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Synthesis 2024; 56(13): 1989-1998
DOI: 10.1055/a-2323-0633
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Remote-Carbonyl-Directed Consecutive Arylation of Terminal Alkenes for the Synthesis of Tetrasubstituted Olefins

Kun Li
a   College of Chemistry & Materials Science, Fujian Normal University, Fuzhou 350007, P. R. of China
b   State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, 155 Yangqiao Road West, Fuzhou 350002, P. R. of China
,
Runze Luan
b   State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, 155 Yangqiao Road West, Fuzhou 350002, P. R. of China
,
Yu Du  ∗
a   College of Chemistry & Materials Science, Fujian Normal University, Fuzhou 350007, P. R. of China
b   State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, 155 Yangqiao Road West, Fuzhou 350002, P. R. of China
c   Fujian Science and Technology Innovation Laboratory for Optoelectronic Information of China, Fuzhou 350108, P. R. of China
,
Weiping Su∗
a   College of Chemistry & Materials Science, Fujian Normal University, Fuzhou 350007, P. R. of China
b   State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, 155 Yangqiao Road West, Fuzhou 350002, P. R. of China
c   Fujian Science and Technology Innovation Laboratory for Optoelectronic Information of China, Fuzhou 350108, P. R. of China
› Author Affiliations

This work was supported by the National Key Research and Development Program of China (2018YFA0704502), the National Natural Science Foundation of China (grant nos. 21871261, 21931011) and the Fujian Science and Technology Innovation Laboratory for Optoelectronic Information of China (2021ZZ105).
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Abstract

The highly efficient synthesis of all-carbon tetrasubstituted olefins has been a challenge for decades, especially of multi-aryl-substituted olefins which are widely used in functional organic materials and pharmaceuticals. This work presents a carbonyl-directed palladium-catalyzed consecutive arylation of terminal alkenes with aryl iodides under mild conditions, in which a series of triarylated tetrasubstituted olefins were obtained in moderate yields. Because a weak chelation effect is generally difficult to support such a thorough trifold Heck arylation, and β-trans-selective alkenyl C–H activation cannot be achieved via a twisted endo-metallocyclic intermediate, the key to success is the compatibility between several mechanisms, including Heck reaction, C–H activation and E/Z-isomerization. Here, the judicious selection of a flexible-alkyl-chain-tethered carbonyl group seems to be critical, as it provides a proper chelation effect that not only assists distal alkenyl functionalization or isomerization, but also avoids byproducts caused by other possible β-H elimination or migration. The strategy developed herein greatly streamlines the preparation of the target molecules, and the protocol covers a range of readily available terminal alkenes bearing a native directing group (i.e., aldehyde, ketone and ester) and aryl iodides.


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Key words

carbonyl-directed - consecutive arylation - E/Z-isomerization - all-carbon tetrasubstituted olefins - alkenyl C–H activation - Mizoroki–Heck reaction

Biographical Sketches

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Kun Li obtained his B.Sc. degree from Xi’an Shiyou University in 2018. At present, he is undertaking his M.Sc. degree at the Fujian Institute of Research on the Structure of Matter (FJIRSM), Chinese Academy of Sciences, under the guidance of Prof. Yu Du and Prof. Weiping Su. His research program concerns C–H bond functionalization reactions.

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Runze Luan obtained his B.Sc. degree from Anhui Normal University in 2020 and M.Sc. degree in 2023 from FJIRSM, Chinese Academy of Sciences (mentors: Prof. Weiping Su and Prof. Yu Du). At present, he is undertaking his Ph.D. research in the group of Prof. Haifeng Du at the Institute of Chemistry, Chinese Academy of Sciences. His research interests focus on asymmetric C–H bond functionalization reactions.

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Yu Du obtained his B.Sc. degree and Ph.D. from Xiamen University (mentor: Prof. Peiqiang Huang). He then conducted his postdoctoral research with Prof. Yonggui Robin Chi and Prof. Mary B. Chan-Park at Nanyang Technological University. He joined FJIRSM, Chinese Academy of Sciences, and started his new research career in 2018. His research interests include organometallics, asymmetric catalysis and synthesis, and materials chemistry.

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Weiping Su graduated from the Anhui Education Institute in 1987 and earned his Ph.D. at FJIRSM in 1999 under the supervision of Prof. Maochun Hong. After one year working as an assistant professor at FJIRSM, he moved to the United States to carry out postdoctoral studies with Prof. Richard H. Holm at Harvard University (2000–2001), Prof. Jin Li at Rutgers University (2001–2002) and Prof. John G. Verkade at Iowa State University (2002–2005). He then joined the faculty at FJIRSM in 2006. His research interests include synthetic methodology, discoveries of metal complex based homogeneous catalysts and nanoparticle-based recyclable catalysts, and the structure–property relationships of catalysts.

Multi-aryl tetrasubstituted olefins are significant structural units used in many drugs and organic materials.[1] The synthesis of fully substituted olefins has been a challenge for decades, especially of multi-aryl-substituted olefins in which the steric interactions of four appendages can severely distort the double bond,[2] thus making such syntheses a tremendous challenge in synthetic chemistry. Besides the widely acknowledged difunctionalization of alkynes or allenes via carbometalation,[3] [4] [5] chelation-assisted alkene derivatization and functionalization, initially designed to address the issue of regiocontrol in intermolecular reactions, has also had rapid growth as a powerful tool to obtain stereodefined, highly substituted olefins. Among them, the directed Heck reaction represents a well-known route to prepare 1,1- and 1,2-diarylated olefins in a regio- and stereocontrolled fashion.[6] [7] [8] A ligand- and also chelation-controlled protocol was adopted by Hallberg and co-workers to create a regiochemical switch,[9] which was employed to realize the two-step synthesis of 1,1,2-triarylated vinyl ethers (Scheme [1a]).[8d]

On the other hand, over the past two decades, chelation-assisted alkenyl C–H functionalization has enjoyed great development, serving as a highly efficient route to prepare valuable olefin derivatives in fewer steps with less waste.[10] Great efforts have been dedicated to vicinal or geminal group directed alkenyl C–H activation, and excellent regio- and stereoselectivity could be achieved (Scheme [1b]).[11] [12] [13] However, reported protocols have mainly focused on reactivity research of specific sites, especially regiocontrolled C–H alkenylation, and little has been done to implement consecutive alkenyl C–H functionalization for highly substituted olefin synthesis.[14] More importantly, β-trans-selective alkenyl C–H activation cannot be achieved via an unfavorable twisted endo-metallocyclic intermediate (Scheme [1b]), which makes it inapplicable for the modular synthesis of tetrasubstituted olefins.

