Asymmetric Synthesis of ( R )‐Fluoxetine: A Practical Approach Using Recyclable and in‐situ Generated Oxazaborolidine Catalyst

A practical route for the synthesis of ( R )‐fluoxetine·HCl ( ee =96%) in 56% overall yield was described. The key intermediate ( R )‐3‐chloro‐1‐phenyl‐1‐propanol was obtained by the asymmetric reduction of prochiral 3‐chloropropiophenone using in‐situ generated oxazaborolidine catalyst derived from ( S )‐ α , α ‐diphenylprolinol. The chiral procatalyst ( S )‐ α , α ‐diphenylprolinol was recovered quantitatively and recycled. An improved practical synthesis of ( S )‐ α , α ‐diphenylprolinol was also discussed.