Electrochemically Enabled One‐Pot Multistep Synthesis of C19 Androgen Steroids

Abstract

The synthesis of many valuable C19 androgens can be accomplished by removal of the C17 side chain from more abundant corticosteroids, followed by further derivatization of the resulting 17‐keto derivative. Conventional chemical reagents pose significant drawbacks for this synthetic strategy, as large amounts of waste are generated, and quenching of the reaction mixture and purification of the 17‐ketosteroid intermediate are typically required. Herein, we present mild, safe, and sustainable electrochemical strategies for the preparation of C19 steroids. A reagent and catalyst free protocol for the removal of the C17 side chain of corticosteroids via anodic oxidation has been developed, enabling several one‐pot, multistep procedures for the synthesis of androgen steroids. In addition, simultaneous anodic C17 side chain cleavage and cathodic catalytic hydrogenation of a steroid has been demonstrated, rendering a convenient and highly atom economic procedure for the synthesis of saturated androgens.

Scaling-up Electroorganic Synthesis Using a Spinning Electrode Electrochemical Reactor in Batch and Flow Mode

“…13 C NMR (125 MHz, chloroform-d): δ 216.8, 207.6, 199.5, 167.9, 124.8, 63.3, 50.4, 50.4, 49.8, 38.3, 36.3, 35.9, 34.7, 33.7, 31.9, 30.9, 21.6, 17.3, 14.7 ppm. These data agree with those previously reported in the literature …”

“…Then, the solvent was evaporated under reduced pressure and the residue was diluted with aqueous NaHCO 3 (sat) and extracted with DCM. The organic phase was dried over Na 2 SO 4 and evaporated under reduced pressure, yielding 141.4 g (94%) of adrenosterone ( 6 ) as an off-white solid, mp 204–205 °C (lit . 206–208 °C).…”

“…The organic phase was dried over Na 2 SO 4 and evaporated under reduced pressure, yielding 163.5 g (91%) of adrenosterone ( 6) as an off-white solid, mp 201−202 °C (lit. 24…”

Efficient Aliphatic Hydrogen-Isotope Exchange with Tritium Gas through the Merger of Photoredox and Hydrogenation Catalysts

“…Evidence for generating iminium intermediates was observed with 1 where N -demethylation was a major impurity, presumably formed via the process outlined in the Supporting Information. This N -demethylation is precedented in amine oxidation chemistry both under photoredox and electrochemical conditions, including aerobic Rh catalysis …”

Chemoselective Electrochemical Oxidation of Secondary Alcohols Using a Recyclable Chloride-Based Mediator

“…A mixture MeCN/H2O was used as solvent in both cases, with a concentration of 1a of 0.1 M. For the TEMPO-mediated oxidation, the water phase contained 0.1 M of a phosphate buffer of pH = 9.2, 5,16 which also acted as supporting electrolyte. As expected, when TEMPO was used as mediator, aldehyde 3a was observed as the major oxidation product (Figure 2).…”