Very recently, with the assistance of a weakly coordinating directing group (DG), we have developed a palladium-catalyzed sequential Heck arylation/isomerization/C(sp2)–H arylation of 1,1-disubstituted olefins for the synthesis of stereodefined 1,1,2-triarylated tetrasubstituted olefins (Scheme [1c]).[15] This is a successful attempt in taking advantage of both the flexibility of chelation-assisted Heck arylation and the excellent regio-/stereocontrol of directed alkenyl C–H activation, in combination with a critical but thermodynamically unfavorable E/Z-isomerization.[16] [17] [18] The protocol provides greater possibility to access distal alkenyl functionalization from simple raw materials by using native DGs.

In order to explore alternative synthetic routes starting from simple raw materials without steric and electronic bias, and also to continue our interest in developing highly efficient assembling methods, we postulated whether the weakly coordinating auxiliary could direct a terminal alkene to undergo multifold arylation to furnish one class of triarylated tetrasubstituted olefins; however, a weak chelation effect seems difficult to support such a consecutive alkenyl C(sp2)–H arylation. Based on previous research achievements, a complicated reaction system was proposed, probably involving consecutive Heck reaction, isomerization and C–H activation, which has never been revealed before. Specifically, challenges arise from the assembly difficulty for the extremely distorted structure, and the competitive side reactions caused by other possible β-H elimination, migration or oxidation. Here, a one-pot remote-carbonyl-directed palladium-catalyzed consecutive arylation of unactivated terminal alkenes with aryl iodides has been developed, delivering a series of triarylated all-carbon tetrasubstituted olefins in moderate yields; some native carbonyl groups, such as aldehyde, ketone and ester, worked well to direct the reaction (Scheme [1d]).

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Scheme 1 Chelation-assisted alkenyl arylation

Initially, a simple alkene, hex-5-en-2-one (1a) bearing a nonconjugated, weakly coordinating carbonyl group, was selected as the model substrate. To examine the feasibility of the proposed consecutive arylation, our study commenced with the coupling reaction between hex-5-en-2-one (1a) and methyl 4-iodobenzoate (2a, Table [1]). Through a series of controlled experiments, the optimal conditions (catalyst, ligand, base, additive, etc.) were determined eventually (see Supporting Information, Tables S1–S6). The desired triarylated product 4aa could be isolated in 65% yield (entry 1), using 10 mol% palladium acetate as the catalyst, in combination with 20 mol% N-Fmoc-phenylglycine (Fmoc-Phg-OH) as a ligand, 0.5 equivalents of arylboronic acid as an additive and 3 equivalents of Ag2CO3 as the halide scavenger, after a 24-hour reaction at 45 °C in hexafluoroisopropanol (HFIP) under air.

Table 1 Selected Optimizationa

Entry

Variation from standard conditions

Yield (%)b

 1

none

 68 (65)

 2

without Pd(OAc)2

  0

 3

Cs2CO3 instead of Ag2CO3

  0

 4

TFE instead of HFIP

<10

 5

EtOH instead of HFIP

  0

 6

without ligand and ArB(OH)2

 <5

 7

without ligand

 20

 8

without ArB(OH)2

 60

 9

25 °C instead of 45 °C

 64

10

1-hexene or 10-undecenal instead of 1a

  0

a Unless otherwise noted, reactions were run on a 0.2-mmol scale.

b Yields were determined by 1H NMR spectroscopic analysis using CH2Br2 (0.1 mmol) as the internal standard; isolated yield is given in parentheses.

Some control experiments were performed to gain insight into the role of each component. As expected, without the palladium catalyst no desired product was formed (entry 2). The role of the silver salt cannot be replaced (entry 3), and fluorinated solvents such as HFIP[19] and 2,2,2-trifluoroethanol (TFE) display a unique solvent effect in facilitating the title reaction (entries 4 and 5). Almost no reaction was observed in the absence of ligand and additive (entry 6). The additive arylboronic acid was found to be able to slightly promote the reaction in the absence of ligand (entry 7), while a little decrease in the yield was obtained when carrying out the reaction without arylboronic acid (entry 8). The use of sterically hindered arylboronic acids (e.g., 2,6-dimethylphenylboronic acid, 2,6-diisopropylphenylboronic acid) does not seem to be effective in promoting the reaction. Moreover, a comparable result was obtained at room temperature (25 °C, entry 9). No arylated product could be detected when using 1-hexene or 10-undecenal as the substrate, verifying the significance of the directing effect (entry 10).

Having established the optimal reaction conditions, we set out to investigate the substrate scope of this consecutive arylation of terminal alkenes (Scheme [2]). para-Substituted electron-deficient aryl iodides (e.g., ester-, halogen-, ketone-, trifluoromethyl- and trifluoromethoxy-substituted aryl iodides) worked well in this reaction; some common carbonyl groups such as ketone (4aa–4ag), aldehyde (4ba–4bg) and ester (4ca–4cf, 4db–4dh, 4ea) can act as the native DG to guide the reaction, delivering the corresponding triarylated products in moderate yields. It is noteworthy that ethyl 3-butenoate (1e) bearing a shorter alkyl chain could react with aryl iodide 2a to give the target molecule 4ea in 50% yield; in contrast, increasing the length of the alkyl chain by even one methylene unit is not accepted by the title reaction. Some electron-rich or meta-substituted or disubstituted aryl iodides are also compatible to generate the target molecules, but always obtained as inseparable mixtures in low yields (Supporting Information, Section 4); only compound 4dh derived from methyl 3-iodobenzoate (2h) could be isolated in 52% yield. ortho-Substituted aryl iodides and heteroaryl (e.g., benzofuryl, indolyl) coupling partners are completely not applicable for this reaction, probably due to unfavorable steric hindrance or a strong coordinating ability.

