Direct Imidation to Construct 1H‐Benzo[d]imidazole through Pd^II‐Catalyzed CH Activation Promoted by Thiourea

Abstract

Die beispiellose Struktur des marinen Naturstoffs Brevetoxin B wurde 1981 von den Arbeitsgruppen um Nakanishi und Clardy aufgeklärt. Das leiterförmige Molekülgerüst dieses kondensierten Polyethers, die starke Toxizität und der faszinierende Wirkmechanismus durch Angriff am spannungsgesteuerten Natriumkanal sorgten für Aufmerksamkeit. Syntheseversuche führten zur Entwicklung zahlreicher neuer Methoden und Strategien zum Aufbau von Etherringen und wurden schließlich durch die Totalsynthesen von Brevetoxin B und einigen verwandten, ähnlich anspruchsvollen Zielverbindungen gekrönt. Unter den marinen Polyethern nimmt Maitotoxin als kompliziertester und giftigster Vertreter eine Sonderstellung ein; die Verbindung ist der größte bekannte nichtpolymere Naturstoff überhaupt. Dieser Aufsatz beginnt mit einer kurzen Geschichte zur Isolierung der Biotoxine und beleuchtet ihre biologischen Eigenschaften und Wirkmechanismen. Dann werden Syntheseversuche beschrieben, wobei besonders neue Methoden berücksichtigt werden, die im Laufe dieser Studien entwickelt wurden. Den Abschluss bilden eine Diskussion der noch nicht abgeschlossenen Totalsynthese von Maitotoxin sowie ein Ausblick auf die weitere Entwicklung des Forschungsgebiets.

Pd‐Catalyzed Z‐Selective Semihydrogenation of Alkynes: Determining the Type of Active Species

“…Its strong p-acceptor properties combined with its strong sdonor properties originate from its resonance structures, which make it as trongly binding ligand for low-valent as well as high-valent complexes (Figure 1). [70] Thioureas have been exploited as ligands for Pd-complexes, [71][72][73] Pd-catalyzed reactions, [74][75][76] the removal of trace metal salts from aqueous solutions [77] andt he preparation of coordination polymers. [78] TMTU possesses qualities that are advantageousf or poison ligands.…”

Copper‐Catalyzed One‐Pot Synthesis of Imidazo/Benzoimidazoquinazolinones by Sequential Ullmann‐Type Coupling and Intramolecular CH Amidation

“…[6] Traditional methods for the synthesis of N-heterocycles substituted with functional groups require the use of prefunctionalized precursors. Recently, there have been great advances in the direct functionalization of C À H bonds, [7] and some N-heterocycles (for example, benzimidazoles, [8] carbazoles, [9] indazoles, [10] N-methoxylactams, [11] and indolines [12] ) have been synthesized through CÀH activation/ CÀN bond-formation sequences, in which expensive palladium-, rhodium-, and ruthenium-based catalysts are usually required. In recent decades, there has been remarkable progress in copper-catalyzed cross-couplings with inexpensive, low-toxicity copper catalysts, and wide applications with good functional group tolerance have been investigated.…”

Orthometallation as a Strategy in Pd-mediated Organic Synthesis

“…This drawback was resolved by the employ of two electron oxidants, specifically F + , generated "in situ" using the pyridinium salt [2,4,6- A novel and straightforward method to construct benzoimidazoles 97 was developed by Yang, Shi et al, 61 which is based on the transformation of N-phenylbenzimides 95 into the aforementioned heterocycles 97 by means of palladacycles 96…”

“…Interestingly, the presence of tetramethylthiourea (TMTU) as additive improved dramatically the yields, probably due to its potential ability to stabilize Pd(II) species. 61 The substitutions on the aromatic moieties were crucial for the success of the reaction, since only electrondonating groups were compatible.…”

“…The acetoxylation protocol was further expanded to a considerable number of derivatives (43,(60)(61)(62)(63), pyridine moieties serving as excellent directing groups ( Figure 14 b,c) as well as others nitrogen-based directing groups, like oximes 34, heterocycles or azobenzene ( Figure 14d). 39 Pyrrolidinones 39 (64,65) and N-benzylpicolinamides Regardless of the success displayed with PhI(OAc) 2 , the fact that one equivalent of toxic iodobenzene is generated, in concert with the high-cost of this stoichometric oxidant, sparked the search for other more environmentally benign and cost-effective oxidants.…”