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.
A convenient approach to 1,3-bifunctional sulfonyl fluorides, sulfonamides and sulfinates bearing a bicyclo-[1.1.1]pentane unit attached to the sulfur atom and (protected) amino or carboxyl group is described. The method relied on photochemical decomposition of Barton [1-hydroxypyridine-2(1H)-thione] esters of the corresponding carboxylic acids as [a] Taras
The idea of introducing (cyclo)alkyl substituents at the C-3 atom of the piperidine ring, that is, formal sp 3 -sp 3 retrosynthetic disconnection, is implemented through a two-step reaction sequence including directed ortho metalation of a pyridine derivative and the subsequent quenching with a carbonyl compound, followed by catalytic hydrogenation. This robust but very efficient method allows for multigram preparation of sp 3 -rich 3-(cyclo)alkylpiperidines, which are valuable building blocks for medicinal chemistry and other areas.
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