In order to verify the potential application of this consecutive arylation reaction, a gram-scale synthesis of tris(4-acetylphenyl)-substituted olefin 4dg was performed in the presence of 5 mol% palladium acetate and 10 mol% Fmoc-Phg-OH, delivering the target molecule in 50% yield (Scheme [3a]). In addition, the native carbonyl groups could be easily converted into other functional groups or connected with bioactive molecules. For example, the drug for the treatment of hyperuricemia and gout, benzbromarone, was introduced into the tetrasubstituted olefin 4dg; after hydrolysis and condensation, the target molecule 6 was obtained over 2 steps in an overall yield of approximately 62% (Scheme [3b]).

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Scheme 2 Substrate generality for the consecutive triple arylation. All data represent the average of (more than) two independent experiments. Reactions were run on a 0.2-mmol scale; yields are isolated yields.
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Scheme 3 Gram-scale experiment and synthetic transformations

To probe the mechanism of this reaction, several control experiments were conducted. Hex-5-en-2-one (1a) could react with 1 equivalent of methyl 4-iodobenzoate (2a) under modified optimal conditions to generate the corresponding monoarylated E-arylolefin 7aa in a high yield (Scheme [4a]). During this reaction, no Z-type olefinic product was observed. In the coupling reaction of hex-5-en-2-one (1a) with 2 equivalents of methyl 4-iodobenzoate (2a), an inseparable mixture of β,β-diarylated product 8aa and α,β-diarylated product 9aa (E/Z = 6.3) was obtained; meanwhile, a small amount of monoarylation (7aa) and triarylation (4aa) was also observed (Scheme [4b]). By comparison, when hex-5-en-2-one (1a) was treated with 4 equivalents of methyl 4-iodobenzoate (2a) under the optimal conditions, besides the main triarylated product 4aa, β,β-diarylated product 8aa was obtained in 28% yield, and a very small amount of 9aa (<5% yield, E/Z ≈1) was also observed (Scheme [4c]).

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Scheme 4 Control experiments. Unless otherwise noted, yields were determined by 1H NMR spectroscopic analysis using CH2Br2 (0.1 mmol) as the internal standard; Ar = p-CO2Me-C6H4.

Based on the experimental results, a possible arylation sequence of this reaction is outlined in Scheme [5]. Terminal alkene 1 can react smoothly with aryl iodide under palladium catalysis to generate the monoarylated E-alkene 7 in high regio- and stereoselectivity. Assisted by the chelation effect, E-arylolefin 7 further undergoes a second arylation at both the β- and α-position to form β,β-diarylated product 8 and α,β-diarylated product 9 respectively, the latter consisting predominantly of the thermodynamically more stable E-type alkene. Based on the structure of products 7 and (E)-9, Heck-type reaction seems to be more fitting to describe their formation. After that, referring to previous research under similar catalytic conditions,[15] a reversible Pd(II)-catalyzed E/Z-isomerization of E-dominated 9 would take place, followed by a vicinal group directed alkenyl C–H arylation of (Z)-9, leading to the formation of the final triarylated olefin 4. In contrast, β,β-diarylated 8 cannot proceed with further arylation, and remains as a byproduct.

Previous studies[15] proved that the use of arylboronic acid effectively inhibits carbonyl-β-H elimination and possibly promotes the formation of active arylpalladium(II) species, which might participate in initial alkenyl arylation directly. However, the arylboronic acid cannot replace the role of aryl iodide in this reaction, even if exogenous oxidants were added, which demonstrates that a Pd(II)/Pd(IV) catalytic cycle works well to support such a thorough trifold arylation of alkenes.

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Scheme 5 Proposed order of arylation

In summary, we have developed a one-pot remote-carbonyl-directed palladium-catalyzed consecutive arylation of terminal alkenes with aryl iodides, delivering a variety of triarylated all-carbon tetrasubstituted olefins in moderate yields. The key to success is the use of a flexible-alkyl-chain-tethered weakly coordinating auxiliary, which might provide a chelation effect to adjust the geometry and the catalytic activity of intermediates to fit the characteristics and requirements of each transformation, thus allowing for a complicated reaction system involving Heck reaction, C–H activation and E/Z-isomerization to implement a thorough consecutive arylation under mild conditions. More diversified alkenyl C–H functionalization and in-depth mechanism studies are ongoing in our laboratory.

All reactions were performed in Schlenk tubes under an atmosphere of air using oven-dried glassware. For reactions that require heating, an oil bath or a hotplate was used as the heat source. Hexafluoroisopropanol (HFIP) was dried over 4-Å molecular sieves. Unless otherwise noted, all commercial reagents were used without further purification. Reactions were conducted with anhydrous solvents, and checked for completion by TLC analysis with visualization of the plates with shortwave UV light (254 nm). Yields refer to products isolated after purification by column chromatography. Flash chromatography was performed with SepaFlash columns produced by Santai Technologies. 1H, 13C and 19F NMR spectra were obtained in CDCl3 using a Bruker BioSpin AVANCE III HD NMR spectrometer at 400, 101 and 376 MHz, respectively. Chemical shifts are reported in parts per million (δ value) calibrated against the residual solvent peak. Signal patterns are indicated as follows: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet. Coupling constants (J) are given in hertz (Hz). High-resolution mass spectra were recorded on a Bruker Impact II UHR TOF LC/MS system (operation mode: ESI positive ion mode or ESI negative ion mode).


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Consecutive Arylation of Alkenes; General Procedure

To an oven-dried 35-mL sealable tube (with a Teflon screw cap) charged with a magnetic stir bar were added Pd(OAc)2 (4.5 mg, 0.02 mmol, 10 mol%), Fmoc-Phg-OH (15 mg, 0.04 mmol, 20 mol%), Ag2CO3 (165 mg, 0.6 mmol, 3.0 equiv), ArI (0.8 mmol, 4.0 equiv), ArB(OH)2 (0.1 mmol, 0.5 equiv), alkene substrate (0.2 mmol, 1.0 equiv) and HFIP (4 mL). The tube was sealed and the reaction mixture was stirred vigorously on a preheated hotplate (45 °C) for 24 h. After cooling to room temperature, the solution was filtered through a short pad of a 1:1 mixture of Celite and silica gel, and the column was washed with ethyl acetate (EA). The filtrate was concentrated in vacuo, and the residue was purified by column chromatography on silica gel (PE/EA, 15:1–4:1) to afford the desired triarylated products.


