Uses
(S)-4-Isopropylthiazolidine-2-thione may be used as a chiral auxiliary for the stereochemical induction at the phosphorus atom during the diastereoselective synthesis of aryloxy phosphoramidate prodrugs of 3μ-deoxy-2μ,3μ-didehydrothymidine monophosphate (d4TMP).', 'A highly selective and efficient chiral auxiliary which can be directly reduced to its corresponding aldehyde and the chiral auxiliary by reductive cleavage with diisobutylaluminum hydride.
Synthesis
The yields of the following procedures are higher than those reported in the literature (Erik Galvez, P. R., Felix Urp. (2009). Organic Synthesis, 86, 70). To a sealed tube was added aqueous KOH (2.7 g, 48.4 mmol, 5 eq., dissolved in 8 mL of water), 2 mL of ethanol, CS2 (2.9 mL, 48.4 mmol, 5 eq.) and (S)-(+)-2-amino-3-methyl-1-butanol (1.0 g, 9.69 mmol, 1 eq.). The reaction mixture was heated at 80 °C for 15 h, followed by purging with N2 to remove excess CS2. The reaction solution was neutralized with 1 M aqueous HCl and extracted with EtOAc (3 x 60 mL). The organic layers were combined, washed with brine (5 mL), dried over MgSO4 and concentrated in vacuum. The crude product was purified by silica gel column chromatography to afford (S)-4-isopropylthiazolidine-2-thione as a yellow solid (1.19 g, 76% yield). The characterization data of the product were in agreement with literature reports.
References
[1] European Journal of Organic Chemistry, 2011, # 23, p. 4397 - 4408
[2] Organic Syntheses, 2009, vol. 86, p. 70 - 80
[3] Tetrahedron, 2008, vol. 64, # 24, p. 5637 - 5644
[4] Organic Letters, 2011, vol. 13, # 21, p. 5916 - 5919
[5] European Journal of Organic Chemistry, 2009, # 33, p. 5841 - 5846
