Practical Synthesis of (±)-Chlorovulone II

Abstract

We describe a total synthesis of (±)-chlorovulone II that is 10 steps shorter than the best alternative currently available (nine vs 19 steps). The key event of the synthesis is an aldol addition of the enolate of ethyl acetate into 4-cyclopentene-1,3-dione, a substance that has received little attention as an educt for prostanoid synthesis and for which little is known about carbonyl 1,2-addition with enolates. In addition, we provide chemical and stereochemical details of a route to a key intermediate toward the title compound that involves a carbonyl−ene reaction and a radical addition to an aldehyde carbonyl.

Studies towards the total synthesis of an epoxy isoprostane phospholipid, a potent activator of endothelial cells

“…10 Wittig reaction using (triphenylphosphoranylidene)acetaldehyde 18 gave an E/Z mixture of the aldehyde 19. 11 Selective reduction at low temperature gave the alcohol 20. Sharpless asymmetric epoxidation 12 of this substrate was earlier reported to be problematic.…”

Enantioselective Total Synthesis of the Osteoclastogenesis Inhibitor (+)‐Symbioimine

“…A Horner–Wadsworth–Emmons reaction between the known aldehyde 6 6 and dimethyl 3,5‐dimethoxybenzylphosphonate7 provided the desired diene 7 with high levels of E / Z selectivity (>11:1) and in good yield (82 %). Preparation of methyl ketone 8 could be achieved in 70 % yield by a one‐step protocol using NHMe(OMe)⋅HCl and excess MeMgCl 8.…”

Experimental and Computational Studies Unraveling the Peculiarity of Enolizable Oxoesters in the Organocatalyzed Mannich-Type Addition to Cyclic N-Acyl Iminium Ions

“…Notwithstanding the increasing importance of organocatalysis in modern synthetic organic chemistry and the large variety of reactions described, the use of oxoesters in organocatalyzed reactions has not been considered to a large extent. For Alkyl 5-oxopentanoates have also been frequently used in Horner-Wadsworth-Emmons (HEW)-olefinations to give a variety of biologically active natural products [2][3][4][5][6][7][8][9]. Notwithstanding the increasing importance of organocatalysis in modern synthetic organic chemistry and the large variety of reactions described, the use of oxoesters in organocatalyzed reactions has not been considered to a large extent.…”