On the intramolecular pyrone Diels–Alder approach to basiliolide B

Short, Enantioselective Total Synthesis of Chatancin

“…With four-step access to an intermediate containing all of the requisite carbons of 1, we were in a position to test the first key C À C bond-forming reaction, a pyrone/alkene cycloaddition; [17,18] elegant synthetic work directed toward the transtaganolide and basiliolide diterpenes served as inspiration. [19] Ultimately it was discovered that heating a toluene solution of the methoxycarbonylated pyrone for 4 days at 100 8C smoothly elicited a [4+2] cycloaddition in high yield (90 %) and without the need for high dilution. This process forges four stereocenters in a single operation (Scheme 1).…”

“…Bicycles 12 and 13 appear to arise from favorable chairlike transition states as opposed to the alternative, boatlike structures shown in Figure 2. Owing to a lack of allylic strain, which has benefitted related intramolecular pyrone/alkene cycloadditions, [19] the pyrone group in this system does not have a biasing element favoring a given pyrone rotamer. [20] The gram-scale synthesis of 12 only became possible after significant exploration of a number of individual cycloaddition reactions, substrates, and conditions (Table 1).…”

Total Syntheses of (−)‐Transtaganolide A, (+)‐Transtaganolide B, (+)‐Transtaganolide C, and (−)‐Transtaganolide D and Biosynthetic Implications

“…[17] Furthermore, transformations analogous to the ensuing Diels–Alder cyclization are known to proceed through allylic (A 1,3 ) strain minimized geometries such as Z - 32 and E - 32 . [16] These proposed reaction pathways result in the formation of diastereomeric intermediates 18 / 27 and 19/28 . Acid 18 was converted to the corresponding methyl ester ( 33 ) by treatment with diazomethane, and anomalous dispersion analysis of a single crystal confirmed the hypothesized stereochemistry of 33 (Scheme 7b).…”

Total Syntheses of (−)‐Transtaganolide A, (+)‐Transtaganolide B, (+)‐Transtaganolide C, and (−)‐Transtaganolide D and Biosynthetic Implications

“…Under this scenario, and assuming that the C9 proton is relatively acidic as a result of the withdrawing nature of the pyrone, it could be anticipated that an enzymatic and presumably enantioselective [15] rearrangement would produce the optically pure C9 diastereomers 30 (with absolute stereocontrol at C8), whereas a nonenzymatically governed process would likely result in a racemic mixture of C9 diastereomers. The demonstrated propensity of these systems to undergo diastereoselective Diels-Alder rearrangements under allylic strain control, [16] would lead to pseudoenantiomeric transtaganolides C (3) and D (4). Having prepared the enantioenriched transtaganolides A-D [(À)-1, (+)-2, (+)-3, and (À)-4] by an analogous, synthetic enantioselective Ireland-Claisen rearrangement, we believed that determination of the absolute stereochemistries of the synthetic transtaganolides could provide insight into this biosynthetic hypothesis.…”

“…[17] Furthermore, transformations analogous to the ensuing Diels-Alder cyclization are known to proceed through allylic-strain-minimized (A 1,3 ) geometries such as shown for (Z)-32 and (E)-32. [16] These proposed reaction pathways result in the formation of the diastereomeric intermediates 18 and 27 and 19 and 28. The acid 18 was converted into the corresponding methyl ester 33 by treatment with diazomethane, and anomalous dispersion analysis of a single crystal confirmed the hypothesized stereochemistry of 33 (Scheme 7 b).…”