A Local Desymmetrization Approach to Piperidinyl Acetic Acid γ‑Secretase Modulators

A desymmetrization-based approach for the synthesis of piperidinyl acetic acid gamma-secretase modulators has been developed. The synthetic sequence features the use of N-tert-butanesulfinyl imine reduction and a diastereoselective lactam formation to set up the chiral centers. The synthetic utility is demonstrated by the concise asymmetric synthesis of gamma-secretase modulator GSM-1.