Efficient Synthesis of 2‐Amino‐1‐Arylethanols Through a Lewis Base‐Catalyzed SiCl4‐Mediated Asymmetric Passerini‐Type Reaction

Abstract

We herein report, a practical and efficient strategy for the synthesis of enantiomerically enriched 2‐amino‐1‐arylethanols, a structural motif commonly encountered in the family of β‐adrenergic blockers or agonists, through a Lewis base‐catalyzed SiCl4‐mediated asymmetric Passerini‐type reaction of isocyanides with aldehydes. The protocol features a simple one‐pot, two‐step procedure, the use of commercially available starting materials, a broad functional group tolerance, and high levels of selectivity up to 98.5:1.5 er. Application to the synthesis of the salbutamol acetate salt, a drug widely used as a bronchodilator to manage asthma and other chronic obstructive airway diseases is also reported.