A Formal Total Synthesis of Palmerolide A

Abstract

Density functional calculations are reported for complexes of general formula [(carbene)RhClL2] featuring model phosphino‐ and aminocarbenes. Both the cis and trans isomers of the rhodium(I) η1‐complexes (1–9) were investigated, and the influence of the rhodium co‐ligands (L=ethylene, phosphine, or carbon monoxide) was evaluated. In the case of phosphinocarbenes and carbon monoxide as a ligand, a somewhat unusual coordination mode was observed, in which a significant intramolecular Cl→Ccarbene interaction is present. The propensity of phosphino‐ and aminocarbenes to behave as four electron donors was also investigated both structurally and energetically on the related η2‐complexes 10–18. These results as a whole emphasize the structural versatility of phosphino‐ compared with aminocarbene complexes.

Secondary Metabolites from Polar Organisms

“…To date, three total syntheses [116,117,118,119,120] of palmerolide A have been reported. Four groups disclosed formal syntheses [121,122,123,124,125,126], and various synthetic approaches have also been described [127,128,129,130,131,132,133,134,135]. The synthesis of the reported structure of palmerolide C has also been achieved, and a structural revision has been proposed [136].…”

Esf-Cost High-Level Research Conference Natural Products Chemistry, Biology and Medicine III

“…Chair: Arthur Catino (Harvard University, MA, USA) Krishna Kaliappan (Indian Institute of Technology Bombay, India) reported the synthesis of palmerolide A (figure 3; 3) [3]. Isolated from Antarctic tunicate Synoicum adareanum, palmerolide is a 20-membered macrolide with a total of five stereocenters and an enamide side chain.…”

Hypervalent iodine reagents in the total synthesis of natural products

“…The crude aldehydes were used in Wittig or Horner-Wadsworth-Emmons reactions. 246 The oxidation of a primary allylic alcohol was reported using 2.5 equiv of IBX in refluxing EtOAc for 4 h during the total synthesis of (À)-englerin A. 151 iii) A mixture of DMSO with another solvent was used in some examples.…”

“…242 In the synthesis of all stereoisomers of phenatic acid B, the oxidation of a secondary alcohol was accomplished with 2 equivalents of IBX in refluxing EtOAc for 20 h. 236 In the formal synthesis of palmerolide A, primary alcohols were oxidized to the corresponding aldehydes using 1.3 to 1.5 equiv of IBX at reflux in EtOAc for 6 h. The crude aldehydes were used in Wittig or Horner-Wadsworth-Emmons reactions. 246 The oxidation of a primary allylic alcohol was reported using 2.5 equiv of IBX in refluxing EtOAc for 4 h during the total synthesis of (─)-englerin A. 151 iii) A mixture of DMSO with another solvent was used in some examples.…”