A deconstruction-reconstruction strategy for pyrimidine diversification.

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• Structure-activity relationship (SAR) studies are crucial for drug and agrochemical development.
• Limited synthetic strategies exist for nitrogen heteroaromatics common in small molecules.

Purpose of the Study:

• To present an alternative synthetic approach for generating diverse nitrogen heteroaromatics.
• To enable heterocycle formation on complex molecules that are difficult to synthesize via other methods.

Main Methods:

• Conversion of pyrimidine-containing compounds into N-arylpyrimidinium salts.
• Cleavage of N-arylpyrimidinium salts into a three-carbon iminoenamine building block.
• Utilizing the building block in various heterocycle-forming reactions.

Main Results:

• Demonstrated a deconstruction-reconstruction sequence to diversify pyrimidine cores.
• Successfully synthesized various heterocycles, including azoles.
• Enabled the formation of complex analogues challenging to obtain through conventional routes.

Conclusions:

• The presented deconstruction-reconstruction strategy offers a versatile method for nitrogen heteroaromatic synthesis.
• This approach expands access to diverse molecular scaffolds for drug discovery.
• The strategy is anticipated to be applicable to other heterocycle classes.