Ethylene in Organic Synthesis. Repetitive Hydrovinylation of Alkenes for Highly Enantioselective Syntheses of Pseudopterosins

Abstract

In this report we highlight the significant potential of ethylene as a reagent for the introduction of a vinyl group with excellent stereoselectivity at three different stages in the synthesis of a broad class of natural products, best exemplified by syntheses of pseudopterosins. The late-stage applications of the asymmetric hydrovinylation reaction further illustrate the compatibility of the catalyst with complex functional groups. We also show that depending on the choice of the catalyst, it is possible to either enhance or even completely reverse the inherent diastereoselectivity in the reactions of advanced chiral intermediates. This should enable the synthesis of diastereomeric analogs of several classes of medicinally relevant compounds that are not readily accessible by the existing methods, which depend on ‘substrate-control’ for the installation of many of the chiral centers, especially in molecules of this class.

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

“…Details of these transformations 44 in the context of pseudopterosin G-J aglycone are shown in Scheme 17, along with the solid-state structure of an intermediate ketone 57 , which further confirms the configurations of all the newly created stereo-genic centers.…”

Übergangsmetallkatalysierte C‐C‐Kupplungen mit Ethylen im Labormaßstab

“…[31] Exzellente Ausbeuten und mittlere Enantioselektivitäten wurden mit den von Hayashi und Mitarbeitern [32] [37] verschiedenen Pyrrolidinoindolinen [38] und Pseudopterosinen. [39] 4 [40,43] Cobaltkatalysierte Hydrovinylierungen von verschiedenen 1,3-Dienen mit Alkenen sind schon seit einiger Zeit bekannt, [44] allerdings waren Vogt und Mitarbeiter die ersten, die eine enantioselektive Hydrovinylierung von Styrol durch chirale zweizähnige Phosphanliganden beschrieben.…”

Asymmetric Hydrovinylation and Hydrogenation with Metal Complexes of C3‐Symmetric Tris‐Binaphthyl Monophosphites

“…The major drawbacks that concern hydrovinylation of vinylarene substrates are the subsequent isomerisation of 3-aryl-1-butenes to more stable 2-aryl-2-butenes, and the formation of homodimers as side products ( Figure 2). [20,21,23,30,33,[44][45][46][47][48][49] Recently, allyl-palladium complexes that contain several types of monodentate Pchiral phosphines, [36,[50][51][52] phosphinite [34] and binaphthylbased diamidophosphite [53] have also achieved high chemoslectivities and remarkable enantioselectivities in the hydrovinylation of styrene ( Figure 3). [16][17][18][19] Although some work on catalytic hydrovinylation has been carried out with cobalt [25,26] and ruthenium [27] complexes, nickel(II) [28][29][30][31][32][33] and palladium(II) [34][35][36][37][38] organometallic precursors modified with P-donor ligands are the most representative systems and they have been extensively studied.…”