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Trimethyl 4,4′,4′′-(5-Oxohex-1-ene-1,1,2-triyl)tribenzoate (4aa)

Isolated by silica gel chromatography (PE/EA, 8:1–4:1); white solid; yield: 65 mg (65%); mp 105–107 °C.

1H NMR (400 MHz, CDCl3): δ = 8.05 (d, J = 8.4 Hz, 2 H), 7.86 (d, J = 8.0 Hz, 2 H), 7.69 (d, J = 8.4 Hz, 2 H), 7.32 (d, J = 8.0 Hz, 2 H), 7.17 (d, J = 8.4 Hz, 2 H), 6.92 (d, J = 8.4 Hz, 2 H), 3.93 (s, 3 H), 3.89 (s, 3 H), 3.83 (s, 3 H), 2.75 (t, J = 8.2 Hz, 2 H), 2.42 (t, J = 8.2 Hz, 2 H), 2.00 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 207.1, 166.7, 166.6, 146.5, 146.2, 145.5, 140.4, 139.7, 130.4, 129.9, 129.5, 129.4, 129.2, 129.1, 129.0, 128.8, 128.1, 52.14, 52.07, 52.0, 42.0, 29.8, 29.5.

HRMS (ESI): m/z [M + Na]+ calcd for C30H28O7Na: 523.1727; found: 523.1731.


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5,6,6-Tris(4-fluorophenyl)hex-5-en-2-one (4ab)

Isolated by silica gel chromatography (PE/EA, 15:1–4:1); colorless oil; yield: 38 mg (50%).

1H NMR (400 MHz, CDCl3): δ = 7.19–7.15 (m, 2 H), 7.07–7.02 (m, 4 H), 6.90–6.86 (m, 2 H), 6.82–6.78 (m, 2 H), 6.75–6.71 (m, 2 H), 2.69 (t, J = 8.4 Hz, 2 H), 2.41 (t, J = 8.4 Hz, 2 H), 2.00 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 207.8, 161.9 (d, J = 246.5 Hz), 161.5 (d, J = 246.5 Hz), 161.1 (d, J = 246.5 Hz), 138.7, 138.5 (d, J = 3.6 Hz), 138.4, 138.2 (d, J = 3.5 Hz), 136.9 (d, J = 3.4 Hz), 132.1 (d, J = 7.9 Hz), 131.1 (d, J = 7.8 Hz), 130.8 (d, J = 8.0 Hz), 115.5 (d, J = 21.4 Hz), 115.3 (d, J = 21.3 Hz), 114.6 (d, J = 21.3 Hz), 42.4, 29.9, 29.8.

19F NMR (376 MHz, CDCl3): δ = –114.99, –115.05, –115.70.

HRMS (ESI): m/z [M + Na]+ calcd for C24H19F3ONa: 403.1280; found: 403.1281.


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5,6,6-Tris(4-bromophenyl)hex-5-en-2-one (4ac)

Isolated by silica gel chromatography (PE/EA, 15:1–4:1); colorless oil; yield: 48 mg (43%).

1H NMR (400 MHz, CDCl3): δ = 7.49 (d, J = 8.0 Hz, 2 H), 7.33 (d, J = 8.0 Hz, 2 H), 7.18 (d, J = 8.4 Hz, 2 H), 7.07 (d, J = 8.4 Hz, 2 H), 6.95 (d, J = 8.4 Hz, 2 H), 6.70 (d, J = 8.0 Hz, 2 H), 2.68 (t, J = 8.2 Hz, 2 H), 2.39 (t, J = 8.2 Hz, 2 H), 2.01 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 207.5, 141.1, 140.6, 139.6, 138.9, 138.6, 132.1, 131.7, 131.6, 131.1, 130.9, 130.8, 121.4, 121.0, 120.6, 42.2, 29.9, 29.6.

HRMS (ESI): m/z [M + Na]+ calcd for C24H19Br3ONa: 582.8878; found: 582.8875.


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5,6,6-Tris(4-(trifluoromethyl)phenyl)hex-5-en-2-one (4ae)

Isolated by silica gel chromatography (PE/EA, 12:1–4:1); colorless oil; yield: 58 mg (55%).

1H NMR (400 MHz, CDCl3): δ = 7.64 (d, J = 8.0 Hz, 2 H), 7.47 (d, J = 8.0 Hz, 2 H), 7.37 (d, J = 8.0 Hz, 2 H), 7.31 (d, J = 8.0 Hz, 2 H), 7.21 (d, J = 8.0 Hz, 2 H), 6.96 (d, J = 8.0 Hz, 2 H), 2.74 (t, J = 7.8 Hz, 2 H), 2.41 (t, J = 7.8 Hz, 2 H), 2.01 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 207.1, 145.3, 144.8, 144.0, 140.3, 139.0, 130.7, 129.7, 129.66 (q, J = 32.3 Hz), 129.5, 129.3 (q, J = 32.3 Hz), 128.7 (q, J = 32.6 Hz), 125.7 (q, J = 3.8 Hz), 125.4 (q, J = 3.8 Hz), 124.0 (q, J = 272.2 Hz), 124.9 (q, J = 3.7 Hz), 123.88 (q, J = 272.2 Hz), 123.86 (q, J = 272.3 Hz), 41.8, 29.9, 29.6.

19F NMR (376 MHz, CDCl3): δ = –62.55, –62.56, –62.63.

HRMS (ESI): m/z [M + Na]+ calcd for C27H19F9ONa: 553.1184; found: 553.1188.


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5,6,6-Tris(4-(trifluoromethoxy)phenyl)hex-5-en-2-one (4af)

Isolated by silica gel chromatography (PE/EA, 12:1–4:1); colorless oil; yield: 74 mg (64%).

1H NMR (400 MHz, CDCl3): δ = 7.27–7.21 (m, 4 H), 7.10–7.03 (m, 4 H), 6.90–6.83 (m, 4 H), 2.72 (t, J = 7.8 Hz, 2 H), 2.42 (t, J = 7.8 Hz, 2 H), 2.01 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 207.5, 148.3 (q, J = 2.1 Hz), 148.0 (q, J = 1.8 Hz), 147.5 (q, J = 1.9 Hz), 140.6, 140.3, 139.22, 139.2, 138.5, 131.8, 130.8, 130.6, 121.0, 120.7, 120.4 (q, J = 257.6 Hz), 120.34 (q, J = 257.2 Hz), 120.3 (q, J = 257.1 Hz), 120.1, 42.1, 29.9, 29.5.

