Lithium/Element Exchange as an Efficient Tool for Accessing Atropo-enriched Biaryls via Arynes

Area of Science:

• Organic Chemistry
• Synthetic Methodology

Background:

• Development of transition metal-free coupling reactions is crucial for sustainable synthesis.
• Aryl-aryl bond formation is a fundamental transformation in organic chemistry.

Purpose of the Study:

• To document the development of aryne-mediated aryl-aryl coupling (ARYNE coupling).
• To highlight the advancements in synthesizing substituted and enantiopure biphenyls using this method.

Main Methods:

• Utilizing aryne intermediates for transition metal-free aryl-aryl coupling.
• Employing regioselective bromine/lithium interconversions for functionalization.
• Using enantiopure sulfoxides as chiral auxiliaries for asymmetric synthesis.

Main Results:

• Multi-gram scale synthesis of ortho,ortho'-di-, tri-, and tetrasubstituted biphenyls achieved.
• Perfect regioselectivity demonstrated in the ARYNE coupling reaction.
• Access to enantiopure biphenyls established through chiral auxiliaries and chemoselective transformations.
• Recent advancements include direct atropo-diastereoselective ARYNE coupling.

Conclusions:

• Transition metal-free ARYNE coupling is a powerful and versatile method for constructing complex biphenyl architectures.
• The methodology offers excellent control over regioselectivity and stereoselectivity.
• This approach provides scalable access to valuable chiral biaryl compounds.