Oxidative Rearrangement of Stilbenes to 2,2-Diaryl-2-hydroxyacetaldehydes

Abstract

A one-pot oxone-mediated/iodine-catalyzed oxidative rearrangement of stilbenes leading to 2,2-diaryl-2-hydroxyacetaldehydes is described. Control experiments revealed that a 2,2-diarylacetaldehyde was initially formed that undergoes subsequent α-hydroxylation. The resulting α-hydroxyaldehydes have been subjected to a one-pot Still–Gennari olefination followed by cyclization, leading to 5,5-diaryl-γ-butenolides.

Introduction

The oxidation/rearrangement/oligomerization of stilbenes is an important biochemical transformation that has inspired great innovation and the use of various oxidizing agents.¹ The direct oxidation of stilbenes resulting in epoxides and/or vicinal diols is well established, and their acid/base-catalyzed rearrangements are well-studied reactions.^2,3 There are occasions where the rearrangement of initially formed epoxides/diols has been noticed during the oxidation of stilbenes.⁴ In this context, the house rearrangement of stilbene oxides leading to diarylacetaldehyde is a well-studied reaction.² In parallel, the Meinwald rearrangement of halohydrins or a one-pot halohydrin synthesis and its rearrangement have been established as an important alternative for the synthesis of diarylacetaldehyde without involving the epoxides.⁵ The diarylacetaldehydes are known to undergo decarbonylation, resulting in the corresponding benzophenones under oxidative and halogenation conditions.⁶ The possibility of combining all these events, i.e, olefin oxidation, pinacol rearrangement, and/or oxidative decarbonylation, is interesting, and this has been executed very recently for the direct synthesis of carbonyl compounds from the styrenes/stilbenes (Figure 1).⁷

Figure 1.

Selected oxidative rearrangement of stilbenes/aryl alkenes and the synthesis of α-hydroxy-2,2-diarylacetaldehyde 2.

In this manuscript, we document the direct conversion of stilbenes 1 to α-hydroxydiarylacetaldehydes 2. The possibility of obtaining α-hydroxydiarylacetaldehyde 2 from stilbenes was speculated considering a recent report from Fry and Merzel on the anodic oxidation of diphenylacetaldehyde leading to benzophenone, which indicated the occurrence of α-hydroxydiphenylacetaldehyde as an intermediate.⁸ Earlier, Weisenborn and Taub and Curtin and Bradley have documented the isolation of α-hydroxydiarylacetaldehydes during the epoxidation of the 1,1′-diaryethylenes.⁹ This option was employed with the idea of developing a general method for the synthesis of a 5,5-diaryl-γ-butenolide core,¹⁰ where the Still–Gennari olefination of α-hydroxydiarylacetaldehyde 2 and subsequent lactonization is a direct proposition.¹¹

Results and Discussion

With this speculation, documented methods for the direct conversion of aryl alkenes to carbonyl compounds have been examined. Among these, the reports of Sinha et al.,^5c Zhu and Zhao,^5f and Nama et al.^5g are interesting. Sinha and co-workers reported the conversion of stilbenes to diarylacetaldehydes employing NBS in the presence of a cationic surfactant under microwave irradiation.^5c Nama et al. and Zhu and Zhao reported the iodine-catalyzed oxidative rearrangement of aryl alkenes to β-arylketones.^5e−5g A close examination of these reports prompted the exploration of the NaI and oxone combination in our pursuit. Initial experiments employing simple stilbene as a substrate under Zhu and Zhao’s conditions (10 mol % NaI, 2 equiv of oxone in a 5:1 CH₃CN/H₂O mixture at rt) gave a mixture of diphenylacetaldehyde 3a (15%), diphenylacetic acid (35%), and benzophenone (10%) (Scheme 1). This prompted us to do parallel screening of reaction conditions by varying the reaction temperature and solvent ratio. Initial experiments with temperature variation revealed the formation of the requisite 2-hydroxy-2,2-diphenylacetaldehyde (2a). For example, when carried out at 80 °C with the same composition of the reaction contents, the required hydroxyacetaldehyde 2a was obtained in 35% yield along with 46% of diphenyl acetic acid. As shown in Table 1, changing the solvent composition also had some positive effect on the reaction outcome. When the reaction was conducted in a 1:1 mixture at rt, the formation of 3a in 42% yield along with the 12% benzaldehyde was observed.

Scheme 1. Selected Conditions for the Oxidative Rearrangement of Stilbene 1a.

Table 1. Optimization^a.

entry	iodine source	solvent ratio	yieldb
1	NaI	5:1	35c
2	NaI	1:1	66
3	I2	1:1	47
4	KI	1:1	48
5	CuI	1:1	42
6	NIS	1:1	19
7	NH4I	1:1	55
8	NBS	1:1	40d
9	NaIe	1:1	23
10	NaIf	1:1	48
11	I2	dioxane/H2O	46
12	NaI	DMSO/H2O	NR
13	NaI	MeOH/H2O	2
14	NaI	DME/H2O	5
15	NaI	DMF/H2O	30
16	NaI	acetone/H2O	1 + diketone
17	NaI + CTAB	1:1	56
18	NaI + TBAI	1:1	48
19	NaIg	1:1	28

^aAll reactions were carried out on an ∼0.5 mmol scale, 2 equiv of oxidant, and 0.1 equiv of iodine source; all reagent and substrate addition was done at room temperature (25 °C) and stirred for the next 15 h at 80 °C.

^bIsolated yields.

^cDiphenyl acetic acid as a major product.

^dBenzoin as a major product.

^e1 equiv of oxone.

^f2.5 equiv of oxone used.

^gReaction was carried out under microwave irradiation at 100 °C.

The best results were obtained when the reaction was conducted at 80 °C in a 1:1 CH₃CN/H₂O mixture for 15 h. The starting stilbene was completely consumed, the required 2,2-diaryl-2-hydroxyacetaldehyde (66%) was obtained as the major product, and a mixture of benzaldehyde/benzophenone (10%) was also isolated. Under similar conditions when different iodine sources such as I₂, KI, CuI, NIS, and NH₄I were employed, the required 2,2-diaryl-2-hydroxyacetaldehyde was obtained in 19–55% yield along with benzaldehyde and/or benzophenone as the minor products (entries 3–7). Furthermore, when NBS was used as the halogen source, benzoin was obtained in 40% yield (entry 8). Decreasing or increasing the amount of oxone was not encouraging (entries 9 and 10). Further experiments were carried out to shift the reaction outcome completely toward the formation of the required product 2a by changing the solvent combination, using additives, and using microwave. The results are not satisfactory.

Having realized the possibility of synthesizing 2,2-diphenyl-2-hydroxyacetaldehyde directly from stilbene, next we looked at the course of the reaction. The next concern was the hydroxylation reaction and the role of the oxone or the byproducts resulting after the initial oxidation. In order to understand this, we conducted a set of control experiments employing freshly prepared diphenylacetaldehyde 3a with the exclusion of the reaction components one after the other. As shown in Scheme 2, when 3a was refluxed under the employed conditions in the presence of oxone and NaI in a mixture of 1:1 acetonitrile/water, benzophenone in 42% yield and an uncharacterized polar product in 22% yield were isolated. Next, a similar outcome was noticed when the reaction was carried out in the absence of NaI. Interestingly, when only oxone was replaced, the requisite hydroxyaldehyde 2a was isolated in 37% yield along with 57% benzophenone, indicating that NaI is playing a role in α-hydroxylation.

