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

7 Citations (Scopus)
40 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)12423-12427
JournalAngewandte Chemie (International ed. in English)
Volume59
Issue number30
Early online date11-Feb-2020
DOIs
Publication statusPublished - 20-Jul-2020

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