Double Cu-Catalyzed Direct Csp3 -H Azidation/CuAAC Reaction: A Direct Approach towards Demanding Triazole Conjugates.
Tobias BrandhoferAysegül ÖzdemirAndrea GiniOlga García MancheñoPublished in: Chemistry (Weinheim an der Bergstrasse, Germany) (2019)
The first one-pot procedure for the double copper(I)-catalyzed oxidative Csp3 -H azidation-CuAAC process, implying unstable azide intermediates and easy-to-remove reagents under water-tolerant conditions, is presented. The combination of tert-butyl hydroperoxide as oxidant and TMSN3 as azide source for the C-H bond azidation, which produces harmless side-products such as tBuOH and H2 O, probed to be perfectly compatible with the following cycloaddition step. Highly demanding 1,2,3-triazoles could be then directly obtained in good overall yields by extraction or simple crystallization, thus avoiding chromatography purifications. The potential of this methodology, has also being highlighted by the successful reaction of alkynes presenting interesting complex biological moieties based for example on biotin, DNA base or cinchona alkaloid units.
Keyphrases
- room temperature
- mass spectrometry
- electron transfer
- circulating tumor
- high speed
- minimally invasive
- cell free
- single molecule
- liquid chromatography
- tandem mass spectrometry
- molecular dynamics simulations
- high performance liquid chromatography
- cancer therapy
- anti inflammatory
- high resolution
- risk assessment
- aqueous solution
- transition metal