A general and highly selective chelate-controlled intermolecular oxidative Heck reaction

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• The Heck reaction is a powerful tool for carbon-carbon bond formation.
• Palladium-hydride (Pd-H) isomerization is a common side reaction in Heck reactions, limiting stereoselectivity.
• Developing selective and broadly applicable Heck reaction methodologies remains an important goal in organic synthesis.

Purpose of the Study:

• To report a novel chelate-controlled intermolecular oxidative Heck reaction.
• To demonstrate the reaction's effectiveness with a wide range of substrates and reagents.
• To achieve high yields and excellent regio- and stereoselectivities in the formation of internal olefins.

Main Methods:

• Utilizing a palladium/bis-sulfoxide complex (1) as the catalyst.
• Employing nonresonance stabilized α-olefin substrates and organoboron reagents.
• Conducting the reaction under mild, oxidative conditions.

Main Results:

• The reaction proceeds with a broad scope of coupling partners, affording internal olefin products in good yields.
• Outstanding regio- and E:Z stereoselectivities (>20:1) were achieved, with no observed Pd-H isomerization.
• The catalytic system demonstrated tolerance for unprotected alcohols and preserved optical purity at proximal stereogenic centers.

Conclusions:

• A novel and highly selective intermolecular oxidative Heck reaction has been developed.
• The Pd/bis-sulfoxide catalyzed reaction offers a mild and efficient route to internal olefins.
• This methodology is anticipated to be widely applicable in the synthesis of complex molecules due to its broad scope and high selectivity.