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

• Published in: European journal of organic chemistry Vol. 2017; no. 43; pp. 6450 - 6456
• Main Authors: Kokhan, Serhii O., Valter, Yevheniia B., Tymtsunik, Andriy V., Komarov, Igor V., Grygorenko, Oleksandr O.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 24.11.2017; Wiley Subscription Services, Inc
• Subjects: Alkynes; Azides; Cage compounds; Carboxylic acids; Chemical synthesis; Chemistry; Chemistry, Organic; Click chemistry; Combinatorial analysis; Homology; Imidazole; Nitrogen heterocycles; Pentanes; Physical Sciences; Propellane; Science & Technology; Substrates; Cage compounds; CUBANES; EXPEDIENT SYNTHESIS; BRIDGEHEAD; TINKERTOY CONSTRUCTION SET; RING-SYSTEM; AZIDE; RECEPTOR ANTAGONIST; MEDICINAL CHEMISTRY; Azides; Propellane; BIOORTHOGONAL REACTIONS; Nitrogen heterocycles; BIOCONJUGATION; Click chemistry; Alkynes
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201701296

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. Syntheses of mono‐ and bifunctional bicyclo[1.1.1]pentane‐derived azides and terminal alkynes – promising building blocks for medicinal, combinatorial, and bioconjugate chemistry – are described. The utility of the title products as substrates for copper‐catalysed click reactions is also demonstrated.