Synthesis of Bis(diaryl)sulfones by Site-Selective Suzuki-Miyaura Reactions of 2,4′-Bis(trifluoromethylsulfonyloxy)diphenylsulfone

Abstract

The Suzuki-Miyaura reaction of the bis(triflate) of 2,4′-bis(hydroxy)diphenylsulfone with two equivalents of boronic acids gave 2,4′-bis(aryl)diphenylsulfones. The reaction with one equivalent of arylboronic acids resulted in site-selective attack onto carbon atom C-4′.

Key words

catalysis - palladium - Suzuki-Miyaura reaction - site ­selectivity - sulfones

References and Notes

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11

Synthesis of 2,4′-Bis(trifluoromethylsulfonyloxy)-diphenylsulfone (2)
To a solution of 1 (1.0 equiv) in CH₂Cl₂ (10 mL per 1 mmol of 1) was added pyridine (4.0 equiv) at -78 ˚C under an argon atmosphere. After stirring for 10 min, Tf₂O (2.4 equiv) was added at -78 ˚C. The mixture was allowed to warm to 0 ˚C and stirred for 4 h. The reaction mixture was filtered, and the filtrate was concentrated in vacuo. The products of the reaction mixture were isolated by rapid column chromatography (flash silica gel, heptanes-EtOAc). Starting with 1 (250 mg, 1.0 mmol), pyridine (0.32 mL, 4.0 mmol), and Tf₂O (0.40 mL, 2.4 mmol), compound 2 was isolated as a white solid (416 mg, 81%), mp 112 ˚C.
^¹H NMR (300 MHz, CDCl₃): δ = 7.32-7.39 (m, 3 H, ArH), 7.50-7.56 (m, 1 H, ArH), 7.63-7.69 (m, 1 H, ArH), 7.99-8.04 (m, 2 H, ArH), 8.21-8.24 (m, 1 H, ArH). ^¹9F NMR (282 MHz, CDCl₃): δ = -73.2, -73.3 CF. ^¹³C NMR (75 MHz, CDCl₃): δ = 114. 5 (q, J _CF = 324.2 Hz, CF₃), 121.8 (q, J _CF = 324.2 Hz, CF₃), 122.4, 122.5, 128.9, 131.1, 131.4 (CH), 133.3 (C), 136.4 (CH), 140.5, 146.5, 152.9 (C). IR (KBr): ν = 3104 (w), 1594 (w), 1484 (w), 1434 (s), 1404 (w), 1325 (m), 1272 (w), 1203 (s), 1161 (s), 1127 (s), 1089 (m), 1054 (m), 992 (w), 966 (w), 870 (s), 749 (s), 781 (m), 726 (m), 688 (m), 629 (m), 599 (s), 562 (s), 552 (s) cm^-¹. GC-MS (EI, 70 eV): m/z (%) = 514 (44) [M]⁺, 317 (1), 273 (27), 225 (05), 209 (33), 177 (100), 155 (06), 115 (17). HRMS (EI, 70 eV): m/z calcd for C₁₄H₈F₆O₈S₃: 514.39262; found: 514. 39351.

12

General Procedure for the Synthesis of 4a-j, 5a-e, and 6a-c
A 1,4-dioxane solution of the arylboronic acid, K₃PO₄, Pd(PPh₃)₄, and 2 or 5 was stirred at 110 ˚C for 4 h under argon atmosphere. After cooling to 20 ˚C, a sat. aq solution of NH₄Cl was added. The organic and the aqueous layer were separated, and the latter was extracted with CH₂Cl₂. The combined organic layers were dried (Na₂SO₄), filtered, and the filtrate was concentrated in vacuo. The residue was purified by column chromatography.

13

2,4′-Bis(4-tolyl)diphenylsulfone (4b)
Starting with 2 (205 mg, 0.4 mmol), K₃PO₄ (254 mg, 1.2 mmol), Pd(PPh₃)₄ (6 mol%), 4-methylphenylboronic acid (136 mg, 1.0 mmol), and 1,4-dioxane (5 mL per 1 mmol of 2), compound 4b was isolated as a white solid (112 mg, 70%), mp 131 ˚C. ^¹H NMR (300 MHz, CDCl₃): δ = 2.29 (s, 3 H, CH₃), 2.30 (s, 3 H, CH₃), 6.77-6.80 (m, 2 H, ArH), 6.89-6.92 (m, 2 H, ArH), 7.11-7.20 (m, 6 H, ArH), 7.26-7.33 (m, 2 H, ArH), 7.44-7.52 (m, 3 H, ArH), 8.31-8.35 (m, 1 H, ArH). ^¹³C NMR (75 MHz, CDCl₃): δ = 21.2, 21.3 (CH₃), 126.6, 127.1, 127.6, 127.8, 128.2, 128.5, 129.8, 130.0, 132.8, 132.9 (CH), 135.4, 136.5, 137.4, 138.5, 139.3, 140.1, 142.3, 145.3 (C). IR (KBr): ν = 3058 (w), 2921 (w), 2854 (w), 1731 (w), 1613 (m), 1484 (m), 4163 (m), 1404 (m), 1392 (m), 1313 (s), 1247 (w), 1151 (s), 1091 (m), 959 (w), 820 (m), 757 (s), 670 (m), 585 (s), 532 (s) cm^-¹. GC-MS (EI, 70 eV): m/z (%) = 398 (100) [M]⁺, 366 (2), 318 (22), 215 (6), 198 (4), 183 (22), 165 (46), 155 (7), 152 (38), 115 (6). HRMS (EI, 70 eV): m/z calcd for C₂₆H₂₂O₂S [M]⁺: 398.13350; found: 398.133551.

