Synthesis and Characterization of the Azido‐Functionalized Ruthenocene Analogue [TpmRu( p ‐N 3 C 6 H 4 )Tp]Cl and Its Attachment to Biomolecules by Copper‐Catalyzed Azide–Alkyne Cycloaddition

The mixed‐ligand tris(pyrazolyl)borate sandwich compound [TpmRuTp′]Cl ( 2 ) was prepared by microwave‐assisted synthesis from Tp′Ru(COD)Cl ( 1 ) [Tp = tris(pyrazolyl)borate; Tp′ = p ‐bromophenyltris(pyrazolyl)borate; Tpm = tris(pyrazolyl)methane; COD = 1,4‐cyclooctadiene]. Subsequently, 2 was converted to the azide‐functionalized [TpmRu( p ‐N 3 C 6 H 4 Tp)] ( 3 ), which can be readily coupled to biomolecules by Cu‐catalyzed azide–alkyne cycloaddition (Cu‐AAC) in solution, as exemplified by the covalent attachment to pentyne‐functionalized HC(CH 2 ) 2 –CO–Val–O t Bu ( 4 ), and an alkyne derivative of the neuropeptide enkephaline HC(CH 2 ) 2 –CO–ENK–OH (ENK = enkephaline, Tyr–Gly–Gly–Phe–Leu). The resulting triazole compounds [TpmRu({ p ‐C 2 N 3 H–(CH 2 ) 2 –CO–Val–O t Bu}Tp)]Cl ( 5 ) and [TpmRu({ p ‐C 2 N 3 H–(CH 2 ) 2 –CO–ENK–OH}Tp)]Cl ( 6 ), represent the first [3+2] cycloaddition products of azide‐functionalized Tp compounds. They were characterized by NMR spectroscopy and mass spectrometry. Furthermore, 1 , 2 , and 3 as well as the reaction intermediate [(κ 2 ‐ N , N ′‐Tpm)RuCl(Tp′)] ( 2a ) were characterized in the solid state by single‐crystal X‐ray diffraction.