Scheme 2. Control Experiments.

Next, when diphenylacetaldehyde 3a was heated in a mixture of 1:1 acetonitrile/water in the absence of both oxone and NaI, the formation of hydroxyaldehyde 2a (6%) and benzophenone (65%) was noticed, and when water was also removed, the starting 3a was seen to be intact. These experiments revealed that the presence of water is essential. In addition, a separate experiment was carried out where the solution of 3a in a mixture of 1:1 acetonitrile/water was purged with argon for 15 min and heated under an argon atmosphere in the dark in a closed flask covered with silver foil. In this case too, complete conversion of the starting diphenylacetaldehyde was noticed and resulted in the isolation of 2a in 6% yield and benzophenone in 65% yield. Interestingly, when the reaction was carried out by adjusting the pH to 5.5 (measured for normal optimized conditions), the yield of hydroxyaldehyde was improved to 18%; however, benzophenone (58%) was the major product, indicating that the pH of the reaction medium plays a role in the stability of the intermediate hydroxyacetaldehyde. As a control, when we replaced water with ethanol as a proton source or in dry acetonitrile, there was no formation of 2a or benzophenone. Finally, to examine the possibility of a radical pathway, the reaction was carried out in the presence of TEMPO as a radical suppresser that resulted in the isolation 2a in 5% yield and benzophenone in 66% yield.

All these results indicate that the reaction is proceeding via oxidation of diphenylacetaldehyde to hydroxyaldehyde, that any external oxidant may not be required for α-hydroxylation,^9,12 that the presence of water is important, and that it does not follow the radical pathway. This is in accordance with earlier reports where water was found to be the source of oxygen for oxidation of diphenylacetaldehyde to hydroxyaldehyde.^8a The ready deformylation of the hydroxyaldehyde to the benzophenone under neutral conditions and the isolation of the hydroxyacetaldehyde in moderate yields when conducted in the presence of acidic buffer suggest that the deformylation is pH-sensitive. Also, though the role of NaI on the α-hydroxylation step is not clear, its presence appears to be important.

Coming to α-hydroxylation of 3a, as discussed previously, there are two proposals postulated. One is a radical pathway comprising of oxygen abstracting the α-hydrogen followed by recombination of the carbon centered and peroxide radicals, which would results in the α-hydroperoxido-diphenylacetaldehyde.^7a The other one is an anodic oxidation pathway that involves the addition of water to a cationic radical generated after adding an electron to the enol of the diphenylacetaldehyde.⁸ The preliminary results in our case favor the second pathway; however, further studies are warranted to understand the course of oxidation and are currently in progress.

With this information in hand and with the help of earlier proposals on the iodine-mediated oxidative rearrangements,⁵ we propose the following tentative mechanism (Scheme 3). Initially, NaI is oxidized to HOI, which adds to the alkene in the presence of water to form the iodohydrin A. Further oxidation of iodine with oxone leads to the unstable hypervalent iodine intermediate B, which undergoes aryl ring migration to form the diphenylacetaldehyde 3, which subsequently undergoes oxidation, leading to the corresponding hydroxyaldehyde 2.

Scheme 3. Tentative Mechanism.

Next, the compatibility of various stilbenes under the current conditions has been examined. In general, substituted stilbenes having either electron-donating or electron-withdrawing groups on the benzene ring are found to be compatible (Scheme 4). However, the yields are moderate to good. In all cases, the corresponding cleaved aldehyde(s), in some cases, the corresponding acid¹³ and/or benzophenone, were obtained as minor products. Initially, stilbenes 1b–1h having substituents at the p-position (OMe, Me, iso-propyl, Cl, Br, I, and NO₂, respectively) on one of the aryl rings have been employed. The reactions proceeded smoothly and provided the corresponding 2,2-diaryl-2-hydroxyacetaldehydes 2b–2h in moderate yields (20–49%). Further ortho-substituted stilbene 1i was employed for the same reaction condition and gave the corresponding ortho-substituted hydroxyacetaldehyde 2i (35%) yield. Similarly, the oxidative rearrangement of unsymmetrical stilbenes having different substituents on both aryl rings 1j and 1k gave the requisite hydroxyacetaldehydes 2j and 2k (41–55%) yield. Next, we examined a benzyloxy-protected stilbene 1l, which gave product 2l in 46% yield. However, an increase in the number of methoxy groups on the aryl ring of stilbenes 1m–1o resulted in the α-hydroxydiarylaldehydes 2m–2o in lower yields (16–33%). The scope of oxidation was further examined employing stilbenes 1p and 1q having a naphthalene ring on one side. Here too, the oxidative rearrangement was facile and provided the hydroxyaldehydes 2p and 2q in good yields. The stilbene 1r having a tert-butyl group on one side of the aryl ring was also compatible under these conditions and gave the corresponding oxidation product 2r (42%). Interestingly, the oxidative rearrangement of stilbene 1s having methyl substitution on alkene was also facile and here we observed that the phenyl group is more prone to such migration than the methyl group, providing the hydroxyketone 2s in 64% yield.

Scheme 4. Substrate Scope.

Having access to a good number of α-hydroxydiarylacetaldehydes, we proceeded further to synthesize γ,γ-diaryl-γ-butenolides employing the Still–Gennari Wittig olefination followed by cyclization (Scheme 5). Generally employed methods for their synthesis involve either adding the aryl Grignard reagents to lactones/esters or starting with the benzophenones. These methods require multiple steps.¹⁰ After screening a couple of conditions reported for cis-Wittig olefination,¹¹ treatment of hydroxyaldehyde 2a with ethyl 2-[bis(2,2,2-trifluoroethoxy)phosphoryl]acetate in the presence of DBU and LiCl at −78 °C gave the required diaryl-γ-butenolide 4a in very good yields. Inspired with this initial success, all the earlier synthezised 2,2-diaryl-2-hydroxyacetaldehydes have been subjected for the cis-Wittig olefination followed by cyclization to obtain the corresponding lactones in moderate to good yields.

Scheme 5. Substrate Scope of γ,γ-Diaryl-γ-butenolide Synthesis.

It was notable that all the diarylhydroxyaldehydes with electron-donating groups as well as electron-withdrawing groups on the benzene ring gave similar yields. When the para-subtituted hydroxyaldehydes 2b–2h were subjected to this lactonization conditions, the corresponding lactones 4b–4h were obtained in good yields (50–78%). Further hydroxyaldehyde 2i having a substituent at the o-position has been employed for the same reaction condition and gave the corresponding o-substituted γ-butenolides 4i in 71%. Similarly, the unsymmetrically substituted hydroxyaldehydes 2j and 2k led to the synthesis of the lactones 4j and 4k in good yields (66% and 51%, respectively). The benzyl-protected hydroxyaldehyde 2l gave the lactone 4l in 65% yield. Furthermore, the highly substituted γ-butenolides (4m–4o) were successfully prepared in good yields (56–66%) using the corresponding hydroxyaldehydes 2m–2o. The olefination cum lactonization of the naphthalene-substituted hydroxyaldehydes 2p and 2q proceeded smoothly to provide the corresponding lactones 4p and 4q in excellent yields (76% and 89%, respectively).

