Oxetanes represent a versatile building block in organic synthesis and drug discovery. While increasing attention has been paid to their preparation and new reactivity discovery, there remains a great need for the development of more enantioselective reactions of oxetanes. The ring strain of an oxetane ring is slightly lower than that of an oxirane, which makes the oxetane ring relatively more difficult to open, particularly when the oxetane is only substituted at the 3-position because there is little stabilization in the reaction intermediate or transition state in the absence of a 2-substituent. As a result, enantioselective desymmetrization of 3-substituted oxetanes by an intermolecular nucleophile remains challenging (Figure). We will present the first highly enantioselective intermolecular desymmetrization of 3-substituted oxetanes. The reaction features mild conditions, broad scope, and high enantioselectivity. Moreover, the three-carbon subunit in the products with a chiral center represents a very versatile moiety that can be easily converted to different useful chiral building blocks that have broad applications in organic synthesis. Details regarding the reaction scope and mechanism as well as product derivatization will be discussed.

Synthesis of useful chiral building blocks via efficient enantioselective desymmetrization of 3-substituted oxetanes

245th National Meeting (2013)

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