An interactive tool has been developed to facilitate solvent selection, allowing consideration of chemical functionality, physical properties, regulatory concerns, and safety/health/environmental (SHE) impact. Appropriate solvents can be identified prior to screening experiments, and less desirable solvents can be replaced in established processes. Once a shortlist has been identified, the data can define experimental programs or else be exported to a molecular properties prediction tool to assess suitability through, e.g., solubility and partitioning.

With a renewed and growing interest in therapeutic oligonucleotides across the pharmaceutical industry, pressure is increasing on drug developers to take more seriously the sustainability ramifications of this modality. With 12 oligonucleotide drugs reaching the market to date and hundreds more in clinical trials and preclinical development, the current state of the art in oligonucleotide production poses a waste and cost burden to manufacturers. Legacy technologies make use of large volumes of hazardous reagents and solvents, as well as energy-intensive processes in synthesis, purification, and isolation. In 2016, the American Chemical Society (ACS) Green Chemistry Institute Pharmaceutical Roundtable (GCIPR) identified the development of greener processes for oligonucleotide Active Pharmaceutical Ingredients (APIs) as a critical unmet need. As a result, the Roundtable formed a focus team with the remit of identifying green chemistry and engineering improvements that would make oligonucleotide production more sustainable. In this Perspective, we summarize the present challenges in oligonucleotide synthesis, purification, and isolation; highlight potential solutions; and encourage synergies between academia; contract research, development and manufacturing organizations; and the pharmaceutical industry. A critical part of our assessment includes Process Mass Intensity (PMI) data from multiple companies to provide preliminary baseline metrics for current oligonucleotide manufacturing processes.

An iron-tetraphenylcyclopentadienone tricarbonyl complex is demonstrated to act as a precursor of a catalyst for the formation of C-N bonds through a "hydrogen-borrowing" reaction between amines and alcohols.

Enantioselective nickel‐catalyzed arylative cyclizations of substrates containing a Z‐allylic phosphate tethered to an alkyne are described. These reactions give multisubstituted chiral aza‐ and carbocycles, and are initiated by the addition of an arylboronic acid to the alkyne, followed by cyclization of the resulting alkenylnickel species onto the allylic phosphate. The reversible E/Z isomerization of the alkenylnickel species is essential for the success of the reactions.

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The application of a series of (cyclopentadienone)iron tricarbonyl complexes to "borrowing hydrogen" reactions between amines and alcohols was completed in order to assess their catalytic activity. The electronic variation of the aromatic groups flanking the C═O of the cyclopentadienone influenced the efficiency of the reactions; however, in other cases, the Knölker catalyst 1, containing trimethylsilyl groups flanking the cyclopentadienone ketone, gave the best results. In some cases, the change of the ratio of amine to alcohol improves the conversion significantly. The application of iron catalysts to the synthesis of a range of amines, including unsaturated amines, was investigated.

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