Oxidative Kinetic Resolution of Cyclic Benzylic Ethers

Area of Science:

• Organic Chemistry
• Asymmetric Catalysis
• Oxidation Reactions

Background:

• Kinetic resolution is crucial for obtaining enantiomerically pure compounds.
• Asymmetric C(sp3)-H oxidation offers a direct route to chiral molecules.
• Cyclic benzylic ethers represent important structural motifs in organic synthesis.

Purpose of the Study:

• To develop a manganese-catalyzed oxidative kinetic resolution of cyclic benzylic ethers.
• To achieve high enantiodiscrimination in the asymmetric C(sp3)-H oxidation.
• To demonstrate the broad applicability of the developed strategy.

Main Methods:

• Utilized a manganese catalyst for asymmetric oxidative kinetic resolution.
• Employed C(sp3)-H oxidation of cyclic benzylic ethers, including 1,3-dihydroisobenzofurans, 2,3-dihydrobenzofurans, and 6H-benzo[c]chromenes.
• Explored late-stage functionalization of bioactive molecules.

Main Results:

• Achieved highly efficient enantiodiscrimination for a wide range of 1,3-dihydroisobenzofurans.
• Demonstrated the generality of the method across different five- and six-membered cyclic benzylic ethers.
• Successfully applied the strategy for direct late-stage oxidative kinetic resolution of complex bioactive compounds.

Conclusions:

• The reported manganese-catalyzed oxidative kinetic resolution is a practical and versatile approach.
• The method provides efficient access to enantiomerically enriched cyclic benzylic ethers.
• This strategy holds significant potential for the synthesis of chiral molecules and late-stage functionalization.