Ketone-, ester-, and amide-containing potassium trifluoroboratohomoenolates were prepared in good to excellent yields from the corresponding unsaturated carbonyl compounds. They were shown to be effective coupling partners in the Suzuki-Miyaura reaction with a variety of electrophiles including electron-rich and electron-poor aryl bromides and -chlorides.

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Potassium- and tetra-n-butylammonium organotrifluoroborates containing hydroxyl groups have been prepared and oxidized using several common oxidants. Aryl-, alkenyl-, and alkyltrifluoroborates containing both primary and secondary hydroxyl groups were oxidized in moderate to excellent yields with complete retention of the trifluoroborate moiety. The utility of these oxidized products was demonstrated in a Suzuki-Miyaura cross-coupling reaction.

The Suzuki-Miyaura cross-coupling of potassium aryland heteroaryltrifluoroborates with aryl-and heteroaryl triflates is reported. The catalyst system provides good to excellent yields using sterically hindered and electronically diverse coupling partners.

Evolution of the process strategies to prepare CEP-28122, an anaplastic lymphoma kinase (ALK) inhibitor, is presented. The initial medicinal chemistry route, used for the preparation of key supplies for biological screening, is reviewed. In addition, the process research and development of the final optimized process for manufacture of preclinical and clinical supplies is discussed. Details regarding a blocking group strategy for selective nitration; discovery of a one-pot transfer hydrogenation to effect a reductive amination, nitro group reduction, and dehalogenation; an enzymatic resolution of a critical intermediate; and the discovery of a novel, stable, in situ generated mixed mesylate hydrochloride salt of the API are disclosed.