19F NMR (376 MHz, CDCl3): δ = –57.74, –57.94, –57.96.

HRMS (ESI): m/z [M + Na]+ calcd for C27H19F9O4Na: 601.1032; found: 601.1032.


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5,6,6-Tris(4-acetylphenyl)hex-5-en-2-one (4ag)

Isolated by silica gel chromatography (PE/EA, 12:1–4:1); colorless oil; yield: 46 mg (51%).

1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 8.0 Hz, 2 H), 7.79 (d, J = 8.0 Hz, 2 H), 7.64 (d, J = 8.1 Hz, 2 H), 7.35 (d, J = 8.0 Hz, 2 H), 7.21 (d, J = 8.1 Hz, 2 H), 6.96 (d, J = 8.1 Hz, 2 H), 2.77 (t, J = 7.8 Hz, 2 H), 2.62 (s, 3 H), 2.56 (s, 3 H), 2.49 (s, 3 H), 2.43 (t, J = 7.8 Hz, 2 H), 2.01 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 207.1, 197.5, 146.6, 146.3, 145.6, 140.5, 139.6, 136.0, 135.7, 135.0, 130.6, 129.6, 129.4, 128.6, 128.4, 127.8, 41.9, 29.8, 29.5, 26.6, 26.5, 26.4.

HRMS (ESI): m/z [M + Na]+ calcd for C30H28O4Na: 475.1880; found: 475.1883.


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Trimethyl 4,4′,4′′-(5-Oxopent-1-ene-1,1,2-triyl)tribenzoate (4ba)

Isolated by silica gel chromatography (PE/EA, 8:1–4:1); white solid; yield: 50 mg (51%); mp 104–106 °C.

1H NMR (400 MHz, CDCl3): δ = 9.60 (s, 1 H), 8.04 (d, J = 8.3 Hz, 2 H), 7.84 (d, J = 8.3 Hz, 2 H), 7.68 (d, J = 8.4 Hz, 2 H), 7.30 (d, J = 8.3 Hz, 2 H), 7.15 (d, J = 8.3 Hz, 2 H), 6.91 (d, J = 8.4 Hz, 2 H), 3.91 (s, 3 H), 3.87 (s, 3 H), 3.82 (s, 3 H), 2.79 (t, J = 7.6 Hz, 2 H), 2.44 (t, J = 7.6 Hz, 2 H).

13C NMR (101 MHz, CDCl3): δ = 200.5, 166.7, 166.62, 166.6, 146.4, 146.0, 145.2, 140.1, 139.8, 130.4, 130.0, 129.7, 129.5, 129.3, 129.2, 129.1, 128.9, 128.3, 52.2, 52.1, 52.0, 42.5, 28.1.

HRMS (ESI): m/z [M + Na]+ calcd for C29H26O7Na: 509.1571; found: 509.1570.


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4,5,5-Tris(4-(trifluoromethoxy)phenyl)pent-4-enal (4bf)

Isolated by silica gel chromatography (PE/EA, 12:1–4:1); colorless oil; yield: 61 mg (54%).

1H NMR (400 MHz, CDCl3): δ = 9.64 (s, 1 H), 7.28–7.21 (m, 4 H), 7.11–7.08 (m, 2 H), 7.05 (d, J = 8.4 Hz, 2 H), 6.90 (d, J = 8.5 Hz, 2 H), 6.88–6.83 (m, 2 H), 2.78 (t, J = 7.7 Hz, 2 H), 2.47 (t, J = 7.7 Hz, 2 H).

13C NMR (101 MHz, CDCl3): δ = 200.8, 148.4 (q, J = 1.7 Hz), 148.1 (q, J = 2.0 Hz), 147.6 (q, J = 2.0 Hz), 140.5, 140.1, 139.0, 138.9, 138.7, 131.7, 130.8, 130.5, 121.1, 120.8, 120.4 (q, J = 257.6 Hz), 120.34 (q, J = 257.3 Hz), 120.3 (q, J = 257.2 Hz), 120.1, 42.6, 28.1.

19F NMR (376 MHz, CDCl3): δ = –57.76, –57.95, –57.96.

HRMS (ESI): m/z [M + Na]+ calcd for C26H17F9O4Na: 587.0875; found: 587.0876.


#

4,5,5-Tris(4-acetylphenyl)pent-4-enal (4bg)

Isolated by silica gel chromatography (PE/EA, 12:1–4:1); colorless oil; yield: 44 mg (50%).

1H NMR (400 MHz, CDCl3): δ = 9.59 (s, 1 H), 7.95 (d, J = 8.3 Hz, 2 H), 7.77 (d, J = 8.3 Hz, 2 H), 7.61 (d, J = 8.4 Hz, 2 H), 7.32 (d, J = 8.3 Hz, 2 H), 7.19 (d, J = 8.3 Hz, 2 H), 6.94 (d, J = 8.4 Hz, 2 H), 2.79 (t, J = 7.7 Hz, 2 H), 2.59 (s, 3 H), 2.53 (s, 3 H), 2.46 (s, 3 H), 2.44 (t, J = 8.0 Hz, 2 H).

13C NMR (101 MHz, CDCl3): δ = 200.49, 200.48, 197.5, 197.48, 197.46, 146.5, 146.1, 145.3, 140.0, 139.9, 136.1, 135.8, 135.2, 130.6, 129.6, 129.4, 128.7, 128.5, 127.9, 42.4, 28.1, 26.58, 26.56, 26.5, 26.48, 26.44, 26.42.

HRMS (ESI): m/z [M + Na]+ calcd for C29H26O4Na: 461.1723; found: 461.1728.


#

Trimethyl 4,4′,4′′-(5-Methoxy-5-oxopent-1-ene-1,1,2-triyl)tribenzoate (4ca)

Isolated by silica gel chromatography (PE/EA, 8:1–4:1); white solid; yield: 46 mg (45%); mp 106–108 °C.

