Kinetic Resolution of Unprotected BINOLs via Lewis Base-Catalyzed O-Boc Protection

Area of Science:

• Organic Chemistry
• Catalysis
• Asymmetric Synthesis

Background:

• 1,1 -bi-2,2 -naphthols (BINOLs) are crucial chiral scaffolds in asymmetric synthesis.
• Developing efficient methods for accessing enantioenriched BINOLs is essential for creating complex chiral molecules.

Purpose of the Study:

• To develop a Lewis base-catalyzed kinetic resolution of BINOLs.
• To achieve atroposelective O-Boc protection of BINOLs using a commercially available catalyst.

Main Methods:

• Utilized a biscinchona alkaloid catalyst for the kinetic resolution.
• Employed Boc anhydride (Boc₂O) as the protecting group reagent.
• Investigated the atroposelective O-Boc protection of various unprotected BINOLs.

Main Results:

• Achieved kinetic resolution of BINOLs with high selectivity factors (s) up to 78.
• Generated enantioenriched BINOLs through selective O-Boc protection.
• Demonstrated the utility of resulting BINOLs in subsequent transition-metal-catalyzed cross-coupling reactions.

Conclusions:

• The described method provides a streamlined approach to structurally diverse BINOL analogs.
• This work expands the toolkit for synthesizing valuable chiral BINOL derivatives.
• The developed resolution is efficient and utilizes readily available catalytic systems.