Silylation-mediated oxidation of 4-aza-3-ketosteroids with DDQ proceeds via DDQ-substrate adducts

Synthesis of Cyclic Enones via Direct Palladium-Catalyzed Aerobic Dehydrogenation of Ketones

“…4 Their preparation typically requires two or more steps 5-7 and/or the use of stoichiometric reagents, such as 2-iodoxybenzoic acid (IBX) 8,9 or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). 10 Catalytic methods for aerobic dehydrogenation of ketones to enones would provide appealing, atom-economical alternatives to these stoichiometric method.…”

Reflections on Process Research II

“…chapter 1 I noted the unusual silylation-mediated [bistrimethylsilyltrifluoroacetamide (BSTFA)] DDQ oxidation of a lactam to form its unsaturated analog proceeding via a substrate-DDQ adduct followed by a thermal loss of the hydroquinone (Figure 1.8). This chemistry forms the nucleus of the finasteride manufacturing process, 14 but the story from the bench to the pilot plant during the early development of this product is much more complex than the scheme indicates. We have all delighted in telling this episode over the years in our finasteride presentations.…”

Reflections on Process Research

“…These observations formed the core of a very practicable approach to finasteride, once again tying together solid new science with hardcore process research. (24,25) During the 90's we foresaw a need for the enantiomers of 21, one of our lead LTD 4 antagonists. The compound was proceeding in development as the racemate, despite the fact that as early as 1960 we were proceeding forward with single enantiomer drugs such as methyldopa, rather than racemates.…”