Bicyclo[1.1.1]pentane (BCP), the smallest bicyclic bridged carbon scaffold, has attracted growing attention as a molecular building block in recent years due to its particular chemical and physical properties and its potential to act as a bioisostere for different organic moieties in drug molecules. This stimulates a need for easy, versatile, and functional-group-tolerant synthetic strategies to modify the BCP skeleton. Herein, we present a methodology by which different BCP triazole building blocks can be synthesized from 1-azido-3-iodobicyclo[1.1.1]pentane and ethynyl-substituted precursors by Cu(I)-catalyzed 1,3-dipolar cycloaddition (“click”) reactions and integrated cycloaddition-Sonogashira coupling reactions. We obtained three different classes of substituted BCP derivatives: 1,4-disubstituted triazoles, 5-iodo-1,4,5-trisubstituted triazoles and 5-alkynylated 1,4,5-trisubstituted triazoles (Figure 1). A special focus was on appending chromophoric units to the BCP core. In this study, we expanded the scope of BCP derivatives accessible by cycloaddition reactions and produced building blocks with functional units and synthetic handles useful for further modification.

Investigation of the reactivity of 1-azido-3-iodobicyclo[1.1.1]pentane under “click” conditions

ACS Spring Meeting 2021

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