Solid-phase asymmetric synthesis using a polymer-supported chiral Evans'-type oxazolidin-2-one.

Area of Science:

• Organic Chemistry
• Polymer Chemistry
• Asymmetric Synthesis

Background:

• Chiral auxiliaries are crucial for controlling stereochemistry in organic synthesis.
• Solid-phase synthesis offers advantages in purification and automation.
• Developing efficient polymer-supported chiral auxiliaries remains an active area of research.

Purpose of the Study:

• To synthesize a novel polymer-supported chiral auxiliary for asymmetric synthesis.
• To demonstrate the utility of this auxiliary in diastereoselective reactions.
• To enable sequential 'on-bead' reactions for complex molecule synthesis.

Main Methods:

• Preparation of (S)-4-(4-hydroxybenzyl)-oxazolidin-2-one from N-Boc-L-tyrosine.
• Attachment of the chiral auxiliary to Merrifield-Cl resin via its phenolic group.
• Performing N-acylation and diastereoselective solid-supported Evans' syn-aldol reactions on the resin.
• Cleavage of aldol products by hydrolysis or reduction.
• Utilizing IRORI Kan resin capsules for polymer support protection.

Main Results:

• Successful synthesis of the solid-supported chiral auxiliary in high yield.
• Demonstration of high diastereoselectivity (>95:5 dr) in Evans' syn-aldol reactions.
• Successful synthesis of a chiral cyclopropane aldol and a γ-lactone via sequential 'on-bead' reactions.
• Protection of the polymer support allowing for multiple reaction cycles.

Conclusions:

• The developed polymer-supported chiral auxiliary is effective for asymmetric synthesis.
• The method allows for efficient and highly diastereoselective synthesis of complex chiral molecules.
• This approach is suitable for sequential 'on-bead' transformations, offering a robust platform for organic synthesis.