The implementation of cyanation chemistry at manufacturing scales using batch equipment can be challenging because of the hazardous nature of the reagents employed and the tight control of reaction parameters, including cryogenic temperatures, that help to afford acceptable selectivity and conversion for the desired reaction. Application of continuous flow chemistry offers a means to mitigate the risk associated with handling large amounts of hazardous reagents and to better control the reaction parameters. A case study describing the cyanation of a glycoside using continuous flow chemistry toward the synthesis of the drug candidate remdesivir is presented.

The palladium-catalyzed selective β-carboelimination and cross-coupling chemistry of benzocyclobutenols is described. In contrast to the base-mediated ring-opening reactions of benzocyclobutenols, this variant proceeds with exclusive cleavage of the proximal bond.

A palladium-catalyzed tandem semipinacol rearrangement/direct arylation reaction using α-aryl isopropenyl-tert-cyclobutanols has been developed. This reaction gives access to benzodiquinanes in moderate to good yields and tolerates alkyl-, alkoxy-, and halogen-substituted aryl groups.

This manuscript describes the development and implementation of a scalable additive system, consisting of a lanthanide salt and a solubilizing quaternary ammonium salt, to improve the yield and robustness of the addition of an organomagnesium reagent to a ribonolactone en route to remdesivir. This system was found to be generally applicable in enhancing other challenging organomagnesium additions to enolizable and hindered carbonyl-containing compounds.

A series of 9-substituted fluorenols and 9,9'-disubstituted-9,9'-bifluorenyls were irradiated to give products derived from fluorenyl radicals. Product distribution was solvent dependent. A TEMPO adduct was isolated from the photoexcitation of 9-fluorenol. An unusual unsymmetrical 3,9'-bifluorenyl was observed from the photolysis of 9-trifluoromethylfluorenol and 9,9'-di(trifluoromethyl)-9,9'-bifluorenyl in more polar or hydrogen-bonding solvents. The electronic nature of 9-substituted fluorenyl radicals was probed using theoretical calculations showing the dipolar character of species with electron-deficient groups. These constitute the first examples of "doubly destabilized" radicals.