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Synlett 2004(6): 1034-1038  
DOI: 10.1055/s-2004-820051
LETTER
© Georg Thieme Verlag Stuttgart · New York

Regioselective Reduction of 5-Substituted 2-Alkylidene-4-Oxothiazolidines by Metal Hydrides

Rade Marković*a,b, Marija Baranaca,b, Milovan Stojanovićb
a Faculty of Chemistry, University of Belgrade, Studentski trg 16, P. O. Box 158, 11001 Belgrade, Serbia and Montenegro
b Center for Chemistry ICTM, P. O. Box 473, 11000 Belgrade, Serbia and Montenegro
Fax: +381(11)636061; e-Mail: markovic@helix.chem.bg.ac.yu;
Further Information

Publication History

Received 23 December 2003
Publication Date:
25 March 2004 (online)

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Abstract

Thiazolidine β-enamino derivatives possessing a 5-substituted acetate substituent were chemoselectively reduced to corresponding alcohols, or new condensed 2-alkylidenethiazolidines. The method is based on the resistance of an enaminone fragment to reduction by metal hydrides.

Key words

thiazolidine - reductions - hydrides - regioselectivity - ring closure

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Typical Experimental Procedure: An appropriate 5-substituted-4-oxothiazolidine 1 (100 mg) dissolved in anhydrous EtOH (10 mL) was added dropwise at r.t. to the tenfold molar excess of NaBH4 in EtOH (ca. 5 mL). When the hydrogen evolution had ceased the reaction mixture was heated under reflux with stirring for a period of time required (2-3 h) to complete the reaction (TLC). The reaction mixture was cooled, neutralized with NH4Cl and extracted with EtOAc. The combined extracts, washed with brine and dried, were evaporated in vacuo. The residue was purified by column chromatography (SiO2, toluene-EtOAc, 10:0 → 8:2) to afford a pure product 5.
Spectroscopic data for (Z)-[5-(2-Hydroxyethyl)-4-oxothiazolidin-2-ylidene]-1-phenylethanone (5a): Colorless solid; mp 158-159 °C. 1H NMR (200 MHz, DMSO-d 6 ): δ = 1.71-1.93 (m, 1 H, CH AHBCHX), 2.14-2.30 (m, 1 H, CHA H BCHX); 3.58 (m, 2 H, CH 2OH), 4.09 (dd, J 1 = 9.5 Hz, J 2 = 4.2 Hz, 1 H, Hx), 4.82 (br s, 1 H, OH; signal disappears upon D2O addition), 6.72 (s, 1 H, =CH), 7.47-7.62 (m, 3 H, p-Ph and m-Ph), 7.83 (dd, 1 H, J 1 = 7.6 Hz, J 2 = 1.6 Hz, o-Ph), 11.85 (br s, 1 H, NH; signal disappears upon D2O addition). 13C NMR (50.3 MHz, DMSO-d 6): δ = 35.7 (CHAHB), 44.1 (CHX), 58.6 (CH2OH), 94.5 (=CH), 127.2 (m-Ph), 129.0 (o-Ph), 132.4 (p-Ph), 138.5 (C1-Ph), 161.2 (C=), 177.3 (COring), 187.3 (COexo). IR (KBr): 3453, 3194, 3068, 2924, 1685, 1631, 1577, 1517, 1468, 1364, 1295, 1198 cm-1. MS (EI): m/z (rel. intensity%) = 263 (100) [M+], 232 (86), 178 (8), 146 (20), 105 (80). UV (DMSO): l max (e) = 335.0 (18000) nm. Anal. Calcd for C13H13NO3S: C, 59.30; H, 4.98; N, 5.32; S, 12.18. Found: C, 59.03; H, 4.92; N, 5.33; S, 12.24.

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Strong intramolecular 1,5-interactions of nonbonded S and O within the SC=CC=O subunit with cis-configuration of C=C bond additionally stabilize the enaminone structure.

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Methylation of (Z)-5a led to alcohol 13f, which, in a one-pot sequence, comprising reduction followed by cyclization, was transformed into the identical bicylic thiazolidine 6f in moderate yield (Scheme [4] ).

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(Z)-(N-Methyltetrahydrofuro[2,3-d]thiazol-2-ylidene)-1-phenylethanone (6f): Colorless solid; mp 121-122 °C. 1H NMR (200 MHz, CDCl3): δ = 2.12-2.43 (m, 2 H, CH A H BCHXS), 3.10 (s, 1 H, NCH3), 3.77-3.89 (m, 1 H, OCHYCH XS), 4.02 (t, 1 H, J = 8.0 Hz, OCH QHZ), 4.12 (t, 1 H, J = 7 Hz, OCHQ H Z), 5.67 (d, 1 H, J XY = 6.6 Hz, OCH YCHXS), 6.08 (s, 1 H, =CH), 7.36-7.47 (m, 3 H, m-Ph, p-Ph), 7.90-7.95 (m, 2 H, o-Ph). 13C NMR (50.3 MHz, CDCl3): δ = 33.7 (NCH3), 35.2 (CHAHB), 44.6 (CHX), 65.8 (CH2O), 87.5 (=CH), 99.1 (CHY), 127.2 (o-Ph), 128.2 (m-Ph), 131.0 (p-Ph), 139.7 (C1Ph), 165.7 (C=), 186.9 (CO). IR (KBr): 3530, 3412, 2974, 2939, 1602, 1571, 1525, 1433, 1355, 1264, 1213, 1028, 973, 727 cm-1. MS (EI, 70 eV): m/z (rel. intensity) = 261 (57) [M+], 260 (100), 245 (34), 191 (20), 184 (42), 163 (32), 105 (97), 86 (39), 82 (58), 51 (26). UV (DMSO): l max (e) = 337.9 (19 700) nm. Anal. Calcd for C14H15NO2S: C, 64.34; H, 5.79; N, 5.36; S, 12.27. Found: C, 64.24; H, 5.82; N, 5.30; S, 12.59.

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In all push-pull thiazolidines 1 and 6 high field 13C chemical shifts (85-96 ppm) for the acceptor-substituted C(α) atoms, and low field shifts (161-169 ppm) for the donor-substituted C(β) atoms are typical.