Rapid Microwave Promoted Sonogashira Coupling Reactions on Solid Phase

Abstract

A microwave-enhanced, rapid, and efficient solid-phase version of the Sonogashira reaction is presented. It has been applied to the coupling of aryl iodides and bromides with various acetylene derivatives giving excellent yields in 15-25 min. The scopes of homogeneous, solventless, and solid-phase conditions for Sonogashira coupling of aryl halides are compared.

Controlled Microwave Heating in Modern Organic Synthesis

“…[36] As in solution-phase chemistry (see Sections 2.2 and 2.3), many transition-metal-catalyzed transformations have been conducted successfully on a solid phase by using microwaveassisted techniques. Examples include solid-phase Suzuki-, [213] Stille-, [213] and Sonogashira couplings, [214] Negishi reactions, [92] Mo-catalyzed allylic alkylations, [117] aminocarbonylations, [110] cyanation reactions, [215] trifluoromethanesulfonations, [82] Buchwald-Hartwig aminations, [216] and Cu-catalyzed Ullmann-type C-N arylations. [217] An interesting example of a transition-metal-mediated microwave-assisted SPOS involving either Cu II -or Pd IImediated cyclizations of 2-alkynylanilides to indoles has been studied by Dai et al (Scheme 45).…”

“…[223,224] Apart from traditional cross-linked polystyrene resins a number of different supports and formats have been used in microwave-assisted SPOS. These include tentagel resins, [117,213,214,225] cellulose membranes (SPOT synthesis), [226,227] cellulose beads, [228] and glass surfaces. [229] Janda and co-workers have described the use of JandaJel as the support in the solid-phase synthesis of oxazoles (Scheme 48).…”

2,3‐Disubstituted Benzo[b]thiophenes from Diarylalkynes via Electrophilic Addition‐Cyclization and Palladium‐Catalyzed Cross‐Coupling

“…Since the Sonogashira reaction has already been applied for the preparation of diarylalkynes in the solid phase [13] and recently we demonstrated the fruitful use of PhtNSCl in the substitution reaction on solid supported b-keto esters, [14] we envisaged to extend the above described methodology (see Scheme 2) using a carboxylic acidmodified Merrifield resin as starting material, as described in Scheme 3. The supported carboxylic acid was reacted with thionyl chloride followed by esterification with 4-iodophenol in the presence of DIPEA and a catalytic amount of DMAP.…”

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

“…Nachfolgend berichteten die Autoren über eine Festphasenvariante ihrer mikrowellenvermittelten Alkinylierung mit Arylhalogeniden, die an ein Polystyrolharz gebunden waren. [150] Pombo-Villar und Sørensen beschrieben eine kupferfreie direkte Kupplung von Phenyl(trimethylsilyl)acetylen an Aryl-und Heteroarylhalogenide zu Diarylacetylenen unter Mikrowellenbestrahlung (Tabelle 21). [151] Ohne Kupferpromotor schwankten die Ausbeuten je nach Substrat.…”