Rapid Access to in Situ Generated (R)- and (S)-2-Furyloxirane and Associated Regioselective Nucleophilic Ring-Opening Studies

Abstract

Reported herein is the facile preparation of (R)- and (S)-2-furyloxirane from d- and l-tri-O-acetyl glucal and associated ­regioselective nucleophilic ring-opening studies.

Key words

epoxide - furan - nucleophilic ring opening - regioselectivity - Umpolung effects

References and Notes

• 1a Merten J. Fröhlich R. Metz P. Angew. Chem. Int. Ed.  2004,  43:  5991 
• 1b Merten J. Hennig A. Schwab P. Fröhlich R. Tokalov SV. Gutzeit HO. Metz P. Eur. J. Org. Chem.  2006,  1144 
• 2 Hamada T. Torii T. Izawa K. Ikariya T. Tetrahedron  2004,  60:  7411 
• 3a Hayashi M. Kawabata H. Yamada K. Chem. Commun.  1999,  965 
• 3b Babu BS. Balasubramanian KK. J. Org. Chem.  2000,  65:  4198 
• 3c Agarwal A. Rani S. Vankar YD. J. Org. Chem.  2004,  69:  6137 
• 3d Yadav JS. Reddy BVS. Madhavi AV. J. Mol. Catal. A: Chem.  2005,  226:  213 
• 5 Yamaguchi Y. Tatsuta N. Haykawa K. Kanematsu K. J. Chem. Soc., Chem. Commun.  1989,  470 
• 9 Tannis SP. Evans BR. Nieman JA. Parker TT. Taylor WD. Heasley SE. Herrinton PM. Perrault WR. Hohler RA. Dolak LA. Hester MR. Seest EP. Tetrahedron: Asymmetry  2006,  17:  2154 
• Peracetylation with Ac₂O/pyridine, formation of the l-glucosyl bromide with HBr/AcOH followed by elimination with zinc dust achieved 53% overall yield. Following the procedure for l-galactal:
• 10a Litjens REJN. den Heeten R. Timmer MSM. Overkleeft HS. van der Marel GA. Chem. Eur. J.  2005,  11:  1010 
• 10b

  Tri-O-acetyl-l-glucal: [α]_D ²⁰ +23.4 (c 1.01, CHCl₃). ¹H NMR (300 MHz, CDC1₃): δ = 6.45 (d, 1 H, J = 6.1 Hz), 5.34-5.30 (m, 1 H), 5.20 (t, 1 H, J = 6.5 Hz), 4.83 (dd, 1 H, J = 6.2, 3.2 Hz), 4.38 (dd, 1 H, J = 11.7, 6.2 Hz), 4.26-4.15 (m, 2 H), 2.08 (s, 3 H), 2.06 (s, 3 H), 2.03 (s, 3 H) ppm. ¹³C NMR (75 MHz, CDC1₃): δ = 170.4, 170.2, 169.4, 145.5, 98.9, 73.8, 67.3, 67.1, 53.3, 20.8, 20.6, 20.6 ppm.

• 11a Alcaide B. Areces P. Borredon E. Biurrun C. Castells JP. Plumet J. Heterocycles  1990,  31:  1997 
• 11b Oh KB. Cha JH. Cho YS. Choi KI. Koh HY. Chang MH. Pae AN. Tetrahedron Lett.  2003,  44:  2911 
• 12a Alcaide B. Biurrun C. Plumet J. Tetrahedron  1992,  48:  9719 
• 12b Sutowardoyo KI. Emziane M. Lhoste P. Sinou D. Tetrahedron  1991,  47:  1435 
• 13 Smith AB. Xian M. J. Am. Chem. Soc.  2006,  128:  66 
• 15 The product from this reaction has been previously characterized; our data agree with the previously published: Blake AJ. Cunningham A. Ford A. Teat SJ. Woodward S. Chem. Eur. J.  2000,  6:  3586 

4

Although d-glucal is commercially available for large-scale reactions, the use of the cheaper peracetyl derivative is recommended.

