555, 1356, 1293, 1090, 961, 820 cm⁻¹; HRMS (EI) calcd for [M]⁺: C₁₂H₉IO₂ 311.9642, found 311.9644.

1-(2-Iodo-5-(phenylethynyl)phenyl)ethanone (1p). Yellow solid; 63% yield; mp 82–84 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.78 (d, J = 8.2 Hz, 1H), 7.48 (d, J = 2.0 Hz, 1H), 7.46–7.39 (m, 2H), 7.27–7.20 (m, 3H), 7.11 (dd, J = 8.2, 2.0 Hz, 1H), 2.50 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 200.8, 143.9, 141.0, 134.3, 131.7, 131.1, 128.8, 128.5, 123.6, 122.5, 91.8, 90.7, 87.6, 29.4; IR (KBr): 3120, 2957, 2764, 1695, 1447, 1356, 1131, 1009, 754, 685 cm⁻¹; HRMS (EI) calcd for [M]⁺: C₁₆H₁₁IO 345.9849, found 345.9850.

1-(4-Amino-2-iodophenyl)ethanone (1s). 3-Iodo-phenylamine (6.4 mmol), AlCl₃ (1.07 g, 8.0 mmol), and anhydrous CS₂ (15 mL) were added to a 50 mL flask under argon atmosphere. To the mixture was dropwise added a solution of acetyl chloride (0.628 g, 8.05 mmol) in anhydrous CS₂ (2.5 mL) at 0 °C. The resulting mixture was allowed to warm to room temperature and stirred for 1 h. Then the mixture was heated to reflux for 12 h. After being cooled to room temperature, the resulting mixture was poured out to ice water and extracted with CH₂Cl₂ (3 × 30 mL). The organic layer was washed with saturated aqueous Na₂CO₃ (20 mL) and brine (20 mL) and then dried over Na₂SO₄. After evaporation of the solvent under vacuum, the residue was purified by column chromatography on silica gel to give the desired compounds 1s. Yellow solid; 32% yield; mp 143–145 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.53 (d, J = 8.0 Hz, 1H), 7.29 (s, 1H), 6.64–6.61 (m, 1H), 4.07 (br, 2H), 2.56 (s, 3H); ¹³C NMR (101 MHz, CDCl3) δ 197.6, 150.2, 132.1, 130.0, 127.5, 113.2, 94.2, 28.3; IR (KBr): 3700, 2917, 2849, 1674, 1581, 1370, 1264, 754, 538 cm⁻¹; HRMS (EI) calcd for [M]⁺: C₈H₈INO 260.9645, found 260.9646.

N-(4-Acetyl-3-iodophenyl)acetamide (1t). A solution of 1-(4-amino-2-iodophenyl)ethanone (1s) (3.7 mmol) in dichloromethane (15 mL) at room temperature was treated with triethylamine (4 mmol) and acetyl chloride (4.5 mmol). The reaction mixture was stirred at room temperature for 3 h. The reaction mixture was diluted with EtOAc and washed with water. The aqueous layer was extracted with ethyl acetate. The combined extracts were rinsed with brine, dried over MgSO₄, and concentrated to provide the desired product 1t after purification via flash column chromatography. Yellow solid; 76% yield; mp 168–170 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.88 (s, 1H), 8.04 (s, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.44 (d, J = 8.0 Hz, 1H), 2.51 (s, 3H), 2.13 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 200.35, 169.7, 141.5, 137.2, 131.9, 130.1, 118.9, 92.0, 29.1, 24.6; IR (KBr): 3652, 2934, 1719, 1584, 1356, 1238, 1013, 754, 542 cm⁻¹. HRMS (EI) calcd for [M + H]⁺: C₁₀H₁₁INO₂ 302.3053, found 302.3077.

1-(2-Iodo-4,5-dimethylphenyl)ethanone (1u). Yellow oil; 60% yield; ¹H NMR (400 MHz, CDCl₃) δ 7.72 (s, 1H), 7.28 (s, 1H), 2.60 (s, 3H), 2.24 (s, 6H); ¹³C NMR (101 MHz, CDCl₃) δ 201.0, 141.8, 141.7, 140.8, 136.8, 130.2, 87.8, 29.2, 19.3, 19.2; IR (KBr): 3662, 3006, 2919, 2849, 1690, 1590, 1354, 1267, 754, 537 cm⁻¹; HRMS (EI) calcd for [M]⁺: C₁₀H₁₁IO 273.9849, found 273.9850.

