Carbene organic catalytic planar enantioselective macrolactonization

Area of Science:

• Organic Chemistry
• Catalysis
• Stereochemistry

Background:

• Macrolactones are crucial in natural products, medicines, and agrochemicals.
• Current macrolactonization methods focus on coupling reagents and substrate chirality for stereocontrol.
• Catalytic control over both macrolactone formation and stereochemistry remains underexplored.

Purpose of the Study:

• To develop a non-enzymatic organocatalytic strategy for constructing macrolactones with planar chirality from achiral precursors.
• To utilize N-heterocyclic carbene (NHC) catalysts for simultaneous macrocyclization and stereochemical control.

Main Methods:

• Employed N-heterocyclic carbene (NHC) as an acylation catalyst.
• Developed a catalytic system for non-enzymatic macrolactonization.
• Utilized achiral substrates to generate macrolactones with planar chirality.

Main Results:

• Successfully synthesized macrolactones with ring sizes from sixteen to twenty members.
• Achieved good-to-excellent yields and enantiomeric ratios for the macrolactone products.
• Demonstrated simultaneous control over macrocyclization and planar chirality induction.

Conclusions:

• This work presents a novel NHC-catalyzed organocatalytic approach for macrolactone synthesis.
• The method enables the creation of macrolactones with planar chirality from achiral starting materials.
• Opens new possibilities for synthesizing diverse macrolactones with various stereogenic elements using small-molecule catalysts.