Cis-difluoromethyl hetarylative dearomatization by a radical docking-migration cascade

Area of Science:

• Organic Chemistry
• Photochemistry
• Synthetic Methodology

Background:

• Dearomatization reactions are crucial in organic synthesis.
• Achieving uncyclized dearomatization to form thermodynamically unstable 1,2-cis-products remains a significant challenge.
• Existing methods often lack selectivity or require harsh conditions.

Purpose of the Study:

• To develop a novel, efficient, and selective method for uncyclized cis-selective dearomatization.
• To incorporate a CF2H group and a hetaryl moiety simultaneously into indoline backbones.
• To expand the scope of dearomatization to include various heteroarenes and polycyclic aromatic hydrocarbons.

Main Methods:

• A radical docking-migration cascade initiated by mild photochemistry.
• Utilizing indoles, benzothiophenes, furans, thiophenes, and polycyclic aromatic hydrocarbons as substrates.
• Employing Density Functional Theory (DFT) calculations to elucidate reaction mechanisms and selectivity.

Main Results:

• Successful uncyclized cis-selective dearomatization under mild photochemical conditions.
• Simultaneous incorporation of CF2H and hetaryl groups into indoline backbones.
• Broad substrate scope including diverse indoles, benzothiophenes, furans, thiophenes, and PAHs.
• High regioselectivities and cis-stereoselectivities were observed.
• The protocol does not require photosensitizers.

Conclusions:

• The developed radical docking-migration cascade offers a powerful new strategy for uncyclized dearomatization.
• This method provides access to valuable 1,2-cis-products with high selectivity and broad applicability.
• DFT calculations successfully rationalize the observed stereochemical outcomes, aiding future reaction design.