3-Hydroxytetrahydrofuran
3-Hydroxytetrahydrofuran is a colorless liquid with a normal boiling point of 179 °C and boiling at 88−89 °C at 17 mmHg, with density. 3-OH THF is a useful pharmaceutical intermediate. The enantiopure version of this compound is an intermediate to launched retroviral drugs.
Synthesis
3-Hydroxytetrahydrofuran was prepared in 1909 by Pariselle via cyclization and hydrolysis of 3,4-Dibromo-1-methoxybutane. Chiral 3-hydroxytetrahydrofuran – and has been synthesized in high enantiomeric purity from - and -1,2,4-butanetriol, respectively, obtained from chiral feedstocks. Thus, the chiral -1,2,4-butanetriol intermediate was cyclized to chiral -3-hydroxytetrahydrofuran in the presence of p-toluenesulfonic acid catalyst at temperatures of 180−220 °C.Similarly, -3-hydroxytetrahydrofuran was prepared in 95.8% optical purity from L-malic acid via an esterification-reduction-cyclodehydration sequence. 3-hydroxytetrahydrofuran has been synthesized via hydroboration of 2,3- and 2,5-dihydrofuran employing various borane reagents and chiral 3-hydroxytetrahydrofurans have also been prepared by catalytic asymmetric hydroboration of 2,3- and 2,5-dihydrofurans with a borane in the presence of a homogeneous chiral platinum complex, followed by oxidation. Racemic 3-hydroxytetrahydrofuran may be prepared in analogous fashion from racemic butanetriol, employing PTSA catalyst for the dehydrocyclization. Alternatively, 1,2,4-butanetriol may be converted to 3-hydroxytetrahydrofuran by treating with ethylene carbonate, followed by pyrolysis of the resulting carbonate ester.