Palladium-catalysed cross-coupling of lithium acetylides

Alkali‐Metal Mediation: Diversity of Applications in Main‐Group Organometallic Chemistry

“…They are masters of a diverse range of metal-mediated reactions, for example, operating as bases in metallation reactions, as nucleophiles in addition reactions to unsaturated molecules, as metal-halide exchange agents in metathesis reactions with organic halides, as ligand-transfer agents in transmetallation reactions with main-group, transition-metal, and lanthanide/actinide compounds, or as cross-coupling partners in Pd catalysis. [2] The mediation tag stems from the action of the organolithium intermediates in these reactions, which make possible onward reactivity towards the desired organic products or organometallic compounds of other metals. By contrast, the other common alkali metals sodium and potassium have contributed to a much lesser degree to this conventional alkali-metal mediation chemistry, although, interestingly, Wanklyn started investigations on organosodium and organopotassium compounds almost half a century before organolithium reagents revolutionized organometallic chemistry.…”

Alkalimetall‐Mediatoren: Vielfältige Anwendungen in der metallorganischen Chemie der Hauptgruppenelemente

“…Durch die Vielzahl ihrer Anwendungen gelten sie als Meister der Metall-Mediation;s ow erden sie zum Beispiel als Basen in Metallierungsreaktionen, als Nukleophile fürA dditionen an ungesättigten Molekülen, als Metall-Halogen-Austauschreagenz in Metathese-Reaktionen mit Organohalogeniden, zum Übertragen von Liganden in Tr ansmetallierungen mit Hauptgruppen-, Übergangsmetall-und Lanthanoid/Actinoid-Verbindungen oder auch als Kupplungspartner in der Palladiumkatalyse genutzt. [2] Der Begriff Mediation beschreibt die Aufgabe der Lithiumintermediate in diesen Reaktionen, nämlich die Weiterreaktion zu den gewünschten organischen oder metallorganischen Verbindungen zu ermçglichen. Im Gegensatz dazu haben die anderen gängigen Alkalimetalle Natrium und Kalium in viel geringerem Maße zu dieser konventionellen Alkalimetall-Mediationschemie beigetragen, obwohl Wanklyn fast ein halbes Jahrhundert vor der Revolutionierung der metallorganischen Chemie durch Organolithiumreagenzien Untersuchungen zu Organonatriumund Organokaliumverbindungen unternommen hatte.D ie allgemein geringe Stabilitätu nd Lçslichkeit dieser Verbindungen erschwerten jedoch ihre Anwendung.…”

Pd-catalyzed sp–sp3 cross-coupling of benzyl bromides using lithium acetylides

“… 19 Recently, we reported a Sonogashira coupling employing lithium acetylides. 20 These reactions proceed at room temperature within 45 min, and display a remarkable functional group tolerance, including organolithium-sensitive functional groups such as esters, nitriles and boronic esters. Having demonstrated the cross-coupling of lithium acetylides with aryl bromides, we envisioned the development of fast and selective methodology for the functionalization of benzyl bromides ( Scheme 1 ).…”

“…Next the screening of a series of different Pd-catalysts and varying the addition time of the lithium acetylide 2a ( Table 1 ) was pursued. Satisfyingly, the use of 5 mol% of oxygen-activated Pd[P( t Bu 3 )] 2 , 14 a catalyst we previously disclosed to be effective for the Sonogashira-type cross-coupling of lithium acetylides with aryl bromides, 20 resulted in 98% conversion into the desired product 3 (entry 1). Lowering the addition time from 30 to 15 min retained quantitative conversion, albeit with slightly lower selectivity (95%, entry 2).…”

“…We also examined the reactions of benzyl bromides bearing both C(sp 2 )- and C(sp 3 )-bromides, as we previously observed that [Pd( μ -I)P t Bu 3 ] 2 is also an effective catalyst for the cross-coupling of lithium acetylides with aryl bromides. 20 We were pleased to obtain the double coupling products 25–27 in 48–52% yield. These products are highly versatile synthons due to their application in various cycloaddition and cyclisation reactions.…”