Abstract
A novel method for the generation of 3,3,3-trifluoropropynyllithium is reported, which involves treatment of trifluoromethyl-substituted enol tosylate, prepared from 1,1-dichloro-3,3,3-trifluoroacetone, with two equivalents of butyllithium. Palladium-catalyzed coupling reaction of sulfonates of the carbonyl adducts with organozinc reagents gave trifluoromethyl-containing tri- and tetrasubstituted allenes.
Key words
alkynes - allenes - fluorine - lithium - palladium
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5 To a solution of 2 (13.6 g, 75 mmol) and p -toluenesulfonyl chloride (15.7 g, 82 mmol) in CH2 Cl2 (100 mL) was added Et3 N (13.0 mL, 90 mmol) at r.t. After stirring at r.t. for 1 h, the reaction mixture was diluted with Et2 O (50 mL). The resulting solution was washed with H2 O and then sat. NaCl aq solution, and dried over anhyd MgSO4 . Removal of organic solvent in vacuo followed by distillation under reduced pressure (122 °C/2 Torr) gave 3 (24.4 g, 97% yield) as a colorless oil. R
f
= 0.33 (hexane-EtOAc, 10:1). 1 H NMR (200 MHz, CDCl3 ): δ = 2.49 (s, 3 H), 7.39 (d, J = 8.6 Hz, 2 H), 7.87 (d, J = 8.6 Hz, 2 H). 13 C NMR (67.8 MHz, CDCl3 ): δ = 21.7, 119.1 (q, J = 275.5 Hz), 127.9, 128.3, 129.9, 132.4, 134.1 (q, J = 39.1 Hz). 19 F NMR (188 Hz, CDCl3 ): δ = -63.1. IR (neat): 1618, 1394, 1196, 1153, 972 cm-1 . MS (EI, 70 eV): m/z (%) = 180 (10) [M+ - Ts], 160 (12), 111 (33), 91 (23), 74 (100). Anal. Calcd for C10 H7 Cl2 F3 O3 S: C, 35.84; H, 2.11. Found: C, 36.3, H, 2.22.
6
Representative Procedure for Carbonyl Addition of 1
To a THF solution of 3 (10.0 g, 30 mmol) was added BuLi (41 mL, 66 mmol, 1.6 M in hexane) at -78 °C. The solution was stirred at -78 °C for 10 min before the addition of 3-phenylpropanal (4.0 g, 30 mmol) in THF (20 mL) at -78 °C. The resulting solution was stirred at -78 °C for 1 h and then at r.t. for 1 h. The reaction mixture was quenched with sat. aq NH4 Cl solution (40 mL) at 0 °C and extracted with EtOAc (3 × 40 mL). The combined organic layer was dried over anhyd MgSO4 and concentrated by rotary evaporator. The crude product was purified by column chromatography on silica gel (hexane-EtOAc, 15:1) to give 4b (6.5 g, 95% yield, CAS No. 94792-93-5) as colorless oil.
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9
Representative Procedure for Preparation of Compounds 5
To a solution of 4b (1.5 g, 6.6 mmol), p -toluenesulfonyl chloride (1.4 g, 7.2 mmol), 4-dimethylaminopyridine (40 mg, 0.33 mmol) in CH2 Cl2 (26 mL) was added Et3 N (1.1 mL, 7.9 mmol) at 0 °C. The resulting solution was stirred at r.t. for 2 h before quenching with sat. aq NH4 Cl solution (20 mL) at 0 °C. The aqueous layer was extracted with CH2 Cl2 (3 × 20 mL) and the combined organic solvent was washed with sat. aq NaCl solution (60 mL), dried over anhyd MgSO4 and concentrated in vacuo. The crude product was purified by silica gel column chromatography (hexane-EtOAc, 15:1) to give 5b (2.4 g, 95% yield) as a colorless solid. Mp 48 °C. R
f = 0.45 (hexane-EtOAc, 4:1). 1 H NMR (400 MHz, CDCl3 ): δ = 2.13-2.28 (m, 2 H), 2.46 (s, 3 H), 2.74-2.82 (m, 2 H), 5.07-5.11 (m, 1 H), 7.15 (d, J = 8.0 Hz, 2 H), 7.21-7.37 (m, 3 H), 7.35 (d, J = 8.4 Hz, 2 H), 7.80 (d, J = 8.4 Hz, 2 H). 13 C NMR (101 MHz, CDCl3 ): δ = 21.5, 30.5, 36.3, 68.3, 74.3 (q, J = 52.9 Hz), 81.9 (q, J = 6.4 Hz), 113.2 (q, J = 257.9 Hz), 126.3, 127.9, 128.2, 128.4, 129.7, 132.7, 138.9, 145.5. 19 F NMR (282 MHz, CDCl3 ): δ = -51.8. IR (KBr): 2361, 2341, 1364, 1271, 1159, 746, 677 cm-1 . MS (EI, 70 eV): m/z (%) = 382 (1) [M+ ], 210 (30), 141 (90), 91 (100). HRMS: m/z calcd for C19 H17 F3 O3 S [M+ ]: 382.0851; found: 382.0839
10
Representative Procedure for the Preparation of Compounds 6
To a solution of 5b (0.10 g, 0.26 mmol) and Pd(PPh3 )4 (15 mg, 0.013 mmol) in THF (2.6 mL) was added PhZnCl (0.79 mL, 0.79 mmol, 1.0 M in THF) at 0 °C. The solution was stirred at r.t for 2 h before quenching with sat. aq NH4 Cl solution (2 mL) at 0 °C. The aqueous layer was extracted with EtOAc (3 × 2 mL). The combined organic solvent was washed with sat. aq NaCl solution (6 mL), dried over anhyd MgSO4 , and concentrated by rotary evaporator. The crude product was purified by column chromatography on silica gel (hexane-EtOAc, 20:1) gave 6b (52 mg, 69% yield) as colorless solid; mp 29 °C; R
f = 0.67 (hexane-EtOAc, 4:1). 1 H NMR (400 MHz, CDCl3 ): δ = 2.54-2.67 (m, 2 H), 2.80-2.91 (m, 2 H), 5.96-6.01 (m, 1 H), 7.21-7.34 (m, 10 H). 13 C NMR (101 MHz, CDCl3 ): δ = 29.9, 34.9, 99.2, 102.1 (q, J = 34.5 Hz), 123.3 (q, J = 273.2 Hz), 126.1, 126.8, 126.8, 127.8, 128.4, 128.5, 129.8, 140.5, 204.0. 19 F NMR (282 MHz, CDCl3 ): δ = -60.9. IR (neat): 3030, 2926, 1497, 1303, 1168, 1121, 934, 694 cm-1 . MS (EI, 70 eV): m/z (%) = 288 (30) [M+ ], 219 (20) [M+ - CF3 ], 129 (45), 91 (100). HRMS: m/z calcd for C18 H15 F3 [M+ ]: 288.1126; found: 288.1128