General procedure for the Pd-catalyzed tandem homocoupling–aldol–dehydration of ortho-acylphenyl iodides

To the solution of ortho-acylphenyl iodides 1 (0.2 mmol) in DMF (1.0 mL) were added PdCl₂ (5 mol%), K₂CO₃ (1.5 equiv.) and DPPP (10 mol%) in a sealed tube under Ar atmosphere. The reaction mixture was stirred at 150 °C for 3 h, then cooled down to room temperature and filtered, and the corresponding filtrate was concentrated under vacuum and further purified by flash column chromatography on silica gel to furnish the target products 2.

7-Methyl-5H-dibenzo[a,c][7]annulen-5-one (2a). Yellow oil; 80% yield; ¹H NMR (400 MHz, CDCl₃) δ 7.71 (dd, J = 6.7, 5.0 Hz, 2H), 7.69–7.61 (m, 2H), 7.55 (t, J = 7.6 Hz, 1H), 7.49–7.33 (m, 3H), 6.53 (s, 1H), 2.36 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 194.0, 144.8, 142.0, 137.5, 137.3, 135.7, 133.2, 131.9, 131.2, 130.0, 128.6, 128.1, 127.8, 127.3, 127.1, 24.4; IR (KBr): 3067, 2983, 2890, 1724, 1636, 1595, 1445, 1222, 1147, 1104, 989, 881, 750 cm⁻¹. HRMS (EI) calcd for [M]⁺: C₁₆H₁₂O 220.0883, found 220.0883.

3,7,9-Trimethyl-5H-dibenzo[a,c][7]annulen-5-one (2b). Yellow oil; 72% yield; ¹H NMR (400 MHz, CDCl₃) δ 7.70 (d, J = 8.1 Hz, 1H), 7.67–7.61 (m, 2H), 7.52 (s, 1H), 7.43 (d, J = 8.1 Hz, 1H), 7.29 (d, J = 8.1 Hz, 1H), 6.61 (s, 1H), 2.46 (s, 6H), 2.44 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 193.0, 143.8, 140.4, 136.9, 136.2, 134.2, 133.8, 133.8, 131.9, 131.1, 130.5, 128.8, 128.5, 126.4, 126.4, 23.5, 20.2, 19.8; IR (KBr): 3635, 2997, 2951, 1731, 1643, 1445, 1268, 1191, 1150, 986, 840, 752 cm⁻¹. HRMS (EI) calcd for [M + H]⁺: C₁₈H₁₇O 249.1273, found 249.1274.

3,9-Dimethoxy-7-methyl-5H-dibenzo[a,c][7]annulen-5-one (2c). Yellow oil; 80% yield; ¹H NMR (400 MHz, CDCl₃) δ 7.68 (dd, J = 10.9, 8.9 Hz, 2H), 7.30 (d, J = 2.8 Hz, 1H), 7.23–7.16 (m, 2H), 7.04 (dd, J = 8.8, 2.7 Hz, 1H), 6.62 (s, 1H), 3.90 (d, J = 2.5 Hz, 6H), 2.44 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 193.5, 159.0, 158.4, 144.7, 142.3, 136.3, 132.9, 132.8, 131.2, 130.5, 130.4, 119.4, 114.5, 112.2, 109.8, 55.5, 55.4, 24.6; IR (KBr): 3547, 3002, 2839, 1702, 1602, 1483, 1271, 1001, 755 cm⁻¹. HRMS (EI) calcd for [M + H]⁺: C₁₈H₁₇O₃ 281.1172, found 281.1172.

3,9-Diamino-7-methyl-5H-dibenzo[a,c][7]annulen-5-one (2d). Yellow solid; 64% yield; mp 155–156 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.50 (d, J = 8.5 Hz, 1H), 7.45 (d, J = 8.5 Hz, 1H), 7.00 (d, J = 2.2 Hz, 1H), 6.88 (d, J = 1.9 Hz, 1H), 6.85 (dd, J = 8.5, 2.2 Hz, 1H), 6.75–6.71 (m, 1H), 6.49 (s, 1H), 3.79 (s, 4H), 2.31 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 193.9, 145.7, 145.0, 144.8, 141.8, 135.9, 132.4, 132.3, 130.8, 128.9, 118.7, 116.2, 112.5, 112.0, 24.7; IR (KBr): 3781, 3662, 3005, 2919, 1666, 1485, 1267, 1018, 754 cm⁻¹. HRMS (EI) calcd for [M + H]⁺: C₁₆H₁₅N₂O 251.1178, found 251.1179.

