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.