| Affiliation: | 1. Pharmacy Department, Drug Design group, University of Groningen, Deusinglaan 1, 9713 AV, Groningen, The Netherlands These authors contributed equally to this work.;2. Pharmacy Department, Drug Design group, University of Groningen, Deusinglaan 1, 9713 AV, Groningen, The Netherlands;3. SSI “Institute for Single Crystals,”, National Academy of Science of Ukraine, 60 Lenina Ave., Kharkiv, 61001 Ukraine;4. Dispendix GmbH, Heßbrühlstraße 7, 70565 Stuttgart, Germany |
| Abstract: | 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. |