N,N′-(7-Methyl-5-oxo-5H-dibenzo[a,c][7]annulene-3,9-diyl)diacetamide (2e). Yellow solid; 72% yield; mp 129–131 °C; ¹H NMR (400 MHz, DMSO) δ 10.26 (d, J = 19.1 Hz, 2H), 8.04 (s, 1H), 7.94 (d, J = 10.4 Hz, 2H), 7.84 (d, J = 7.0 Hz, 2H), 7.77 (d, J = 8.7 Hz, 1H), 6.65 (s, 1H), 2.40 (s, 3H), 2.11 (s, 6H). ¹³C NMR (101 MHz, DMSO) δ 192.6, 168.7, 144.5, 141.2, 139.0, 138.7, 135.0, 132.4, 131.9, 131.2, 130.5, 122.1, 119.6, 116.9, 116.0, 24.0, 24.0, 23.9; IR (KBr): 3700, 3462, 3008, 2922, 1662, 1268, 1022, 999, 825, 755 cm⁻¹. HRMS (EI) calcd for [M + Na]⁺: C₂₀H₁₉N₂O₃Na 357.1209, found 357.1204.

3,9-Dichloro-7-methyl-5H-dibenzo[a,c][7]annulen-5-one (2f). Yellow solid; 35% yield; mp 141–142 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J = 2.2 Hz, 1H), 7.70 (dd, J = 5.3, 3.2 Hz, 2H), 7.65 (d, J = 8.6 Hz, 1H), 7.60 (dd, J = 8.5, 2.3 Hz, 1H), 7.46 (dd, J = 8.6, 2.1 Hz, 1H), 6.63 (s, 1H), 2.44 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 191.0, 143.10, 141.7, 136.0, 134.0, 133.9, 133.7, 133.3, 132.7, 132.0, 130.4, 130.2, 127.8, 126.2, 23.3; IR (KBr): 3680, 2921, 2854, 1730, 1647, 1460, 1260, 1091, 1023, 804 cm⁻¹. HRMS (EI) calcd for [M + H]⁺: C₁₆H₁₁Cl₂O 289.0181, found 289.0181.

1-Phenanthren-3-yl-ethanone (2g). Yellow oil; 35% yield; ¹H NMR (400 MHz, CDCl₃) δ 8.11 (s, 1H), 7.86 (d, J = 7.7 Hz, 1H), 7.72 (d, J = 7.7 Hz, 1H), 7.55 (d, J = 7.3 Hz, 2H), 7.47 (t, J = 7.7 Hz, 1H), 7.40 (t, J = 7.5 Hz, 2H), 7.31 (t, J = 7.3 Hz, 1H), 2.59 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 197.1, 140.7, 139.1, 136.6, 130.7, 128.0, 127.9, 126.8, 126.1, 126.1, 125.9, 25.7; IR (KBr): 3009, 2947, 2852, 1680, 1622, 1501, 1324, 1233, 1009, 870, 765 cm⁻¹. MS (EI, 70 eV): m/z= 220.09 [M]⁺.

Diethyl-7-methyl-5-oxo-5H dibenzo[a,c][7]annulene-3,9-dicarboxylate (2i). Yellow solid; 46% yield; mp 122–124 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.44 (d, J = 1.6 Hz, 2H), 8.30 (dd, J = 8.3, 1.9 Hz, 1H), 8.13 (dd, J = 8.3, 1.7 Hz, 1H), 7.89 (d, J = 8.3 Hz, 1H), 7.84 (d, J = 8.3 Hz, 1H), 6.66 (d, J = 1.0 Hz, 1H), 4.45 (dd, J = 14.1, 7.0 Hz, 4H), 2.52 (d, J = 1.0 Hz, 3H), 1.44 (td, J = 7.1, 6.0 Hz, 6H). ¹³C NMR (101 MHz, CDCl₃) δ 192.8, 165.7, 165.5, 144.6, 142.2, 140.4, 140.1, 136.1, 133.7, 132.2, 131.8, 130.8, 130.4, 129.1, 128.9, 128.7, 61.5, 24.4, 14.3; IR (KBr): 3462, 2923, 2855, 1718, 1650, 1285, 1252, 1196, 1115, 754, 685 cm⁻¹. HRMS (EI) calcd for [M + Na]⁺: C₂₂H₂₀O₅Na 387.1202, found 387.1219.

