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Synlett 2007(7): 1163-1165  
DOI: 10.1055/s-2007-977422
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© Georg Thieme Verlag Stuttgart · New York

Novel Generation of 3,3,3-Trifluoropropynyllithium and Transformation of the Carbonyl Adducts to Trifluoromethyl-Substituted Allenes

Masaki Shimizu*, Masahiro Higashi, Youhei Takeda, Guofang Jiang, Masahito Murai, Tamejiro Hiyama
Department of Material Chemistry, Graduate School of Engineering, Kyoto University Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
Fax: +81(75)3832445; e-Mail: shimizu@npc05.kuic.kyoto-u.ac.jp;
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Publication History

Received 2 February 2007
Publication Date:
13 April 2007 (online)

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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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  • 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 CH2Cl2 (26 mL) was added Et3N (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 NH4Cl solution (20 mL) at 0 °C. The aqueous layer was extracted with CH2Cl2 (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). 1H 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). 13C 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. 19F 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 C19H17F3O3S [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 NH4Cl 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). 1H 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). 13C 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. 19F 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 C18H15F3 [M+]: 288.1126; found: 288.1128
5

To a solution of 2 (13.6 g, 75 mmol) and p-toluenesulfonyl chloride (15.7 g, 82 mmol) in CH2Cl2 (100 mL) was added Et3N (13.0 mL, 90 mmol) at r.t. After stirring at r.t. for 1 h, the reaction mixture was diluted with Et2O (50 mL). The resulting solution was washed with H2O 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). 1H 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). 13C 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). 19F 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 C10H7Cl2F3O3S: 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 NH4Cl 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.