Discovering Enantioselective Protodeauration in Gold Catalysis: Asymmetric Synthesis of Cyclobutenes

The accessibility to highly enantiomerically enriched organic compounds via asymmetric gold catalysis has grown exponentially for the past two decades. In the present study, we disclose the possibility to conduct asymmetric gold transformations exploiting asymmetric protodeauration events that are generally assumed as “innocent” elementary steps from a stereoselective viewpoint. As a proof of concept, we hereby report the synthesis of densely functionalized cyclobutenes (yields up to 82%), featuring an all-carbon quaternary stereogenic center, via a gold-catalyzed chemo-, regio-, and enantioselective (ee up to 96%) desymmetrization of bicyclo[1.1.0]butanes with allenamides. The “chelating” activation mode exerted by the binuclear chiral gold complex was ascertained by dedicated DFT calculations, while a deep understanding of the key role played by the protodeauration (genuine intramolecular profile, stereochemistry rationalization) was achieved via combined experimental and theoretical investigations.