3-(([1,1′-Biphenyl]-4-ylmethyl)thio)-6-methyl-1,2,4,5-tetrazine (b-Tz) is a minimal tetrazine derivative capable of undergoing [4+2] Diels-Alder cycloaddition reactions with strained alkenes, which makes it highly useful in bioorthogonal labeling and cell detection applications. Tetrazines are often incorporated into chemical probes or other small-molecule tools using linkers that may impact physicochemical properties or the performance of the resulting conjugate product. Here, Lambert et al demonstrated the linker-free incorporation of b-Tz via silver-mediated Liebeskind-Srogl cross-coupling with a variety of aryl and heteroaryl boronic acids. This ″minimal″ tetrazine approach will facilitate the introduction of tetrazine into diverse complex molecules and improved probes for live-cell imaging and in vivo chemistry.

Supporting products
PdCl₂(dppf): 697230
Ag₂O: 226831