Asymmetric Epoxidation of Allyl Alcohol: Efficient Routes to Homochiral /3-Adrenergic Blocking Agents

Since the discovery of the titanium-catalyzed asymmetric epoxidation of allylic alcohols in 1980,¹ ongoing efforts in these laboratories have been directed toward expanding the scope and synthetic utility of the reaction. A serious limitation of the original procedure has been its failure when applied to substrates with a strong propensity for undergoing ring-opening reactions. Of the many reaction modifications which have been explored, the recent development of an effective catalytic procedure² has offered the most general solution to this important problem and has allowed even allyl alcohol to be included for the first time on the roster of successful substrates. Although a full description of this new development will be reported shortly, the practical importance of homochiral glycidol in the synthesis of β-adrenergic blocking agents (β-blockers) prompts us to disclose here two very efficient routes to (2S)-propranolol, each utilizing the asymmetric epoxidation of allyl alcohol.