One-Pot C–N/C–C Cross-Coupling of Methyliminodiacetic Acid Boronyl Arenes Enabled by Protective Enolization

Grob, Jonathan E.; Dechantsreiter, Michael A.; Tichkule, Ritesh; Connolly, MJ; Honda, Ayako; Tomlinson, Ronald; Hamann, Lawrence G.

doi:10.1021/ol302702q

Cited by 32 publications

(21 citation statements)

References 38 publications

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“…Hamann and coworkers have pioneered a strategy that selectively protects MIDA boronates in situ through enolization with LiHMDS at low temperatures. 180 This more robust Li-MIDA enolate enabled the authors to perform an efficient one-pot ICC synthesis of the histamine H3 agonist through iterative C-N then C-C coupling reactions (Figure 7d). This Li-MIDA enolate strategy may have applications beyond C-N coupling where strong base causes loss/cleavage of the MIDA protecting group.…”

Section: Iterative Cross-coupling With Mida Boronatesmentioning

confidence: 99%

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Towards the generalized iterative synthesis of small molecules

2018

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Small molecules have extensive untapped potential to benefit society, but access to this potential is too often restricted by limitations inherent to the customized approach currently used to synthesize this class of chemical matter. In contrast, the “building block approach”, i.e., generalized iterative assembly of interchangeable parts, has now proven to be a highly efficient and flexible way to construct things ranging all the way from skyscrapers to macromolecules to artificial intelligence algorithms. The structural redundancy found in many small molecules suggests that they possess a similar capacity for generalized building block-based construction. It is also encouraging that many customized iterative synthesis methods have been developed that improve access to specific classes of small molecules. There has also been substantial recent progress toward the iterative assembly of many different types of small molecules, including complex natural products, pharmaceuticals, biological probes, and materials, using common building blocks and coupling chemistry. Collectively, these advances suggest that a generalized building block approach for small molecule synthesis may be within reach.

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Section: Iterative Cross-coupling With Mida Boronatesmentioning

confidence: 99%

“…4–5 MIDA boronates have been employed independent of iteration on a wide range of other small molecule synthesis applications as well. 140–141, 143, 150, 180, 186–193 …”

Section: Iterative Cross-coupling With Mida Boronatesmentioning

confidence: 99%

Towards the generalized iterative synthesis of small molecules

2018

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“…By virtue of an sp The scope of MIDA boronates as protecting groups has been underlined in other related coupling reactions e.g. Negishi, Heck, Sonogashira, Stille and Buchwald-Hartwig amination, [6][7][8][9][10] as well as in various functional group interconversions on arenes. Examples of the latter include oxidations under Jones or Swern conditions or cycloisomerization of arylethynyl MIDA boronates.…”

Section: Introductionmentioning

confidence: 99%

Microwave-mediated synthesis of N-methyliminodiacetic acid (MIDA) boronates

Kemmitt

Emmerson

et al. 2014

Tetrahedron

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(2014) Microwavemediated synthesis of N-methyliminodiacetic acid (MIDA) boronates. Tetrahedron, 70 (47). pp. [9125][9126][9127][9128][9129][9130][9131] This version is available from Sussex Research Online: http://sro.sussex.ac.uk/53847/ This document is made available in accordance with publisher policies and may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the URL above for details on accessing the published version. Copyright and reuse:Sussex Research Online is a digital repository of the research output of the University.Copyright and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable, the material made available in SRO has been checked for eligibility before being made available.Copies of full text items generally can be reproduced, displayed or performed and given to third parties in any format or medium for personal research or study, educational, or not-for-profit purposes without prior permission or charge, provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. ABSTRACT: A library of over twenty, mainly aryl or heteroaryl, N-methyliminodiacetic acid (MIDA) boronates has been synthesized. A rapid microwave-mediated (MW) method (5-10 mins) has been developed using polyethylene glycol 300 (PEG 300) as solvent. However, acetonitrile (MeCN) and dimethylformamide (DMF) were found to be alternative solvents, the latter especially for 2-substituted aryl boronic acids.

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“…The stability of MIDA boronates towards many reaction conditions (26, 27) and the synthetic versatility of boronic acids (28) allowed us to add carbon-heteroatom bond formations to the same platform. The synthesizer successfully executed a series of automated carbon-heteroatom bond formation, including a Buchwald-Hartwig amination, O-alkylation, and amide bond formations (Table S3).…”

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Synthesis of many different types of organic small molecules using one automated process

Ballmer

Gillis

et al. 2015

Science

482

370

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Small molecule synthesis usually relies on procedures highly customized for each target. A broadly applicable automated process could greatly increase the accessibility of this class of compounds to enable investigations of their practical potential. Here we report the synthesis of 14 distinct classes of small molecules using the same fully automated process. This was achieved by strategically expanding the scope of a building block-based synthesis platform to include even Csp3-rich polycyclic natural product frameworks and discovering a catch-and-release chromatographic purification protocol applicable to all of the corresponding intermediates. With thousands of compatible building blocks already commercially available, many small molecules are now accessible with this platform. More broadly, these findings illuminate an actionable roadmap to a more general and automated approach for small molecule synthesis.

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One-Pot C–N/C–C Cross-Coupling of Methyliminodiacetic Acid Boronyl Arenes Enabled by Protective Enolization

Cited by 32 publications

References 38 publications

Towards the generalized iterative synthesis of small molecules

Towards the generalized iterative synthesis of small molecules

Microwave-mediated synthesis of N-methyliminodiacetic acid (MIDA) boronates

Synthesis of many different types of organic small molecules using one automated process

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