Temperature‐Controlled Diene Cyclization Toward Trifluoromethyl Biphenyl Derivatives: Synthetic and Computational Study

Varga, Bálint and Jaradat, Khaled T. and Polyák, Martin and Kele‐Jókuthy, János and Herczegh, Attila and Kotschy, András and Novák, Zoltán and Daru, János (2026) Temperature‐Controlled Diene Cyclization Toward Trifluoromethyl Biphenyl Derivatives: Synthetic and Computational Study. CHEMCATCHEM, 18. No. e71064. ISSN 1867-3880 (print); 1867-3899 (online)

Preview

Text ChemCatChem - 2026 - Varga - Temperature‐Controlled Diene Cyclization Toward Trifluoromethyl Biphenyl Derivatives .pdf - Published Version Available under License Creative Commons Attribution. Download (1MB) | Preview

Abstract

A temperature-controlled palladium-catalyzed cyclization of polyfluorinated dienes provides direct access to both functionalized 1,3,5-conjugated trienes and trifluoromethylated biphenyls. These dienes are readily accessible via Heck coupling of fluorinated vinyl iodides prepared through atom transfer radical addition (ATRA) of hydrofluoroolefins (HFOs). At elevated temperatures, the dienes undergo transformation into trifluoromethylated biphenyl derivatives—a pathway not previously described. Detailed mechanistic investigation, including intermediate isolation, 19F NMR monitoring, and computational studies, suggests a sequence involving β-fluoro elimination to a triene intermediate, followed by electrocyclization and aromatization. Experimental data support that the triene intermediate cyclizes through a free triene pathway, though the palladium-mediated triene cyclization remains possible. Control experiments confirm that phosphine ligands play a dual role as both stabilizing ligands and reductants. The reaction can be tuned by modulating temperature and reductant conditions, enabling stepwise access to either diene or biphenyl products. This dual-stage Pd-mediated transformation expands the synthetic utility of fluorinated building blocks and offers new opportunities in designing functionalized aromatic frameworks via in situ generated triene intermediates.

Actions (login required)

View Item