Asymmetric Oxidative Cycloetherification of Naphtholic Alcohols

Area of Science:

• Organic Chemistry
• Asymmetric Catalysis
• Hypervalent Iodine Chemistry

Background:

• Previous research focused on enantioselective oxidative cyclizations of naphthol-derived carboxylic acids using chiral hypervalent iodine reagents.
• Analogous reactions involving non-carboxylic substrates remained largely unexplored, presenting a gap in synthetic methodologies.

Purpose of the Study:

• To develop a catalytic, enantioselective, hypervalent iodine-promoted oxidative cycloetherification reaction for naphtholic alcohols.
• To investigate the efficacy of a modified Uyanik-Ishihara catalyst for these transformations.
• To explore the application of this new catalytic system to naphtholic sulfonamides and assess its performance in kinetic resolution.

Main Methods:

• Design and synthesis of a modified Uyanik-Ishihara catalyst with stereogenic centers repositioned closer to the iodine atom.
• Application of the new catalyst in the enantioselective oxidative cycloetherification of naphtholic alcohols and sulfonamides.
• Kinetic resolution of naphtholic alcohols using the developed catalytic system.
• Determination of the absolute configuration of products via X-ray diffractometry.

Main Results:

• The modified catalyst achieved optical yields comparable to existing Uyanik-Ishihara iodides but with significantly higher chemical yields for naphtholic alcohols.
• For the more challenging cyclization of naphtholic sulfonamides, the new catalyst demonstrated substantially improved optical inductions.
• The successful kinetic resolution of specific naphtholic alcohols was achieved, showcasing the catalyst's versatility.

Conclusions:

• A novel and efficient catalytic system for enantioselective oxidative cycloetherification of naphtholic alcohols and sulfonamides has been established.
• The redesigned chiral hypervalent iodine catalyst offers improved performance over previous catalysts, particularly in terms of chemical yield and optical induction.
• This methodology expands the scope of asymmetric oxidative cyclizations and provides a valuable tool for synthesizing enantioenriched naphthol derivatives.