Remote Central-to-Axial Chirality Conversion: Direct Atroposelective Ester to Biaryl Transformation

Area of Science:

• Organic Chemistry
• Stereochemistry
• Asymmetric Synthesis

Background:

• Chirality is crucial in pharmaceuticals and materials science.
• Developing efficient methods for creating chiral molecules, particularly axially chiral compounds, remains a significant challenge in synthetic chemistry.
• Atropisomeric biaryls are important structural motifs with applications as ligands and chiral auxiliaries.

Purpose of the Study:

• To present a novel strategy for remote central-to-axial chirality conversion.
• To develop a method for the direct synthesis of structurally diverse atropisomeric biaryls.
• To establish a facile route to chiral biaryl silanes as versatile synthetic intermediates.

Main Methods:

• A diastereoselective double addition of a chiral 1,5-bifunctional organomagnesium alkoxide reagent to aryl ester substrates.
• Simultaneous planarization of an encoding and a transient stereocenter.
• In situ reduction to yield the final axially chiral products.

Main Results:

• Direct access to axially chiral biaryls from aryl esters.
• Successful synthesis of various structurally distinct atropisomeric biaryl silanes.
• High enantiomeric ratio (e.r.) values achieved, up to 98:2.
• The method provides chiral biaryl anion surrogates in a single step.

Conclusions:

• The presented strategy offers an efficient and direct route for central-to-axial chirality conversion.
• The developed method enables the synthesis of valuable atropisomeric biaryl silanes with high stereoselectivity.
• This approach expands the toolkit for asymmetric synthesis and the preparation of important chiral building blocks.