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Flow Technology for Telescoped Generation, Lithiation and Electrophilic (C 3 ) Functionalization of Highly Strained 1‐Azabicyclo[1.1.0]butanes
Author(s) -
Musci Pantaleo,
Keutz Timo,
Belaj Ferdinand,
Degennaro Leonardo,
Cantillo David,
Kappe C. Oliver,
Luisi Renzo
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202014881
Subject(s) - electrophile , intramolecular force , context (archaeology) , reagent , chemistry , combinatorial chemistry , computer science , stereochemistry , organic chemistry , catalysis , paleontology , biology
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.