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Synlett 2016; 27(07): 1073-1076
DOI: 10.1055/s-0035-1561265
DOI: 10.1055/s-0035-1561265
letter
Regioselective Suzuki–Miyaura Reactions of the Bis(triflate) of 6,7-Dihydroxy-2,2-dimethylchroman-4-one
Further Information
Publication History
Received: 03 November 2015
Accepted after revision: 06 December 2015
Publication Date:
21 January 2016 (online)
![](https://www.thieme-connect.de/media/synlett/201607/lookinside/thumbnails/st-2015-d0863-l_10-1055_s-0035-1561265-1.jpg)
Dedicated in memory to our dear colleague and friend Professor Tamás Patonay, PhD, DSc
Abstract
6,7-Diarylchromanone derivatives were prepared by Suzuki–Miyaura reactions of the bis(triflate) of 6,7-dihydroxy-2,2-dimethylchroman-4-one. Due to electronic factors the first attack proceeded with very good site selectivity at position 7.
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References and Notes
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- 53 Procedure for Synthesizing 6,7-Diaryl-2,2-dimethylchroman-4-one Derivatives To a mixture of 2,2-dimethyl-6,7-ditriflyloxychroman-4-one (150 mg, 0.318 mmol), K3PO4 (202 mg, 0,95 mmol), and boronic acid (0.70 mmol) in dry 1,4-dioxane (4 mL) was added Pd(PPh3)4 (22 mg, 0.019 mmol) in a dried pressure tube under argon. The reaction mixture was stirred and heated in an aluminium heating block. The solvent was evaporated in vacuum, and the solid mixture was submitted to adsorptive filtration on silica gel using acetone as eluent removing the inorganic compounds. Silica was added to the solution, the acetone was evaporated, and the mixture was purified by column chromatography (eluent: heptane–EtOAc, the ratio is given below) giving the diarylated product. 6,7-Bis(4-methoxyphenyl)-2,2-dimethylchroman-4-oneStarting with 4 (150 mg, 0.32 mmol), K3PO4 (202 mg, 0.95 mmol), Pd(PPh3)4 (22 mg, 6 mol%), (4-methoxyphenyl)boronic acid (5b, 106 mg, 0.70 mmol), and 1,4-dioxane (4 mL), 6b was isolated as a white solid (84 mg 68%), mp 150–152.5 °C. 1H NMR (300 MHz, 298 K, CDCl3): δ = 7.61 (s, 1 H, 5-H), 7.05 (d, J= 10.5 Hz, 2 H, 2′,6′′-H) 6.98 (d, J= 10.5 Hz, 2 H, 2′,6′-H), 6.93 (s, 1 H, 8-H), 6.81 (m, 4 H, 3′,5′-H, 3′′,5′′-H), 3.72 (s, 3 H, 4′′-OCH3), 3.71 (s, 3 H, 4′-OCH3), 2.83 (s, 2 H, 3-H), 1.44 (s, 6 H, 2-CH3). 13C NMR (75 MHz, 298 K, CDCl3): δ = 191.7.7 (C-4), 158.6 (C-8a), 158.3 (C-4′′), 157.9 (C-4′), 147.5 (C-7), 132.5 (C-1′′), 132.3 (C-1′), 132.0 (C-6), 130.4 (C-2′,6′, C-2′′,6′′), 127.4 (C-5), 119.3 (C-8), 118.5 (C-4a), 113.6 (C-3′,5′, C-3′′5′′), 79.6 (C-2), 55.0 (OCH3), 48.0 (C-3), 26.2 (CH3). IR (ATR): υ = 2994, 2954, 2835, 1683, 1606, 1512, 1466, 1430, 1403, 1296, 1243, 1167, 1109, 1025, 951, 831, 655, 564, 549 cm–1. GC–MS (EI, 70 eV): m/z = 388 [M+∙, 100%], 373, 333, 261, 189. HRMS: m/z calcd for C25H24O4: 388.16691; found: 388.16649.
