Chemodivergent assembly of ortho-functionalized phenols with tunable selectivity via rhodium(III)-catalyzed and solvent-controlled C-H activation
Ortho -functionalized phenols and their derivatives represent prominent structural motifs and building blocks in medicinal and synthetic chemistry. While numerous synthetic approaches exist, the development of atom-/step-economic and practical methods for the chemodivergent assembly of diverse ortho...
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Veröffentlicht in: | Communications chemistry 2021-06, Vol.4 (1), p.81-81, Article 81 |
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Hauptverfasser: | , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Ortho
-functionalized phenols and their derivatives represent prominent structural motifs and building blocks in medicinal and synthetic chemistry. While numerous synthetic approaches exist, the development of atom-/step-economic and practical methods for the chemodivergent assembly of diverse
ortho
-functionalized phenols based on fixed catalyst/substrates remains challenging. Here, by selectively controlling the reactivities of different sites in methylenecyclopropane core, Rh(III)-catalyzed redox-neutral and tunable C-H functionalizations of
N
-phenoxyacetamides are realized, providing access to both
ortho
-functionalized phenols bearing linear dienyl, cyclopropyl or allyl ether groups, and cyclic 3-ethylidene 2,3-dihydrobenzofuran frameworks under mild cross-coupling conditions. These divergent transformations feature broad substrate compatibility, synthetic applications and excellent site-/regio-/chemoselectivity. Experimental and computational mechanistic studies reveal that distinct catalytic modes involving selective β-C/β-H elimination, π-allylation, inter-/intramolecular nucleophilic substitution cascade and β-H’ elimination processes enabled by different solvent-mediated and coupling partner-controlled reaction conditions are crucial for achieving chemodivergence, among which a structurally distinct Rh(V) species derived from a five-membered rhodacycle is proposed as the corresponding active intermediates.
Ortho functionalisation of phenols can be achieved using N-phenoxy amide directing groups. Here a method for chemodivergent C-H alkenylation, alkylation, carboetherification, or [3 + 2] annulation is presented, with product selectivity determined by the choice of solvent. |
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ISSN: | 2399-3669 2399-3669 |
DOI: | 10.1038/s42004-021-00518-x |