A Catalytic Asymmetric Protecting-Group-Free Total Synthesis of (4S,5S)-4,8-Dihydroxy-3,4-dihydrovernoniyne and Its Enantiomer

Abstract

A catalytic asymmetric second generation synthesis of (4S,5S)-4,8-dihydroxy-3,4-dihydrovernoniyne has been completed employing the asymmetric dihydroxylation strategy. Further, a four-step protecting-group-free synthesis of the natural product and its enantiomer has been achieved through the modified Knoevenagel reaction, asymmetric dihydroxylation, and Cadiot–Chodkiewicz coupling. The protecting-group-free synthesis is completed in four steps and 41% overall yield.

Total Synthesis and Structural Revision of Cephalosporolide J

“…For the synthesis of the optically active -lactone 7 corresponding to the right-hand segment D, we implemented a method consisting of the modification of the approach reported by Fernandes et al 16 Briefly, aldehyde 5, prepared from butane-1,4-diol by a known method, 17 was converted into ,-unsaturated ester 6 via modified Knoevenagel condensation with monomethyl malonate (Scheme 3). 18 A Sharpless asymmetric dihydroxylation 19 of compound 6 afforded the -lactone 7 in 94% yield with up to 84% ee (>95% ee after recrystallization, as determined by chiral HPLC analysis).…”

Diastereoselective Allylation in the Divergent Total Syntheses of Guaianolides (+)-Ligustrin and (+)-Grosheimin and the Formal Synthesis of (−)-Eupalinilide E

“…However, the applications of these in total syntheses have largely remained underexplored. With our interest in the synthesis of γ-butyrolactones and γ-butenolide-based natural products and considering the potential of more functionalized allyl bromolactone addition diastereoselectively to aldehydes creating two stereocentres and mapping them with those present in guaianolides, we embarked on their efficient protecting-group-free and concise total synthesis (Scheme c).…”

Concise Stereoselective Synthesis of β-Hydroxy-γ-lactones: (4R,5R)-4-Hydroxy-γ-decalactone from the Japanese Orange Fly and Enantiomers of Arachnid Harvestmen Isolates

“…It can be concluded from these synthetic studies that the syn -lactones are easily accessible but the isomeric anti -lactones are not. With our interest in the synthesis of γ-butyrolactones and the recent use of the chiral pool material d -glucono-δ-lactone in efficient one-pot conversion to γ-vinyl-β-hydroxy-γ-lactone and thereby synthesis of various natural products, , we envisaged a concise synthesis of both diastereomers of the 4-hydroxy-γ-butyrolactones.…”