Asymmetric Hydride Shift Reactions Catalyzed by Chiral Aluminium Complexes

Area of Science:

• Organic Chemistry
• Asymmetric Catalysis

Background:

• Intramolecular hydride shifts are crucial for synthesizing complex organic molecules.
• Developing enantioselective methods for these transformations remains a significant challenge in organic synthesis.

Purpose of the Study:

• To develop a novel asymmetric intramolecular hydride shift reaction.
• To achieve high enantioselectivity in the transformation of racemic substrates into valuable cyclohexene products.

Main Methods:

• Utilizing aluminum Lewis acids in combination with a chiral BINOL-derived ligand.
• Employing racemic tetrahydropyran (THP) substrates that undergo ring-opening to a prochiral enone intermediate.
• Facilitating a key 1,5-hydride shift within the reaction mechanism.

Main Results:

• The reaction successfully transforms racemic THP substrates into cyclohexene products with very high enantioselectivity (up to >98:2 e.r.).
• The developed method is operationally simple and scalable to gram quantities.
• The resulting cyclohexene products possess readily derivatizable functionality, demonstrated within the study.

Conclusions:

• The developed asymmetric intramolecular hydride shift is an efficient and highly enantioselective method.
• This reaction provides access to functionalized cyclohexenes with excellent stereochemical control.
• A mechanistic model, supported by DFT studies, explains the observed enantioselectivity.