Bicyclo[1.1.1]pentane-Derived Building Blocks for Click Chemistry

Syntheses of bicyclo[1.1.1]pentane-derived azides and terminal alkynes - interesting substrates for click reactions - are described. With a few exceptions, these compounds were prepared in two or three steps starting from common synthetic intermediates - the corresponding carboxylic acids. The key step in the synthesis of 1-azidobicyclo[1.1.1]pentanes is a copper-catalysed diazo-transfer reaction with imidazole-1-sulfonyl azide. The preparation of bicyclo[1.1.1]pentyl-substituted alkynes relies on a Seyferth-Gilbert homologation with dimethyl 1-diazo-2-oxopropylphosphonate (Ohira-Bestmann reagent). Both types of target compounds were found to be suitable substrates for click reactions, and thus they are promising building blocks for medicinal, combinatorial and bioconjugate chemistry. A practically important side result of this study was a multigram preparation of Boc-monoprotected 1,3-diaminobicyclo[1.1.1]pentane - a representative bicyclic conformationally restricted diamine derivative.