One-pot Pd/C catalysed ‘domino’ HALEX and Sonogashira reactions: a ligand- and Cu-free alternative

Abstract

The advantages of combining heterogeneous catalysis and aryl chloride substrates for cross-coupling are introduced. A heterogeneous Pd/C catalyst is used for activating aryl bromides and electron withdrawing aryl chlorides via a one-pot 'domino' HALEX-Sonogashira reaction. No ligand or co-catalyst is required, and the cross-coupling products are obtained in moderate to good yields. The influence of the solvent, base, iodide source and catalyst is evaluated. The catalyst is reusable for at least six consecutive reaction cycles. A variation on this reaction using catalytic amounts of KI is also proposed.

Metal-catalysed halogen exchange reactions of aryl halides

“…11 In a recent report, Pd/C was used to catalyse the formation of aryl iodides from a limited range of aryl chlorides and sodium iodide in DMF at 130°C (Scheme 16). 45 This procedure was then applied to a direct one-pot Sonigashira coupling reaction 35 of aryl chlorides, which was demonstrated to proceed via the intermediate aryl iodide. Unfortunately, this convenient procedure for halogen exchange was only applicable to electron-deficient aryl chlorides.…”

“…This offers the advantage that the fluorine atom can be introduced into any 40 position which has been functionalised with a boronic acid, rather than requiring the presence of an adjacent directing group. This Pd (II)/Pd (IV) approach could potentially be adapted to a general halogen exchange protocol, if suitable conditions 45 could be developed to initiate a catalytic cycle (Scheme 20), although this would be a somewhat ambitious undertaking. Thus, oxidative addition of the starting halide ArX to Pd(0) 50 would give complex 93 after halogen exchange.…”

“…Substitution via an S N Ar mechanism is possible on electron deficient compounds, and this is an 45 important method for the preparation of aryl fluorides [4][5][6][7] (Scheme 2, 13). However, a general transformation has yet to be developed for aromatic halogen exchange.…”

“…Clearly the reductive elimination of aryl fluorides is not a straightforward process, 40 as can be seen from the many studies of arylpalladium fluorides, and this step may well prevent any nickel or palladium mediated process from being developed. The fact that a copper (I) fluoride complex has been succesfully used in one case, suggests that suitable conditions may be found for 45 a more general copper-mediated fluorination of other aryl halides, and this area certainly merits futher investigation.…”

Palladium‐Katalysatorsysteme für die Synthese von konjugierten Eninen durch Sonogashira‐Kupplungen und verwandte Alkinylierungen

“…Eine Innovation war die Anwendung kupferfreier Pd/CKatalysatorsysteme zur Aktivierung von Arylbromiden und elektronenarmen Arylchloriden über ein zweistufiges Verfahren aus einem Halogenaustausch und anschließender Alkinylierung mit Phenylacetylen (Schema 54). [133] Bei der Kupplung von 4-Cyanchlorbenzol an Phenylacetylen durchlief der Pd/C-Katalysator fünf Wiederverwendungszyklen. Versuche, den Halogenaustauschschritt mit KI zu katalysieren, blieben erfolglos.…”