Ir-catalysed allylic substitution is supplementing the traditional Pd-catalysed variant. With simple, easily available monosubstituted allylic acetates and carbonates as substrates, Ir catalysts generally favour chiral, branched products, while Pd catalysts typically give rise to linear, achiral products. With phosphorus amidites as ligands, regioselectivities >10 : 1 and enantiomeric excess in the range 95-99 %ee are currently routinely achieved. A broad range of nucleophiles can be employed: for example stabilised carbanions, amines including their sulfonyl- and diacyl-derivatives, phenolates and alkoxides. A few applications, based on combinations of the allylic substitution and ring closing metathesis, indicate considerable potential of the method for the synthesis of biologically active compounds.

Four chelating nitrogen ligands 2-5 derived from N,N-bis(2-picolyl)amine (bpa, 1) were synthesized, namely, (PyCH(2))(2)N-CH(2)-p-C(6)H(4)-CO(2)R (R = Me, 2, and R = H, 3) and (PyCH(2))(2)N-(CH(2))(n)-CO(2)H (n = 2, 4, and n = 5, 5). Amino acid conjugates 6 and 7 were formed by condensation of 3 with H-Phe-OMe and H-betaAla-OMe, respectively. Cu(II) and Zn(II) complexes of 1-7 were prepared and fully characterized. The X-ray structures of 1(Zn), 2(Zn), 4(Cu), and 7(Cu) were determined. The Zn complexes 1(Zn) and 2(Zn) as well as 7(Cu) show a distorted trigonal bipyramidal coordination environment in the solid state. An octahedral complex is observed for 4(Cu) which forms chains along the crystallographic b axis by intermolecular coordination of the carboxylic acid to the metal ion of a neighboring complex. Ligand 3 was used to prepare the peptide bioconjugate 8 (3-Ahx-Pro-Lys-Lys-Lys-Arg-Lys-Phe-NH(2)) with a nuclear localization signal (nls) heptapeptide by solid phase synthesis. Cu(II) and Zn(II) complexes of 8 were synthesized in situ and studied by FAB-MS, ESI-MS, UV/vis, and EPR (for 8(Cu)), and FAB-MS, ESI-MS, and NMR (for 8(Zn)). All spectroscopic results clearly support metal coordination to the bpa ligand in the bioconjugates 8(M), even in the presence of other potential ligands from amino acid side chains of the peptide. We suggest metal-peptide conjugates like 8(M) as artificial metallochaperones because they have the potential to deliver metal ions to specific compartments in the cell as determined by the peptide moieties.

[reaction: see text] Enantioselective Ir-catalyzed intramolecular allylic aminations and etherifications are described. Up to 97% ee was achieved using catalysts prepared by in situ activation of mixtures of phosphorus amidites and [Ir(COD)Cl]2. Sequential aminations of bis-allylic carbonates, involving an inter- followed by an intramolecular reaction, gave trans-N-benzyl-2,5-divinylpyrrolidine and trans-N-benzyl-2,6-divinylpiperidine with > or = 99% ee. New phosphorus amidites as well as improved conditions for intermolecular aminations are reported.

A broadly applicable synthesis of chiral 2- or 2,4-substituted cyclopent-2-enones has been developed by combining asymmetric iridium-catalyzed allylic alkylation reactions and ruthenium-catalyzed ring-closing metathesis. Enantiomeric excesses (ee values) in the range of 95-99 % ee have been achieved. This method offers a straightforward access to biologically active prostaglandins of the PGA type. As an example, an enantioselective synthesis of the prostaglandin-analogue 13,14-dihydro-15-deoxy-Delta(7)-prostaglandin-A1-methyl ester (TEI-9826) has been carried out. Furthermore, the carbonucleoside 2'-methylcarbovir has been prepared from O-protected 4-hydroxymethyl-2-methyl-cyclopent-2-enone by Pd-catalyzed allylic amination.

Classy combo: Together, the asymmetric iridium‐catalyzed allylic alkylation and ruthenium‐catalyzed ring‐closing metathesis lead to an efficient synthesis of chiral cyclopentenones (see scheme). One example is the synthesis of the antitumor agent TEI‐9826 with high enantiomeric purity.

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Short routes to chiral 2-substituted pyrrolidines based on rhodium-catalyzed hydroformylations of allylamines and their Nalkyl and N-acyl derivatives, which were prepared by asymmetric allylic substitutions, are described. The outcome of the hydroformylation reaction was controlled by the substituent at nitrogen, not by the substituent at carbon. In the case of N-alkylallylamines in situ reduction to the pyrrolidines occurred, with N-acyl derivatives hemiaminals and with primary amines cyclic imines were formed. Very short syntheses of (S)-nicotine and the alkaloid 225C are presented.

Cyclopentenone sind wichtige Strukturmotive von Natur-und Wirkstoffen.[1] Wegen der zahlreichen möglichen Substitutionsmuster ist ihre stereoselektive Synthese eine Herausforderung.[2] Wir berichten hier über eine neue enantioselektive Methode zur Synthese von 2,4-disubstituierten Cyclopentenonen und die Anwendung dieser Methode auf interessante Syntheseziele. Auch als Zwischenprodukte sind diese Verbindungen von Interesse, da sie in 3-Position für Reaktionen mit Nucleophilen und in 5-Position für Reaktionen mit Elektrophilen geeignet sind, sodass vielfältige weitere Funktionalisierungen durchgeführt werden können (Schema 1). [3] Der neuen Methode liegt folgendes Konzept zugrunde (Schema 2): a) Durch Iridium-katalysierte allylische Alkylierung mit dem Enolat des Amids 1, eines neuen Pränu-Schema 1.