Hydroxamic acids in asymmetric synthesis

Area of Science:

• Organic Chemistry
• Asymmetric Catalysis

Background:

• Chiral ligands are crucial for metal-catalyzed stereoselective reactions.
• Hydroxamic acids possess high metal affinity and potential as chiral ligands.
• Few highly enantioselective reactions have utilized metal-hydroxamic acid catalysts since their initial discovery.

Purpose of the Study:

• To explore the utility of hydroxamic acids as chiral ligands in metal-catalyzed asymmetric epoxidation.
• To design and synthesize novel hydroxamic acid ligands for enhanced catalytic performance.
• To expand the scope of asymmetric epoxidation reactions using diverse metal-hydroxamic acid complexes.

Main Methods:

• Design and synthesis of novel hydroxamic acids, including C2-symmetric bis-hydroxamic acids (BHAs).
• Investigation of various metal complexes (V, Mo, Zr, Hf) with BHA ligands.
• Catalytic asymmetric epoxidation of various substrates including alcohols, olefins, sulfides, and imines.

Main Results:

• V-BHA catalysts demonstrated superior activity and stereoselectivity compared to the Sharpless asymmetric epoxidation in many cases.
• Mo-BHA catalysts enabled asymmetric epoxidation of single olefins and sulfides.
• Zr- and Hf-BHA catalysts facilitated unprecedented asymmetric epoxidation of homoallylic and bishomoallylic alcohols, as well as N-alkenyl sulfonamides and N-sulfonyl imines.
• The reactions consistently produced chiral epoxides in good yields and high enantioselectivities.

Conclusions:

• Novel hydroxamic acid derivatives, particularly BHAs, are effective chiral ligands for metal-catalyzed asymmetric epoxidation.
• These new catalytic systems offer improved performance and expanded substrate scope compared to established methods.
• The developed metal-hydroxamic acid catalysts provide access to uniquely functionalized chiral epoxides.