1,2-Difunctionalized bicyclo[1.1.1]pentanes: Long-sought-after mimetics for ortho/ meta-substituted arenes

The development of a versatile platform for the synthesis of 1,2difunctionalized bicyclo[1.1.1]pentanes to potentially mimic ortho/ meta-substituted arenes is described. The syntheses of useful building blocks bearing alcohol, amine, and carboxylic acid functional handles have been achieved from a simple common intermediate. Several ortho- and meta-substituted benzene analogs, as well as simple molecular matched pairs, have also been prepared using this platform. The results of in-depth ADME (absorption, distribution, metabolism, and excretion) investigations of these systems are presented, as well as computational studies which validate the orthoor meta-character of these bioisosteres.

Automated summary

This paper describes a new method for synthesizing 1,2difunctionalized bicyclo[1.1.1]pentanes that potentially mimic ortho/meta-substituted arenes, and successfully synthesizes useful building blocks. Additionally, it can prepare various substituted benzene analogs and simple molecular matched pairs.