1H NMR (400 MHz, CDCl3): δ = 8.06 (d, J = 8.3 Hz, 2 H), 7.85 (d, J = 8.2 Hz, 2 H), 7.70 (d, J = 8.4 Hz, 2 H), 7.32 (d, J = 8.2 Hz, 2 H), 7.18 (d, J = 8.2 Hz, 2 H), 6.92 (d, J = 8.4 Hz, 2 H), 3.93 (s, 3 H), 3.89 (s, 3 H), 3.84 (s, 3 H), 3.56 (s, 3 H), 2.82 (t, J = 8.1 Hz, 2 H), 2.31 (t, J = 8.0 Hz, 2 H).

13C NMR (101 MHz, CDCl3): δ = 172.9, 166.8, 166.7, 146.4, 146.1, 145.2, 140.1, 140.0, 130.4, 129.9, 129.6, 129.5, 129.3, 129.14, 129.05, 128.8, 128.2, 52.2, 52.12, 52.05, 51.7, 32.8, 30.8.

HRMS (ESI): m/z [M + Na]+ calcd for C30H28O8Na: 539.1676; found: 539.1675.


#

Methyl 4,5,5-Tris(4-(trifluoromethoxy)phenyl)pent-4-enoate (4cf)

Isolated by silica gel chromatography (PE/EA, 10:1–4:1); colorless oil; yield: 55 mg (46%).

1H NMR (400 MHz, CDCl3): δ = 7.29–7.20 (m, 4 H), 7.14–7.02 (m, 4 H), 6.93–6.81 (m, 4 H), 3.57 (s, 3 H), 2.80 (t, J = 8.0 Hz, 2 H), 2.32 (t, J = 8.0 Hz, 2 H).

13C NMR (101 MHz, CDCl3): δ = 173.0, 148.4, 148.0, 147.6, 140.5, 140.3, 139.0, 138.9, 131.8, 130.9, 130.6, 121.0, 120.7, 120.44 (q, J = 257.5 Hz), 120.37 (q, J = 257.3 Hz), 120.3 (q, J = 257.3 Hz), 120.1, 51.6, 32.9, 30.8.

19F NMR (376 MHz, CDCl3): δ = –57.78, –57.98, –57.99.

HRMS (ESI): m/z [M + Na]+ calcd for C27H19F9O5Na: 617.0981; found: 617.0983.


#

Ethyl 4,5,5-Tris(4-fluorophenyl)pent-4-enoate (4db)

Isolated by silica gel chromatography (PE/EA, 8:1–4:1); colorless oil; yield: 52 mg (64%).

1H NMR (400 MHz, CDCl3): δ = 7.21–7.15 (m, 2 H), 7.09–7.02 (m, 4 H), 6.91–6.84 (m, 2 H), 6.83–6.77 (m, 2 H), 6.76–6.69 (m, 2 H), 4.02 (q, J = 7.2 Hz, 2 H), 2.76 (t, J = 8.0 Hz, 2 H), 2.28 (t, J = 8.0 Hz, 2 H), 1.18 (t, J = 7.2 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 172.8, 161.8 (d, J = 246.5 Hz), 161.5 (d, J = 246.4 Hz), 161.1 (d, J = 246.3 Hz), 138.8, 138.4 (d, J = 3.4 Hz), 138.17 (d, J = 3.5 Hz), 138.15, 136.6 (d, J = 3.5 Hz), 132.1 (d, J = 8.0 Hz), 131.1 (d, J = 8.0 Hz), 130.8 (d, J = 8.0 Hz), 115.4 (d, J = 21.4 Hz), 115.2 (d, J = 21.3 Hz), 114.6 (d, J = 21.3 Hz), 60.4, 33.2, 31.0, 14.1.

19F NMR (376 MHz, CDCl3): δ = –114.99, –115.12, –115.67.

HRMS (ESI): m/z [M + Na]+ calcd for C25H21F3O2Na: 433.1386; found: 433.1387.


#

Ethyl 4,5,5-Tris(4-bromophenyl)pent-4-enoate (4dc)

Isolated by silica gel chromatography (PE/EA, 8:1–4:1); colorless oil; yield: 61 mg (52%).

1H NMR (400 MHz, CDCl3): δ = 7.49 (d, J = 8.4 Hz, 2 H), 7.33 (d, J = 8.4 Hz, 2 H), 7.17 (d, J = 8.5 Hz, 2 H), 7.07 (d, J = 8.4 Hz, 2 H), 6.97 (d, J = 8.5 Hz, 2 H), 6.70 (d, J = 8.5 Hz, 2 H), 4.02 (q, J = 7.1 Hz, 2 H), 2.74 (t, J = 8.1 Hz, 2 H), 2.26 (t, J = 8.1 Hz, 2 H), 1.19 (t, J = 7.1 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 172.6, 141.0, 140.6, 139.4, 138.8, 138.7, 132.1, 131.7, 131.5, 131.1, 130.93, 130.9, 121.4, 121.0, 120.6, 60.5, 33.1, 30.8, 14.1.

HRMS (ESI): m/z [M + Na]+ calcd for C25H21Br3O2Na: 612.8984; found: 612.8981.


#

Ethyl 4,5,5-Tris(4-chlorophenyl)pent-4-enoate (4dd)

Isolated by silica gel chromatography (PE/EA, 8:1–4:1); colorless oil; yield: 50 mg (55%).

1H NMR (400 MHz, CDCl3): δ = 7.34 (d, J = 8.4 Hz, 2 H), 7.17 (d, J = 8.4 Hz, 2 H), 7.14 (d, J = 8.4 Hz, 2 H), 7.03 (d, J = 8.5 Hz, 2 H), 7.02 (d, J = 8.5 Hz, 2 H), 6.77 (d, J = 8.5 Hz, 2 H), 4.02 (q, J = 7.1 Hz, 2 H), 2.76 (t, J = 8.1 Hz, 2 H), 2.27 (t, J = 8.1 Hz, 2 H), 1.19 (t, J = 7.1 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 172.6, 140.6, 140.2, 138.9, 138.8, 138.6, 133.2, 132.7, 132.3, 131.8, 130.8, 130.5, 128.7, 128.5, 128.0, 60.5, 33.1, 30.9, 14.1.

HRMS (ESI): m/z [M + Na]+ calcd for C25H21Cl3O2Na: 481.0499; found: 481.0496.


#

Ethyl 4,5,5-Tris(4-acetylphenyl)pent-4-enoate (4dg)

Isolated by silica gel chromatography (PE/EA, 8:1–4:1); colorless oil; yield: 57 mg (59%).

