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DOI: 10.1055/s-2008-1042736
Direct Aminoalkylation via Nickel-Catalyzed Negishi Cross-Coupling Reactions
Contributor(s):Paul Knochel, Tobias ThalerLudwig-Maximilians-Universität München, Germany
Direct Aminoalkylation of Arenes and Hetarenes via Ni-Catalyzed Negishi Cross-Coupling Reactions
Org. Lett. 2007, 9: 5529-5532
Publication History
Publication Date:
21 February 2008 (online)
Key words
nickel - aminoalkylation - Negishi cross-coupling
Significance
A new general method for the one-pot introduction of aminoalkyl groups via Negishi-type cross-coupling is reported. It was applied to the cross-coupling with both aryl and hetaryl halides and triflates furnishing the respective products with good to excellent yields. It is noteworthy that cross-coupling of tropanyl zinc reagents proceeds with 100% exo-selectivity. This is due to the stereospecific formation of the corresponding Grignard reagent.
Comment
Molander described the first direct coupling of potassium aminoalkyltrifluoroborates with aryl and hetaryl halides (Org. Lett. 2007, 9, 203; Org. Lett. 2007, 9, 1597). So far, however, no other cross-coupling reaction of an aminoalkyl organometallic species possessing a basic nitrogen has been reported. In this article the first Negishi-type cross-coupling between aminoalkylzinc reagents and aryl, hetaryl halides and triflates is presented. The easy accessibility of the aminoalkylzinc reagents via magnesium insertion and transmetallation and the frequent occurrence of aminoalkyl moieties in biologically active materials make this method a promising tool for the development of new drug libraries.