Jason Williams

Previous enantioselective Pd⁰-catalyzed C−H activation reactions proceeding via the concerted metalation-deprotonation mechanism employed either a chiral ancillary ligand, a chiral base, or a bimolecular mixture thereof. This study describes the development of new chiral bifunctional ligands based on a binaphthyl scaffold which incorporates both a phosphine and a carboxylic acid moiety. The optimal ligand provided high yields and enantioselectivities for a desymmetrizing C(sp²)−H arylation leading to 5,6-dihydrophenanthridines, whereas the corresponding monofunctional ligands showed low enantioselectivities. The bifunctional system proved applicable to a range of substituted dihydrophenanthridines, and allowed the parallel kinetic resolution of racemic substrates.

Chiral chimera: Bifunctional ligands incorporating both a phosphine and a carboxylate moiety provide high enantioselectivities in the synthesis of 5,6-dihydrophenanthridines. In contrast, the corresponding bimolecular systems are poorly stereoselective.

NMR spectroscopy is an indispensable method of analysis in chemistry, which until recently suffered from high demands for space, high costs for acquisition and maintenance, and operational complexity. This has changed with the introduction of compact NMR spectrometers suitable for small-molecule analysis on the chemical workbench. These spectrometers contain permanent magnets giving rise to proton NMR frequencies between 40 and 80 MHz. The enabling technology is to make small permanent magnets with homogeneous fields. Tabletop instruments with inhomogeneous fields have been in use for over 40 years for characterizing food and hydrogen-containing materials by relaxation and diffusion measurements. Related NMR instruments measure these parameters in the stray field outside the magnet. They are used to inspect the borehole walls of oil wells and to test objects nondestructively. The state-of-the-art of NMR spectroscopy, imaging and relaxometry with compact instruments is reviewed.

NMR spectroscopy is known not only for its outstanding analytical power but also for the large size and costs of the instruments. In recent years, the family of instruments with bulky superconducting magnets has been complemented with compact tabletop and portable devices suitable for small-molecule analysis and nondestructive materials testing. The state of the art of compact NMR instruments is reviewed and illustrated with selected examples.

C−H activation reactions with high catalyst turnover numbers are still very rare in the literature and 10 mol % is a common catalyst loading in this field. We offer a representative overview of efficient C−H activation catalysis to highlight this neglected aspect of catalysis development and inspire future effort towards more efficient C−H activation. Examples ranging from palladium catalysis, Cp*Rh^III- and Cp*Co^III-catalysis, the C−H borylation and silylation to methane C−H activation are presented. In these reactions, up to tens of thousands of catalyst turnovers have been observed.

Go, catalyst, go! C−H activation reactions with high catalyst turnover numbers are still very rare in the literature and 10 mol % is a common catalyst loading in this field. A representative overview of efficient C−H activation catalysis is presented here to highlight this neglected aspect of catalysis development and inspire future effort towards more efficient C−H activation.

Coupling of readily available boronic acids and diazo compounds has emerged recently as a powerful metal-free carbon–carbon bond forming method. However, the difficulty in forming the unstable diazo compound partner in a mild fashion has hitherto limited their general use and the scope of the transformation. Here, we report the application of oxadiazolines as precursors for the generation of an unstable family of diazo compounds using flow UV photolysis and their first use in divergent protodeboronative and oxidative C(sp²)−C(sp³) cross-coupling processes, with excellent functional-group tolerance.

Photo finish: A mild versatile method for the generation of highly unstable diazo compounds through photolysis of oxadiazolines and subsequent coupling with boronic acids is described. Simple changes in the workup conditions allow the divergent generation of protodeboronated and oxidized products, along with boronic pinacol esters, with excellent functional-group tolerance.

Azolium cations are widely employed in organocatalysis to catalyse highly valuable synthetic processes in the presence of a base. These reactions are called “N-heterocyclic carbene catalysis”, based on the assumption that they are initiated by the formation of a free carbene through deprotonation, which can then react with the substrates and thereby affect their reactivity to obtain the desired products. However, we herein provide evidence that an electrophilic aromatic substitution mechanism is energetically more favourable, in which the azolium cation reacts directly with the substrate, avoiding the formation of the free carbene in solution.

Another alternative: A novel reaction pathway for N-heterocyclic carbene organocatalysis has been identified. In this process, proton transfer and the binding of the substrate to the catalyst occur simultaneously in a single elementary reaction step, without the formation of a free carbene molecule in the reaction mixture.

Aliphatic amines, oxygenated at remote positions within the molecule, represent an important class of synthetic building blocks to which there are currently no direct means of access. Reported herein is an efficient and scalable solution that relies upon decatungstate photocatalysis under acidic conditions using either H₂O₂ or O₂ as the terminal oxidant. By using these reaction conditions a series of simple and unbiased aliphatic amine starting materials can be oxidized to value-added ketone products. Lastly, NMR spectroscopy using in situ LED-irradiated samples was utilized to monitor the kinetics of the reaction, thus enabling direct translation of the reaction into flow.

Going with the floW: Decatungstate anion, a UV absorbing photocatalyst, was utilized in the conversion of unprotected aliphatic amines, into products containing a ketone functionality at a remote position, by using either H₂O₂ or O₂ as the terminal oxidant. NMR studies employing LED-irradiated samples aided in the identification of a key reaction intermediate, and ultimately allowed the transformation to be translated into flow.

A new Pummerer-type C−C coupling protocol is introduced based on turbo-organomagnesium amides, which unlike traditional Pummerer reactions, does not require strong electrophilic activators, engages a broad range of C(sp³)-, C(sp²)-, and C(sp)-nucleophiles, and seamlessly integrates with C−H and C−X magnesiation. Given the central character of sulfur compounds in organic chemistry, this protocol allows access to unrelated carbonyls, olefins, organometallics, halides, and boronic esters through a single strategy.

The Pummerer coupling allows C−C bond formation to be performed in a single operation but it is limited by the need of electrophilic activators. Reported herein is an efficient and orthogonal protocol for electrophile-free Pummerer C−C coupling, which addresses the scope and limitations of traditional approaches, by using DIPAMgCl⋅LiCl.