1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 8.3 Hz, 2 H), 7.80 (d, J = 8.4 Hz, 2 H), 7.64 (d, J = 8.4 Hz, 2 H), 7.36 (d, J = 8.3 Hz, 2 H), 7.23 (d, J = 8.4 Hz, 2 H), 6.96 (d, J = 8.5 Hz, 2 H), 4.03 (q, J = 7.2 Hz, 2 H), 2.84 (t, J = 8.0 Hz, 2 H), 2.63 (s, 3 H), 2.56 (s, 3 H), 2.49 (s, 3 H), 2.30 (t, J = 8.0 Hz, 2 H), 1.18 (t, J = 7.2 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 197.6, 197.5, 172.3, 146.5, 146.3, 145.4, 140.2, 139.9, 136.0, 135.7, 135.1, 130.6, 129.7, 129.5, 128.7, 128.4, 127.9, 60.5, 32.9, 30.8, 26.6, 26.5, 26.45, 14.1.

HRMS (ESI): m/z [M + Na]+ calcd for C31H30O5Na: 505.1985; found: 505.1989.


#

Trimethyl 3,3′,3′′-(5-Ethoxy-5-oxopent-1-ene-1,1,2-triyl)tribenzoate (4dh)

Isolated by silica gel chromatography (PE/EA, 8:1–4:1); colorless oil; yield: 55 mg (52%).

1H NMR (400 MHz, CDCl3): δ = 8.00 (m, 1 H), 7.94 (m, 1 H), 7.85 (m, 1 H), 7.82 (dt, J = 7.3, 1.7 Hz, 1 H), 7.69 (dt, J = 6.5, 1.6 Hz, 1 H), 7.57 (m, 1 H), 7.48 (d, J = 5.3 Hz, 2 H), 7.28–7.22 (m, 2 H), 7.12–7.05 (m, 2 H), 4.01 (q, J = 7.2 Hz, 2 H), 3.91 (s, 3 H), 3.88 (s, 3 H), 3.79 (s, 3 H), 2.80 (t, J = 8.0 Hz, 2 H), 2.31 (t, J = 8.0 Hz, 2 H), 1.17 (t, J = 7.2 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 172.5, 166.8, 166.74, 166.7, 142.1, 141.8, 140.7, 139.6, 134.9, 134.4, 133.6, 131.4, 130.5, 130.3, 130.14, 130.07, 129.7, 128.7, 128.5, 128.3, 128.1, 127.8, 127.6, 60.4, 52.2, 52.1, 52.0, 33.0, 30.8, 14.0.

HRMS (ESI): m/z [M + Na]+ calcd for C31H30O8Na: 553.1833; found: 553.1836.


#

Trimethyl 4,4′,4′′-(4-Ethoxy-4-oxobut-1-ene-1,1,2-triyl)tribenzoate (4ea)

Isolated by silica gel chromatography (PE/EA, 8:1–4:1); white solid; yield: 52 mg (50%); mp 101–103 °C.

1H NMR (400 MHz, CDCl3): δ = 8.05 (d, J = 8.2 Hz, 2 H), 7.85 (d, J = 8.3 Hz, 2 H), 7.73 (d, J = 8.5 Hz, 2 H), 7.40 (d, J = 8.3 Hz, 2 H), 7.23 (d, J = 8.5 Hz, 2 H), 6.96 (d, J = 8.4 Hz, 2 H), 4.03 (q, J = 7.1 Hz, 2 H), 3.93 (s, 3 H), 3.88 (s, 3 H), 3.84 (s, 3 H), 3.54 (s, 2 H), 1.11 (t, J = 7.1 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 170.7, 166.7, 166.6, 146.1, 145.8, 145.5, 142.4, 134.2, 130.6, 129.9, 129.6, 129.5, 129.4, 129.1, 128.8, 128.5, 60.9, 52.2, 52.09, 52.06, 41.5, 14.0.

HRMS (ESI): m/z [M + Na]+ calcd for C30H28O8Na: 539.1676; found: 539.1678.


#

Synthetic Transformations


#

Synthesis of Compound 6

A solution of LiOH·H2O (252 mg, 6.0 mmol, 3 equiv) in H2O (10 mL, 0.2 M) was added to a solution of 4dg (965 mg, 2.0 mmol, 1 equiv) in i-PrOH (10 mL, 0.2 M); the mixed solution was stirred at room temperature for 1 h (monitored by TLC). After adjusting the pH to 3–6 with diluted hydrochloric acid (1 M), the mixture was extracted with EA (3 × 15 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to provide the crude product 5 (898 mg, 99% yield), which could be used in the next step without further purification.

To a CH2Cl2 (20 mL, 0.1 M) solution of acid 5 were added benzbromarone (933 mg, 2.2 mmol, 1.1 equiv) and 4-(dimethylamino)pyridine (74 mg, 0.6 mmol, 0.3 equiv). After cooling with ice–water, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (460 mg, 2.4 mmol, 1.2 equiv) was added thereto, and the resulting mixture was warmed to 45 °C on a preheated hotplate and stirred overnight. The reaction mixture was washed with diluted hydrochloric acid (1 M), saturated NaHCO3 solution and brine, then dried over anhydrous Na2SO4. After filtration and concentration under reduced pressure, the residue was purified by flash column chromatography on silica gel (PE/EA, 5:1–2:1) to afford compound 6 as a pale yellow solid; yield: 1.06 g (62% over 2 steps).


#

4,5,5-Tris(4-acetylphenyl)pent-4-enoic Acid (5)

Pale yellow solid; mp 100–102 °C.

1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 8.2 Hz, 2 H), 7.79 (d, J = 8.2 Hz, 2 H), 7.64 (d, J = 8.3 Hz, 2 H), 7.34 (d, J = 8.2 Hz, 2 H), 7.23 (d, J = 8.2 Hz, 2 H), 6.96 (d, J = 8.3 Hz, 2 H), 2.83 (t, J = 8.0 Hz, 2 H), 2.62 (s, 3 H), 2.55 (s, 3 H), 2.49 (s, 3 H), 2.34 (t, J = 8.0 Hz, 2 H).

13C NMR (101 MHz, CDCl3): δ = 197.78, 197.76, 197.75, 177.3, 146.5, 146.2, 145.2, 140.0, 139.9, 136.0, 135.7, 135.1, 130.6, 129.6, 129.4, 128.7, 128.4, 127.9, 32.6, 30.6, 26.6, 26.5, 26.4.

