Expeditious and scalable preparation of a Li−Thiele reagent for amine-based bioconjugation

ABSTRACT Chemoselective amine bioconjugation has long been a challenge for native protein modification. Inspired by Thiele’s seminal discovery, Li and co-workers recently developed an ortho-phthalaldehyde (OPA) based reagent for labeling the amino group of a protein. Here we report an expeditious and scalable synthesis of a Li − Thiele reagent featuring an arene construction strategy. The reagent contains an alkyne side chain as a handle for secondary modification.