Fast Alkene Functionalization In Vivo by Photoclick Chemistry: HOMO Lifting of Nitrile Imine Dipoles

Abstract

Extremely fast fluorescence labeling (<1 min) of a recombinant alkene-encoded protein in living Escherichia coli cells was observed with tetrazole 1. The electron-donating methoxy substituent raises the energy of the highest occupied molecular orbital of the nitrile-imine intermediate derived from 1. This strategy greatly accelerates the functionalization of alkenes by 1,3-dipolar cycloaddition in living systems.