A SmI₂-mediated reductive cyclisation reaction using the trifluoroacetamide group as the radical precursor

Area of Science:

• Organic Chemistry
• Synthetic Methodology
• Fluorine Chemistry

Background:

• Reductive cyclization reactions are crucial for synthesizing heterocyclic compounds.
• Samarium(II) iodide (SmI₂) is a powerful reducing agent often used in organic synthesis.
• Acyclic amide groups are typically unreactive in samarium(II) iodide-mediated reductive cyclizations.

Purpose of the Study:

• To develop a novel samarium(II)-mediated reductive cyclization reaction.
• To synthesize 2-trifluoromethylindolines using an acyclic trifluoroacetamide precursor.
• To demonstrate the utility of this method for accessing valuable fluorinated heterocycles.

Main Methods:

• Utilized samarium(II) iodide as the reducing agent.
• Employed an aminoketyl radical generated from a trifluoroacetamide group.
• Performed a reductive cyclization to form the indoline ring system.

Main Results:

• Successfully synthesized 2-trifluoromethylindolines via samarium(II)-mediated reductive cyclization.
• Demonstrated the first use of a challenging acyclic amide group in SmI₂-mediated reductive cyclization.
• Achieved subsequent conversion of the 2-trifluoromethylindoline product to 2-trifluoromethylindole.

Conclusions:

• Developed an efficient synthetic route to 2-trifluoromethylindolines.
• Overcame the inherent difficulty of using acyclic amides in SmI₂-mediated reductive cyclizations.
• Provided a valuable method for synthesizing fluorinated indoline and indole derivatives.