Flow Technology for Telescoped Generation, Lithiation and Electrophilic (C3) Functionalization of Highly Strained 1‐Azabicyclo[1.1.0]butanes

Strained compounds are privileged moieties in modern synthesis. In this context, 1‐azabicyclo[1.1.0]butanes are appealing structural motifs that can be employed as click reagents or precursors to azetidines. We herein report the first telescoped continuous flow protocol for the generation, lithiation, and electrophilic trapping of 1‐azabicyclo[1.1.0]butanes. The flow method allows for exquisite control of the reaction parameters, and the process operates at higher temperatures and safer conditions with respect to batch mode. The efficiency of this intramolecular cyclization/C3‐lithiation/electrophilic quenching flow sequence is documented with more than 20 examples. Strained….in Flow! The first telescoped continuous flow protocol for the generation, lithiation, and electrophilic trapping of 1‐azabicyclo[1.1.0]butane is reported. Several structurally unique C3‐functionalized 1‐azabicyclo[1.1.0]butanes were prepared using this strategy starting from readily available starting materials.