6

Synthesis of ( R )-1-(Furan-2-yl)ethane-1,2-diol ( 3)
A catalytic amount of NaOMe was added to a solution of 4 (5.44 g, 20 mmol) in MeOH (20 mL) and stirred for 4 h at r.t. After evaporation of the solvent the resulting syrup was dissolved in MeCN (20 mL) and FeCl₃·6H₂O (270 mg, 1 mmol) was added. Usually the reaction is complete within 1 h. The whole reaction mixture was subjected to column chromatography on silica (PE-EtOAc = 1:2, R _f = 0.3) to obtain 2.1 g (82%).

7

Synthesis of Compound 6
To a solution of 3 (2.1 g, 16.3 mmol) in pyridine (20 mL) was added TsCl (3.83 g, 20.6 mmol) and the reaction mixture was stirred over night at r.t. The whole mixture was poured onto a slurry of ice (300 mL) and concd HCl ( ca. 10 mL). The resulting mixture was extracted with Et₂O (200 mL) and the organic layer was washed with sat. NaHCO₃ solution (50 mL), H₂O (50 mL) and brine (50 mL). The organic layer was dried (MgSO₄) and concentrated to approx. 60 mL. The so-prepared solution was used without further purification, but stored in the fridge over 4 Å MS (0.14 M); [α]_D ²⁰ +36.7 (c 4.01, Et₂O). ¹H NMR (300 MHz, CDC1₃): δ = 7.79-7.75 (m, 2 H), 7.35-7.31 (m, 3 H), 6.32-6.30 (m, 2 H), 4.95 (dd, 1 H, J = 4.4, 7.0 Hz), 4.31-4.19 (m, 2 H), 2.65 (br s, OH), 2.44 (s, 3 H), ppm. ¹³C NMR (75 MHz, CDC1₃): δ = 151.4, 145.1, 142.6, 132.5, 129.9, 128.0, 110.4, 107.9, 71.4, 65.9, 21.6 ppm. MS (ESI): m/z = 305 [M + N]⁺. HRMS: m/z calcd for C₁₃H₁₄NaO₅S: 305.0460; found: 305.0467. Note: Tosylate 6 is stable in solution and on silica gel, however, if concentrated at elevated temperatures (40-50 °C) rapid polymerization occurs affording a dark-green gum. Analytical samples were obtained after column chromatography, concentration at 20 °C and finally evaporation of the remaining solvent under high vacuum. Compound 6 is stable under argon for several hours in pure form.

8

For other 2-furyloxirane precursors, such as 2-chlorofuryl alcohols, sensitivity towards amines has been reported, [3a] [9] whereas tosylate 6 is stable in the presence of benzylamine and even thioethane at r.t. as observed over 96 h.

