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Hoff_et_al_ChemRXiv.pdf (8.99 MB)

Cross-coupling Reactions of Monosubstituted Tetrazines

preprint
submitted on 07.05.2021, 11:13 and posted on 12.05.2021, 13:01 by Lukas Hoff, Simon Schnell, Andrea Tomio, Anthony Linden, Karl Gademann

A fast and mild method for the Pd-catalyzed cross-coupling reaction of monosubstituted 3-bromo-1,2,4,5-tetrazine is presented. Investigation of silver-based additives revealed that Ag2CO3 is the optimal mediator, enabling the process without the need for strong bases or high temperatures. Electronic modification of the classical 1,1′- bis(diphenylphosphine)ferrocene (dppf) ligand proved to be a powerful strategy in tailoring the catalytic system to the requirements set by the process. Under the optimized conditions a scope comprising a variety of alkyl-, heteroatom-, and halide substituted aryl- and heteroaryl-tetrazines were prepared in good to excellent yields (29 examples, up to 87% yield). This method constitutes the first example of a direct cross-coupling reaction of monosubstituted tetrazines.

History

Email Address of Submitting Author

karl.gademann@uzh.ch

Institution

University of Zurich

Country

Switzerland

ORCID For Submitting Author

0000-0003-3053-0689

Declaration of Conflict of Interest

None