An Acid-Catalyzed Addition and Dehydration Sequence for the Synthesis of Heteroarylated Steroidal Dienes

Abstract

Additions of heteroarenes to hormone steroids containing an α,β-unsaturated ketone are reported. Additions of a range of electron-rich heteroarene nucleophiles, including indoles, a pyrrole, and a thiophene, to a variety of commercially available steroids and subsequent dehydration formed 3-heteroarylated steroidal dienes in up to 93% yield. This atom-economical reaction sequence occurs under mild reaction conditions in the presence of catalytic bismuth triflate.

Benign Synthesis of Thiazolo-androstenone Derivatives as Potent Anticancer Agents

“…6–9,31 Recently, Stanley et al have reported the synthesis of heteroarylated steroidal diene by using bismuth triflate as a catalyst. 32…”

“…[6][7][8][9]31 Recently, Stanley et al have reported the synthesis of heteroarylated steroidal diene by using bismuth triflate as a catalyst. 32 In our pursuit of synthesizing bioactive heterocycles, 33−36 we envisaged the synthesis of thiazolino-androstanedione derivatives via our recently developed methodology that entails a 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) mediated domino reaction of γ-bromo enones (3) with thioamides and thioureas to form thiazoline products (4) under refluxing conditions. 37 Surprisingly, hitherto unknown 3,4-thiazolo-androstenone product (5) was formed instead of the expected 5,6thiazolino-androstenedione derivative (4) (Scheme 1).…”

“…In view of the importance of heterocycle-bearing steroidal derivatives, a large number of methodologies and synthetic schemes have been described, − often involving multistep synthesis. − , Recently, Stanley et al have reported the synthesis of heteroarylated steroidal diene by using bismuth triflate as a catalyst …”

Hexafluoroisopropanol-Mediated Domino Reaction for the Synthesis of Thiazolo-androstenones: Potent Anticancer Agents

“…25−31 Novel molecules based on the steroidal core structure are synthesized in a multistep synthesis 7,12,32−34 and using catalyst. 29…”

“…Pyrazole-fused sterone, stanazolol, derivative is known for potent anabolic activities (Figure ). Not surprisingly, syntheses of heterocycle-incorporated steroidal derivatives have been reported in a large number of literature. − Novel molecules based on the steroidal core structure are synthesized in a multistep synthesis ,,− and using catalyst …”