Rh2(II)-Catalyzed Enyne Cycloisomerization toward 6-6-5 Tricycles

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Developing efficient synthetic routes for complex molecular frameworks is crucial in organic chemistry.
• Cycloaddition reactions catalyzed by transition metals offer powerful tools for constructing cyclic systems.
• Tethered enynes present versatile substrates for metal-catalyzed transformations.

Purpose of the Study:

• To develop a novel dirhodium-catalyzed diastereoselective cycloisomerization of cyclohexadienone-tethered ynals.
• To establish a concise synthetic pathway toward 6-6-5 fused tricyclic frameworks.
• To explore the trapping of proposed dirhodium carbene intermediates for generating more complex structures.

Main Methods:

• Dirhodium-catalyzed cycloisomerization of enynes derived from cyclohexadienone-tethered ynals.
• Diastereoselective synthesis of fused tricyclic frameworks.
• Mechanistic studies involving intermediate trapping with external alkenes.

Main Results:

• A highly diastereoselective cycloisomerization protocol was established, yielding 6-6-5 fused tricyclic frameworks with three consecutive stereocenters.
• Mechanistic investigations suggested the involvement of a dirhodium carbene intermediate.
• Trapping experiments with alkenes successfully generated intricate fused/spirocyclic adducts containing five stereocenters with complete diastereoselectivity.

Conclusions:

• The developed dirhodium-catalyzed cycloisomerization provides an efficient and diastereoselective route to complex fused tricyclic systems.
• The protocol's ability to trap intermediates opens avenues for synthesizing highly functionalized molecules with multiple stereocenters.
• This methodology offers a valuable tool for accessing diverse and structurally complex molecular architectures in organic synthesis.