2,3,9,10-Bis(di-1,3-benzodioxol)-7-methyl-5H-dibenzo[a,c][7]annulen-5-one (2j). Yellow solid; 62% yield; mp 222–224 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.26 (d, J = 3.8 Hz, 1H), 7.14 (d, J = 5.4 Hz, 3H), 6.54 (s, 1H), 6.06 (d, J = 7.2 Hz, 4H), 2.38 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 191.8, 150.5, 148.0, 147.9, 147.2, 143.6, 137.0, 133.7, 132.7, 131.6, 130.3, 110.9, 109.2, 106.8, 106.4, 102.0, 101.8, 24.9; IR (KBr): 3838, 3581, 3008, 2923, 1668, 1591, 1482, 1267, 1037, 754, 537 cm⁻¹. HRMS (EI) calcd for [M]⁺: C₁₈H₁₂O₅ 308.0679, found 308.0680.

7-Methyl-3,9-diphenyl-5H-dibenzo[a,c][7]annulen-5-one (2k). Yellow solid; 66% yield; mp 164–166 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.07 (s, 1H), 7.98–7.82 (m, 4H), 7.69 (d, J = 8.1 Hz, 3H), 7.65 (d, J = 7.5 Hz, 2H), 7.47 (dd, J = 15.5, 7.7 Hz, 4H), 7.38 (dt, J = 12.3, 6.3 Hz, 2H), 6.68 (s, 1H), 2.51 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 193.8, 144.9, 142.2, 140.9, 140.7, 140.1, 139.4, 136.1, 136.1, 136.0, 133.4, 132.3, 130.6, 129.8, 129.0, 129.0, 127.9, 127.9, 127.4, 127.2, 127.1, 125.9, 125.8, 24.6. IR (KBr): 3638, 3005, 2919, 2848, 1722, 1665, 1455, 1268, 754, 696 cm⁻¹. HRMS (EI) calcd for [M]⁺: C₂₈H₂₀O 372.1509, found 372.1507.

7-Methyl-3,9-di(thiophen-3-yl)-5H dibenzo[a,c][7]annulen-5-one (2l). Yellow solid; 80% yield; mp 226–227 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.94 (s, 1H), 7.82 (s, 1H), 7.76–7.70 (m, 2H), 7.67 (d, J = 8.2 Hz, 1H), 7.56 (d, J = 8.3 Hz, 1H), 7.49 (d, J = 1.1 Hz, 1H), 7.43 (s, 1H), 7.38 (d, J = 4.9 Hz, 1H), 7.32 (dd, J = 9.0, 5.9 Hz, 3H), 6.57 (s, 1H), 2.39 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 193.7, 144.8, 142.1, 141.2, 140.7, 136.0, 135.9, 135.8, 135.6, 135.3, 133.3, 132.2, 130.5, 129.1, 126.7, 126.7, 126.6, 126.2, 126.1, 125.0, 124.9, 121.3, 121.2, 24.6. IR (KBr): 3464, 2901, 2778, 1640, 1425, 1358, 1147, 1036, 780, 664 cm⁻¹. HRMS (EI) calcd for [M + H]⁺: C₂₄H₁₇OS₂ 385.0715, found 385.0740.

3,9-Di(furan-2-yl)-7-methyl-5H dibenzo[a,c][7]annulen-5-one (2m). Yellow solid; 61% yield; mp 188–189 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.11 (s, 1H), 8.04 (s, 1H), 7.93 (d, J = 8.3 Hz, 1H), 7.83 (d, J = 8.3 Hz, 1H), 7.76 (q, J = 8.6 Hz, 2H), 7.55 (s, 2H), 6.80 (d, J = 15.9 Hz, 2H), 6.68 (s, 1H), 6.54 (s, 2H), 2.53 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 193.5, 152.9, 152.7, 144.9, 142.8, 142.7, 142.0, 136.0, 136.0, 135.8, 133.2, 132.0, 130.7, 130.3, 130.2, 126.3, 123.9, 122.4, 122.2, 111.9, 111.9, 106.5, 106.2, 24.6. IR (KBr): 3546, 3402, 2922, 1642, 1428, 1359, 1054, 742 cm⁻¹. HRMS (EI) calcd for [M + Na]⁺: C₂₄H₁₆O₃Na 375.0991, found 375.1001.