Conclusions

In conclusion, an unprecedented NaI-catalyzed oxone-mediated oxidative rearrangement of stilbenes to 2,2-diaryl-2-hydroxyacetaldehydes has been documented. With the help of control experiments, a tentative mechanism postulating the possible oxygen transfer from the water to the initially formed diarylacetaldehyde for the final α-hydroxylation has been proposed. These diarylhydroxyacetaldehydes have been converted to 5,5-diaryl-γ-butenolides by employing a two-carbon cis-Wittig reaction and intramolecular lactonization. Currently, work in the direction of understanding the mechanism of α-hydroxylation is in progress.

Experimental Section

General Information

Commercial reagents were used without any purification. Column chromatography was carried out by using silica gels (60–120, 100–200, and 230–400 mesh). ¹H and ¹³C NMR chemical shifts are reported relative to chloroform-d (δ = 7.25) or TMS, and coupling constants (J) are reported in hertz (Hz). The following abbreviations have been used to designate signal multiplicity: s = singlet, d = doublet, t = triplet, q = quartet, sxt = sextet, hept = septet, m = multiplet, and b = broad. High-resolution mass spectra (HRMS) were recorded on a Q Exactive Hybrid Quadrupole Orbitrap mass spectrometer, where the mass analyzer used for analysis is an Orbitrap. Melting points were recorded on a digital microscopy melting apparatus and uncorrected. All starting stilbenes were prepared according to well-known literature procedures.¹⁴

General Procedure for the Oxidation of Stilbenes 1

In general, all reactions were carried out employing 100 mg of stilbene 1.

At rt, a solution of stilbene 1 (100 mg, 0.55 mmol, 1 equiv) in a 1:1 CH₃CN:H₂O system (4 mL) was treated with sodium iodide (8.3 mg, 0.05 mmol, 10 mol %) and stirred for 5 min and then oxone (337 mg, 1.1 mmol, 2 equiv) was added slowly. The resulting suspension was heated at 80 °C for 15 h by which time the TLC showed the complete disappearance of the starting stilbene. The reaction mixture was concentrated under reduced pressure and partitioned between EtOAc (20 mL) and water (10 mL). The organic layer was separated, and the aqueous layer was extracted with EtOAc (2 × 20 mL). The combined organic layer was washed with Na₂S₂O₈ (3 × 20 mL), brine (20 mL), dried (Na₂SO₄), and concentrated under reduced pressure. The resulting crude was purified by column chromatography to afford the hydroxyaldehyde 2 along with small amounts of side product aldehyde and sometimes ketone.

Representative Procedure for a 5 mmol Scale

At rt, to a solution of stilbene 1a (900 mg, 5 mmol) in 1:1 CH₃CN:H₂O (40 mL) was added sodium iodide (75 mg, 0.5 mmol) and then stirred for 5 min followed by addition of oxone (3072 mg, 10 mmol) slowly at 25 °C and the contents were heated at 80 °C for 15 h. Usual workup followed by purification by column chromatography afforded compound 2a (699 mg, 66% yield) as a white solid.

General Procedure for the Preparation of γ,γ-Disubstituted α,β-Unsaturated-γ-lactones 4

In general, all reactions were carried out employing 100 mg of hydroxyaldehyde 2.

To a suspension of anhydrous lithium chloride (2 equiv) in dry THF (5 mL) under a nitrogen atmosphere, ethyl [bis(2,2,2-trifluoroethoxy)phosphinyl]acetate (1.5 equiv) was added and stirred for 15 min at 25 °C. Then, the reaction mixture was cooled to 0 °C, treated with DBU (2 equiv), and stirred at the same temperature for an additional 30 min. Next, the reaction mixture was cooled to −78 °C and a solution of aldehyde 2 (1 equiv) in THF (5 mL) was added dropwise and continuously stirred for 3 h. Then, the reaction mixture was warmed to 0 °C, quenched by adding sat. NH₄Cl, and concentrated on a rotary evaporator under reduced pressure. The crude was dissolved in ethyl acetate (20 mL), washed with H₂O (10 mL) followed by brine, and concentrated. The crude was purified by column chromatography to procure the γ,γ-disubstituted α,β-unsaturated-γ-lactone product 4.

2-Hydroxy-2,2-diphenylacetaldehyde (2a)

Purified by column chromatography (5% EtOAc in petroleum ether, R_f = 0.5); yield: 78 mg (66%); colorless solid; mp: 55–57 °C (lit.¹⁵ 52–55 °C); IR(neat) ν_max 3477, 2925, 1723, 1491, 1448, 1336, 1176, 962, 794, 754, 699 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 9.9 (s, 1H), 7.3 (s, 10H), 3.9 (br. s, 1H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 198.0 (d), 139.3 (s, 2C), 128.8 (d, 4C), 128.5 (d, 2C), 127.4 (d, 4C), 83.4 (s) ppm; HRMS (ESI): calcd. for C₁₄H₁₂O₂Na: 235.0730 [M + Na]⁺; found 235.0729.

2-Hydroxy-2-(4-methoxyphenyl)-2-phenylacetaldehyde (2b)

Purified by column chromatography (5% EtOAc in petroleum ether, R_f = 0.5); yield: 55 mg (48%); colorless solid; mp: 72–74 °C (lit.^9b 73–74 °C); IR(neat) ν_max 3477, 2951, 1721, 1608, 1511, 1448, 1302, 1252, 1173, 102, 964, 831, 751, 701 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 10.0 (s, 1H), 7.38–7.45 (m, 5H), 7.29 (d, J = 8.5 Hz, 2H), 6.95 (d, J = 9.2 Hz, 2H), 4.38 (s, 1H), 3.84 (s, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 198.0 (d), 159.6 (s), 139.3 (s), 131.3 (s), 128.7 (d, 2C), 128.7 (d, 2C), 128.3 (d), 127.3 (d, 2C), 114.1 (d, 2C), 83.1 (s), 55.2 (q) ppm; HRMS (ESI) m/z: calcd. for C₁₅H₁₄O₃Na: 265.0835 [M + Na]⁺; found: 265.0832.

2-Hydroxy-2-phenyl-2-(p-tolyl)acetaldehyde (2c)¹⁶

Purified by column chromatography (5% EtOAc in petroleum ether, R_f = 0.5); yield: 49 mg (42%); colorless syrup; IR(neat) ν_max 3477, 2921, 1720, 1512, 1448, 1173, 1014, 815, 751, 699 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 9.86 (s, 1H), 7.29 (s, 5H), 7.14 (d, J = 2.4 Hz, 4H), 4.29 (s, 1H), 2.27 (s, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 198.2 (d), 139.5 (s), 138.4 (s), 136.5 (s), 129.6 (d, 2C), 128.8 (d, 2C), 128.5 (d), 127.5 (d, 2C), 127.4 (d, 2C), 83.4 (s), 21.2 (q) ppm; HRMS (ESI): calcd. for C₁₅H₁₄O₂Na: 249.0886 [M + Na]⁺; found: 249.0883.

