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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Communications chemistry 2021-06, Vol.4 (1), p.81-81, Article 81
Hauptverfasser: Zhang, Haiman, Lin, Shuang, Gao, Hui, Zhang, Kaixin, Wang, Yi, Zhou, Zhi, Yi, Wei
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
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.
ISSN:2399-3669
2399-3669
DOI:10.1038/s42004-021-00518-x