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DOI: 10.1055/s-0031-1290084
BF3×OEt2-Catalyzed
Unusual Formation of cis-2,3-Disubstituted
Tetrahydrofuran
Scaffolds
Publication History
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
-
1a
Polyether
Antibiotics
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References and Notes
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.