Lipase resolution of new (±)-3-aryloxy-1-halogenopropan-2-ols: Versatile building blocks for β-adrenergic receptor antagonists

Using two commercial immobilized lipases Lipozyme^® TL and Novozym^® 435 effective kinetic resolution of several novel 3-aryloxy-1-halogenopropan-2-ols was achieved by acyl transfer reaction in organic solvents, yielding both enantiomers with 89–99% ee. In preparative resolutions carried out in tert-butyl methyl ether at 25 °C with vinyl acetate as acyl donor enantioselectivity ratio E was from 64 to 99. The resolved enantiomers were successfully used as chiral building blocks in the synthesis of new 1-alkylamino-3-aryloxypropan-2-ols, by nucleophilic halogen substitution with isopropylamine and tert-butylamine. The obtained products will be evaluated in vitro as potential new β-adrenergic receptors antagonists.