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

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

References and Notes

• 1a Welch JT. Tetrahedron  1987,  43:  3123 
• 1b Fluorine-Containing Molecules: Structure, Reactivity, Synthesis, and Applications   Liebman JF. Greenberg A. Dolbier WR. VCH; Weinheim: 1988.  p.1 
• 1c Begue J.-P. Bonnet-Delpon D. Tetrahedron  1991,  47:  3207 
• 1d McClinton MA. McClinton DA. Tetrahedron  1992,  48:  6555 
• 1e Banks RE. Smart BE. Tatlow JC. Organofluorine Chemistry: Principles and Commercial Applications   Plenum Press; New York: 1994. 
• 1f Chemistry of Organic Fluorine Compounds II: A Critical Review   Hudlicky M. Pavlath AE. ACS Mono-graph 187, American Chemical Society; Washington/DC: 1995. 
• 1g Hiyama T. Organofluorine Compounds - Chemistry and Applications   Springer; Berlin: 2000. 
• 1h Shimizu M. Hiyama T. Angew. Chem. Int. Ed.  2005,  44:  214 
• 2a Yoneda N. Matsuoka S. Miyaura N. Fukuhara T. Suzuki A. Bull. Chem. Soc. Jpn.  1990,  63:  2124 
• 2b Yamazaki T. Mizutani K. Kitazume T. J. Org. Chem.  1995,  60:  6046 
• 2c Jeong IH. Jeon SL. Kim BT. Tetrahedron Lett.  2003,  44:  7213 
• 2d Chae J. Konno T. Ishihara T. Yamanaka H. Chem. Lett.  2004,  33:  314 
• 2e Konno T. Daitoh T. Noiri A. Chae J. Ishihara T. Yamanaka H. Tetrahedron  2005,  61:  9391 
• 2f Konno T. Chae JH. Miyabe T. Ishihara T. J. Org. Chem.  2005,  70:  10172 
• 2g Hanamoto T. Egashira M. Ishizuka K. Furuno H. Inanaga J. Tetrahedron  2006,  62:  6332 
• 3a Drakesmith FG. Stewart OJ. Tarrant P. J. Org. Chem.  1968,  33:  280 
• 3b

  Ref. 2b.

• 3c Katritzky AR. Qi M. Wells AP. J. Fluorine Chem.  1996,  80:  145 
• 3d Brisdon AK. Crossley IR. Chem. Commun.  2002,  2420 
• 3e Konno T. Chae J. Kanda M. Nagai G. Tamura K. Ishihara T. Yamanaka H. Tetrahedron  2003,  59:  7571 
• 4a Shimizu M. Fujimoto T. Minezaki H. Hata T. Hiyama T. J. Am. Chem. Soc.  2001,  123:  6947 
• 4b Shimizu M. Fujimoto T. Liu X. Minezaki H. Hata T. Hiyama T. Tetrahedron  2003,  59:  9811 
• 4c Liu X. Shimizu M. Hiyama T. Angew. Chem. Int. Ed.  2004,  43:  879 
• 4d Shimizu M. Fujimoto T. Liu X. Hiyama T. Chem. Lett.  2004,  33:  438 
• 4e Shimizu M. Jiang G. Murai M. Takeda Y. Nakao Y. Hiyama T. Shirakawa E. Chem. Lett.  2005,  34:  1700 
• Review on transition-metal-catalyzed synthesis of allenes:
• 7a Ogasawara M. Hayashi T. In Modern Allene Chemistry   Vol. 1:  Krause N. Hashmi ASK. Wiley-VCH; Weinheim: 2004.  p.93 
• 7b Review on Pd-catalyzed cross-coupling reactions of propargylic compounds: Tsuji J. Mandai T. Angew. Chem., Int. Ed. Engl.  1995,  34:  2589 
• Yamazaki and coworkers reported three-step transformation of alcohols 4 into trifluoromethyl-containing allenes CF₃-CHC=C=CR¹R². See:
• 8a Yamazaki T. Yamamoto T. Ichihara R. J. Org. Chem.  2006,  71:  6251 
• Examples of trifluoromethyl-substituted allenes:
• 8b Bosbury PWL. Fields R. Haszeldine RN. Moran D. J. Chem. Soc., Perkin Trans. 1  1976,  1173 
• 8c Bosbury PWL. Fields R. Haszeldine RN. J. Chem. Soc., Perkin Trans. 1  1978,  422 
• 8d Hanzawa Y. Kawagoe K.-i. Yamada A. Kobayashi Y. Tetrahedron Lett.  1985,  26:  219 
• 8e Burton DJ. Hartgraves GA. Hsu J. Tetrahedron Lett.  1990,  31:  3699 
• 8f Konno T. Tanikawa M. Ishihara T. Yamanaka H. Chem. Lett.  2000,  1360 
• 8g Han HY. Kim MS. Son JB. Jeong IH. Tetrahedron Lett.  2006,  47:  209 
• 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.