HRMS (ESI): m/z [M – H]– calcd for C29H25O5: 453.1707; found: 453.1707.


#

2,6-Dibromo-4-(2-ethylbenzofuran-3-carbonyl)phenyl 4,5,5-Tris(4-acetylphenyl)pent-4-enoate (6)

Pale yellow solid; yield: 1.06 g (62% over 2 steps); mp 91–93 °C.

1H NMR (400 MHz, CDCl3): δ = 8.03–7.98 (m, 4 H), 7.84 (d, J = 7.9 Hz, 2 H), 7.66 (d, J = 8.1 Hz, 2 H), 7.50 (d, J = 8.2 Hz, 1 H), 7.42 (d, J = 7.9 Hz, 2 H), 7.38 (d, J = 7.7 Hz, 1 H), 7.32–7.23 (m, 4 H), 6.99 (d, J = 8.0 Hz, 2 H), 3.05 (t, J = 7.9 Hz, 2 H), 2.90 (q, J = 7.5 Hz, 2 H), 2.72 (t, J = 7.9 Hz, 2 H), 2.62 (s, 3 H), 2.58 (s, 3 H), 2.50 (s, 3 H), 1.36 (t, J = 7.6 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 197.5, 187.7, 168.3, 167.4, 153.6, 149.1, 146.4, 146.1, 145.0, 140.5, 139.4, 139.0, 136.2, 136.0, 135.3, 133.0, 130.6, 129.7, 129.5, 128.8, 128.6, 128.0, 126.1, 124.8, 124.0, 120.9, 118.0, 115.1, 111.2, 32.5, 30.5, 26.63, 26.56, 26.5, 22.0, 12.2.

HRMS (ESI): m/z [M + Na]+ calcd for C46H36O7Br2Na: 883.0705; found: 883.0704.


#

Methyl (E)-4-(5-Oxohex-1-en-1-yl)benzoate (7aa)[20]

Isolated by silica gel chromatography (PE/EA, 6:1); pale yellow oil; yield: 38 mg (82%).

1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 8.4 Hz, 2 H), 7.38 (d, J = 8.4 Hz, 2 H), 6.44 (d, J = 15.9 Hz, 1 H), 6.33 (dt, J = 15.8, 6.6 Hz, 1 H), 3.90 (s, 3 H), 2.64 (t, J = 7.2 Hz, 2 H), 2.51 (q, J = 6.9 Hz, 2 H), 2.18 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 207.8, 166.9, 141.8, 131.8, 129.9, 129.8, 128.5, 125.8, 52.0, 42.8, 30.0, 27.0.


#

Dimethyl (E)-4,4′-(5-Oxohex-1-ene-1,2-diyl)dibenzoate [(E)-9aa]

1H NMR (400 MHz, CDCl3): δ = 8.05 (d, J = 8.6 Hz, 4 H), 7.51 (d, J = 8.5 Hz, 2 H), 7.38 (d, J = 8.2 Hz, 2 H), 6.82 (s, 1 H), 3.94 (s, 3 H), 3.93 (s, 3 H), 3.02 (t, J = 7.9 Hz, 2 H), 2.50 (t, J = 8.0 Hz, 2 H), 2.05 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 207.3, 166.79, 166.76, 146.3, 142.3, 141.9, 129.9, 129.74, 129.71, 129.3, 128.6, 126.6, 52.2, 52.1, 42.0, 29.9, 24.0.

HRMS (ESI): m/z [M + H]+ calcd for C22H23O5: 367.1540; found: 367.1538.


#

Dimethyl (Z)-4,4′-(5-Oxohex-1-ene-1,2-diyl)dibenzoate [(Z)-9aa]

1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 8.5 Hz, 2 H), 7.75 (d, J = 8.4 Hz, 2 H), 7.20 (d, J = 8.2 Hz, 2 H), 6.94 (d, J = 8.3 Hz, 2 H), 6.57 (s, 1 H), 3.92 (s, 3 H), 3.85 (s, 3 H), 2.82 (t, J = 7.6 Hz, 2 H), 2.52 (t, J = 7.6 Hz, 2 H), 2.11 (s, 3 H).


#

Dimethyl 4,4′-(5-Oxohex-1-ene-1,1-diyl)dibenzoate (8aa)

1H NMR (400 MHz, CDCl3): δ = 8.07 (d, J = 7.7 Hz, 2 H), 7.92 (d, J = 8.3 Hz, 2 H), 7.25 (d, J = 8.2 Hz, 2 H), 7.23 (d, J = 7.7 Hz, 2 H), 6.20 (t, J = 7.5 Hz, 1 H), 3.93 (s, 3 H), 3.89 (s, 3 H), 2.58 (t, J = 7.2 Hz, 2 H), 2.39 (q, J = 7.3 Hz, 2 H), 2.13 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 207.4, 166.7, 145.9, 143.9, 141.0, 130.7, 129.72, 129.65, 129.4, 129.1, 128.7, 126.9, 52.1, 52.0, 43.0, 29.8, 24.0.

HRMS (ESI): m/z [M + H]+ calcd for C22H23O5: 367.1540; found: 367.1536.


#
#

Conflict of Interest

The authors declare no conflict of interest.

Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/a-2323-0633.
  • Supporting Information

Corresponding Authors

Yu Du
State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences
155 Yangqiao Road West, Fuzhou 350002
P. R. of China   

Weiping Su
State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences
155 Yangqiao Road West, Fuzhou 350002
P. R. of China   

Publication History

Received: 15 April 2024

Accepted after revision: 10 May 2024

Accepted Manuscript online:
10 May 2024

Article published online:
23 May 2024

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Scheme 1 Chelation-assisted alkenyl arylation
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Scheme 2 Substrate generality for the consecutive triple arylation. All data represent the average of (more than) two independent experiments. Reactions were run on a 0.2-mmol scale; yields are isolated yields.
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Scheme 3 Gram-scale experiment and synthetic transformations
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Scheme 4 Control experiments. Unless otherwise noted, yields were determined by 1H NMR spectroscopic analysis using CH2Br2 (0.1 mmol) as the internal standard; Ar = p-CO2Me-C6H4.
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Scheme 5 Proposed order of arylation