The Palladium-Catalyzed Enyne Cycloisomerization Reaction in a General Approach to the Asymmetric Syntheses of the Picrotoxane Sesquiterpenes. Part I. First-Generation Total Synthesis of Corianin and Formal Syntheses of Picrotoxinin and Picrotin

Abstract

The palladium-catalyzed enyne cycloisomerization is used as a key ring-forming process for the obtention of the cis-fused hydrindane carbon skeleton characteristic of the picrotoxanes sesquiterpenes. The enyne cycloisomerization product is suitably functionalized so that each carbon of the hydrindane core can be modified to permit access to many members of the picrotoxane family, not only to picrotoxinin itself. Part I of this report describes our first-generation approach to the picrotoxane sesquiterpenes as illustrated by the asymmetric synthesis of corianin and the asymmetric formal syntheses of picrotoxinin and picrotin. A new catalyst system to effect the cycloisomerization emerged from this study. Subsequent work proved the generality of this catalyst system.

Asymmetric Synthesis of the Aminocyclitol Pactamycin, a Universal Translocation Inhibitor

“…Trost and coworkers have demonstrated its use in their synthesis of corianin. 34 The Cao group likewise has shown the use of CH 2 O in aldol reactions en route to a total synthesis of malyngamide U. 35 After significant experimentation in our system, we found that bubbling gaseous CH 2 O (generated by the pyrolysis of paraformaldehyde) through a solution of the lithium enolate of 40 at −45 °C furnished the desired primary alcohol 41 in 70% yield.…”

Carvone as a Versatile Chiral Building Block for Total Syntheses of Heterocyclic Sesquiterpenoids

“…Among them, picrotoxinin (106) (Scheme 9) is known to be a potent and specific inhibitor of the antagonist of the neurotransmitter suppressor -aminobutyric acid (GABA). Trost et al synthesized Yoshikoshi intermediate 76 [14] for picrotoxane synthesis employing their original palladium catalyzed ene-yne cycloisomerization as a key reaction (Scheme 6) [15].…”

“…Corey's intermediate 80 [16] for picrotoxane synthesis was also synthesized from the same PMBO derivative of 73 (Scheme 7) [14]. Allyl inversion provided chloride 77, which was transformed into triol 78 after substitution with cesium acetate, followed by deprotection.…”

Pd(0)‐ and Pd(II)‐Catalyzed Reactions of Alkynes and Benzynes

“…However, smooth cyclization took place to give the Alder-ene product in a quantitative yield at 50 • C when N ,N -bis(benzylidene)ethylenediamine (BBEDA) was used as a ligand, and the triol 142 was obtained in 75 % yield after deprotection, and the asymmetric synthesis of picrotoxinin has been carried out. The effect of the BBEDA ligand is remarkable [44]. The cycloisomerization of 1,6-enynes proceeds smoothly in the presence of AcOH or HCO 2 H and the reaction is explained by the following mechanism (hydridopalladium acetate mechanism) [45].…”