7-Methyl-3,9-bis(phenylethynyl)-5H-dibenzo[a,c][7]annulen-5-one (2n). Yellow solid; 48% yield; mp 174–175 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.96 (d, J = 1.2 Hz, 1H), 7.89 (d, J = 1.4 Hz, 1H), 7.78 (dd, J = 8.7, 4.9 Hz, 2H), 7.74 (d, J = 8.2 Hz, 1H), 7.63 (dd, J = 8.3, 1.5 Hz, 1H), 7.57 (ddd, J = 9.2, 6.6, 3.0 Hz, 4H), 7.42–7.34 (m, 6H), 6.65 (d, J = 0.7 Hz, 1H), 2.48 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.9, 144.4, 141.8, 136.6, 136.3, 135.9, 133.8, 133.5, 131.8, 131.7, 131.7, 131.4, 130.6, 130.5, 130.0, 128.7, 128.6, 128.4, 128.4, 123.8, 123.3, 122.8, 122.8, 91.8, 91.2, 88.5, 88.2, 24.5. IR (KBr): 3480, 3120, 2922, 2780, 1750, 1690, 1510, 1440, 1358, 1120, 864, 687 cm⁻¹. HRMS (EI) calcd for [M]⁺: C₃₂H₂₀O 420.1509, found 420.1509.

2,7,10-Trimethyl-5H-dibenzo[a,c][7]annulen-5-one (2o). Yellow oil; 74% yield; ¹H NMR (400 MHz, CDCl₃) δ 7.74 (d, J = 7.9 Hz, 1H), 7.64 (d, J = 8.0 Hz, 2H), 7.59 (s, 1H), 7.37 (d, J = 7.9 Hz, 1H), 7.31 (d, J = 8.1 Hz, 1H), 6.60 (s, 1H), 2.53 (s, 3H), 2.49 (s, 3H), 2.45 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 193.6, 144.7, 141.5, 139.7, 138.5, 137.5, 137.4, 133.2, 132.7, 132.3, 130.5, 129.1, 128.6, 127.6, 127.1, 24.5, 21.6, 21.3; IR (KBr): 3441, 2921, 2855, 1644, 1577, 1445, 1358, 1301, 1035, 823, 743 cm⁻¹. HRMS (EI) calcd for [M + Na]⁺: C₁₈H₁₆ONa 271.1093, found 271.1093.

2,10-Dimethoxy-7-methyl-5H-dibenzo[a,c][7]annulen-5-one (2p). Yellow oil; 75% yield; ¹H NMR (400 MHz, CDCl₃) δ 7.73 (d, J = 8.7 Hz, 1H), 7.58 (d, J = 8.9 Hz, 1H), 7.17 (s, 2H), 6.99 (d, J = 8.7 Hz, 1H), 6.94 (dd, J = 8.8, 2.0 Hz, 1H), 6.44 (s, 1H), 3.83 (s, 3H), 3.81 (s, 3H), 2.32 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 192.4, 161.7, 159.2, 144.1, 139.3, 139.2, 135.5, 131.9, 130.1, 129.0, 116.8, 114.9, 114.2, 113.7, 55.5, 55.4, 24.6; IR (KBr): 3454, 2936, 2854, 1637, 1594, 1454, 1359, 1298, 1237, 1028, 857, 820 cm⁻¹. HRMS (EI) calcd for [M + H]⁺: C₁₈H₁₇O₃ 281.1172, found 281.1174.

