1-(Trifluoromethyl)vinylation via Oxirane or Oxetane Ring-Opening: A Facile Synthesis of 4- or 5-Hydroxy-Functionalized 2-Trifluoromethyl-1-alkenes

Abstract

Introduction of a 1-(trifluoromethyl)vinyl group has been accomplished by the reaction of thermally unstable 1-(trifluoromethyl)vinyllithium (1) with strained cyclic ethers. Treatment of 2-bromo-3,3,3-trifluoropropene with butyllithium generates 1, which in turn reacts with several oxiranes or an oxetane at -100 °C in the presence of BF₃·OEt₂ to afford the corresponding 2-trifluoromethyl-1-alkenes bearing a hydroxy group on the 4- or 5-position. An enantiopure oxirane undergoes ring-opening without racemization, providing an optically active homoallyllic alcohol with a 3-trifluoromethyl group.

Key words

(trifluoromethyl)vinyl group - ring-opening - oxirane - unsaturated alcohol - lithium-halogen exchange

References

• 1a Percy J. Top. Curr. Chem.  1997,  193:  131 
• 1b Hiyama T. Organofluorine Compounds: Chemistry and Applications   Springer; Berlin: 2000. 
• 1c Shimizu M. Hiyama T. Angew. Chem. Int. Ed.  2005,  44:  214 
• 2 Lebel H. Paquet V. Org. Lett.  2002,  4:  1674 ; and references therein
• For the S_N2′ reaction of 1-(trifluoromethyl)vinyl compounds, CH₂=C(Y)CF₃, see: Y = CO₂R (CO₂H):
• 3a Kitazume T. Ohnogi T. Miyauchi H. Yamazaki T. J. Org. Chem.  1989,  54:  5630 
• 3b Fuchikami T. Shibata Y. Suzuki Y. Tetrahedron Lett.  1986,  27:  3173 
• Y = SPh, SePh:
• 3c Feiring AE. J. Org. Chem.  1980,  45:  1962 
• Y = Ph:
• 3d Bégué J.-P. Bonnet-Delpon D. Rock MH. J. Chem. Soc., Perkin Trans. 1  1996,  1409 
• Y = H (Me):
• 3e Hiyama T. Obayashi M. Sawahata M. Tetrahedron Lett.  1983,  24:  4113 
• 3f Kendrick DA. Kolb M. J. Fluorine Chem.  1989,  45:  265 
• 3g Bergstrom DE. Ng MW. Wong JJ. J. Org. Chem.  1983,  48:  1902 
• 4 Ichikawa J. Fukui H. Ishibashi Y. J. Org. Chem.  2003,  68:  7800 
• 5a Ichikawa J. Mori T. Iwai Y. Chem. Lett.  2004,  33:  1354 
• 5b Mori T. Ichikawa J. Chem. Lett.  2004,  33:  1206 
• 5c Mori T. Iwai Y. Ichikawa J. Chem. Lett.  2005,  34:  778 
• For reports on 1-(trifluoromethyl)vinyl palladium species generated via oxidative addition of 2, see:
• 6a Fuchikami T. Yamanouchi A. Ojima I. Synthesis  1984,  766 
• 6b Hu C.-M. Hong F. Xu Y. J. Fluorine Chem.  1993,  63:  1 
• 6c Hu C.-M. Hong F. Xu Y.-Y. J. Fluorine Chem.  1993,  64:  1 
• 7a Jiang B. Xu Y. J. Org. Chem.  1991,  56:  7336 
• 7b Xu Y. Jiang B. Tetrahedron Lett.  1992,  33:  511 
• 7c Hong F. Tang X. Hu C.-M. J. Chem. Soc., Chem. Commun.  1994,  289 
• 7d Peng S. Qing F.-L. Guo Y. Synlett  1998,  859 
• 8 Xu Y. Jin F. Huang W. J. Org. Chem.  1994,  59:  2638 
• 9 Jiang B. Wang Q.-F. Yang C.-G. Xu M. Tetrahedron Lett.  2001,  42:  4083 
• 10a Drakesmith FG. Stewart OJ. Tarrant P. J. Org. Chem.  1967,  33:  280 
• 10b Iseki K. Kuroki Y. Nagai T. Kobayashi Y. J. Fluorine Chem.  1994,  69:  5 
• 11a Yamaguchi M. Hirao I. Tetrahedron Lett.  1983,  24:  391 
• 11b Yamaguchi M. Nobayashi Y. Hirao I. Tetrahedron Lett.  1983,  24:  5121 
• 11c Eis MJ. Wrobel JE. Ganem B. J. Am. Chem. Soc.  1984,  106:  3693 
• 11d See also: Brown HC. Racherla UR. Singh SM. Tetrahedron Lett.  1984,  25:  2411 
• For reports on the synthesis of 3-(trifluoromethyl)homoallylic alcohols, see:
• 13a Yamazaki T. Ishikawa N. Chem. Lett.  1984,  521 
• 13b Hanzawa Y. Ishizawa S. Kobayashi Y. Taguchi T. Chem. Pharm. Bull.  1990,  38:  1104 
• 13c Faure S. Piva O. Synlett  1998,  1414 
• 15 Galons H. Girurdeau JF. Combet FC. Miocque M. Dupont C. Wepierre J. Eur. J. Med. Chem.  1979,  14:  165 
• 17 Dorling EK. Öhler E. Mulzer J. Tetrahedron Lett.  2000,  41:  6323 
• 18 Kwon DW. Kim YH. J. Org. Chem.  2002,  67:  9488 

12

The two competing reactions of n-BuLi and PhLi with an oxirane were conducted as follows: To a soln of n-BuLi (0.96 mmol) and PhLi (0.96 mmol) in THF (8 mL) were added BF₃·OEt₂ and then 2-phenethyloxirane (0.8 mmol) at -78 °C. After the mixture was stirred for 30 min, phosphate buffer was added to quench the reaction. Usual work-up followed by column chromatography on silica gel gave 1,4-diphenylbutan-2-ol (the phenyl adduct: 139 mg, 77%) and 1-phenyloctan-3-ol (the butyl adduct: 20 mg, 12%).

14

In the reaction of 2 with benzaldehyde (Scheme [2] ), addition of BF₃·OEt₂ (1.0 equiv) did not cause a considerable change in the ratio of 3 and 4.

16

2-Phenethyloxirane was prepared by oxidation of 4-phenyl-­but-1-ene with MCPBA.