Enantiocontrolled Total Synthesis of (−)-Retigeranic Acid A

Abstract

The asymmetric total synthesis of (−)-retigeranic acid A has been realized. The key features of the current synthesis include (1) a Pt-catalyzed Conia-ene 5-exo-dig cyclization of enolyne to establish the key quaternary stereochemical center of C-10 (D/E ring), (2) an intramolecular diastereoselective Prins cyclization to construct the trans-hydrindane backbone (A/B ring), and(3) a late-stage intramolecular Fe-mediated hydrogen atom transfer (HAT) Baldwin-disfavored 5-endo-trig radical cyclization to rapidly assemble vicinal quaternary centers and the core structure of (−)-retigeranic acid A (C ring).

Controllable skeletal reorganizations in natural product synthesis

“…However, in the vast majority of angular triquinanes-including retigeranic acid A (130), silphinenes, and bipolarolides-at least one of these stereocenters is tertiary or oxa-quaternary. Therefore, to synthesize 130, [133][134][135][136][137][138] the Ding group developed a new rearrangement in 2023, when they reported a reductive skeletal reorganization strategy (Scheme 13C). 139 First, vinylphenol 131, which was prepared in eight steps from commercially available compounds, was exposed to the ODI-[5 + 2]/pinacol rearrangement cascade conditions, which furnished diketone 132.…”

Iron-Mediated Hydrogen Atom Transfer Radical Cyclization of Alkenyl Indoles and Pyrroles Gives Their Fused Derivatives: Total Synthesis of Bruceolline E and H

“…Further, MHAT radical cyclization has been extensively used for the synthesis of carbo- and heterocycles. Recently, during the preparation of this manuscript, the first example of an iron-catalyzed, Baldwin-disfavored 5- endo - trig radical cyclization was reported for the installation of the pentacyclic core structure of retigeranic acid A (Scheme C). , …”

Total Synthesis of Penicibilaenes Enabled by a Tandem Double Conia-ene Type Reaction

“…Conia-ene cyclization of an alkyne bearing an enolizable carbonyl group is a classic example of a thermal ene reaction and has proved to be useful for synthesis of carbocycles in a step- and atom-economical manner . The utility of this cyclization methodology has been significantly expanded in recent years by the use of metal catalysts, which enable the reaction to occur at lower temperatures and render this reaction as a powerful methodology for complex molecule synthesis . Herein, we report our effort to develop the tandem Conia-ene type reaction as a key step to forge the sterically rigid tricyclo­[6.3.1.0 1,5 ]­dodecane core (Scheme ).…”