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

Abstract

Herein, we report on ac omparative Stille and Suzuki cross-coupling study of steroidal vinyl (pseudo)halides with different boronic acids and tributyltin organyls.F urthermore,w eh ave investigated the "inverse" case of those cross-coupling reactions, i.e., the reactiono fas teroidal vinylpinacolatoborane or at ributyltins teroid with various bromides.T he development of bothm ethods allows the introduc-tion of different residues at C-17 of steroid skeletons providing access to ab road variety of steroid analogues which are of high interest for biological screenings or natural product synthesis.

Synthesis of Functionalized Alkenes by a Transition-Metal-Free Zweifel Coupling

“…A range of different aromatic boronic esters could also be coupled with this vinyl lithium enabling the synthesis of a series of derivatives of the anticancer agent Abiraterone (32-36). 16 Notably, in contrast to 31, the syn elimination for these examples did not require addition of TBAF and could be carried out with sodium methoxide. The enhanced rate of elimination observed in these cases is likely a consequence of the benzylic nature of the β-iodoboronic ester intermediates.…”

Towards the synthesis of calotropin and related cardenolides from 3-epiandrosterone: A-ring related modifications

“…It is noteworthy that this route requires two additional steps including the cleavage of the protecting group and reoxidation of C-17 for being applicable for the synthesis of calotropin since the installation of the butenolide moiety demands a keto functionality at C-17 as it was previously shown by us. 49 The obtained poor overall yield of the required precursor along with the number of synthetic steps, encouraged us to search for an alternative route maintaining the oxidation state at C-17 (Scheme 2, green route). The novel approach relies on a Sharpless dihydroxylation of androst-2-ene 15 followed by a regioselective acetylation of the C-3 hydroxyl group.…”

Synthesis, Characterization, and Biological Properties of Steroidal Ruthenium(II) and Iridium(III) Complexes Based on the Androst-16-en-3-ol Framework

“…As previously shown by our group, pyridine containing substituents are best introduced by the Stille cross-coupling reaction. [15] Starting from epiandrosterone (3), the desired ligands were easily accessible by a two-step procedure (Scheme 1).…”

“…(3) via a two-step procedure. [15] Since numerous procedures exist in literature for the synthesis of cyclic ruthenium(II) complexes of 2-phenylpyridines, [16] we tried analogous reaction conditions with 2-(4-bromophenyl)pyridine. .…”