Synlett 2012(7): 1090-1094  
DOI: 10.1055/s-0031-1290621
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Imine Domino Reactions Generate Novel Scaffolds: Fused Bisthiazolidines or Bisthiiranes

Cecilia Saiz, Valerie Castillo, S. Graciela Mahler*
Cátedra de Química Farmacéutica, DQO, Facultad de Química, Universidad de la República, CC 1157, Montevideo, Uruguay
e-Mail: [email protected];
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Publikationsverlauf

Received 27 December 2011
Publikationsdatum:
15. März 2012 (online)

Abstract

Novel domino processes that involve sequential reactions via iminium ions derived from β-amino thiols or β-amino alcohols were developed to form bisthiazolidines or bisthiiranes, respectively. The heterocycles were synthesized from readily available starting materials, forming four new chemical bonds in one process without the use of metals. The regioselectivity of the transformation could be explained on the basis of calculations of the coefficients of the frontier orbitals.

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11

Representative Procedure for the Preparation of Bisthiazolidines: Synthesis of anti -1a
To a stirred suspension of cysteamine˙HCl (3a, 0.32 g,
2.8 mmol) in EtOH (15 mL) was added Et3N (0.39 mL, 2.8 mmol), 1,4-dithiane-2,5-dithiol 4 (0.51 g, 3.4 mmol), and
p-TsOH (0.025 g, 0.12 mmol). The mixture was heated at reflux for 2 h. Then, it was cooled and poured into a sat. solution of NaCl (15 mL), extracted with CH2Cl2 (5 × 30 mL), dried (Na2SO4), and filtered. The solvent was removed under reduced pressure, and the residue was purified by chromatography on SiO2 (EtOAc-hexanes = 1:6) to afford 1a (0.42 g, 78%, anti/syn = 92:08) as an oil (anti-1a). ¹H NMR (400 MHz, CDCl3): δ = 4.97 (dd, J = 5.2, 3.7 Hz, 1 H), 4.24 (dd, J = 7.0, 6.0 Hz, 1 H), 3.54 (ddd, J = 11.6, 5.2, 0.5 Hz, 1 H), 3.48 (ddd, J = 11.5, 5.7, 4.8 Hz, 1 H), 3.21 (ddd, J = 11.5, 7.2, 6.6 Hz, 1 H), 3.12 (m, 1 H), 3.08 (m, 2 H), 2.82 (ddd, J = 13.6, 7.6, 7.0 Hz, 1 H), 2.65 (ddd, J = 13.6, 9.1, 6.0 Hz, 1 H), 1.84 (dd, J = 9.1, 7.6 Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 74.5, 73.2, 57.1, 38.4, 33.5, 31.8. HRMS: m/z calcd for C6H12NS3 [M + H]+: 194.0132; found: 194.0156.

12

Representative Procedure for the Preparation of Bisthiiranes: Synthesis of 2a To a stirred solution of ethanolamine (5a, 0.30 g, 4.1 mmol) in EtOH (8 mL) was added 1,4-dithiane-2,5-dithiol 4 (0.70 g, 4.9 mmol) and p-TsOH (3 mg, 0.17 mmol). The mixture was heated at reflux for 1.30 h, and stirred overnight at r.t. under N2. Then, it was cooled and poured into a sat. solution of NaCl, extracted with EtOAc (5 × 30 mL), dried (Na2SO4), and filtered. The solvent was removed under reduced pressure, and the residue was purified by chromatography on SiO2 (EtOAc-hexanes = 1:1) to afford 2a (0.48 g, 66%) as an oil. ¹H NMR (400 MHz, CDCl3): δ = 4.91 (d, J = 3.0 Hz, 2 H), 3.72 (m, 2 H), 3.35 (dd, J = 9.5, 3.0 Hz, 2 H), 3.25 (d, J = 9.5 Hz, 2 H), 2.72 (m, 1 H), 2.59 (m, 1 H), 2.39 (t, J = 9.9 Hz, 1 H, OH). ¹³C NMR (101 MHz, CDCl3): δ = 70.0, 60.5, 50.7, 43.9. HRMS: m/z calcd for C6H12NOS2 [M + H]+: 178.0360; found: 178.0350.