2-Hydroxy-2-(4-isopropylphenyl)-2-phenylacetaldehyde (2d)

Purified by column chromatography (5% EtOAc in petroleum ether, R_f = 0.5); yield: 51 mg (45%); colorless solid; mp: 50–52 °C; IR(neat) ν_max 3482, 2951, 1720, 1509, 1450, 1338, 1175, 1014, 829, 793, 741, 699 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 9.88 (s, 1H), 7.31 (s, 5H), 7.18 (s, 4H), 4.28 (s, 1H), 2.84 (quin, J = 6.9 Hz, 1H), 1.17 (d, J = 6.9 Hz, 6H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 198.1 (s), 149.3 (s), 139.4 (s), 136.7 (s), 128.8 (d, 2C), 128.4 (d, 2C), 127.4 (d, 3C), 126.9 (d, 2C), 83.3 (s), 33.8 (d), 23.9 (q, 2C) ppm; HRMS (ESI): calcd. for C₁₇H₁₈O₂Na⁺: 277.1199 [M + Na]⁺; found: 277.1196.

2-Chloro-2-(4-chlorophenyl)-2-phenylacetaldehyde (2e)¹⁷

Purified by column chromatography (5% EtOAc in petroleum ether, R_f = 0.5); yield: 55 mg (45%); yellow syrup; IR(neat) ν_max 3466, 2922, 1720, 1490, 1400, 1092, 1011, 823, 823, 792, 758, 698 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 9.96 (s, 1H), 7.28–7.55 (m, 9H), 4.41 (s, 1H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 197.5 (d), 139.0 (s), 137.7 (s), 134.6 (s), 129.0 (d, 2C), 128.9 (d, 2C), 128.8 (d), 128.7 (d, 2C), 127.3 (d, 2C), 83.0 (s) ppm; HRMS (ESI): calcd. for C₁₄H₁₀O₂Cl:245.0373 [M – H]⁺; found: 245.0364.

2-(4-Bromophenyl)-2-hydroxy-2-phenylacetaldehyde (2f)

Purified by column chromatography (5% EtOAc in petroleum ether, R_f = 0.5); yield: 55 mg (49%); colorless syrup; IR(neat) ν_max 3451, 2922, 1720, 1487, 1448,1395, 1153, 1072, 1006, 898, 817, 791, 756, 697, 653 cm^–1; ¹H NMR (500 MHz, CDCl₃): δ 9.98 (s, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.40–7.46 (m, 3H), 7.35–7.37 (m, 2H), 7.30 (d, J = 8.4 Hz, 2H), 4.41 (s, 1H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ 197.5 (d), 138.9 (s), 138.3 (s), 132.0 (d, 2C), 129.1 (d, 2C), 129.0 (d), 128.7 (d, 2C), 127.3 (d, 2C), 122.8 (s), 83.0 (s) ppm; HRMS (ESI): calcd. for C₁₄H₁₀O₂Br: 288.9871 [M – H]⁺; found: 288.9859.

2-Hydroxy-2-(4-iodophenyl)-2-phenylacetaldehyde (2g)

Purified by column chromatography (5% EtOAc in petroleum ether, R_f = 0.5); yield: 47 mg (43%); colorless syrup; IR(neat) ν_max 3463, 2921, 1721, 1484, 1448, 1392, 1174, 1003, 817, 789, 755, 699 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 9.95 (s, 1H), 7.75 (d, J = 7.93 Hz, 2H), 7.38–7.43 (m, 3H), 7.34 (d, J = 7.32 Hz, 2H), 7.14 (d, J = 8.55 Hz, 2H), 4.40 (s, 1H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 197.6 (d), 139.0 (s), 138.0 (d, 2C), 129.4 (d, 2C), 129.1 (d, 2C), 128.9 (d), 128.6 (s), 127.5 (d, 2C), 94.8 (s), 83.3 (s) ppm; HRMS (ESI): calcd. for C₁₄H₁₂O₂I: 338.9876 [M + H]⁺; found: 338.9868.

2-Hydroxy-2-(4-nitrophenyl)-2-phenylacetaldehyde (2h)

Purified by column chromatography (10% EtOAc in petroleum ether, R_f = 0.5); yield: 23 mg (20%); yellow syrup; IR(neat) ν_max 3492, 2923, 1720, 1603, 1518, 1345, 1176, 852, 791, 751, 699 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 10.01 (s, 1H), 8.26 (d, J = 8.39 Hz, 2H), 7.63 (d, J = 9.16 Hz, 2H), 7.35–7.50 (m, 3H), 7.30 (d, J = 6.87 Hz, 2H), 4.48 (s, 1H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 197.0 (d), 147.9 (s), 146.2 (s), 138.8 (s), 129.3 (d, 2C), 129.2 (d, 2C), 128.5 (d, 2C), 127.3 (d), 124.0 (d, 2C), 83.2 (s) ppm; HRMS (ESI): calcd. for C₁₄H₁₂O₄N: 258.0761 [M + H]⁺; found: 258.0752.

2-(2-Fluorophenyl)-2-hydroxy-2-phenylacetaldehyde (2i)

Purified by column chromatography (5% EtOAc in petroleum ether, R_f = 0.5); yield: 41 mg (35%); colorless gum; IR(neat) ν_max 3492, 2962, 1721, 1485, 1450, 1337, 1175, 962, 755, 699, 665 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 10.06 (d, J = 5.49 Hz, 1H), 7.38–7.49 (m, 7H), 7.20–7.26 (m, 1H), 7.10–7.17 (m, 1H), 4.65 (br. s, 1H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 196.7 (dd, ⁴J_C–F = 5.4 Hz), 159.8 (ds, ¹J_C–F = 246.6 Hz), 137.9 (s), 130.8 (dd, ³J_C–F = 8.5 Hz), 129.9 (dd, ⁴J_C–F = 3.9 Hz), 128.8 (d, 2C), 128.6 (d), 127.5 (ds, ²J_C–F = 13.9 Hz), 126.9 (d, 2C), 124.8 (dd, ⁴J_C–F = 3.1 Hz), 115.9 (dd, ²J_C–F = 22.4 Hz), 82.1 (ds, ⁴J_C–F = 3.1 Hz) ppm; HRMS (ESI): calcd. for C₁₄H₁₂O₂F: 231.0816 [M + H]⁺; found: 231.0805.

2-(4-Fluorophenyl)-2-hydroxy-2-(4-methoxyphenyl)acetaldehyde (2j)

Purified by column chromatography (5% EtOAc in petroleum ether, R_f = 0.5); yield: 64 mg (55%); colorless syrup; IR(neat) ν_max 3509, 2962, 1719, 1603, 1506, 1302, 1250, 1159, 1031, 828, 774.5 cm^–1; ¹H NMR (500 MHz, CDCl₃): δ 9.91 (s, 1H), 7.38 (dd, J = 8.39, 5.34 Hz, 2H), 7.27 (d, J = 8.77 Hz, 2H), 7.11 (t, J = 8.58 Hz, 2H), 6.95 (d, J = 8.77 Hz, 2H), 4.43 (s, 1H), 3.83 (s, 3H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ 197.6 (d), 162.6 (ds, ¹J_C–F = 248.0 Hz), 159.7 (s), 135.2 (s), 131.1 (s), 129.3 (dd, 2C, ³J_C–F = 8.6 Hz), 128.6 (d, 2C), 115.6 (dd, 2C, ²J_C–F = 22.0 Hz), 114.2 (d, 2C), 82.7 (s), 55.2 (q) ppm; HRMS (ESI): calcd. for C₁₅H₁₄O₃: 261.0921 [M + H]⁺; found: 261.0914.

