Enantiodivergent Approach to Trifluoromethylated Amines: A Concise Route to Both Enantiomeric Analogues of Calcimimetic NPS R‐568

Abstract

Abstract Reported herein is a straightforward and enantiodivergent synthesis of both enantiomers of trifluoromethylated analogues of calcimimetic NPS R‐569 in a highly estereoselective manner. The synthesis features a diastereoselective synthesis of the N ‐(isopropylsulfinyl)imine unit by the “DAG methodology” and a diastereoselective addition of Ruppert–Prakash's reagent to the imine as the key steps. No protecting groups were necessary, permitting an atom economic synthesis in only six steps. Further addition reactions of the CF 3 anion to different N ‐(isopropylsulfinyl)imines were performed to demonstrate the suitability of the sulfinyl substituent to balance perfectly reactivity and diastereoselectivity.