Efficient regio- and stereoselective access to novel fluorinated β-aminocyclohexanecarboxylates

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Fluorine Chemistry

Background:

• Fluorinated compounds are crucial in pharmaceuticals and agrochemicals.
• Developing stereoselective fluorination methods is a key challenge in synthetic chemistry.
• Cyclohexanecarboxylic acid derivatives have diverse biological activities.

Purpose of the Study:

• To develop a novel regio- and stereoselective synthesis for 4-fluorinated 2-aminocyclohexanecarboxylic acid derivatives.
• To explore the utility of cis- and trans-β-aminocyclohex-4-enecarboxylic acids as starting materials.
• To establish a versatile method for introducing fluorine into the cyclohexane ring.

Main Methods:

• Synthesis initiated from cis- or trans-β-aminocyclohex-4-enecarboxylic acids.
• Regio- and stereoselective transformation of the C-C double bond via iodooxazine intermediate.
• Hydroxylation followed by hydroxy-fluorine or oxo-fluorine exchange reactions.

Main Results:

• Successful synthesis of novel fluorinated 2-aminocyclohexanecarboxylic acid derivatives.
• Demonstration of regio- and stereoselectivity in fluorine incorporation at position 4.
• Versatility shown using both cis- and trans- starting materials.

Conclusions:

• A robust and stereoselective method for synthesizing 4-fluorinated 2-aminocyclohexanecarboxylic acids has been established.
• This method provides access to valuable fluorinated building blocks for drug discovery.
• The developed strategy highlights efficient C-C double bond functionalization for fluorine introduction.