Pd(PPh3)4/AgOAc-catalyzed coupling of 17-steroidal triflates and alkynes: Highly efficient synthesis of D-ring unsaturated 17-alkynylsteroids

Chemicals from Alkynes with Palladium Catalysts

“…Vinyl triflates, prepared easily by trapping the corresponding enolate from ketones, can also be used for the palladium-catalyzed Sonogashira coupling with terminal alkynes, giving rise to conjugated enynes. A useful example of this methodology is the cross-coupling of 17-steroidal triflates, such as 284 , and terminal alkynes, such as but-3-yn-1-ol, to give 17-alkynylsteroids such as 285 (Scheme ) . The process was catalyzed by the combination of Pd(PPh 3 ) 4 (5 mol %)/CuI (20 mol %) in the presence of diisopropylethylamine and in DMF as solvent at room temperature, although it was observed that the use of silver acetate as cocatalyst instead of CuI gave rise to higher yields.…”

Stille and Suzuki Cross‐Coupling Reactions as Versatile Tools for Modifications at C‐17 of Steroidal Skeletons – A Comprehensive Study

“…For this purpose, epi ‐androsterone was converted to the corresponding vinyl bromide/iodide 1a‐Br / 1a‐I (see the Supporting Information for synthesis of 1a‐Br and its crystal structure) using first hydrazine to build the hydrazone and then NBS and pyridine as base or iodine and trimethylamine, respectively, according to known protocols . The vinyl triflate 1b‐OTf was accessible by protection of the OH group of epi ‐androsterone as an acetate followed by the treatment with KHMDS and PhN(Tf) 2 at −78 °C . Then we tested several sets of general reaction conditions for the Stille coupling of 4‐tributyltinvinylfuran‐2(3 H )‐one 2a and vinyl bromide 1a‐Br , vinyl iodide 1a‐I and vinyl triflate 1b‐OTf constructing the cardenolide 3a/3b (Table ) with 20 mol% Pd(PPh 3 ) 4 as catalyst.…”

Site-Selective Synthesis of 3,17-Diaryl-1,3,5,16-estratetraenes

“…5b,8 In 2010, Sun et al reported the twofold Sonogashira reaction of the bis(triflate) of estradione. 9 Due to the biological importance of 3-and 17-funtionalised 1,3,5,16-estratetraenes, we decided to study arylation reactions of the bis(triflate) of estrone, i.e., of 3,17-(trifluorosulfonyloxy)-1,3,5,16estratetraene. Herein, we report what are, to the best of our knowledge, the first Suzuki-Miyaura reactions of the bis(triflate) of estradione.…”