Programmable arene ring opening unlocks the diversification of phenols.

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Materials Science

Background:

• Aromatic systems, particularly phenols, possess stable carbon-carbon bonds hindering direct functionalization.
• Existing methods for arene modification (enzymatic, energy-intensive) offer limited control and diversity.
• Controlled ring-opening of phenols to access skeletal and functional group diversity remains a significant synthetic challenge.

Purpose of the Study:

• To develop an efficient and operationally simple strategy for cleaving phenolic arene rings.
• To convert phenols into diverse acyclic N-containing products and N-heterocycles.
• To demonstrate the utility of this method in late-stage modifications and materials development.

Main Methods:

• A novel nitrogenation strategy was employed to cleave phenolic arene rings.
• The reaction converts phenols into acyclic N-containing compounds such as cyanopenta-dienoates, cyanopenta-dienamides, and cyanopenta-dienoic acids.
• Scaffold hopping of arene rings was achieved, yielding various N-heterocycles.

Main Results:

• The nitrogenation strategy efficiently cleaves phenolic arene rings under mild conditions.
• A range of uniquely structured acyclic N-containing products were synthesized.
• The method successfully generated five-, six-, and seven-membered N-heterocycles through scaffold hopping.
• Broad utility was demonstrated in late-stage modification of bioactive molecules and skeletal remodeling of phenolic feedstocks.
• Ring-opening products found applications in polymer development.

Conclusions:

• The developed nitrogenation strategy provides a programmable approach to diversify phenolic feedstocks.
• This method unlocks access to underexplored chemical space, offering significant potential for synthetic chemistry.
• The transformation of phenols into versatile N-containing scaffolds opens new avenues in materials science and drug discovery.