Ligand Tuning in Asymmetric Hydrovinylation of 1,3-Dienes: A Stereoselective Route to Either Steroid-C₂₀ (S) or -C₂₀ (R) Derivatives

Abstract

Abstract1,3-Dienes derived from steroidal D-ring C 17 -ketones undergo Ni(II)-catalyzed hydrovinylation to give 1,2-or 1,4-addition of ethylene. Using finely tuned phosphoramidite ligands it is possible to synthesize either the C 20 (R)-or the C 20 (S)-derivatives without mutual contamination. The proportion of the 1,4-adduct, which is also formed stereoselectively, can be minimized by optimizing the reaction conditions. Since the two alkenes in the resultant dienes have differing steric demands for many potential reactions, and are ideally juxtaposed for further D-ring functionalization, these intermediates could be useful for the preparation of biologically important compounds such as vitamin D analogs and various antitumor steroidal glycosides.

Phosphoramidite: privilegierte Liganden in der asymmetrischen Katalyse

“…[373,374] Hierbei konnten die leicht zu modifizierenden modularen Phosphoramidit-Liganden ihre Vielseitigkeit unter Beweis stellen. Ein breites Screening verschiedener Binaphtholgerüste und Amine führte zur Identifizierung des Phosphoramidit-Liganden (R a ,S c )-L20 (Schema 22), der die Regio-und Enantioselektivitäten der Hydrovinylierung von Styrolen deutlich verbesserte (bis 98 % Ausbeute, 99 % ee für 246).…”

P-Stereogenic monophosphines in Pd-catalysed enantioselective hydrovinylation of styrene

“…Hydrovinylation has much interest in enantioselective synthesis because it provides a short route to 2-arylpropionic acids, the most important family of nonsteroidal antiinflammatory drugs, including naproxen or ibuprofen [6,7]. More recently it has also been employed in the stereoselective construction of benzylic all-carbon quaternary stereocentres [8e10], a structural motif present in pharmacologically important compounds, and in the short synthesis of natural products [11,12]. In spite of its enormous potential and its long history [13,14], hydrovinylation is still an underused reaction even in the synthesis of fine chemicals.…”

Broadly Applicable Stereoselective Syntheses of Serrulatane, Amphilectane Diterpenes, and Their Diastereoisomeric Congeners Using Asymmetric Hydrovinylation for Absolute Stereochemical Control

“…Moving forward, there was some uncertainty about how we might install the C 4 configuration, even though earlier we had shown in model systems (Scheme 1, b and c) hydroboration followed by catalytic heterogeneous (Pd/C) or homogeneous Ir-catalyzed directed hydrogenation using Crabtree’s catalyst 26 would result in high diastereoselectivity at the ring carbon in some model systems. 21a,27 Single electron-transfer reductions have also been shown to have modest control in the installation of benzylic configuration in related systems. 28 The generic structure represented by the alcohol 18 is a key compound in our plans since it sets the stage for further elaboration into serrulatanes and amphilectanes including several more complex members of the family.…”