A Short, Enantioselective Synthesis of the AB-Ring Substructure of the Brevetoxins via endo-Selective Alkynol Cycloisomerization

C-Glycosides to Fused Polycyclic Ethers. A Formal Synthesis of (±)-Hemibrevetoxin B

“…The synthesis of the A−B ring system from a similar precursor proved to be problematic in McDonald's hemibrevetoxin work involving alkynyl-tungsten cyclizations. See ref a.…”

“…Our hemibrevetoxin B efforts began with a hetero-Diels Alder cycloaddition reaction to the A-ring (Scheme ). From the Danishefsky diene 12 , a hetero-Diels Alder cycloaddition with aldehyde 13 provided dihydropyrone 14 in 92% yield. , Attempted reduction of 14 using L-selectride gave predominantly products resulting from 1,4-reduction. Fortunately, the reduction of 14 using Luche's conditions (NaBH 4 , CeCl 3 ·7H 2 O) gave the corresponding allylic alcohol 15 having the desired C-3 stereochemistry for hemibrevetoxin B. , Because of its sensitivity to chromatography and storage, 15 was carried into the subsequent epoxidation reaction immediately following its synthesis without purification.…”

“…Our starting point for this approach was hydroxy-acetal 17 (Scheme ). Allyl incorporation using allylsilane and TMSOTf gave 31 having the desired relative stereochemistry in 89% yield 16b. The incorporation of the necessary C-ring carbon atoms was accomplished through the esterification of the secondary alcohol with 32 .…”

A Highly Efficient Synthesis of the Hemibrevetoxin B Ring System

“…The synthesis of the hemibrevetoxin A-ring is depicted in Scheme . From the Danishefsky−Kitahara diene 6 , a hetero-Diels−Alder cycloaddition with 7 provided dihydropyrone 8 in 92% yield. , Leuche reduction and hydroxyl-directed m -CPBA epoxidation in methanol 11b provided diol acetal 9 as a single isomer in 65% yield for the two steps. Differentiation of the 2° hydroxyls via stannyl ketal formation and equatorial benzyl ether generation gave 10 in 88% yield 8b.…”