Automated, Accelerated Nanoscale Synthesis of Iminopyrrolidines

Angelina Osipyan, Shabnam Shaabani, Robert Warmerdam, Svitlana V Shishkina, Harry Boltz, Alexander Dömling*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)12423-12427
JournalAngewandte Chemie (International ed. in English)
Issue number30
Early online date11-Feb-2020
Publication statusPublished - 20-Jul-2020

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