A telescoped Knochel-Hauser/Kumada-Corriu coupling strategy to functionalized aromatic heterocycles. Issue 1 (3rd January 2019)

• Record Type: Journal Article
• Authors: Clagg, Kyle; Hold, Sara; Kumar, Archana; Koenig, Stefan G.; Angelaud, Remy
• Is Part Of: Tetrahedron letters. Volume 60:Issue 1(2019)
• Page Start: 5
• Page End: 7
• Publication Date: 2019-01-03
• Subjects: Kumada-Corriu cross-coupling -- Knochel-Hauser base -- CH functionalization -- Sustainability -- ReactIR; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2018.11.014
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: CH functionalization via Knochel-Hauser deprotonation under mild conditions. Telescoped Kumada-Corriu cross-coupling to variety of heterocycles. Exclusion of stoichiometric zinc salts (and transmetalation for Negishi coupling) Benign conditions: room temperature, common solvents, short reaction timeframe. Monitoring reaction progress by ReactIR to demonstrate straightforward methodology. Abstract: The direct application of Knochel-Hauser derivative arylmagnesium halides in Kumada-Corriu couplings is described. By utilizing the in situ-generated Grignard reagents, the transmetalation with stoichiometric zinc salts to known Negishi coupling conditions is avoided, thereby streamlining the transformation. Several aromatic hetereocycles participate in the deprotonation and couple with a variety of phenyl iodides and bromides in isolated yields up to 81%. The parent system is demonstrated on 6 g scale with 79% yield, and monitored via ReactIR to show the stability of the Grignard and progression of the deprotonation/CC coupling reaction.