Photochemical syntheses, transformations, and bioorthogonal chemistry of trans-cycloheptene and sila trans-cycloheptene Ag(i) complexesElectronic supplementary information (ESI) available: Full procedures, computational details and characterization data. CCDC 1583975 and 1583976. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc04773h

A photochemical synthesis of AgNO 3 complexes of trans -cycloheptene (TCH) and trans -1-sila-4-cycloheptene (Si-TCH) derivatives is described. A low temperature flow photoreactor was designed to enable the synthesis of carbocyclic TCH derivatives due to their thermal sensitivity in the absence of metal coordination. Unlike the free carbocycles, TCH·AgNO 3 complexes can be handled at rt and stored for weeks in the freezer (−18 °C). Si-TCH·AgNO 3 complexes are especially robust, and are bench stable for days at rt, and for months in the freezer. X-ray crystallography was used to characterize a Si-TCH·AgNO 3 complex for the first time. With decomplexation of AgNO 3 in situ , metal-free TCO and Si-TCH derivatives can engage in a range of cycloaddition reactions as well as dihydroxylation reactions. Computation was used to predict that Si-TCH would engage in bioorthogonal reactions that are more rapid than the most reactive trans -cyclooctenes. Metal-free Si-TCH derivatives were shown to display good stability in solution, and to engage in the fastest bioorthogonal reaction reported to date ( k 2 1.14 × 10 7 M −1 s −1 in 9 : 1 H 2 O : MeOH). Utility in bioorthogonal protein labeling in live cells is described, including labeling of GFP with an unnatural tetrazine-containing amino acid. The reactivity and specificity of the Si-TCH reagents with tetrazines in live mammalian cells was also evaluated using the HaloTag platform. The cell labeling experiments show that Si-TCH derivatives are best suited as probe molecules in the cellular environment. Synthesis and transformations of AgNO 3 complexes of trans -cycloheptene (TCH) and trans -1-sila-4-cycloheptene (Si-TCH) derivatives are described.