Automated Synthesis for the Safe Production of Organic Azides from Primary Amines.

Described herein is the development of an automated and reproducible process for the conversion of primary amines to organic azides utilizing prepacked capsules containing all the required reagents, including imidazole-1-sulfonyl azide tetrafluoroborate. Apart from manually loading the primary amine into the reaction vessel, the entire reaction and product isolation process can be achieved automatically, with no further user involvement, and delivers the desired organic azide in high purity. This practical and simple automated capsule-based method offers a convenient and safe way of generating organic azides without handling or exposure of potentially explosive reagents.

Automated, Capsule-Based Suzuki-Miyaura Cross Couplings.

The development of an automated process for Suzuki-Miyaura cross couplings is described, in which the complete reaction, workup, and product isolation are effected automatically with no user involvement, aside from loading of the starting materials and reaction capsule. This practical and simple method was successfully demonstrated to provide the desired biaryl products using a range of aryl bromides and boronic acids and is also effective for the late-stage functionalization of aryl halides in bioactive molecules.

Nitrene transfers mediated by natural and artificial iron enzymes.

Amines are ubiquitous in biology and pharmacy. As a consequence, introducing N functionalities in organic molecules is attracting strong continuous interest. The past decade has witnessed the emergence of very efficient and selective catalytic systems achieving this goal thanks to engineered hemoproteins. In this review, we examine how these enzymes have been engineered focusing rather on the rationale behind it than the methodology employed. These studies are put in perspective with respect to in vitro and in vivo nitrene transfer processes performed by cytochromes P450. An emphasis is put on mechanistic aspects which are confronted to current molecular knowledge of these reactions. Forthcoming developments are delineated.

Imidazoline synthesis: mechanistic investigations show that Fe catalysts promote a new multicomponent redox reaction.

Multicomponent reactions are attracting strong interest because they contribute to develop more efficient synthetic chemistry. Understanding their mechanism at the molecular level is thus an important issue to optimize their operation. The development of integrated experimental and theoretical approaches has very recently emerged as most powerful to achieve this goal. In the wake of our recent investigation of amidine synthesis, we used this approach to explore how an Fe-catalyzed aziridination can lead to an imidazoline when run in acetonitrile. We report that the synthesis of imidazoline by combination of styrene, acetonitrile, an iron catalyst and a nitrene precursor occurs along a new kind of multicomponent reaction. The formation of imidazoline results from acetonitrile interception of a benzyl radical styrene aziridination intermediate within Fe coordination sphere, as opposed to classical nucleophilic opening of the aziridine by a Lewis acid. Comparison of this mechanism to that of amidine formation allows a rationalization of the modes of intermediates trapping by acetonitrile according to the oxidation state Fe active species. The molecular understanding of these processes may help to design other multicomponent reactions.

Redox Self-Adaptation of a Nitrene Transfer Catalyst to the Substrate Needs.

The development of iron catalysts for carbon-heteroatom bond formation, which has attracted strong interest in the context of green chemistry and nitrene transfer, has emerged as the most promising way to versatile amine synthetic processes. A diiron system was previously developed that proved efficient in catalytic sulfimidations and aziridinations thanks to an FeIII FeIV active species. To deal with more demanding benzylic and aliphatic substrates, the catalyst was found to activate itself to a FeIII FeIV L. active species able to catalyze aliphatic amination. Extensive DFT calculations show that this activation event drastically enhances the electron affinity of the active species to match the substrates requirements. Overall this process consists in a redox self-adaptation of the catalyst to the substrate needs.