The synthesis of amides remains one of the most important transformations and it is one of the more frequently performed reactions. In the pharmaceutical industry, building of the amide group is pivotal and among the more important transformations in the design of the synthetic plan. This review presents an overview of only very recent contributions, published in the last three years, to highlight the latest progresses in this "dateless" reaction, with a special focus on metal-free methodologies. New, more efficient and/or greener stoichiometric methods as well as catalytic strategies have been discussed, either for the "classical" coupling approach between an amine and a carboxylic acid (or its activated equivalent), and for more innovative approaches, mainly involving oxidation procedures to generate amides starting from amines.
Three distinct stereoselective reactions, catalysed by using a chiral primary amine through different activation methods, have been successfully carried out for the first time in bio-based eutectic mixtures, thereby affording functionalised molecules in very high enantioselectivity. The use of these unconventional and biorenewable reaction media also provides opportunities for facilitating the recovery and the recycling of the chiral catalyst
SignificanceBacterial pathogens cause plant diseases that threaten the global food supply. To control diseases, it is important to understand how pathogenic bacteria evade plant defense and promote infection. We identify from the phytopathogen Pseudomonas syringae a small-molecule virulence factor—phevamine A. Both the chemical structure and mode of action of phevamine A are different from known bacterial phytotoxins. Phevamine A promotes bacterial growth by suppressing plant immune responses, including both early (the generation of reactive oxygen species) and late (the deposition of cell wall reinforcing callose in leaves and leaf cell death) markers. This work uncovers a widely distributed, small-molecule virulence factor and shows the power of a multidisciplinary approach to identify small molecules important for plant infection.
One of the most important chemical transformations is the reduction of multiple bonds, carbon-carbon as well as carbon-heteroatom double bonds, since it leads very often to the generation of new stereocenters in the molecule. The replacement of metal-based catalysts with equally efficient metal-free counterparts is very appealing in view of possible future applications of non toxic, low cost, and environmentally friendly promoters on an industrial scale. This perspective will focus specially, but not exclusively, on the enantioselective reduction of the carbon nitrogen double bond; despite the historical need for and continued interest in chiral amines, their synthesis remains challenging. Three metal-free catalytic methodologies available for the reduction of carbon-nitrogen double bond will be discussed: i) binaphthol-derived phosphoric acids catalyzed reductions, with dihydropyridine-based compound as the reducing agent; ii) trichlorosilane mediated reductions, in the presence of catalytic amounts of chiral Lewis bases; iii) metal-free hydrogenation of imines through FLP (Frustrated Lewis Pair) methodology, that involves the use of a combination of a strong Lewis acid with a variety of sterically encumbered Lewis bases, for examples phosphines or tertiary amines, to activate hydrogen at ambient conditions. Special attention will be devoted to the most recent applications of the last five years.
The enantioselective organocatalytic reduction of trifluoromethyl aryl and alkyl ketoimines afforded the corresponding fluorinated amines with high chemical and stereochemical efficiency. The Lewis base catalyzed reaction with trichlorosilane led to chiral products with a trifluoromethyl group directly linked to the newly generated stereocenter typically in >90% yield and up to 98% e.e.Organofluorine compounds find applications in several fields of scientific research, like pharmaceuticals, agrochemicals and veterinary, but also in materials science.
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