Bicyclo[1.1.1]pentane Embedded in Porphyrinoids

Abstract

We report a two-step approach to obtain synthetically versatile bicyclo[1.1.1]pentane (BCP) derivatives using Grignard reagents. This method allows the incorporation of BCP units in tetrapyrrolic macrocycles and the synthesis of a new class of calix[4]pyrrole analogues by replacing two bridging methylene groups with two BCP units. In addition, a doubly N-confused system was also formed in the presence of electron-withdrawing substituents at the BCP bridgeheads. The pyrrole rings in BCP containing macrocycles exist in 1,3-alternate or αβαβ conformations, as observed from single-crystal X-ray diffraction analyses and 2D NMR spectroscopy.

Bioisosteres are chemical moieties that can be substituted for common functional groups or linkages; for example, bicyclo[1.1.1]pentane offers a linear connection similar to para-phenylene, and this replacement can inhibit usual aggregation and metabolic inactivation in drugs.1 BCP derivatives are also used as liquid crystals, molecular rotors, and as spacer unit in chromophoric arrays.2 To meet the increased demand for BCPs in pharmaceutical and material sciences several research groups are developing synthetic protocols for novel BCP building blocks. Most BCP derivatives have been synthesized via ring opening of [1.1.1]propellane followed by multi-step chemical transformation to append functional groups at bridgehead positions.