Stereoselective Entry into α,α’‐C‐Oxepane Scaffolds through a Chalcogen Bonding Catalyzed Strain‐Release C‐Septanosylation Strategy

Abstract The utility of unconventional noncovalent interactions (NCIs) such as chalcogen bonding has lately emerged as a robust platform to access synthetically difficult glycosides stereoselectively. Herein, we disclose the versatility of a phosphonochalcogenide (PCH) catalyst to facilitate access into the challenging, but biologically interesting 7‐membered ring α,α’‐ C ‐disubstituted oxepane core through an α‐selective strain‐release C ‐glycosylation. Methodically, this strategy represents a switch from more common but entropically less desired macrocyclizations to a thermodynamically favored ring‐expansion approach. In light of the general lack of stereoselective methods to access C ‐septanosides, a remarkable palette of silyl‐based nucleophiles can be reliably employed in our method. This include a broad variety of useful synthons, such as easily available silyl‐allyl, silyl‐enol ether, silyl‐ketene acetal, vinylogous silyl‐ketene acetal, silyl‐alkyne and silylazide reagents. Mechanistic investigations suggest that a mechanistic shift towards an intramolecular aglycone transposition involving a pentacoordinate silicon intermediate is likely responsible in steering the stereoselectivity.