14

Representative Experimental Procedure and Characterization Data for Selected Compounds
To a solution of 6 (5.0 mL, 0.71 mmol, 0.14 M) in Et₂O [7] was added NaH (2 equiv, 60 mg, 60% in mineral oil) under an argon atmosphere at r.t. After 30 min a solution of Li-TBS-dithiane [13] (1.2 equiv) in anhyd THF (2 mL) containing HMPA (0.7 mL) was added at r.t. The reaction was quenched after 2 h with sat. NH₄Cl solution (10 mL) and extracted with Et₂O (20 mL). The organic layer was washed with H₂O (10 mL), brine (10 mL), dried (MgSO₄), and evaporated. The residue was further purified by column chromatography on silica gel (PE-EtOAc, 50:1) affording 8 (122 mg, 50%; R _f = 0.5) and 9 (81 mg, 33%; R _f = 0.41).
Compound 8: [α]_D ²⁰ +77.0 (c 0.5, CHCl₃). ¹H NMR (300 MHz, CDC1₃): δ = 7.34-7.32 (m, 1 H), 6.30-6.27 (m, 1 H), 6.19-6.17 (m, 1 H), 4.96 (dd, J = 8.9, 4.8 Hz, 1 H), 4.07 (dd, J = 9.3, 5.4 Hz, 1 H), 2.86-2.75 (m, 4 H), 2.34-2.23 (m, 1 H), 2.16-2.06 (m, 2 H), 1.94-1.84 (m, 1 H), 0.85 (s, 9 H), 0.06 (s, 3 H), -0.11 (s, 3 H) ppm. ¹³C NMR (75 MHz, CDC1₃): δ = 156.1, 141.6, 110.0, 106.3, 64.8, 43.4, 42.2, 30.1, 29.6, 26.0, 25.8, 18.2, -5.0, -5.2 ppm. ESI-MS: m/z = 367 [M + Na⁺]. The ee determination by derivatization unfortunately resulted in elimination giving 19.
Compound 9: ¹H NMR (300 MHz, CDC1₃): δ = 7.36-7.34 (m, 1 H), 6.32-6.30 (m, 1 H), 6.24-6.22 (m, 1 H), 4.45 (d, J = 6.5 Hz, 1 H), 4.03 (dd, J = 9.9, 6.5 Hz, 1 H), 3.90 (dd, J = 9.9, 6.5 Hz, 1 H), 3.29 (td, J = 6.5, 6.5 Hz, 1 H), 2.88-2.82 (m, 4 H), 0.85 (s, 9 H), 0.02 (s, 3 H), -0.01 (s, 3 H) ppm. ¹³C NMR (75 MHz, CDC1₃): δ = 152.6, 141.3, 110.2, 108.1, 62.3, 48.6, 46.8, 30.7, 30.5, 29.7, 25.8, 18.2, -5.5 ppm. ESI-MS: m/z = 367 [M + Na⁺].
NMR Data of Selected Compounds
Compound 10: [α]_D ²⁰ +15.5 (c 4.02, CHCl₃). ¹H NMR (400 MHz, CDC1₃): δ = 7.37-7.35 (m, 1 H), 6.32-6.30 (m, 1 H), 6.26-6.24 (m, 1 H), 5.01 (dd, J = 8.9, 4.6, 1 H), 4.17 (dd, J = 8.8, 5.8 Hz, 1 H), 2.91-2.78 (m, 4 H), 2.36-2.20 (m, 2 H), 2.15-2.05 (m, 2 H), 1.95-1.80 (m, 2 H) ppm. ¹³C NMR (100 MHz, CDC1₃): δ = 155.5, 142.3, 110.2, 106.3, 64.7, 43.3, 40.8, 29.9, 29.7, 25.9 ppm. ESI-MS: m/z = 253 [M + Na⁺].
Compound 13: [α]_D ²⁰ -19.8 (c 0.5, CHCl₃). ¹H NMR (300 MHz, CDC1₃): δ = 7.33-7.32 (m, 1 H), 6.30-6.28 (m, 1 H), 6.09-6.07 (m, 1 H), 3.72 (br d, J = 6.2 Hz, 2 H), 2.87 (app quin, J = 5.4 Hz, 1 H), 1.65-1.57 (m, 2 H), 1.53 (br s, OH), 1.34-1.19 (m, 4 H), 0.85 (t, J = 7.0 Hz, 3 H) ppm. ¹³C NMR (75 MHz, CDC1₃): δ = 156.3, 141.4, 110.0, 106.2, 65.2, 42.1, 29.7, 29.4, 22.6, 13.9 ppm.
Compound 18: ¹H NMR (300 MHz, CDC1₃): δ = 7.37-7.36 (m, 1 H), 6.33-6.31 (m, 1 H), 6.24-6.22 (m, 1 H), 4.07-4.02 (m, 1 H), 4.00-3.91 (m, 1 H), 3.88-3.80 (m, 1 H), 2.56-2.44 (m, 2 H), 1.20 (t, J = 7.4 Hz, 3 H) ppm. ¹³C NMR (125 MHz, CDC1₃): δ = 152.8, 142.3, 110.4, 107.4, 63.0, 45.6, 24.7, 14.8 ppm.