Some Items of Interest to Process R&D Chemists and Engineers

Abstract

Although the conversion of alcohols into chlorides is a classical transformation in organic chemistry, most standard protocols suffer from the generation of a large amount of waste or poor functional group tolerance. Huy and co-workers have developed an alternative method based on Lewis base-catalyzed nucleo-philic substitution to synthesize alkyl chlorides (Angew. Chem. Int. Ed. 2016, 55, 10145). The key findings were the identification of formyl pyrrolidine as catalyst and benzoyl chloride as chlorinating agent. In addition of being cheaper and safer than the classical halogenating agents, benzoyl chloride avoids the stoichiometric generation of HCl which results in improved functional group compatibility. Importantly, the reaction can be run in the absence of solvent even if the utilization of MTBE or acetone improved yields. The substrate scope is quite large with primary, secondary, and even tertiary alcohols being chlorinated in good to high yields and conservation of the enantiomeric excess in the case of chiral molecules. Furthermore, upon in situ reaction with a range of nucleophiles, the obtained chloride can be converted to amines, ethers, sulfides, azides, or nitriles. ■ IRIDIUM PHOTOREDOX AND NICKEL CATALYSIS FOR THE CROSS-COUPLING OF PRIMARY ARYL AMINES WITH ARYL HALIDES Transition-metal-catalyzed coupling of amines with aryl(pseudo)-halides remains the most versatile method of synthesizing aryl amines with palladium catalysis as the most developed approach. The nickel-catalyzed analogous reaction is much more difficult to achieve due to the known reluctance of Ni II aryl amido complexes to undergo reductive elimination. A joint team of AstraZeneca and Montreál University has recently reported that Ir-photoredox catalysis, by promoting the oxidation of Ni II to Ni III