3.7. Palladium Nanoparticles as Catalysts 888 3.8. Other Transition-Metal Complexes 888 3.9. Transition-Metal-Free Reactions 889 4. Applications 889 4.1. Alkynylation of Arenes 889 4.2. Alkynylation of Heterocycles 891 4.3. Synthesis of Enynes and Enediynes 894 4.4. Synthesis of Ynones 896 4.5. Synthesis of Carbocyclic Systems 897 4.6. Synthesis of Heterocyclic Systems 898 4.7. Synthesis of Natural Products 903 4.8. Synthesis of Electronic and Electrooptical Molecules 906

https://www.chem.ccu.edu.tw/~joyce/referance/ericyang/Chem.%20Rev/Chem.%20Rev.%202007,%20107,%20874-922.pdf

The Sonogashira Reaction: A Booming Methodology in Synthetic Organic Chemistry†

Conjugated alkynes are recurring building blocks in natural products, a wide range of industrial intermediates, pharmaceuticals and agrochemicals, and molecular materials for optics and electronics. The palladium-catalyzed cross-coupling between sp2-hybridized carbon atoms of aryl, heteroaryl, and vinyl halides with sp-hybridized carbon atoms of terminal acetylenes is one of the most important developments in the field of alkyne chemistry over the past 50 years. The seminal work of the 1970s has initiated an intense search for more general and reliable reaction conditions. The interest in the catalytic activation of demanding substrates, the need to minimize the consumption of depletive resources, and the search for easy access to an increased variety of functionalized enynes has led to the current generations of high-turnover catalysts. This Review gives an overview of the highly efficient palladium catalyst systems for the direct alkynylation of C(sp2) halides with terminal alkynes, both in homogeneous and heterogeneous phases.

Palladium-based catalytic systems for the synthesis of conjugated enynes by Sonogashira reactions and related alkynylations

Recent Advances in Palladium‐Catalyzed Cross‐Coupling Reactions at ppm to ppb Molar Catalyst Loadings

Konjugierte Alkine sind stets wiederkehrende Synthesebausteine in Naturstoffen, zahlreichen unverzichtbaren industriellen Zwischenstufen, in Pharmazeutika und Agrochemikalien sowie in molekularen Materialien fur Optik und Elektronik. Daher zahlt die palladiumkatalysierte Verknupfung der sp2-hybridisierten Kohlenstoffatome von Aryl-, Heteroaryl- und Vinylhalogeniden mit den sp-hybridisierten Kohlenstoffatomen von terminalen Acetylenen in einer Kreuzkupplung unbestreitbar zu den bedeutendsten Entwicklungen der Alkinchemie in den vergangenen funfzig Jahren. Auf die grundlegenden Arbeiten der 1970er folgte eine intensive Suche nach allgemeineren und verlasslicheren Reaktionsbedingungen. Das Interesse an einer katalytischen Aktivierung anspruchsvoller Substrate, die unbedingte Notwendigkeit, den Ressourcenverbrauch zu minimieren, und die einfache Synthese einer stetig wachsenden Zahl an funktionalisierten Eninen fuhrte allmahlich zu den aktuellen Katalysatoren mit hohen Umsatzzahlen. Der vorliegende Aufsatz gibt einen Uberblick uber hoch wirksame Palladium-Katalysatorsysteme fur die direkte Alkinylierung von C(sp2)-Halogeniden mit terminalen Alkinen in homogener oder heterogener Phase.

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

Conjugated enynes have attracted considerable attention owing to their biological importance, their occurrence in various natural products, and their versatility as building blocks for the synthesis of organic conducting polymers. As a result, enormous effort has been devoted to the regioand stereoselective synthesis of conjugated enynes. Among the various methods developed in the past decades for the synthesis of enynes, the metal-catalyzed dimerization of terminal alkynes is a straightforward and atom-efficient approach (Scheme 1a, R = R’’, R’= H). However, the complicated regioand stereoselectivity of the dimerization process hampers the wide application of this method. Moreover, only in limited cases is the selective cross-coupling of two different alkynes possible. A solution to overcome this setback is the coupling of alkynes with structurally defined organometallic alkenes (Scheme 1b). However, organometallic substrates are usually difficult to handle and are toxic in general. The coupling of terminal alkynes with vinyl halides under the catalysis of palladium complexes and copper(I) iodide, namely, the Sonogashira reaction, is another option for the synthesis of conjugated enynes (Scheme 1c). This elegant process does not require a stoichiometric amount of an organometallic reagent and can produce enynes in a stereoselective manner. The major limitation of this method is that multiple steps are generally required for the preparation of the vinyl halide. In view of the limitations and shortcomings of these established methods, we conceived that it would be desirable to further develop a new type of coupling reaction that may circumvent these drawbacks. Palladium-catalyzed cross-coupling reactions involving diazo compounds as coupling partners have emerged as a new type of C=C bond-forming reaction. In pioneering studies, Van Vranken and co-workers demonstrated palladium-catalyzed coupling reactions with trimethylsilyldiazomethane. 8] Barluenga et al. first discovered a palladiumcatalyzed coupling reaction of N-tosylhydrazones with aryl bromides. We have also reported a series of palladiumcatalyzed cross-coupling reactions with a-diazocarbonyl compounds or N-tosylhydrazones as coupling partners. 14] Migratory insertion involving a palladium carbene is proposed to account for these cross-coupling reactions. Aryl, 10] benzyl, vinyl, allyl, and acyl groups have so far been used as the migratory group. As a continuation of our interest in palladium-catalyzed migratory-insertion reactions, we report the palladium-catalyzed cross-coupling of terminal alkynes with N-tosylhydrazones or diazoesters. The reaction involves an unprecedented alkynyl migratory insertion of a palladium carbene to afford conjugated enynes in a highly stereoselective manner (Scheme 1d). Initially, we chose phenylbromoethyne (2 a) as the crosscoupling partner and examined its reaction with the N-tosylhydrazone 1a in the presence of various palladium catalytic systems. However, none of the desired product was obtained. We then decided to explore an oxidative coupling process with a terminal alkyne. Li and co-workers reported a palladium-catalyzed 1,4-addition of terminal alkynes to C=C bonds in which the reactivity of the alkynyl C Pd bond could be increased by an electron-rich ligand. Enlightened by this report, we attempted the coupling of phenylacetylene (2b) Scheme 1. Synthesis of conjugated enynes. EWG =electron-withdrawing group, Ts = p-toluenesulfonyl.

Ludovic Chahen

Papers

Efficient synthesis of enynes by tetraphosphine–palladium-catalysed reaction of vinyl bromides with terminal alkynes

Suzuki Cross-Coupling Reactionof Benzylic Halides with Arylboronic Acids in the Presence of aTetraphosphine/Palladium Catalyst

Efficient Synthesis of Enynes by Tetraphosphine—Palladium‐Catalyzed Reaction of Vinyl Bromides with Terminal Alkynes.