Abstract
A strategy for the β-sp3 functionalisation of cyclic amines is described. Regioselective conversion of protected amines to enecarbamates is achieved through electrochemical oxidation; these intermediates can be derivatised by functionalised alkyl halides under photoredox catalysis. The potential of the methods is highlighted by direct growth of a DCP2B-binding fragment.
Highlights
A strategy for the b-sp[3] functionalisation of cyclic amines is described
Regioselective conversion of protected amines to enecarbamates is achieved through electrochemical oxidation; these intermediates can be derivatised by functionalised alkyl halides under photoredox catalysis
Fragments are typically smaller molecules than those used in high-throughput screening, meaning they explore chemical space more efficiently and, while the absolute potency of hit molecules is generally low, they bind their targets with high ligand efficiency
Summary
Regioselective conversion of protected amines to enecarbamates is achieved through electrochemical oxidation; these intermediates can be derivatised by functionalised alkyl halides under photoredox catalysis. Many methods have been developed for direct functionalization of saturated cyclic amines a-to nitrogen[9] and a recent report describes a-amino radical generation/Minisci heteroarylation as a means of selective a-functionalisation of protected cyclic amines in the context of fragment growth.[10] By contrast, methods for the b- and g-functionalisation of cyclic amines are much less common,[11] meaning fragment growth along these vectors would likely fall back upon scaffold re-synthesis.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
