Additive‐free: The chemoselective amide‐bond‐forming ligation between N‐alkylhydroxylamines and α‐ketoacids requires no reagents and the only by‐products are water and carbon dioxide. This process proceeds on unprotected peptide substrates without epimerization, and as such, this process has the potential to serve as a novel chemoselective ligation for the synthesis of peptides and complex materials.

Heteroarenes are important structural moieties in many chemical industry fields. A highly efficient Pd/Cu-catalyzed C-H arylation method for a range of heterocycles has been discovered. It was found that the key to the success of this transformation is a combination of a palladium catalyst and a well-defined copper cocatalyst. The efficiency and low loadings of catalyst (0.25 mol %) and cocatalyst (1 mol %) together with the mild reaction conditions demonstrate this method to be practically useful and mechanistically interesting.

Rh(II)-catalyzed oxidative coupling of aldehydes and sulfonamides has been developed to provide N-sulfonylcarboxamides in one step. A variety of sulfonamides were found to react with aromatic and aliphatic aldehydes to afford the desired products in good to excellent yields. Mechanistic data, including kinetic isotope effect experiments, suggest that the transformation proceeds through a concerted asynchronous nitrene insertion into an aldehydic hydrogen.

Ganz ohne Additiv: Die chemoselektive Ligation zwischen N‐Alkylhydroxylaminen und α‐Ketosäuren unter Bildung einer Amidbindung erfordert keine Reagentien und hat als einzige Begleitprodukte Wasser und Kohlendioxid. Nicht geschützte Peptidsubstrate werden dabei nicht epimerisiert, was dem Prozess Potenzial als neuartige chemoselektive Ligation zur Synthese von Peptiden und komplexen Materialien verleiht.

The development and kilogram-scale demonstration of an improved process for the synthesis of the epoxyketone warhead of carfilzomib is described. Critical to the success of this process was: (1) development of a scalable asymmetric epoxidation protocol; (2) identification of a crystalline intermediate with improved physical properties for isolation; (3) discovery and optimization of epimerization conditions to set the target stereochemistry; and (4) introduction of a seeded-bed coaddition crystallization to facilitate isolation of the final low-melting target. The results of kilogram-scale demonstration runs are shared, including details of a continuous process for the safe execution of an exothermic Barbier-type Grignard process.