CuBr₂-Promoted Tetrahydrofuranylation of Alcohols and 1,3-Dione

Abstract

A method for the CuBr₂-promoted tetrahydrofuranylation of alcohols and 1,3-dione has been developed. A variety of different alcohols were efficiently converted into the corresponding 2-tetrahydrofuran ethers in the presence of CuBr₂. It is noteworthy that this protocol also successfully converted 1,3-diphenyl-1,3-dione into the corresponding 2-tetrahydrofuran derivative in good yield.

Key words

copper - protecting groups - alcohols - diones - ethers

• References and Notes

• 1 Greene TW, Wuts PG. M. Protective Groups in Organic Chemistry . Wiley; New York: 1999. Chap. 2, 57-58

For recent tetrahydropyranylations, see:
• 2a Miyashita M, Yoshikoshi A, Grieco PA. J. Org. Chem. 1977; 42: 3772
• 2b Bongini A, Cardillo G, Orena M, Sandri S. Synthesis 1979; 618
• 2c Morizawa Y, Mori I, Hiyama T, Nozaki H. Synthesis 1981; 899
• 2d Olah GA, Husain A, Singh BP. Synthesis 1985; 703
• 2e Bolitt V, Mioskowski C, Shin DS, Falck JR. Tetrahedron Lett. 1988; 29: 4583
• 2f Ranu BC, Saha M. J. Org. Chem. 1994; 59: 8269
• 2g Bhalerao UT, Davis KJ, Rao BV. Synth. Commun. 1996; 26: 3081
• 2h Habibi MH, Tangestaninejad S, Mohammadpoor-Baltork I, Mirkhani V, Yadollahi B. Tetrahedron Lett. 2001; 42: 2851
• 2i Stephens JR, Butler PL, Clow CH, Oswald MC, Smith RC, Mohan R. Eur. J. Org. Chem. 2003; 3827

For recent tetrahydrofuranylations, see:
• 3a Kruse CG, Broekhof NL. J. M, van der Gen A. Tetrahedron Lett. 1976; 1725
• 3b Kruse CG, Poels EK, Jonkers FL, van der Gen A. J. Org. Chem. 1978; 43: 3548
• 3c Yu B, Hui Y. Synth. Commun. 1995; 25: 2037
• 3d Hon YS, Lee CF. Tetrahedron Lett. 1999; 40: 2389
• 3e Barks JM, Gilbert BC, Parsons AF, Upeandran B. Tetrahedron Lett. 2000; 41: 6249
• 3f French AN, Cole J, Wirth T. Synlett 2004; 2291
• 4 Maione AM, Romeo A. Synthesis 1987; 250
• 5 Van Boom JH, Herschied JD. M, Reese CB. Synthesis 1973; 169
• 6 Baati R, Valleix A, Mioskowski C, Barma DK, Falk JR. Org. Lett. 2000; 2: 485
• 7 Masahito O, Takuya S. Tetrahedron Lett. 2004; 45: 3557
• 8 Jung JC, Choi HC, Kim YH. Tetrahedron Lett. 1993; 34: 3581
• 9 Falck JR, Li DR, Bejot R, Mioskowski C. Tetrahedron Lett. 2006; 47: 5111
• 10 Williams DB. G, Simelane SB, Lawton M, Kinfe HH. Tetrahedron 2010; 66: 4573
• 11 Troisi L, Granito C, Ronzini L, Rosato F, Videtta V. Tetrahedron Lett. 2010; 51: 5980
• 12 Typical Procedure: To a Schlenk tube were added phenylmethanol 1 (0.3 mmol), CuCl₂ (10 mol%), and THF (2 mL). The tube was stirred at 100 °C (oil bath temperature) under an air atmosphere for the indicated time until complete consumption of starting material was monitored by TLC and GC-MS analyses. When the reaction was finished, the mixture was cooled to room temperature, diluted in diethyl ether, and washed with brine. The aqueous phase was re-extracted with diethyl ether and the combined organic extracts were dried over Na₂SO₄ and concentrated in vacuum, and the resulting residue was purified by silica gel column chromatography (hexane–EtOAc) to afford the target product 3. 2-(Benzyloxy)tetrahydrofuran (3): Colorless liquid. ¹H NMR (300 MHz, CDCl₃): δ = 7.36–7.27 (m, 5 H), 5.25–5.23 (m, 1 H), 4.73 (d, J = 12.0 Hz, 1 H), 4.49 (d, J = 12.0 Hz, 1 H), 4.01–3.88 (m, 2 H), 2.10–1.84 (m, 4 H). ¹³C NMR (125 MHz, CDCl₃): δ = 138.4, 128.4, 127.85 (s), 127.5, 103.1, 68.8, 67.0, 32.4, 23.5. MS (EI, 70 eV): m/z (%) = 178 (2) [M]⁺, 91 (100), 71 (48), 108 (28), 92 (25).