Total Syntheses of (+)‐Sarcophytin, (+)‐Chatancin, (−)‐3‐Oxochatancin, and (−)‐Pavidolide B: A Divergent Approach

Abstract

A concise and divergent approach for the total syntheses of four cembrane diterpenoids, namely (+)‐sarcophytin, (+)‐chatancin, (−)‐3‐oxochatancin, and (−)‐pavidolide B, has been developed, and it also led to the structural revision of (−)‐isosarcophytin. The key steps of the strategy feature a double Mukaiyama Michael addition/elimination, a Helquist annulation, two substrate‐controlled facial‐selective hydrations, and a pinacol rearrangement. The described syntheses not only achieved these natural products in an efficient manner, but also provided insight into the biosynthetic relationship between the two different skeletons.

Total Syntheses of (+)‐Sarcophytin, (+)‐Chatancin, (−)‐3‐Oxochatancin, and (−)‐Pavidolide B: A Divergent Approach

“…However,s ubjection of mesylate 26 to various Lewis acids [7a] resulted in decomposition, and an intramolecular aldol cyclization occurred to give pentacycle 27 under basic conditions.P leasingly,t he corresponding triflate 26' ' without isolation was capable of transformation into the anticipated product 27' ' in the presence of tBuOK/tBuOH in 69 %yield. [24] Finally,aregioselective formation of the D 8,9 -olefin was achieved through Mukaiyama dehydrogenation procedure, [25] accompanied by epimerization at C11 to furnish (À)-pavidolide B(5,ORTEP drawing, Scheme 5) [15] in 75 %y ield. Despite initial failures in the direct lactonization of 27' ' by Mitsunobu reaction, the intramolecular S N 2c yclization of the corresponding mesylate delivered 29 with low efficiency(< 10 %yield), which was likely due to the steric effect from the equatorial isopropyl group at C1.…”

“…[22] Subsequently,anumber of reducing reagents such as Zn-(BH 4 ) 2 ,NaBH 4 /Et 3 B, l-Selectride,DIBAL-H, and SmI 2 were screened for the regio-and diastereoselective reduction of the ketone at C11, and either caused the over-reduction to yield amixture of isomeric triols or gave exclusively the trans-diol C11-epi-8 (ORTEP drawing, Scheme 5). [15] Fortunately,itwas found that by treatment of 25 with NaBH 4 in pyridine, [23] 8 was obtained as amajor isomer in 78 %yield, setting the stage for the challenging pinacol rearrangement. However,s ubjection of mesylate 26 to various Lewis acids [7a] resulted in decomposition, and an intramolecular aldol cyclization occurred to give pentacycle 27 under basic conditions.P leasingly,t he corresponding triflate 26' ' without isolation was capable of transformation into the anticipated product 27' ' in the presence of tBuOK/tBuOH in 69 %yield.…”

“…After exhaustive trials,w ef ound the use of as ub-stoichiometric amount of BF 3 ·Et 2 Ocould trigger aring contraction of 27' ' to provide [3,5,5,7] tetracycle 28,w hich then underwent as uccessive intramolecular nucleophilic addition of the carboxylic acid to open the electron-withdrawing cyclopropane ring and afforded 29 in 84 %yield. [24] Finally,aregioselective formation of the D 8,9 -olefin was achieved through Mukaiyama dehydrogenation procedure, [25] accompanied by epimerization at C11 to furnish (À)-pavidolide B(5,ORTEP drawing, Scheme 5) [15] in 75 %y ield.…”

“…[10] Finally,t he preparation of 11 could be traced back to the readily available chiral alcohol (À)-12 [6,11] and Rawal diene 13 [12] by taking advantage of ad ouble Mukaiyama Michael addition/elimination process. [15] Through treatment with tBuOK and dimethyl carbonate,the installation of the lactone was realized and afforded 17 in 75 %y ield. Benzoylation of (À)-12 in the presence of Bz 2 O, Et 3 N, and 4-DMAP afforded 14 in 95 % yield.…”

“…The stereochemistry of the quaternary carbon center at C4 was unambiguously determined by X-ray crystallographic analysis (ORTEP drawing, Scheme 2). [15] Through treatment with tBuOK and dimethyl carbonate,the installation of the lactone was realized and afforded 17 in 75 %y ield. Presumably,t he reaction occurred through at ransesterification/Dieckmann condensation sequence via the intermediacyo f16,s ince subjection of the corresponding methyl ether 10' ' to such conditions only caused the recovery of the starting material.…”