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Synlett 2011(20): 2951-2954  
DOI: 10.1055/s-0031-1290084
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

BF3×OEt2-Catalyzed Unusual Formation of cis-2,3-Disubstituted
Tetrahydrofuran Scaffolds

B. V. Subba Reddy*, S. Rehana Anjum, G. Madhusudhan Reddy, T. Prabhakar Rao
Division of Organic Chemistry, Centre for Nuclear Magnetic Resonance, Indian Institute of Chemical Technology, Hyderabad - 500 007, India
e-Mail: basireddy@iict.res.in;
Further Information

Publication History

Received 8 July 2011
Publication Date:
28 November 2011 (online)

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Abstract

Aldehydes undergo smooth cyclization with 4-(phenylthio)but-3-en-1-ol in the presence of BF3˙OEt2 in dichloromethane at room temperature to afford a novel class of 2,3-disubstitued tetrahydrofurans in good yields with all-cis-selectivity. This method is simple, selective, and convenient for the synthesis of tetrahydrofuran scaffolds in a single step.

Keywords

Lewis acid - aldehydes - 4-(phenylthio)but-3-en-1-ol - tetrahydrofuran scaffolds

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General Procedure
To a mixture of aldehyde (1.0 mmol) and (E)-4-(phenylthio)-but-3-en-1-ol (2.1 mmol) in dry CH2Cl2 (3 mL) was added BF3˙OEt2 (0.2 mmol), and the mixture was stirred for the time specified. After complete consumption of alcohol as indicated by TLC, the reaction mixture was quenched with sat. aq NaHCO3 and extracted with CH2Cl2 (3 × 10 mL). The combined organic layers were dried over anhyd Na2SO4. Removal of solvent under reduced pressure, followed by purification over silica gel (Merck, 100-200 mesh, hexane) gave pure product. The products thus obtained were characterized by NMR and IR spectroscopy.
3-[Bis(phenylthio)methyl]-2-(4-bromophenyl)-tetrahydrofuran (3c) IR (neat): νmax = 3445, 3020, 2920, 2852, 1902, 1724, 1595, 1486, 1447, 1403, 1254, 1208, 1182, 1060, 1008, 983, 811, 754, 495 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 7.41-7.67 (m, 4 H), 7.35 (d, J = 8.3 Hz, 2 H), 7.17-7.30 (m, 6 H), 6.97 (d, J = 8.3 Hz, 2 H), 4.89 (d, J = 7.5 Hz, 1 H), 4.37 (d, J = 4.5 Hz, 1 H), 3.98-4.11 (m, 2 H), 2.50-2.59 (m, 1 H), 2.15-2.32 (m, 2 H). ¹³C NMR (75 MHz, CDCl3): δ = 140.6, 138.2, 138.1, 133.1, 132.9, 131.3, 130.5, 129.9, 129.7, 128.2, 121.4, 82.5, 68.1, 61.7, 52.7, 29.4. ESI-MS: m/z = 479 [M + Na].
3-[Bis( p -tolylthio)methyl]-2-(4-bromophenyl)-tetrahydrofuran (3h) IR (neat): νmax = 3447, 3021, 2922, 2856, 1901, 1722, 1593, 1489, 1449, 1402, 1252, 1208, 1180, 1066, 1010, 981, 810, 756, 498 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 7.37 (d, J = 8.3 Hz, 2 H), 7.19-7.22 (m, 4 H), 7.01-7.08 (m, 6 H), 4.9 (d, J = 6.9 Hz, 1 H), 4.24 (d, J = 4.7 Hz, 1 H), 3.96-4.09 (m, 2 H), 2.45-2.55 (m, 1 H), 2.33 (d, J = 2.8 Hz, 6 H), 2.14-2.28 (m, 2 H). ¹³C NMR (75 MHz, CDCl3): δ = 140.6, 138.2, 138.1, 133.1, 132.9, 131.3, 130.5, 129.9, 129.7, 128.2, 121.4, 82.5, 68.1, 61.7, 52.7, 29.4, 21.1. ESI-MS: m/z = 507 [M + Na]. HRMS: m/z calcd for C25H25OS2BrNa: 507.0427; found: 507.0410.
3-[Bis( p -tolylthio)methyl]tetrahydro-2-propylfuran (3j) IR (neat): νmax = 3449, 3021, 2924, 2864, 1727, 1642, 1490, 1455, 1375, 1180, 1101, 1038, 946, 807, 749, 499 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 7.36 (t, J = 7.9 Hz, 4 H), 7.11 (t, J = 7.9 Hz, 4 H), 4.13 (d, J = 9.9 Hz, 1 H), 3.97-4.02 (m, 1 H), 3.88-3.92 (m, 1 H), 3.69-3.74 (m, 1 H), 2.46-2.53 (m, 1 H), 2.38 (d, J = 3.9 Hz, 6 H), 2.17-2.24 (m, 1 H), 1.85-1.93 (m, 1 H), 1.53-1.60 (m, 2 H), 1.33-1.45 (m, 2 H), 0.97 (t, J = 6.9 Hz, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 133.8, 133.4, 129.7, 129.6, 79.8, 65.9, 60.6, 47.1, 30.6, 30.2, 21.1, 19.4, 14.0. ESI-MS: m/z = 390 [M + NH4].
3,3a,4,9b-Tetrahydro-4-(phenylthio)-2 H -furo[3,2- c ]-chromene (4)
IR (neat): νmax = 3061, 2926, 1726, 1586, 1483, 1452, 1368, 1305, 1225, 1107, 1075, 1039, 949, 848, 749, 695, 480 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 7.30-7.42 (m, 5 H), 7.19 (t, J = 8.3 Hz, 1 H), 7.07 (d, J = 8.3 Hz, 1 H), 6.83-6.89 (m, 2 H), 5.81 (d, J = 5.2 Hz, 1 H), 4.41 (d, J = 2.1 Hz, 1 H), 4.01-4.06 (m, 1 H), 3.89-3.94 (dd, J = 16.7, 8.3 Hz, 1 H), 2.81-2.87 (m, 1 H), 1.96-2.04 (m, 1 H), 1.58-1.67 (m, 1 H). ¹³C NMR (75 MHz, CDCl3): δ = 152.7, 133.4, 130.0, 129.5, 129.1, 128.1, 120.9, 117.1, 99.2, 67.7, 45.6, 43.1, 27.7. ESI-MS: m/z = 307 [M + Na]. HRMS: m/z calcd for C17H16O2SNa: 307.0768; found: 307.0752.