2-(4-Bromophenyl)-2-hydroxy-2-(4-methoxyphenyl)acetaldehyde (2k)

Purified by column chromatography (5% EtOAc in petroleum ether, R_f = 0.5); yield: 46 mg (41%); colorless syrup; IR(neat) ν_max 3492, 2925, 1719, 1650, 1602, 1510, 1253, 1172, 1072, 1009, 828, 764 cm^–1; ¹H NMR (500 MHz, CDCl₃): δ 9.81 (s, 1H), 7.46 (d, J = 8.59 Hz, 2H), 7.03–7.27 (m, 4H), 6.84 (d, J = 8.84 Hz, 2H), 4.27 (s, 1H), 3.74 (s, 3H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ 197.4 (d), 159.9 (s), 138.4 (s), 131.9 (d, 2C), 131.0 (s), 129.1 (d, 2C), 128.73 (d, 2C), 122.8 (s), 114.4 (d, 2C), 82.8 (s), 55.4 (q) ppm; HRMS (ESI): calcd. for C₁₅H₁₄O₃Br: 321.0121 [M + H]⁺; found: 321.0107.

2-(4-(Benzyloxy)-3,5-dimethoxyphenyl)-2-hydroxy-2-phenylacetaldehyde (2l)

Purified by column chromatography (10% EtOAc in petroleum ether, R_f = 0.5); yield: 50 mg (46%); colorless solid; mp: 98–100 °C; IR(neat) ν_max 3493, 2952, 1720, 1588, 1502, 1454, 1414, 1324, 1236, 1125, 981, 737, 699 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 9.87 (s, 1H), 7.18–7.43 (m, 10H), 6.49 (s, 2H), 4.94 (s, 2H), 4.33 (s, 1H), 3.69 (s, 6H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 197.6 (s), 153.8 (s, 2C), 139.2 (s), 137.7 (s), 137.2 (s), 134.5 (s) 128.9 (d, 2C), 128.6 (d), 128.4 (d, 2C), 128.2 (d, 2C), 127.9 (d), 127.5 (d, 2C), 104.8 (d, 2C), 83.4 (s), 75.0 (t), 56.2 (q, 2C) ppm; HRMS (ESI): calcd. for C₂₃H₂₂O₅Na: 401.1359 [M + Na]⁺; found: 4011349.

2,2-Bis(3,4-dimethoxyphenyl)-2-hydroxyacetaldehyde (2m)

Purified by column chromatography (20% EtOAc in petroleum ether, R_f = 0.5); yield: 37 mg (33%); colorless solid; mp: 132–134 °C; IR(neat) ν_max 3492, 2958, 1720, 1592, 1509, 1460, 1413, 1255, 1135, 1021, 864, 811, 759, 645 cm^–1; ¹H NMR (500 MHz, CDCl₃): δ 9.89 (s, 1H), 6.92 (d, J = 1.3 Hz, 2H), 6.84–6.90 (m, 4H), 4.34 (br. s, 1H), 3.89 (s, 6H), 3.83 (s, 6H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ 197.5 (d), 149.4 (s, 2C), 149.2 (s, 2C), 131.7 (s, 2C), 120.1 (d, 2C), 111.0 (d, 2C), 110.5 (d, 2C), 83.0 (s), 56.0 (q, 4C) ppm; HRMS (ESI): calcd. for C₁₈H₂₀O₆Na: 335.1152 [M + Na]⁺; found: 335.1148.

2-Hydroxy-2,2-bis(3,4,5-trimethoxyphenyl)acetaldehyde (2n)

Purified by column chromatography (20% EtOAc in petroleum ether, R_f = 0.5); yield: 17 mg (16%); yellow syrup; IR(neat) ν_max 3492, 2925, 1720, 1588, 1504, 1456, 1414, 1324, 1237, 1124, 1003 cm^–1; ¹H NMR (500 MHz, CDCl₃): δ 9.90 (s, 1H), 6.59 (s, 4H), 4.39 (s, 1H), 3.87 (s, 6H), 3.83 (s, 12H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ 197.0 (d), 153.6 (s, 4C), 138.4 (s, 2C), 134.2 (s, 2C), 104.9 (d, 4C), 83.5 (s), 60.9 (s, 2C), 56.3 (s, 4C) ppm; HRMS (ESI): calcd. for C₂₀H₂₃O₈: 391.1387 [M – H]⁺; found: 391.1384.

2-Hydroxy-2,2-bis(4-isopropoxy-3,5-dimethoxyphenyl)acetaldehyde (2o)

Purified by column chromatography (20% EtOAc in petroleum ether, R_f = 0.5); yield: 32 mg (30%); yellow syrup; IR(neat) ν_max 3492, 2974, 1719, 1585, 1500, 1457, 1413, 1322, 1231, 1103, 929, 839, 733, cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 9.91 (s, 1H), 6.57 (s, 4H), 4.42 (s, 1H), 4.34–4.41 (hept, 2H), 3.78 (s, 12H), 1.31 (s, 12H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 197.2 (d), 154.0 (s, 4C), 136.3 (s, 2C), 133.8 (s, 2C), 104.8 (d, 4C), 83.5 (s), 75.4 (d, 2C), 56.1 (q, 4C), 22.5 (q, 4C) ppm; HRMS (ESI): calcd. for C₂₄H₃₃O₈: 449.2170 [M + H]⁺; found: 449.2166.

2-Hydroxy-2-(naphthalen-1-yl)-2-phenylacetaldehyde (2p)¹⁸

Purified by column chromatography (5% EtOAc in petroleum ether, R_f = 0.5); yield: 77 mg (68%); colorless solid; mp: 92–94 °C; IR(neat) ν_max 3462, 2925, 1717, 1509, 1448, 1345, 1166, 1059, 947, 776, 745, 700 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 10.20 (s, 1H), 7.78–8.04 (m, 3H), 7.14–7.65 (m, 9H), 4.70 (s, 1H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 198.5 (s), 139.3 (s), 136.6 (s), 135.2 (s), 131.0 (s), 130.0 (d), 129.1 (d, 2C), 128.9 (d), 128.5 (d), 127.0 (d, 2C), 126.7 (d), 126.2 (d), 125.9 (d), 125.4 (d), 124.6 (d), 84.1 (s) ppm; HRMS (ESI): calcd. for C₁₈H₁₄O₂Na: 285.0886 [M + Na]⁺; found: 285.0881.

2-Hydroxy-2-(4-methoxyphenyl)-2-(naphthalen-1-yl)acetaldehyde (2q)

Purified by column chromatography (5% EtOAc in petroleum ether, R_f = 0.5); yield: 54 mg (46%); colorless solid; mp: 128–130 °C; IR(neat) ν_max 3492, 2963, 1716, 1604, 1507, 1507, 1460, 1301, 1249, 1173, 1104, 1029, 951, 832, 802, 778, 647 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 10.10 (d, J = 1.4 Hz, 1H), 7.94 (d, J = 8.7 Hz, 1H), 7.81–7.89 (m, 2H), 7.38–7.46 (m, 3H), 7.23–7.33 (m, 3H), 6.88 (d, J = 9.2 Hz, 2H), 4.60 (d, J = 1.4 Hz, 1H), 3.78 (s, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 198.1 (s), 159.6 (s), 136.5 (s), 135.0 (s), 131.0 (s), 130.9 (s), 129.9 (d, 1C), 128.8 (d, 1C), 128.2 (d, 2C), 126.7 (d, 1C), 126.0 (d, 1C), 125.8 (d, 1C), 125.2 (d, 1C), 124.5 (d, 1C), 114.4 (d, 2C), 83.6 (s), 55.2 (s) ppm; HRMS (ESI): calcd. for C₁₉H₁₇O₃: 293.1172 [M + H]⁺; found: 293.1159.

