Strategies for Direct, Transition Metal‐Free Addition of Nitrogen Synthons to AlkenesHemric, Brett N.; Garcia, Thalia A.; Barni, Adriana E.
doi: 10.1002/hlca.202300160pmid: N/A
The incorporation of nitrogen into small molecules is one of the highest‐demanded transformations in modern synthetic chemistry. Alkene difunctionalization and aziridination offer desirable approaches to the incorporation of these amino synthons from feedstock precursors. Although amino groups can be added to alkenes following alkene reaction with an initiation reagent, the most desirable approach involves direct addition of the nitrogen group to the alkene, allowing for a range of possible secondary functionalization outcomes. Although many of these strategies have been accomplished through the use of transition metals, the utility of a transition metal‐free approach is still at the forefront of synthetic chemistry, both in development and demand. This review aims to present a comprehensive review of the history and current state‐of‐the‐art in the transition metal‐free, direct addition of nitrogen to alkenes.
Probing the Nature of Surface Hydrides by Deuterium Quadrupolar Parameters: A Case Study on Silica‐Supported Zirconium HydridesDocherty, Scott R.; Schärz, Philipp; Gioffrè, Domenico; Yakimov, Alexander V.; Copéret, Christophe
doi: 10.1002/hlca.202300173pmid: N/A
Supported metal hydrides are key reactive intermediates in various catalytic processes, such as hydrogenation and dehydrogenation, but are often challenging to characterize spectroscopically. Here, deuterium solid state nuclear magnetic resonance spectroscopy is used to understand the structure of the corresponding silica‐supported zirconium hydrides after H/D exchange as an illustrative example of supported metal hydrides, which have been shown to display notable reactivity towards small molecules (e. g., CO2 and N2O) and to activate both C−H and C−C bonds, hence their use in to the conversion of hydrocarbons (alkanes, polyolefins etc.)
Development of Photoredox‐Assisted Direct α‐Alkylation Reactions of Ketones with Arylalkenes Using a Catalytic Amount of LiOtBu as a Brønsted BaseHirata, Tsubasa; Hisada, Tomoya; Ogasawara, Yoshihiro; Kobayashi, Shū; Yamashita, Yasuhiro
doi: 10.1002/hlca.202300139pmid: N/A
Photoinduced direct α‐alkylation reactions of ketones with arylalkenes using an organophotocatalyst and a Brønsted base were developed. It was found that the choice of both Brønsted base and photocatalyst was crucial, and in the presence of catalytic amounts of 2,4,6‐tris(diphenylamino)‐3,5‐difluorobenzonitrile (3DPA2FBN) and LiOtBu, the desired reactions of ketones with styrene analogues proceeded smoothly under blue‐LED light irradiation to afford the products in moderate to high yields. This method constitutes an atom‐economical alkylation process for α‐functionalization of both cyclic and acyclic ketones.
Improved Synthesis of Chiral 1,4,7‐Triazacyclononane Derivatives and Their Application in Ni‐Catalyzed Csp3−Csp3 Kumada Cross‐CouplingHu, Chi‐Herng; Byeong Chae, Ju; Mirica, Liviu M.
doi: 10.1002/hlca.202300170pmid: N/A
Herein, we report four new chiral 1,4,7‐triazacyclononane (TACN) derivatives and their corresponding nickel(II) chloride complexes. All TACN ligands are bearing one chiral N‐substituent and two alkyl (methyl or tert‐butyl) N‐substituents, and we have developed a new synthetic method for the dimethyl‐substituted TACN derivative, in order to prevent the rotational isomers that hinder the cyclization reaction. The nickel complexes change their coordination geometry significantly depending on the steric bulk of the N‐alkyl substituents, from a dinuclear tris(μ‐chloro)dinickel complex to mononuclear Ni‐dichloride and Ni‐chloride complexes. These complexes were then employed in the alkyl‐alkyl Kumada cross‐coupling reaction and revealed that the more sterically hindered ligands produced more homocoupled product rather than the cross‐coupled product, while the mononuclear Ni‐dichloride complex exhibited significantly lower catalytic activity. These chiral complexes were also employed in enantioconvergent cross‐coupling reactions as well, to afford significant enantioenrichment. Overall, the least sterically hindered Ni complex yields the best yields in the alkyl‐alkyl Kumada cross‐coupling reaction among the four complexes investigated, as well as the highest enantioselectivity.
Synthesis and Olfactory Properties of Lower‐Ring Homologues of the Linear Alicyclic Musk RomandolideDacho, Vladimír; Nikipelov, Artem; Tóthová, Michaela; Kraft, Philip; Szolcsányi, Peter
doi: 10.1002/hlca.202300181pmid: N/A
In order to expand the knowledge on linear alicyclic musks, a set of 29 small‐ring (racemic) analogues of the biodegradable and renewable alicyclic musk Romandolide was designed, prepared, and evaluated. The common short and modular synthesis employs either commercially available or easily accessible (substituted) cyclopropyl/cyclobutyl ketones and acids. These were transformed in three/four steps to the target compounds. Their qualitative olfactory analysis reveals that contraction of cyclohexane ring of Romandolide to smaller rings annihilates the genuine musk scent, though many of these share the metallic hot‐iron off‐note of some macrocyclic musks. Indeed, these new derivatives exhibit a plethora of pleasant, interesting, and potentially useful scents including herbal, green, fruity, or chocolate ones accompanied by various undertones. The powdery, fruity ionone odor of the dimethyl cyclobutyl compound was found to be most interesting as it possesses a very natural raspberry and violet character. Computational modelling suggest that the lowest‐energy conformers of the target compounds do either not adopt a true U‐shape as was speculated to be a prerequisite for a musk odor, or that the quaternary carbon atom of the dimethyl‐substituted cyclobutane is not well placed to fit into a hydrophobic binding pocket on the corresponding receptor site.
Tailoring the Hybridization Density of DNA Biosensors through Tunable Surface FunctionalizationRobin, Perrine; Mayoraz, Lucas; Skigin, Pauline; Mensi, Mounir; Gerber‐Lemaire, Sandrine
doi: 10.1002/hlca.202300150pmid: N/A
DNA biosensors are promising candidates for the development of point‐of‐care diagnosis methods. They can be inserted in microfluidic platforms, are often non‐expensive, and can be produced for a variety of targeted analytes. However, their development faces several challenges, some of which arise from their surface design. Among the characteristics which affect the binding efficiency of DNA probes to their targeted genes, the packing density and lateral spacing of the probe sequences must be controlled to provide enough binding sites and avoid crowding effect. It has also been demonstrated that increasing the space between the probe and the substrate can enhance the sensitivity of the sensing surface. Herein, we describe a methodology to control the vertical distance between DNA probes and a glass support, and lateral spacing between the probes. Such functionalization strategy could help the development of sensing surface with high hybridization density, and therefore high sensitivity.