A Dynamic Thermodynamic Resolution Strategy for the Stereocontrolled Synthesis of Streptonigrin

Area of Science:

• Organic Chemistry
• Asymmetric Synthesis
• Catalysis

Background:

• Axially chiral biaryl compounds are important structural motifs in pharmaceuticals and materials.
• Controlling atroposelectivity in biaryl synthesis remains a significant challenge.
• Dynamic thermodynamic resolution offers a pathway for selective synthesis.

Purpose of the Study:

• To develop a method for generating axially chiral biaryl boronic esters with high atroposelectivity.
• To demonstrate the utility of these intermediates in stereoretentive functionalization.
• To achieve the first highly stereoselective total synthesis of P-streptonigrin.

Main Methods:

• Binol-mediated dynamic thermodynamic resolution of biaryl precursors.
• Stereoretentive functionalization of the carbon-boron bond in boronic esters.
• Application of the developed methodology to total synthesis.

Main Results:

• Successful generation of axially chiral biaryl boronic esters with controlled atroposelectivity.
• Demonstration of stereoretentive C-B bond functionalization to yield enantioenriched products.
• Completion of the first highly stereoselective total synthesis of P-streptonigrin using this approach.

Conclusions:

• The developed Binol-mediated dynamic thermodynamic resolution provides efficient access to valuable chiral building blocks.
• Stereoretentive functionalization of boronic esters is a viable strategy for accessing complex chiral molecules.
• This methodology represents a significant advancement in asymmetric synthesis and natural product synthesis.