2-(3,5-Di-tert-butyl-2-methoxyphenyl)-2-hydroxy-2-phenylacetaldehyde (2r)

Purified by column chromatography (5% EtOAc in petroleum ether, R_f = 0.5); yield: 42 mg (42%); colorless solid; mp: 132–134 °C; IR(neat) ν_max 3492, 2958, 1715, 1475, 1363, 1229, 1164, 1135, 998, 887, 799, 756, 700 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 10.15 (s, 1H), 7.74–7.94 (m, 7H), 5.20 (s, 1H), 4.08 (s, 3H), 1.94 (s, 9H), 1.63 (s, 9H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 193.7 (s), 155.2 (s), 146.7 (s), 141.9 (s), 139.4 (s), 135.7 (s), 128.3 (d, 2C), 127.9 (d, 1C), 127.2 (d, 2C), 127.0 (d, 1C), 125.9 (d, 1C), 82.6 (s), 63.4 (q, 1C), 35.6 (s), 34.5 (s), 31.7 (q, 3C), 31.2 (q, 3C) ppm; HRMS (ESI): calcd. for C₂₃H₃₁O₃: 355.2268 [M + H]⁺; found: 355.2262.

1-Hydroxy-1,1-diphenylpropan-2-one (2s)

Purified by column chromatography (5% EtOAc in petroleum ether, R_f = 0.5); yield: 75 mg (64%); colorless solid; mp: 64–66 °C (lit.¹⁷ 64–66 °C); IR(neat) ν_max 3462, 2925, 1706, 1492, 1447, 1335, 1157, 1055, 754, 696 cm^–1; cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 7.28 (s, 10H), 4.76 (s, 1H), 2.17 (s, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 208.7 (s), 141.4 (s, 2C), 128.5 (d, 4C), 128.3 (d, 4C), 128.1 (d, 2C), 85.8 (s), 26.3 (q) ppm; HRMS (ESI): calcd. for C₁₅H₁₄O₂Na: 249.0886 [M + Na]⁺; found: 249.0884.

5,5-Diphenylfuran-2(5H)-one (4a)

Purified by column chromatography (10% EtOAc in petroleum ether, R_f = 0.5); yield: 69 mg (62%); colorless solid; mp: 134–136 °C (lit.^10e 133–134 °C); IR(neat) ν_max 2925, 1760, 1449, 1211, 1095, 985, 921, 818, 759, 697 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 7.96 (d, J = 5.49 Hz, 1H), 7.30–7.43 (m, 10H), 6.20 (d, J = 5.49 Hz, 1H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 172.1 (s), 158.8 (d), 139.2 (s, 2C), 128.7 (d, 4C), 128.6 (d, 2C), 126.6 (d, 4C), 119.7 (d), 92.2 (s) ppm; HRMS (ESI): calcd. for C₁₆H₁₃O₂: 237.0910 [M + H]⁺; found: 237.0908.

5-(4-Methoxyphenyl)-5-phenylfuran-2(5H)-one (4b)

Purified by column chromatography (10% EtOAc in petroleum ether, R_f = 0.5); yield: 79 mg (72%); colorless solid; mp: 118–120 °C (lit.¹⁹ 118.6–119.6 °C); IR(neat) ν_max 2951, 1762, 1609, 1512, 1254, 1179, 1092, 1032, 918, 832, 758, 699 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 7.91 (d, J = 5.49 Hz, 1H), 7.30–7.40 (m, 5H), 7.22 (d, J = 9.16 Hz, 2H), 6.88 (d, J = 9.16 Hz, 2H), 6.18 (d, J = 5.49 Hz, 1H), 3.81 (s, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 172.2 (s), 159.8 (s), 159.0 (d), 139.4 (s), 131.3 (s), 128.7 (d, 2C), 128.6 (d), 128.1 (d, 2C), 126.5 (d, 2C), 119.5 (d), 114.0 (d, 2C), 92.2 (s), 55.3 (q) ppm; HRMS (ESI): calcd. for C₁₇H₁₅O₃: 267.1016 [M + H]⁺; found: 267.1012.

5-Phenyl-5-(p-tolyl)furan-2(5H)-one (4c)

Purified by column chromatography (10% EtOAc in petroleum ether, R_f = 0.5); yield: 86 mg (78%); colorless solid; mp: 70–72 °C; IR(neat) ν_max 2921, 1764, 1211, 1092, 919, 820, 757, 699 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 7.93 (d, J = 5.49 Hz, 1H), 7.35 (d, J = 6.71 Hz, 5H), 7.16–7.22 (m, 4H), 6.18 (d, J = 5.49 Hz, 1H), 2.36 (s, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 172.2 (s), 158.9 (d), 139.4 (s), 138.6 (s), 136.3 (s), 129.4 (d, 2C), 128.7 (d, 2C), 128.6 (d, 2C), 126.8 (d), 126.5 (d, 2C), 119.6 (d), 92.2 (s), 21.1 (s) ppm; HRMS (ESI): calcd. for C₁₇H₁₅O₂: 251.1067 [M + H]⁺; found: 251.1064.

5-(4-Isopropylphenyl)-5-phenylfuran-2(5H)-one (4d)

Purified by column chromatography (10% EtOAc in petroleum ether, R_f = 0.5); yield: 77 mg (70%); colorless solid; mp: 88–90 °C; IR(neat) ν_max 2951, 1766, 1092, 919, 818, 699 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 7.94 (d, J = 5.5 Hz, 1H), 7.33–7.38 (m, 5H), 7.23 (s, 4H), 6.19 (d, J = 5.5 Hz, 1H), 2.91 (hept, J = 6.9 Hz, 1H), 1.25 (d, J = 6.9 Hz, 6H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 172.2 (s), 158.9 (d), 149.5 (s), 139.4 (s), 136.5 (s), 128.7 (d, 2C), 128.5 (d), 126.8 (d, 2C), 126.6 (d, 2C), 126.5 (d, 2C), 119.5 (d), 92.3 (s), 33.8 (d), 23.8 (q, 2C) ppm; HRMS (ESI): calcd. for C₁₉H₁₉O₂: 279.1380 [M + H]⁺; found: 279.1378.

5-(4-Chlorophenyl)-5-phenylfuran-2(5H)-one (4e)

Purified by column chromatography (10% EtOAc in petroleum ether, R_f = 0.5); yield: 55 mg (50%); colorless gum; IR(neat) ν_max 2950, 1761, 1491, 1208, 1092, 1055, 985, 915, 815, 761, 697 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 7.92 (d, J = 5.5 Hz, 1H), 7.26–7.40 (m, 9H), 6.23 (d, J = 5.5 Hz, 1H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 171.7 (s), 158.3 (d), 138.8 (s), 137.8 (s), 134.8 (s), 128.9 (d, 2C), 128.9 (d), 128.9 (d, 2C), 128.0 (d, 2C), 126.5 (d, 2C), 120.0 (d), 91.6 (s) ppm; HRMS (ESI): calcd. for C₁₆H₁₂O₂Cl: 271.0520 [M + H]⁺; found: 271.0520.

