Copper-Catalyzed Hydroamination of Allenes: from Mechanistic Understanding to Methodology Development

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Copper-Catalyzed Hydroamination of Allenes: from Mechanistic Understanding to Methodology Development, ACS Catalysis2017, 7 (7), pp 4253–4264

 

The development of synthetic protocols that employ easily available starting materials for the construction of valuable compounds is a far-reaching goal of organic chemistry. In this perspective, hydroamination, i.e. the reaction in which an R2N-H moiety is added across a carbon-carbon double or triple bond, is one of the most desirable transformations to access amines. Indeed, it perfectly fits the requirements of green chemistry, since it has complete atom economy and it does not require the preparation of reactive intermediates such as organic halides or electrophilic nitrogen reagents.

 

Over the last two decades, an impressive number of protocols have been proposed for the hydroamination of unsaturated compounds, and most often late transition metals have been revealed the most flexible platform to perform this transformation. In this context, expensive catalyst featuring precious metals and designer ligands are being more and more frequently replaced by systems based on cheaper metals, such as iron and copper.

 

 

We recently reported an efficient protocol for the Cu-catalyzed regio- and stereoselective intermolecular hydroamination of terminal allenes. Our research efforts aim to gain mechanistic insight useful to support the rational development of new synthetically valuable transformations. In this perspective, we undertook a comprehensive mechanistic study of the aforementioned reaction, using a combined experimental and theoretical approach.

 

We present here the results of our work, that allowed to shed light on the actual nature of the catalytically active species and to rationalize the observed regio- and stereoselectivity. Mechanistic understanding allowed the extension of the methodology to a new class of substrates – allenamides – under exceptionally mild conditions.

 

Pour plus d'information, consultez le communiqué associé à cet article : Quand théorie et expérience dissèquent une catalyse au cuivre !

 

Résumé: 

ACS Catalysis2017, 7 (7), pp 4253–4264

Experimental and theoretical mechanistic studies on the Cu(OTf)2-catalyzed hydroamination reaction of terminal allenes with secondary amines reveal that in-situ generated cationic Cu(I) is the catalytically active species and explain the observed regio- and stereoselectivity for the unbranched E product. Insight about the structure of the relevant transition states allowed the generalization of this methodology to allenamides and N-allenylcarbamates under unprecedentedly mild and functional group tolerant conditions. Chelation effect by the amide oxygen in addition to electronic effects explain the high innate reactivity of this class of substrates.

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Copper-Catalyzed Hydroamination of Allenes: from Mechanistic Understanding to Methodology Development

 

Luca Alessandro Perego, Rémi Blieck, Antoine Groué, Florian Monnier, Marc Taillefer, Ilaria Ciofini, Laurence Grimaud

 

ACS Catalysis2017, 7 (7), pp 4253–4264

 

DOI: 10.1021/acscatal.7b00911