Type II Intramolecular [5+2] Cycloaddition: Facile Synthesis of Highly Functionalized Bridged Ring Systems

A type II intramolecular oxidopyrylium‐mediated [5+2] cycloaddition reaction allows the efficient and diastereoselective formation of various highly functionalized and synthetically challenging bridged seven‐membered ring systems (such as bicyclo[4.4.1]undecane, bicyclo[4.3.1]decane, bicyclo[5.4.1]dodecane, and bicyclo[6.4.1]]tridecane). This simple, thermal, direct transformation has a broad substrate scope and is high yielding, with high functional‐group tolerance and unique endo selectivity. The highly strained tricyclic cores of ingenol mebutate (picato) and cyclocitrinol are synthesized efficiently and diastereoselectively using this methodology. Bridged: The title reaction proceeds via an oxidopyrylium ylide and allows the efficient diastereoselective formation of various synthetically challenging bridged 7‐membered ring systems. This direct transformation has a broad substrate scope with high functional‐group tolerance and unique endo selectivity and gives the bridged ring systems, including the highly strained tricyclic cores of ingenol and cyclocitrinol, in high yields. TMP=2,2,6,6‐tetramethylpiperidine.