5-(4-Bromophenyl)-5-phenylfuran-2(5H)-one (4f)

Purified by column chromatography (10% EtOAc in petroleum ether, R_f = 0.5); yield: 77 mg (71%); colorless solid; mp: 72–74 °C; IR(neat) ν_max 2925, 1767, 1488, 1209, 1091, 918, 821, 760, 699 cm^–1; ¹H NMR (500 MHz, CDCl₃): δ 7.91 (d, J = 5.3 Hz, 1H), 7.50 (d, J = 8.8 Hz, 2H), 7.34–7.40 (m, 3H), 7.29–7.32 (m, 2H), 7.20 (m, J = 8.8 Hz, 2H), 6.21 (d, J = 5.7 Hz, 1H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ 171.7 (s), 158.2 (d), 138.7 (s), 138.4 (s), 131.9 (d, 2C), 128.9 (d), 128.8 (d, 2C), 128.3 (d, 2C), 126.5 (d, 2C), 122.9 (s), 120.0 (d), 91.6 (s) ppm; HRMS (ESI): calcd. for C₁₆H₁₂O₂Br: 315.0015 [M + H]⁺; found: 315.0009.

5-(4-Iodophenyl)-5-phenylfuran-2(5H)-one (4g)

Purified by column chromatography (10% EtOAc in petroleum ether, R_f = 0.5); yield: 74 mg (69%); colorless solid; mp: 80–82 °C, IR(neat) ν_max 2951, 1758, 1484, 1393, 1202, 1090, 985, 816, 759, 697 cm^–1; ¹H NMR (500 MHz, CDCl₃): δ 7.91 (d, J = 5.3 Hz, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.35–7.39 (m, 3H), 7.28–7.31 (m, 2H), 7.07 (d, J = 8.4 Hz, 2H), 6.21 (d, J = 5.7 Hz, 1H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ 171.7 (s), 158.2 (d), 139.1 (s), 138.8 (s), 137.9 (d, 2C), 128.9 (d), 128.9 (d, 2C), 128.4 (d, 2C), 126.5 (d, 2C), 120.0 (d), 94.67 (s), 91.74 (s) ppm; HRMS (ESI): calcd. for C₁₆H₁₂O₂I: 362.9876 [M + H]⁺; found: 362.9879.

5-(4-Nitrophenyl)-5-phenylfuran-2(5H)-one (4h)

Purified by column chromatography (10% EtOAc in petroleum ether, R_f = 0.5); yield: 79 mg (72%); colorless gum; IR(neat) ν_max 2920, 1759, 1519, 1347, 1207, 1091, 915, 851, 815, 760, 697 cm^–1; ¹H NMR (500 MHz, CDCl₃): δ 8.24 (d, J = 9.2 Hz, 2H), 7.97 (d, J = 5.3 Hz, 1H), 7.53–7.57 (d, J = 8.9 Hz, 2H), 7.38–7.44 (m, 3H), 7.28–7.33 (m, 2H), 6.29 (d, J = 5.3 Hz, 1H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ 171.1 (s), 157.4 (d), 147.9 (s), 146.2 (s), 138.2 (s), 129.3 (d), 129.1 (d, 2C), 127.5 (d, 2C), 126.5 (d, 2C), 124.0 (d, 2C), 120.7 (d), 91.2 (s) ppm; HRMS (ESI): calcd. for C₁₆H₁₂O₄N: 282.0761 [M + H]⁺; found: 282.0750.

5-(2-Fluorophenyl)-5-phenylfuran-2(5H)-one (4i)

Purified by column chromatography (10% EtOAc in petroleum ether, R_f = 0.5); yield: 78 mg (71%); colorless solid; mp: 120–122 °C; IR(neat) ν_max 2924, 1761, 1486, 1451, 1219, 1087, 984, 915, 820, 758, 696 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 8.18 (dd, J = 5.6, 3.38 Hz, 1H), 7.64–7.71 (m, 1H), 7.33–7.46 (m, 4H), 7.15–7.33 (m, 3H), 7.08 (dd, J = 11.3, 8.3 Hz, 1H), 6.23 (d, J = 5.3 Hz, 1 H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 171.7 (s), 159.3 (ds, ¹J_C-F = 247 Hz), 157.6 (dd, ³J_C-F = 6.3 Hz), 138.3 (s), 130.7 (dd, ³J_C-F = 8.5 Hz), 129.0 (d), 128.8 (d, 2C), 127.6 (dd, ⁴J_C-F = 3.1 Hz), 126.8 (ds, ³J_C-F = 12.3 Hz), 126.8 (d, 2C), 124.8 (dd, ⁴J_C-F = 3.1 Hz), 120.1 (d), 116.2 (dd, ²J_C-F = 22.4 Hz), 90.0 (s) ppm; HRMS (ESI): calcd. for C₁₆H₁₂O₂F: 255.0816 [M + H]⁺; found: 255.0815.

5-(4-Fluorophenyl)-5-(4-methoxyphenyl)furan-2(5H)-one (4j)

Purified by column chromatography (10% EtOAc in petroleum ether, R_f = 0.5); yield: 72 mg (66%); colorless solid; mp: 96–98 °C; IR(neat) ν_max 2933, 1764, 1606, 1510, 1304, 1232, 1181, 1086, 1032, 964, 918, 832 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 7.89 (d, J = 6.0 Hz, 1H), 7.30 (dd, J = 9.0, 5.26 Hz, 2H), 7.21 (m, J = 8.3 Hz, 2H), 7.04–7.09 (m, 2H), 6.90 (m, J = 9.0 Hz, 2 H), 6.20 (d, J = 5.3 Hz, 1H), 3.83 (s, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 172.0 (s), 163.4 (ds, ¹J_C-F = 248.9 Hz), 159.9 (s), 158.7 (d), 135.3 (s), 131.0 (s), 128.5 (dd, ³J_C-F = 8.5 Hz, 2C), 128.0 (d, 2C), 119.6 (d), 115.7 (dd, ²J_C-F = 21.6, 2C), 114.1 (d, 2C), 91.64 (s), 55.33 (q) ppm; HRMS (ESI): calcd. for C₁₇H₁₄O₃F: 285.0921 [M + H]⁺; found:285.0918.

5-(4-Bromophenyl)-5-(4-methoxyphenyl)furan-2(5H)-one (4k)

Purified by column chromatography (10% EtOAc in petroleum ether, R_f = 0.5); yield: 55 mg (51%); colorless solid; mp: 90–92 °C; IR(neat) ν_max 2930, 1762, 1607, 1511, 1305, 1253, 1179, 1085, 1031, 982, 919, 823 cm^–1; ¹H NMR (500 MHz, CDCl₃): δ 7.86 (d, J = 5.7 Hz, 1H), 7.50 (d, J = 8.4 Hz, 2H), 7.14–7.21 (m, 4H), 6.88 (d, J = 9.2 Hz, 2H), 6.19 (d, J = 5.7 Hz, 1H), 3.81 (s, 3H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ 171.9 (s), 159.9 (s), 158.4 (d), 138.5 (s), 131.8 (d, 2C), 130.7 (s), 128.2 (d, 2C), 128.1 (d, 2C), 122.8 (s), 119.8 (d), 114.1 (d, 2C), 91.6 (s), 55.3 (s) ppm; HRMS (ESI): calcd. for C₁₇H₁₄O₃: 345.0121 [M + H]⁺; found: 345.0107.

