Synthesis of the Adrenergic Bronchodilators (R)-Terbutaline and (R)-Salbutamol from (R)-Cyanohydrins1

摘要: Stereoselective syntheses of (R)-terbutaline and (R)-salbutamol acetal, which are important bronchodilators, starting from O-protected (R)-cyanohydrins described. (R)-Terbutaline hydrochloride (R)-9·HCl is obtained in an overall yield 44% with >98% ee the O-bisallyl-protected cyanohydrin (R)-4k via a Ritter N-tertiary butylation to amide (R)-6a, hydrogenation amino alcohol (R)-7a, deprotection hydroxyl functions. (R)-Salbutamol acetals (R)-7b,c can be corresponding either route described for or selective protected (R)-11 imino derivative, transimination tert-butylamine, followed by NaBH4 give 2-amino derivative (R)-12. Desilylation (R)-12 (R)-7c performed LiAlH4. Hydrolytic cleavage (R)-7b c was not yet possible without racemization.