A Novel Crystallization-Induced Diastereomeric Transformation Based on a Reversible Carbon−Sulfur Bond Formation. Application to the Synthesis of a γ-Secretase Inhibitor

This paper describes a remarkably efficient process for the preparation of γ-secretase inhibitor 1. The
target is synthesized in only five steps with an overall yield of 58%. The key operation is a highly
selective and practical, crystallization-driven transformation for the conversion of a mixture of tertiary
benzylic alcohols into the desired sulfide diastereomer with 94:6 dr. This unprecedented process is based
upon a reversible carbon−sulfur bond formation under acidic conditions.

本论文报道了一种合成γ-分泌酶抑制剂1（γ-secretase inhibitor 1）的高效工艺。该目标产物仅需五步反应即可制备，总收率达58%。其核心操作为一种高选择性、实用性强的结晶驱动转化反应，可将叔苄醇混合物转化为非对映选择性比例为94:6（dr）的目标硫化物非对映异构体。该前所未有的工艺基于酸性条件下可逆的碳-硫键形成反应。