(R)-(-)-2,2-Dimethyl-1,3-dioxolan-4-ylmethyl p-toluenesulfonate

Chemical Properties

Uses

Synthesis

22323-82-6

98-59-9

23788-74-1

To a solution of (S)-(+)-2,2-dimethyl-4-(hydroxymethyl)-1,3-dioxolane (19a) (4.0 g, 30.2 mmol) in anhydrous pyridine (50 mL) was added p-toluenesulfonyl chloride (6.18 g, 31.7 mmol) in batches over a period of 10 min under ice bath conditions. The reaction mixture was slowly brought to room temperature and stirred overnight, during which a white precipitate was observed to form. Upon completion of the reaction, the pyridine was removed under reduced pressure and the residue was diluted with ethyl acetate (50 mL) and washed sequentially with cold aqueous 1M HCl solution (2 x 150 mL), saturated NaHCO3 solution (100 mL) and brine (200 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated to give a light yellow oil. The crude product was purified by silica gel column chromatography using a 10-30% ethyl acetate/hexane gradient elution to afford (R)-(-)-3-toluenesulfonyloxy-1,2-propanediol acetone compound (20a) (8.54 g, 99% yield, 99.9% ee) as a colorless viscous oily substance. rf = 0.37 (20% ethyl acetate/hexanes). [α]D20 -4.8 (c 1.0, EtOH) (literature value [α]D24 -4.6 (c 13.0, EtOH)). ftir (film) νmax 3073, 2987, 2937, 2891, 1598, 1495, 1455, 1368, 1257, 1213, 1190, 1177, 1096, 1055 , 979, 829, 788, 665, 555 cm-1.1H NMR (600MHz, CDCl3) δ1.31(s, 3H, CH3-2), 1.34(s, 3H, CH3-2), 2.45(s, 3H, ArCH3), 3.76(dd, J=5.1 and 8.8Hz, 1H, CH2-5), 3.98 (dd, J=6.0 and 10.2 Hz, 1H, CH2-1'), 3.99-4.05 (m, 2H, CH2-1' and CH2-5), 4.28 (m, 1H, CH-4), 7.35 (m, 2H, aromatic H-3 and H-5), 7.79 (m, 2H, aromatic H-2 and H-6) ppm.13C NMR ( 150MHz, CDCl3) δ21.5(Ar-CH3), 25.1(CH3-2), 26.5(CH3-2), 66.1(C-5), 69.4(C-1'), 72.8(C-4), 109.9(C-2), 127.9(2C, aromatic C-2 and C-6), 129.8(2C, aromatic C-3 and C-5), 132.6(m, 2H, aromatic C-3 and C-6) ppm. HRMS (ESI): C13H18NaO5S [M+Na]+ Calculated value 309.07672; Measured value 309.0762 Chiral HPLC analysis: Chiralpak IA column (5 μm, 250×4.6 mm), mobile phase hexane/2-propanol/methanol (2C, aromatic C-2 and C-6), 129.8 (2C, aromatic C-3 and C-5), 132.6 (aromatic C-1), 145.0 (aromatic C-4) ppm. Chiralpak IA column (5 μm, 250×4.6 mm), mobile phase hexane/2-propanol/methanol (97:2:1, v/v/v), flow rate 1.0 mL/min, tR=21.71 min (0.06% 20b), tR=24.20 min (99.94% 20a), 99.88% ee. All physical and spectroscopic data are in good agreement with those reported in the literature.

References