2,10-Diamino-7-methyl-5H-dibenzo[a,c][7]annulen-5-one (2q). Yellow solid; 72% yield; mp 202–204 °C; ¹H NMR (400 MHz, DMSO) δ 7.47 (dd, J = 10.0, 8.6 Hz, 2H), 6.95 (d, J = 2.3 Hz, 1H), 6.89 (d, J = 2.0 Hz, 1H), 6.73 (ddd, J = 8.4, 4.3, 2.3 Hz, 2H), 6.25 (s, 1H), 5.87 (s, 4H), 2.30 (s, 3H). ¹³C NMR (101 MHz, DMSO) δ 190.0, 151.7, 149.1, 143.5, 139.6, 139.2, 130.3, 129.5, 128.7, 123.8, 115.4, 113.9, 113.6, 113.2, 24.3; IR (KBr): 3781, 3636, 2922, 1665, 1590, 1315, 1117, 995, 754 cm⁻¹. HRMS (EI) calcd for [M + H]⁺: C₁₆H₁₅N₂O 251.1178, found 251.1178.

N,N′-(7-Methyl-5-oxo-5H-dibenzo[a,c][7]annulene-2,10-diyl)diacetamide (2r). Yellow solid; 68% yield; mp 132–134 °C; ¹H NMR (400 MHz, DMSO) δ 10.42 (s, 1H), 10.32 (s, 1H), 8.15 (s, 1H), 8.07 (s, 1H), 7.89–7.73 (m, 3H), 7.65 (d, J = 8.5 Hz, 1H), 6.53 (s, 1H), 2.40 (s, 3H), 2.12 (d, J = 9.2 Hz, 6H). ¹³C NMR (101 MHz, DMSO) δ 191.4, 169.0, 168.8, 144.3, 142.1, 139.6, 137.6, 137.4, 136.5, 131.8, 130.1, 128.4, 128.2, 120.9, 119.1, 118.8, 118.7, 24.1, 24.0, 23.9; IR (KBr): 3636, 2923, 1722, 1667, 1489, 1324, 1268, 1021, 755, 537 cm⁻¹. HRMS (EI) calcd for [M + Na]⁺: C₂₀H₁₈N₂O₃Na 357.1209, found 357.1215.

2,3,7,9,10-Pentamethyl-5H-dibenzo[a,c][7]annulen-5-one (2s). Yellow oil; 78% yield; ¹H NMR (400 MHz, CDCl₃) δ 7.58 (d, J = 7.1 Hz, 2H), 7.54 (s, 1H), 7.47 (s, 1H), 6.57 (d, J = 0.9 Hz, 1H), 2.42 (d, J = 1.0 Hz, 3H), 2.41 (s, 3H), 2.38 (s, 3H), 2.36 (d, J = 2.3 Hz, 6H). ¹³C NMR (101 MHz, CDCl₃) δ 193.6, 144.7, 140.4, 139.5, 137.4, 136.8, 136.1, 135.3, 135.1, 133.3, 132.6, 132.6, 130.9, 128.3, 128.1, 24.6, 20.0, 19.7, 19.6, 19.2; IR (KBr): 3436, 2920, 2854, 1640, 1587, 1452, 1360, 1054, 742 cm⁻¹. HRMS (EI) calcd for [M + Na]⁺: C₂₀H₂₀ONa 299.1406, found 299.1423.

7-Ethyl-6-methyl-5H-dibenzo[a,c][7]annulen-5-one (2t). Yellow oil; 34% yield; ¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J = 7.9 Hz, 1H), 7.68–7.65 (m, 1H), 7.64–7.57 (m, 2H), 7.53–7.45 (m, 2H), 7.39 (ddt, J = 14.9, 7.3, 3.7 Hz, 2H), 2.76 (q, J = 7.5 Hz, 2H), 2.18 (s, 3H), 1.08 (t, J = 7.5 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 201.3, 143.5, 142.2, 138.5, 136.9, 136.8, 136.7, 130.9, 130.7, 128.3, 127.7, 127.5, 127.3, 127.0, 125.8, 27.0, 17.3, 13.1; IR (KBr): 3439, 2919, 2852, 1649, 1457, 1359, 1054, 987, 741 cm⁻¹. HRMS (EI) calcd for [M + Na]⁺: C₁₈H₁₆ONa 271.1093, found 271.1103.

