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Photoredox Iridium-Nickel Dual Catalyzed Decarboxylative Arylation Cross-Coupling: From Batch to Continuous Flow via Self-Optimizing Segmented Flow Reactor

Hsieh, Hsiao-Wu and Robinson, Richard and Coley, Connor and Jensen, Klavs and Baumgartner, Lorenz (2018) Photoredox Iridium-Nickel Dual Catalyzed Decarboxylative Arylation Cross-Coupling: From Batch to Continuous Flow via Self-Optimizing Segmented Flow Reactor. Organic process research & development, 22 (4). pp. 542-550. ISSN 1520-586X; 1083-6160

Abstract

Photoredox decarboxylative arylation cross-coupling via Iridium-Nickel dual catalysis has emerged as a valuable method for Csp2—Csp3 bond formation and the demand for finding scalable continuous flow conditions is high. Herein, we describe the application of the segmented flow (“microslug”) reactor equipped with a newly designed photochemistry module for material-efficient reaction screening and optimization. The study utilized Cbz-protected proline and 4’-bromoacetophenone as the model substrates to validate the chemistry on the fully automated system. Through the deployment of a self-optimizing algorithm, we were able to develop optimal flow conditions for the model reaction, simultaneously accounting for the effects of continuous variables (temperature and time), and discrete variables (base and catalyst). The optimized conditions identified at microscale were found to directly transfer to Vapourtec® UV-150 continuous flow photoreactor, enabling predictable scale-up operation at hundreds of milligrams per hour scale. This optimization approach was expanded to other halide coupling partners that were low-yielding in batch reactions, highlighting the practical application of this optimization platform when developing conditions for photochemical synthesis in continuous flow.

Item Type: Article
Keywords: Flow photochemistry, droplet microfluidics, micro-reactor, photoredox cross-coupling, process development, reaction optimization, self optimizing reactor
Date Deposited: 09 May 2018 00:45
Last Modified: 09 May 2018 00:45
URI: https://oak.novartis.com/id/eprint/35056

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