Chiral Bifunctional Selenide Catalysts for Asymmetric Iodolactonizations

Area of Science:

• Organic Chemistry
• Catalysis
• Medicinal Chemistry

Background:

• 1,1'-Bi-2-naphthol (BINOL)-derived chiral bifunctional catalysts are effective for enantioselective bromolactonizations.
• Chiral γ-butyrolactones are important intermediates in medicinal chemistry.
• Previous studies showed good performance of chiral bifunctional selenides in enantioselective iodolactonizations.

Purpose of the Study:

• To investigate the roles of chalcogenide moieties (sulfide vs. selenide) and hydroxy groups in bifunctional catalysts for asymmetric iodolactonizations.
• To clarify the importance of both a selenide moiety and a hydroxy group for achieving high enantioselectivity.
• To demonstrate the utility of optimized chiral bifunctional selenide catalysts in synthesizing valuable chiral lactones.

Main Methods:

• Asymmetric iodolactonization reactions using 4-pentenoic acids and α,α-diallyl carboxylic acids.
• Comparison of BINOL-derived chiral sulfide and selenide catalysts possessing a hydroxy group.
• Investigation of catalyst structure-activity relationships.

Main Results:

• Chiral bifunctional selenide catalysts with a hydroxy group effectively yielded enantiomerically enriched γ-butyrolactones.
• BINOL-derived chiral sulfide catalysts with a hydroxy group resulted in nearly racemic iodolactonization products.
• The study clarified that both a selenide moiety and a hydroxy group are essential for high enantioselectivity in these reactions.

Conclusions:

• Chiral bifunctional selenide catalysts featuring a hydroxy group are superior to their sulfide counterparts for enantioselective iodolactonizations.
• The optimized chiral bifunctional selenide catalyst enables the asymmetric synthesis of chiral γ-butyrolactones and phthalides.
• These catalysts are also effective for the desymmetrizing iodolactonization of α,α-diallyl carboxylic acids, showcasing broad applicability.