Synthesis of (±)‐Merrilactone A and (±)‐Anislactone A

Abstract

Eine gemeinsame Route führte zu einer kurzen Synthese der Sesquiterpenoide Merrilacton A und Anislacton A. Eine reduktive Epoxid‐Spaltung mit TiIII und eine radikalische Cyclisierung wurden genutzt, um das quartäre C9‐Zentrum im Kern des BC‐Bicyclus einzurichten. Selektive Lactonisierungssequenzen legen dann regiodivergente Pfade zum Merrilacton A (formale Synthese) und zum Anislacton A (Totalsynthese) fest.

Synthesis of (±)‐Merrilactone A by a Desymmetrization Strategy

“…Then the polarity of the newly formed epoxide was postulated to enforce exclusive anti ‐addition of allenyl organometallics to the sterically biased ketone, and this provided epoxyalcohol 11 as a single diastereomer (stereochemistry established by NOESY). This type of stereo‐preference was observed by Greaney on a similar substrate without the closed A‐ring lactone . However, treating 10 with 4‐TMS‐3‐butynyl lithium led to undifferentiated addition to both carbonyls, whereas 4‐TMS‐3‐butynyl Grignard reagent caused an unexpected ketone reduction.…”

“…This type of stereo‐preference was observed by Greaney on a similar substrate without the closed A‐ring lactone . However, treating 10 with 4‐TMS‐3‐butynyl lithium led to undifferentiated addition to both carbonyls, whereas 4‐TMS‐3‐butynyl Grignard reagent caused an unexpected ketone reduction. Hereafter, homologation of 11 was effected under Crabbé’s condition, and afforded epoxy‐allene 12 in 65 % yield along with 10 (20 %), presumably due to steric congestion that facilitated depropargylation.…”

“…Hereafter, homologation of 11 was effected under Crabbé’s condition, and afforded epoxy‐allene 12 in 65 % yield along with 10 (20 %), presumably due to steric congestion that facilitated depropargylation. Upon exposure to freshly prepared Cp 2 TiCl, 12 underwent the anticipated reductive epoxide cleavage and subsequent 5‐exo‐dig cyclization of a tertiary radical onto the pendant allene. This resulted in A‐B‐C tricycle 13 (55 %) along with caged hemiketal 14 (40 %), which arose by a competing 5‐endo‐dig cyclization followed by tandem radical trapping with the proximal carbonyl of the A‐ring lactone.…”

Neurotrophic Natural Products: Chemistry and Biology

“…[82] Key to the first-generation synthesis was a Cp 2 TiCl 2 /Zn-triggered reductive epoxide cleavage followed by radical cyclization, which furnished the A ring of 48 containing the C9 quaternary center. The second-generation synthesis was based on a cyanide 1,4-addition/aldol reaction cascade [83] that constructed the A ring and the C9 quaternary center.…”

Development of Chiral Building Blocks Having a Bicyclo[3.3.0]Octane Framework Using a Diastereomeric Resolution‐Selective Deprotection

“…Enantiomerically pure compounds could become important chiral building blocks in the production of fine chemicals with applications as pharmaceuticals, or of valuable chiral auxiliaries with applications as ligands of enantiomerically pure reagents or catalysts in organic synthesis. [1][2][3][4][5][6][7][8][9] Specifically, enantiomerically pure bicyclo [3.3.0]octane derivatives could become useful chiral building blocks because the bicyclo [3.3.0]octane framework is a common structural building block of a variety of natural products and pharmaceutical compounds that contain substituted pentalenes such as some carbacyclins, [10][11][12] sesquiterpenoids, 11,[13][14][15][16][17][18] macrolactams, 18,19 and so on 18,20 (Fig. 1) 13,21 .…”