Reduction, please! The title reaction affords α-hydroxyketones, a common structural motif in biologically active natural products, in good yields and high enantioselectivities at room temperature. The commercially available ansa-titanocene 1 was found to be an efficient catalyst for this process, which presumably proceeds by addition of a ketyl radical to a nitrile.
A sequence of two titanium(III)-catalyzed reductive umpolung reactions is reported that allows the rapid construction of benzazo- and benzoxozine building blocks. The first step is a reductive cross-coupling of quinolones or chromones with Michael acceptors. This reaction proceeds with complete syn-selectivity for the quinolone functionalization while the anti-diastereomers are obtained as the major products from chromones. With different reaction conditions, the stereochemical outcome can be altered to afford the syn-chromanone products as well. A subsequent reductive ketyl radical cyclization forges the tricyclic title compounds in good yields. A stereochemical model explaining the observed stereoselectivities is provided and the product configurations were unambiguously verified by X-ray analyses and 2D NMR spectroscopic experiments.
A simple modification of our recently published protection scheme for carboxylic acids as amides resulted in a new protecting group with significantly improved properties. It requires shorter reaction times for deprotection and allows us to replace Cu(OTf)(2) by CuCl(2), indicating at the same time the importance of the nature of the anion of the Cu(2+) source. Since the new scheme fulfills all criteria required for an ideal protection group it should find widespread application in synthetic organic chemistry.
The titanium(iii)-catalysed cross-selective reductive umpolung of Michael-acceptors represents a unique direct conjugate β-alkylation reaction. It allows the cross-selective preparation of 1,6- and 1,4-difunctionalised building blocks without the requirement of stoichiometric organometallic reagents. In this full paper, the development and scope of the titanium(iii)-catalysed cross-selective reductive umpolung of Michael-acceptors is described. Based on the observed selectivities and additional mechanistic experiments a refined mechanistic proposal is presented.
Auf zwei Arten: Eine Titan(III)‐katalysierte reduktive radikalische Cyclisierung von Iminonitrilen wurde entwickelt, die zur direkten Synthese von α‐aminierten Ketonen führt. Je nach Anbindung des Nitrils an den Iminkohlenstoff oder ‐stickstoff werden α‐tetrasubstituierte cyclische Aminoketone oder Pyrrolidin‐3‐one in bis zu quantitativer Ausbeute erhalten. Im letzten Fall entsprechen Iminkondensation und TiIII‐Katalyse einer formalen [4+1]‐Cycloaddition.
Bitte reduzieren! Die Titelreaktion liefert α‐Hydroxyketone, die ein Strukturmerkmal vieler biologisch aktiver Naturstoffe sind, in guten Ausbeuten und hohen Enantioselektivitäten. Das kommerziell erhältliche Ansa‐Titanocen 1 wird als effizienter Katalysator für diesen Prozess eingesetzt, der vermutlich über die Addition eines Ketylradikals an ein Nitril verläuft.
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