5-(4-(Benzyloxy)-3,5-dimethoxyphenyl)-5-phenylfuran-2(5H)-one (4l)

Purified by column chromatography (10% EtOAc in petroleum ether, R_f = 0.5); yield: 69 mg (65%); colorless solid; mp: 124–126 °C; IR(neat) ν_max 2921, 1760, 1589, 1503, 1453, 1414, 1328, 1214, 1126, 970, 920, 835, 734, 699 cm^–1; ¹H NMR (500 MHz, CDCl₃): δ 7.91 (d, J = 5.7 Hz, 1H), 7.48 (d, J = 7.3 Hz, 2H), 7.27–7.41 (m, 8H), 6.51 (s, 2H), 6.20 (d, J = 5.7 Hz, 1H), 5.01 (s, 2H), 3.77 (s, 6H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ 173.0 (s), 158.7 (d), 153.7 (s, 2C), 139.1 (s), 137.7 (s), 137.3 (s), 134.7 (s), 128.8 (d), 128.7 (d, 2C), 128.4 (d, 2C), 128.2 (d, 2C), 127.9 (d), 126.6 (d, 2C), 119.7 (d), 104.3 (d, 2C), 90.2 (s), 75.0 (t), 56.3 (q, 2C) ppm; HRMS (ESI): calcd. for C₂₅H₂₃O₅: 403.1540 [M + H]⁺; found: 403.1538.

5,5-Bis(3,4-dimethoxyphenyl)furan-2(5H)-one (4m)

Purified by column chromatography (30% EtOAc in petroleum ether, R_f = 0.5); yield: 60 mg (56%); yellow solid; mp: 113–115 °C; IR(neat) ν_max 2931, 1762, 1515, 1463, 1414, 1263, 1143, 1025, 922, 840, 765 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 7.88 (d, J = 5.5 Hz, 1H), 6.82 (s, 6H), 6.17 (d, J = 5.5 Hz, 1H), 3.88 (s, 6H), 3.82 (s, 6H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 172.3 (s), 159.0 (d), 149.3 (s, 2C), 149.1 (s, 2C), 131.6 (s, 2C), 119.2 (d, 2C), 110.7 (d, 4C), 109.8 (d), 92.1 (s), 56.0 (q, 4C) ppm; HRMS (ESI): calcd. for C₂₀H₂₁O₆: 357.1333 [M + H]⁺; found: 357.1328.

5,5-Bis(3,4,5-trimethoxyphenyl)furan-2(5H)-one (4n)

Purified by column chromatography (30% EtOAc in petroleum ether, R_f = 0.5); yield: 64 mg (60%); yellow solid; mp: 166–168 °C; IR(neat) ν_max 2922, 1766, 1590, 1507, 1459, 1416, 1329, 1242, 1128, 1004, 830 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 7.88 (d, J = 5.5 Hz, 1H), 6.51 (s, 4H), 6.20 (d, J = 5.5 Hz, 1H), 3.82 (s, 12H), 3.86 (s, 6H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 172.0 (s), 158.6 (d, 2C), 153.3 (s, 4C), 138.4 (s, 2C), 134.4 (s), 119.6 (d), 104.1 (d, 4C), 92.1 (s), 60.9 (q, 3C), 56.3 (q, 3C) ppm; HRMS (ESI): calcd. for C₂₂H₂₅O₈: 417.1544 [M + H]⁺; found: 417.1539.

5,5-Bis(4-isopropoxy-3,5-dimethoxyphenyl)furan-2(5H)-one (4o)

Purified by column chromatography (30% EtOAc in petroleum ether, R_f = 0.5); yield: 69 mg (66%); colorless solid; mp: 160–162 °C; IR(neat) ν_max 2925, 1729, 1587, 1501, 1459, 1415, 1325, 1236, 1125, 926, 766 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 7.88 (d, J = 6.1 Hz, 1H), 6.49 (s, 4H), 6.20 (d, J = 5.5 Hz, 1H), 4.37 (hept, J = 12.2, 6.10 Hz, 2H), 3.77 (s, 12H), 1.29 (d, J = 6.1 Hz, 12H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 172.2 (s), 158.7 (d), 153.9 (s, 4C), 136.5 (s, 2C), 133.9 (s, 2C), 119.4 (d), 104.2 (d, 4C), 92.3 (s), 75.4 (d, 2C), 56.2 (q, 4C), 22.43 (q, 4C) ppm; HRMS (ESI): calcd. for C₂₆H₃₃O₈: 473.2170 [M + H]⁺; found: 473.2166.

5-(Naphthalen-1-yl)-5-phenylfuran-2(5H)-one (4p)

Purified by column chromatography (10% EtOAc in petroleum ether, R_f = 0.5); yield: 97 mg (89%); colorless solid; mp: 184–186 °C; IR(neat) ν_max 2925, 1763, 1199, 1089, 969, 924, 778, 699 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 8.15 (d, J = 5.5 Hz, 1H), 7.94 (d, J = 7.9 Hz, 1H), 7.88 (d, J = 8.5 Hz, 2H), 7.68 (d, J = 7.3 Hz, 1H), 7.49–7.55 (m, 1H), 7.44 (t, J = 7.6 Hz, 1H), 7.24–7.38 (m, 6H), 6.23 (d, J = 5.5 Hz, 1H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 172.1 (s), 159.5 (d), 139.3 (s), 134.7 (s), 134.6 (s), 130.5 (d), 130.3 (s), 129.0 (d, 2C), 128.8 (d), 128.6 (d), 126.4 (d), 126.2 (d), 125.8 (d), 125.7 (d, 2C), 125.2 (d), 124.6 (d), 119.1 (d), 92.9 (s) ppm; HRMS (ESI): calcd. for C₂₀H₁₄O₂Na: 309.0886 [M + H]⁺; found: 309.0873.

5-(4-Methoxyphenyl)-5-(naphthalen-1-yl)furan-2(5H)-one (4q)

Purified by column chromatography (10% EtOAc in petroleum ether, R_f = 0.5); yield: 82 mg (76%); colorless solid; mp: 100–102 °C; IR(neat) ν_max 2921, 1763, 1607, 1511, 1253, 1178, 1087, 1032, 919, 832, 777 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ 8.14 (d, J = 6.0 Hz, 1H), 7.80–7.98 (m, 3H), 7.70 (d, J = 7.5 Hz, 1H), 7.40–7.54 (m, 2H), 7.25–7.37 (m, 1H), 7.16 (d, J = 8.3 Hz, 2H), 6.83 (d, J = 9.0 Hz, 2H), 6.21 (d, J = 5.3 Hz, 1H), 3.78 (s, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 172.2 (s), 159.8 (s), 159.4 (d), 134.8 (s), 134.6 (s), 131.1 (s), 130.5 (s), 130.2 (d), 128.8 (d), 127.3 (d, 2C), 126.4 (d), 126.2 (d), 125.8 (d), 125.0 (d), 124.7 (d), 119.1 (d), 114.3 (d, 2C), 92.9 (s), 55.3 (q) ppm; HRMS (ESI): calcd. for C₂₁H₁₇O₃: 317.1172 [M + H]⁺; found: 317.1169.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.0c03328.

• ¹H and ¹³C NMR spectra of all new compounds (PDF)

The authors declare no competing financial interest.