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Online HPLC Analysis of Buchwald-Hartwig Aminations from Within an Inert Environment

preprint
submitted on 17.08.2020 and posted on 18.08.2020 by Thomas C. Malig, Lars P. E. Yunker, Sebastian Steiner, Jason E. Hein
We have developed a reaction monitoring platform capable of automated sampling and online HPLC analysis to generate temporal profiles for reactions performed from within a glovebox. The device allows for facile reaction progress analysis to aid in mechanistic studies of air-sensitive chemical transformations. The platform has demonstrated high reproducibility regarding sample mixing, dilution, delivery, and analysis. We employed the sampling platform to acquire temporal profiles for a series of Buchwald-Hartwig aminations. Parallel coupling reactions using iodobenzene and bromobenzene both exhibit complex kinetics. A competition reaction including both aryl halides demonstrated high selectivity for iodobenzene indicative of catalyst monopoly. The temporal profile for the difunctionalized substrate 1,4-iodobromobenzene was unexpected based a priori and is indicative of a distinct underlying mechanism. We attribute this unanticipated reactivity to intramolecular catalysts transfer through the π system as seen in “living” polymerization transfer catalyst systems. This automated sampling platform has greatly increased mechanistic understanding by performing only a small subset of experiments.

Funding

CFI-35883

RCPIN-2016-04613

CRDPJ 530118-18

History

Email Address of Submitting Author

jhein@chem.ubc.ca

Institution

University of British Columbia

Country

Canada

ORCID For Submitting Author

0000-0002-4345-3005

Declaration of Conflict of Interest

The authors declare no competing financial interests.

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