Premium
Automated, Accelerated Nanoscale Synthesis of Iminopyrrolidines
Author(s) -
Osipyan Angelina,
Shaabani Shabnam,
Warmerdam Robert,
Shishkina Svitlana V.,
Boltz Harry,
Dömling Alexander
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202000887
Subject(s) - isocyanide , chemistry , ugi reaction , combinatorial chemistry , nanotechnology , miniaturization , nanoscopic scale , organic chemistry , materials science
Miniaturization and acceleration of synthetic chemistry is an emerging area in pharmaceutical, agrochemical, and materials research and development. Herein, we describe the synthesis of iminopyrrolidine‐2‐carboxylic acid derivatives using chiral glutamine, oxo components, and isocyanide building blocks in an unprecedented Ugi‐3‐component reaction. We used I‐DOT, a positive‐pressure‐based low‐volume and non‐contact dispensing technology to prepare more than 1000 different derivatives in a fully automated fashion. In general, the reaction is stereoselective, proceeds in good yields, and tolerates a wide variety of functional groups. We exemplify a pipeline of fast and efficient nanomole‐scale scouting to millimole‐scale synthesis for the discovery of a useful novel reaction with great scope.