- 54 Procedure for Synthesizing 7-Aryl-2,2-dimethyl-6-triflyloxy-chroman-4-one Derivatives To a mixture of 2,2-dimethyl-6,7-ditriflyloxychroman-4-one (150 mg, 0.318 mmol), K3PO4 (135 mg, 0,64 mmol), and boronic acid (0.349 mmol) in dry 1,4-dioxane (4 mL) was added Pd(PPh3)4 (11 mg, 0.0095 mmol) in a dried pressure tube under argon. The reaction mixture was stirred and heated in an aluminium heating block. The solvent was evaporated in vacuum, then the solid mixture was submitted to adsorptive filtration on silica gel using acetone as eluent removing the inorganic compounds. Silica was added to the solution, the acetone was evaporated, and the mixture was purified by column chromatography (eluent: heptane–EtOAc mixture, the ratio is given below) giving the monosubsituted product. 7-(4-Methoxyphenyl)-2,2-dimethyl-6-(triflyloxy)chroman-4-oneStarting with 4 (150 mg, 0.32 mmol), K3PO4 (135 mg, 0.64 mmol), Pd(PPh3)4 (11 mg, 3 mol%), (4-methoxyphenyl)boronic acid (5b, 53 mg, 0.35 mmol), and 1,4-dioxane (4 mL), 7b was isolated as a yellow oil (93 mg 68%), eluent: toluene–heptane (6:1). 1H NMR (300 MHz, 298 K, DMSO-d 6): δ = 7.71 (s, 1 H, 5-H), 7.47 (d, 2 H, J= 8.7 Hz, 2′,6′-H), 7.06 (d, 2 H, J= 8.7 Hz, 3′,5′-H), 3.82 (s, 3 H, OCH3), 2.92(s, 2 H, 3-H), 1.44 (s, 6 H, CH3). 13C NMR (75 MHz, 298 K, DMSO-d 6): δ = 190.7 (C-4), 160.0 (C-4′), 158.6 (C-8a), 142.1 (C-6), 140.1 (C-7), 130.5 (C-2′,6′), 126.1 (C-1′), 120.9 (C-5), 118.9 (C-8), 118.8 (C-4a), 114.2 (C-3′,5′), 80.6 (C-2), 55.3 (OCH3), 47.3 (C-3), 26.0 (CH3). IR (ATR): υ = 2978, 2839, 1696, 1607, 1518, 1423, 1205, 1136, 1097, 1030, 915, 890, 832, 613, 564, 513 cm–1. GC–MS (EI, 70 eV): m/z = 430 [M+∙], 297, 255, 241 (100%), 215, 185, 157, 83. HRMS: m/z calcd for C19H17F3O6S: 430.06979; found: 430.06967.
- 55 Procedure for Synthesizing Differently Substituted 6,7-Diaryl-2,2-dimethylchroman-4-one DerivativesTo a mixture of 7-aryl-2,2-dimethyl-6-triflyloxychroman-4-one (0.120 mmol), K3PO4 (76 mg, 0,360 mmol), and boronic acid (0.264 mmol) in dry 1,4-dioxane (4 mL) was added Pd(PPh3)4 (8.3 mg, 0.0072 mmol) in a dried pressure tube under argon. The reaction mixture was stirred and heated in an aluminium heating block. The solvent was evaporated in vacuum, and then the solid mixture was submitted to adsorptive filtration on silica gel using acetone as eluent removing the inorganic compounds. Silica was added to the solution, the acetone was evaporated, and the mixture was purified by column chromatography (eluent: heptane–EtOAc mixture, the ratio is given below) giving the differently substituted product.6-(4-Hydroxyphenyl)-7-(4-methoxyphenyl)-2,2-dimethylchroman-4-oneStarting with 7b (50 mg, 0.12 mmol), K3PO4 (76 mg, 0.36 mmol), Pd(PPh3)4 (8.1 mg, 6 mol%), (4-hydroxyphenyl)boronic acid (5e, 35 mg, 0.264 mmol), and 1,4-dioxane (4 mL), 8g was isolated as a light yellow solid (36 mg 83%), mp 182.5–185°C, eluent: heptane–EtOAc (2:1). 1H NMR(300 MHz, 298 K, CDCl3): δ = 9.37 (s, 1 H, 5-H), 7.59 (s, 1 H, 8-H), 7.06 (d, J= 8.7 Hz, 2 H, 2′′,6′′-H), 6.86 (d, J= 8.7 Hz, 2 H, 2′,6′-H), 6.82 (d, J= 8.7 Hz, 2 H, 3′′,5′′-H), 6.62 (d, J= 8.7 Hz, 2 H, 3′,5′-H), 6.55 (s, 1 H, OH), 3.73 (s, 3 H, OCH3), 2.82 (s, 2 H, 3-H), 1.44 (s, 6 H, CH3). 13C NMR (75 MHz, 298 K, CDCl3): δ = 191.7 (C-4), 158.6 (C-8a), 158.1 (C-4′′), 156.1 (C-4′), 147.5 (C-7), 132.9 (C-1′′), 132.1 (C-1′), 130.6 (C-6), 130.4 (C-2′,6′, C-2′′,6′′), 127.2 (C-5), 119.2 (C-8), 118.4 (C-4a), 115.0 (C-3′,5′), 113.5 (C-3′′,5′′), 79.6 (C-2), 55.0 (OCH3), 48.0 (C-3), 26.2 (CH3). IR (ATR): υ = 3299, 2921, 2847, 1737, 1668, 1602, 1512, 1406, 1243, 1163, 1109, 1026, 950, 834, 654, 560 cm–1. GC–MS (EI, 70 eV): m/z = 374 [M+∙, 100%], 359, 319, 290, 247, 219, 202, 179, 152. HRMS: m/z calcd for C24H22O4: 374.15126; found: 374.15110.