Anodic Cyclizations, Densely Functionalized Synthetic Building Blocks, and the Importance of Recent Mechanistic...

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Electrochemistry

Background:

• Anodic cyclization offers a route to functionalized cyclic compounds from chiral lactols.
• Traditional methods require substrate modification based on nucleophile polarity (heteroatom vs. C-C bond formation).
• This limitation necessitates optimizing reactions by resynthesizing starting materials.

Purpose of the Study:

• To develop a more versatile anodic cyclization method.
• To eliminate the need for substrate redesign based on nucleophile type.
• To enable efficient synthesis using polar radical cations with heteroatom nucleophiles.

Main Methods:

• Conversion of lactols to electron-rich olefins.
• Oxidative generation of radical cations.
• Employing a faster second oxidation step and mediated electrolysis to drive cyclization.
• Trapping of radical cations by nucleophiles.

Main Results:

• Successful anodic cyclizations were achieved using polar radical cations and heteroatom nucleophiles.
• The developed methods circumvented the need for substrate manipulation.
• Both faster oxidation and mediated electrolysis proved effective in driving the reaction equilibrium towards products.

Conclusions:

• The new anodic cyclization strategy enhances versatility by avoiding substrate redesign.
• Faster oxidation and mediated electrolysis are effective in promoting cyclization with polar radical cations.
• This approach simplifies the synthesis of densely functionalized cyclic building blocks from chiral lactols.