Functionalization at Will of Rim-Differentiated Pillar[5]arenes

Area of Science:

• Organic Chemistry
• Supramolecular Chemistry
• Macrocyclic Chemistry

Background:

• Pillar[5]arenes (P[5]s) are macrocyclic compounds with C5 symmetry.
• Achieving differential functionalization on the two rims of P[5]s is challenging.
• This limits their application in complex molecular architectures.

Purpose of the Study:

• To develop an efficient synthetic route for gram-scale production of C5-symmetric penta-hydroxy P[5] precursors.
• To demonstrate selective functionalization of either rim of the P[5] scaffold.
• To enable successive transformations of the macrocyclic structure.

Main Methods:

• Gram-scale synthesis of a C5-symmetric penta-hydroxy P[5] precursor.
• Selective functionalization of one rim using sulfur(VI) fluoride exchange (SuFEx) reactions, esterifications, or Suzuki-Miyaura coupling.
• Subsequent BBr3 demethylation to activate the second rim for further functionalization.

Main Results:

• Successful gram-scale synthesis of the penta-hydroxy P[5] precursor.
• High efficiency in selective rim functionalization via SuFEx, esterification, and Suzuki-Miyaura coupling.
• Demonstrated sequential functionalization capabilities of the pillararene scaffold.

Conclusions:

• An efficient and scalable method for producing rim-differentiated P[5]s has been established.
• The developed synthetic strategy allows for precise and sequential modification of the macrocyclic scaffold.
• This work provides a versatile platform for constructing complex pillararene-based molecules.