14

2-(Trifluoromethylsulfonyloxy)-4′-(4-ethylphenyl)-diphenylsulfone (5a)
Starting with with 2 (205 mg, 0.4 mmol), K₃PO₄ (127 mg, 0.6 mmol), Pd(PPh₃)₄ (3 mol%), 4-ethylphenylboronic acid (66 mg, 0.44 mmol), and 1,4-dioxane (5 mL per 1 mmol of 2), compound 5a was isolated as a white solid (141 mg, 75%), mp 78 ˚C. ^¹H NMR (300 MHz, CDCl₃): δ = 1.19 (t, J = 7.6 Hz, 3 H, CH₃), 2.64 (q, J = 7.6 Hz, 2 H, CH ₂CH₃), 7.18-7.24 (m, 2 H, ArH), 7.32-7.35 (m, 1 H, ArH), 7.42-7.53 (m, 3 H, ArH), 7.58-7.66 (m, 3 H, ArH), 7.93-7.97 (m, 2 H, ArH), 8.23-8.27 (m, 1 H, ArH). ^¹9F NMR (282 MHz, CDCl₃): δ = -73.4. ^¹³C NMR (75 MHz, CDCl₃): δ = 15.4 (CH₃), 28.5 (CH₂), 118.8 (q, J _CF = 320.1 Hz, CF₃), 122.2, 127.3, 127.5, 128.5, 128.6, 128.9, 130.9 (CH), 134.4 (C), 135.5 (CH), 136.3, 138.3, 145.1, 146.5, 146.9 (C). IR (KBr): ν = 3108, 3053, 2965, 2852 (w), 1591 (m), 1555, 1520, 1448 (w), 1468 (m), 1433 (s), 1391, 1267 (w), 1247 (m), 1200, 1157, 1128, 1056 (s), 1002 (m), 965 (w), 870, 818, 786 (s), 739, 716, 684 (m), 619, 584, 545 (s) cm^-¹. GC-MS (EI, 70 eV): m/z (%) = 470 (100) [M]⁺, 337 (10), 309 (02), 244 (42), 229 (16), 197 (24), 181 (07), 165 (28), 152 (15), 115 (05). HRMS (EI, 70 eV): m/z calcd for C₂₁H₁₇O₅S₂F₃ [M + H]⁺: 471.05423; found: 471.05405.

15

2-(4-Ethylphenyl)-4′-(4-methylphenyl)diphenyl-sulfone (6a)
Starting with 5e (182 mg, 0.40 mmol), K₃PO₄ (127 mg, 0.60 mmol), Pd(PPh₃)₄ (3 mol%), 4-ethylphenylboronic acid (66 mg, 0.44 mmol), and 1,4-dioxane (5 mL per 1 mmol of 5e), compound 6a was isolated as a solid (98 mg, 60%). ^¹H NMR (300 MHz, CDCl₃): δ = 1.18 (t, J = 7.7 Hz, 3 H, CH₂CH ₃), 2.31 (s, 3 H, CH₃), 2.61 (q, J = 7.6Hz, 2 H, CH ₂CH₃), 6.80-6.82 (m, 2 H, ArH), 6.89-6.93 (m, 2 H, ArH), 7.07-7.20 (m, 5 H, ArH), 7.23-7.36 (m, 4 H, ArH), 7.44-7.48 (m, 2 H, ArH), 8.32-8.36 (m, 1 H, ArH). ^¹³C NMR (75 MHz, CDCl₃): δ = 15.4, 21.1 (CH₃), 28.5 (CH₂), 127.1 (C), 127.2, 127.3, 127.5, 127.6, 128.6, 128.9, 129.8, 130.9, 135.5, 136.1 (CH), 138.3, 138.8, 139.7, 145.1, 146.5, 146.7, 146.9 (C). IR (KBr): ν = 3104 (w)3058 (w), 2967 (w), 2920 (w), 2873 (w), 1592 (m), 1555 (w), 1484 (w), 1450 (w), 1423 (s), 1406 (w), 1333 (s), 1297 (m), 1228 (m), 1209 (s), 1157 (s), 1128 (s), 1089 (m), 1054 (m), 1003 (m), 958 (w), 884 (s), 781 (m), 717 (m), 685 (m), 622 (m), 595 (s), 560 (s) cm^-¹. GC-MS (EI, 70 eV): m/z (%) = 412 (100) [M]⁺, 348 (12), 333 (22), 318 (26), 197 (26), 165 (50), 152 (32). HRMS (EI, 70 eV): m/z calcd for C₂₇H₂₄O₂S: 412.14973; found: 412.14882.