Total Synthesis of (–)‐Heliespirone A and (+)‐Heliespirone C

Abstract

Total syntheses of the spiro‐epimeric natural products (–)‐heliespirone A and (+)‐heliespirone C are described. The successful strategy involved an aromatic Claisen rearrangement, a diastereoselective Sharpless asymmetric dihydroxylation (AD) reaction, and an intramolecular oxa‐Michael addition.

Total synthesis of heliespirone B

“…11 It was followed in total synthesis of these molecules by the Shishido group, 12 and the MeErlean group. 13 This IMOMA methodology was further extended to the first total synthesis of heliespirone B by the Shishido group. 14 However, it is worth noting that neither the diasteroselectivity nor the yield in the IMOMA step is satisfactory, which limits the further application in organic synthesis (Scheme 1).…”

“…[11][12][13][14] The reaction was sluggish and afforded a complex mixture, probably due to the less electrophilicity of the double bond (entry 1). Strong bases, such as NaOMe and LDA, resulted in complex mixture as well (entries 2 and 3), while mild bases including imidazole, pyrrolidine, and DBU could not promote the reaction at all (entries 4-6).…”