As part of the dramatic changes associated with the need for preparing compound libraries in pharmaceutical and agrochemical research laboratories, industry searches for new technologies that allow for the automation of synthetic processes. Since the pioneering work by Merrifield polymeric supports have been identified to play a key role in this field however, polymer-assisted solution-phase synthesis which utilizes immobilized reagents and catalysts has only recently begun to flourish. Polymer-assisted solution-phase synthesis has various advantages over conventional solution-phase chemistry, such as the ease of separation of the supported species from a reaction mixture by filtration and washing, the opportunity to use an excess of the reagent to force the reaction to completion without causing workup problems, and the adaptability to continuous-flow processes. Various strategies for employing functionalized polymers stoichiometrically have been developed. Apart from reagents that are covalently or ionically attached to the polymeric backbone and which are released into solution in the presence of a suitable substrate, scavenger reagents play an increasingly important role in purifying reaction mixtures. Employing functionalized polymers in solution-phase synthesis has been shown to be extremely useful in automated parallel synthesis and multistep sequences. So far, compound libraries containing as many as 88 members have been generated by using several polymer-bound reagents one after another. Furthermore, it has been demonstrated that complex natural products like the alkaloids (+/-)-oxomaritidine and (+/-)-epimaritidine can be prepared by a sequence of five and six consecutive polymer-assisted steps, respectively, and the potent analgesic compound (+/-)-epibatidine in twelve linear steps ten of which are based on functionalized polymers. These developments reveal the great future prospects of polymer-assisted solution-phase synthesis.

Abstractα-Amino acid thiol esters derived from N-protected mono-, di-, and tripeptides couple with aryl, π-electron-rich heteroaryl, or alkenyl boronic acids in the presence of stoichiometric Cu(I) thiophene-2-carboxylate (CuTC) and catalytic Pd 2 (dba) 3 /triethylphosphite to generate the corresponding Nprotected peptidyl ketones in good to excellent yields and in high enantiopurity. Triethylphosphite plays a key role as a supporting ligand by mitigating an undesired palladium-catalyzed decarbonylation-β-elimination of the α-amino thiol esters. The peptidyl ketone synthesis proceeds at room temperature under non-basic conditions and demonstrates a high tolerance to functionality.

[reaction: see text] A versatile approach to ketone synthesis is described. The reaction relies on the palladium-catalyzed, copper diphenylphosphinate-mediated coupling of thiol esters with organostannanes under neutral reaction conditions. This reaction complements the previously described coupling of thiol esters with boronic acids that used dual thiophilic-borophilic activation methodology.

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As part of the dramatic changes associated with the need for preparing compound libraries in pharmaceutical and agrochemical research laboratories, industry searches for new technologies that allow for the automation of synthetic processes. Since the pioneering work by Merrifield polymeric supports have been identified to play a key role in this field however, polymer‐assisted solution‐phase synthesis which utilizes immobilized reagents and catalysts has only recently begun to flourish. Polymer‐assisted solution‐phase synthesis has various advantages over conventional solution‐phase chemistry, such as the ease of separation of the supported species from a reaction mixture by filtration and washing, the opportunity to use an excess of the reagent to force the reaction to completion without causing workup problems, and the adaptability to continuous‐flow processes. Various strategies for employing functionalized polymers stoichiometrically have been developed. Apart from reagents that are covalently or ionically attached to the polymeric backbone and which are released into solution in the presence of a suitable substrate, scavenger reagents play an increasingly important role in purifying reaction mixtures. Employing functionalized polymers in solution‐phase synthesis has been shown to be extremely useful in automated parallel synthesis and multistep sequences. So far, compound libraries containing as many as 88 members have been generated by using several polymer‐bound reagents one after another. Furthermore, it has been demonstrated that complex natural products like the alkaloids (±)‐oxomaritidine and (±)‐epimaritidine can be prepared by a sequence of five and six consecutive polymer‐assisted steps, respectively, and the potent analgesic compound (±)‐epibatidine in twelve linear steps ten of which are based on functionalized polymers. These developments reveal the great future prospects of polymer‐assisted solution‐phase synthesis.

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[structure: see text] The first enantioselective total synthesis of tonantzitlolone, a novel 15-membered macrocyclic diterpene, utilized a Julia olefination, a highly selective, potassium enolate-based anti-Felkin aldol reaction, and an E-selective ring-closing metathesis as key C-C bond-forming steps. The absolute configuration of tonantzitlolone is established.

Der Bedarf der pharmazeutischen und agrochemischen Forschung an Substanzbibliotheken hat eine verstärkte Suche der Industrie nach neuen Technologien, die die Automatisierung von Syntheseprozessen erlauben, zur Folge. Seit den Pionierarbeiten von Merrifield spielen polymere Trägermaterialien eine Schlüsselrolle in diesem Gebiet, doch werden jetzt immer häufiger Polymer‐unterstützte Synthesen in Lösung unter Nutzung von funktionalisierten Polymeren als Träger für Reagentien oder Katalysatoren untersucht. Die Polymer‐unterstützte Synthese in Lösung bietet gegenüber der konventionellen Lösungschemie vielerlei Vorteile, z. B. die leichte Abtrennbarkeit der Polymer‐gebundenen Spezies vom Reaktionsgemisch durch Filtration oder Waschen sowie die Möglichkeit, das Reagens im Überschuss einzusetzen, um einen vollständigen Umsatz ohne Probleme bei der Aufarbeitung zu erzielen. Außerdem lassen sich mit diesem Konzept auf sehr einfache Weise Durchflussreaktoren betreiben. Verschiedene Strategien zum stöchiometrischen Einsatz von funktionalisierten Polymeren wurden entwickelt. Neben Reagentien, die kovalent oder ionisch an den polymeren Träger gebunden sind und in Anwesenheit eines geeigneten Substrats in Lösung gehen, spielen Abfangreagentien (scavenger) eine zunehmend größere Rolle bei der Reinigung von Reaktionsmischungen. Das Konzept funktionalisierter Polymere für die Synthese in Lösung erweist sich als nützlich für die automatisierte Parallelsynthese und in der Durchführung von mehrstufigen Synthesesequenzen. Bisher konnten Bibliotheken mit bis zu 88 Verbindungen durch den Einsatz mehrerer, sukzessiv verwendeter Polymer‐gebundener Reagentien erzeugt werden. Weiterhin wurden erstmals komplexe Naturstoffe wie die Alkaloide (±)‐Oxomaritidin und (±)‐Epimaritidin durch eine Reihe von fünf und sechs aufeinander folgenden, durch Polymer‐verankerte Reagentien vermittelten Reaktionen synthetisiert. Noch bemerkenswerter erscheint die Herstellung des potenten Analgetikums (±)‐Epibatidin, bei der zehn von zwölf linearen Stufen durch funktionalisierte Polymere realisiert wurden. Diese Entwicklungen zeigen die große Zukunft der Polymer‐unterstützten Synthese in Lösung auf.