Stereocontrolled Synthesis and Structural Revision of Plebeianiol A

Abstract

We report the structural revision via synthesis of the abietane diterpenoid plebeianiol A. The synthesis was accomplished by a short and convergent sequence that featured our previously established cobaltcatalyzed hydrogen-atom-transfer-induced radical bicyclization. We further connected plebeianiol A as the likely biogenetic precursor to another previously reported ether-bridged abietane. Finally, we demonstrated that the key cyclization event is efficient with the A-ring diol protected as two different cyclic acetals or in unprotected form.Letter pubs.acs.org/OrgLett

Hydrogen‐Atom‐Transfer‐Initiated Radical/Polar Crossover Annulation Cascade for Expedient Access to Complex Tetralins

“…Inspired in part by recent reports from the groups of Shenvi [4] and Shigehisa, [5] we recently disclosed a method for stereoselective radical bicyclizations initiated by cobalt‐catalyzed hydrogen atom transfer (HAT) (Figure 1, top) [6] . Subsequently, this method enabled concise syntheses of several abietane diterpenoid natural products [7, 8] . Owing to our initial design as a cationic process (for R=CH 3 )—via HAT from cobalt to the alkene to generate a tertiary radical and radical/polar crossover by oxidation to the cation—canonical benzylgeraniol‐like precursors were chosen as starting materials to engage in concerted bicyclizations that should take advantage of preorganization [9] .…”

Synthesis of a Complex Brasilicardin Analogue Utilizing a Cobalt-Catalyzed MHAT-Induced Radical Bicyclization Reaction

“…We planned to prepare the diene by convergent Horner–Wadsworth–Emmons (HWE) alkenylation, which required aldehyde 8 and cyanophosphonate 9 . We recently reported a synthesis of the enantiomer of 9 , which was employed in our synthesis and structural revision of plebeianiol A . We were confident that this approach would allow for rapid construction of the unnatural core of 3 , further testing the limits of the bicyclization method with the presence of the amino acid side chain, and provide us with sufficient quantities of a complex brasA analogue for biochemical evaluation of immunosuppressive activity.…”

“…The desired enantiomer of cyanophosphonate 24 was made following our previously reported procedures . This compound is available in six steps from commercial materials in excellent levels of enantiopurity (98:2 er) using (DHQ) 2 PHAL as a chiral ligand (Scheme ).…”

“…Recently, our group developed a cobalt-catalyzed, MHAT-induced radical bicyclization method that efficiently produces highly oxidized diterpene-like tricyclic products ( 4 ). − We recognized that this protocol might rapidly provide a more rigid but still-simplified analogue of brasA, such as 3 . Indeed, an overlay of the calculated conformational minima of the aglycones of brasA and 3 (Figure b) suggested a reasonable approximation in terms of the potential display of both the disaccharide and amino acid motifs.…”

Au-Catalyzed Asymmetric Polyene Cyclization and Its Application in the Total Synthesis of (+)-2-Ketoferruginol, (+)-Fleuryinol B, (+)-Salviol, and (−)-Erythroxylisin A

“…And the enantioselective control of some transformations has also been achieved. However, the efficiency of these cyclization modes for the construction of 2,3-functionalized tricyclic skeleton is not satisfactory, and additional late-stage manipulation is often required for the synthesis of corresponding natural products …”