7-Benzyl-6-phenyl-5H-dibenzo[a,c][7]annulen-5-one (2u). Yellow solid; 40% yield; mp 75–77 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.69 (d, J = 7.8 Hz, 1H), 7.64 (dt, J = 8.7, 3.8 Hz, 1H), 7.60–7.51 (m, 2H), 7.44 (dd, J = 13.7, 5.4 Hz, 1H), 7.37 (dd, J = 7.6, 1.2 Hz, 1H), 7.29–7.19 (m, 7H), 7.02–6.91 (m, 3H), 6.76 (d, J = 6.9 Hz, 2H), 3.96 (s, 2H). ¹³C NMR (101 MHz, CDCl₃) δ 199.1, 145.9, 144.8, 139.3, 138.6, 137.6, 137.5, 136.5, 135.5, 131.1, 130.9, 129.1, 128.5, 128.4, 128.2, 128.0, 128.0, 127.7, 127.7, 127.5, 125.8, 125.2, 39.1. IR (KBr): 3572, 2441, 2922, 2853, 1644, 1434, 1359, 1067, 737, 696 cm⁻¹. HRMS (EI) calcd for [M + Na]⁺: C₂₈H₂₀ONa 395.1465, found 395.1438.

Mechanistic studies about this transformation

4-(2-Acetylphenyl)-7-methyl-5H-dibenzo[a,c][7]annulen-5-one (3a). To the solution of ortho-acylphenyl bromide 1 (0.2 mmol) in DMF (1.0 mL) were added PdCl₂ (5 mol%), K₂CO₃ (1.5 equiv.) and DPPP (10 mol%) in a sealed tube under Ar atmosphere. The reaction mixture was stirred at 150 °C for 3 h, then cooled down to room temperature and filtered, and the corresponding filtrate was concentrated under vacuum and further purified by flash column chromatography on silica gel to furnish the target products 3a. Yellow solid; 39% yield; mp 125–126 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.73–7.63 (m, 3H), 7.58 (dd, J = 5.9, 3.4 Hz, 1H), 7.49 (t, J = 7.8 Hz, 1H), 7.39 (ddd, J = 9.3, 4.2, 1.6 Hz, 3H), 7.37–7.32 (m, 1H), 7.21 (dd, J = 7.5, 0.9 Hz, 1H), 7.15–7.13 (m, 1H), 6.30 (d, J = 1.0 Hz, 1H), 2.29 (d, J = 1.0 Hz, 3H), 2.19 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 202.1, 195.6, 141.7, 140.7, 140.0, 138.5, 137.2, 137.1, 136.1, 133.4, 132.0, 130.6, 130.2, 129.7, 129.4, 128.2, 128.1, 127.9, 127.4, 126.5, 29.5, 23.3; HRMS (EI) calcd for [M + Na]⁺: C₂₄H₁₈O₂Na 361.1199, found 361.1207; IR (KBr): 3700, 2918, 2846, 1758, 1669, 1481, 1385, 1266, 1128, 755 cm⁻¹.

7-Hydroxy-7-methyl-6,7-dihydro-5H-dibenzo[a,c][7]annulen-5-one (3b). To the solution of ortho-acylphenyl iodide (1c) (0.2 mmol) in DMF (1.0 mL) were added PdCl₂ (5 mol%), K₂CO₃ (1.5 equiv.) and DPPP (10 mol%) in a sealed tube under Ar atmosphere. The reaction mixture was stirred at 150 °C for 1.5 h, then cooled down to room temperature and filtered, and the corresponding filtrate was concentrated under vacuum and further purified by flash column chromatography on silica gel to furnish the target products 3b. Yellow oil; ¹H NMR (400 MHz, CDCl₃) δ 7.66 (dd, J = 6.2, 1.9 Hz, 2H), 7.59 (td, J = 7.7, 1.3 Hz, 1H), 7.46–7.32 (m, 5H), 3.17 (q, J = 19.1 Hz, 2H), 2.80 (s, 1H), 1.54 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 202.6, 143.9, 140.2, 137.7, 136.4, 132.9, 131.8, 129.7, 128.5, 128.3, 128.3, 127.8, 71.0, 61.2, 28.2; HRMS (EI) calcd for [M]⁺: C₁₆H₁₄O₂ 238.0988, found 238.0989; IR (KBr): 3686, 2975, 2865, 1722, 1669, 1543, 1458, 1269, 1052, 754 cm⁻¹.

Acknowledgements

We thank the NSFC (no. 21372085) for financial support.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: Detailed experimental procedures and characterization of products. CCDC 998466. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4ra02055c

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