Enantioselective synthesis of (−)-paeonilide

Abstract

The first enantioselective synthesis of (À)-paeonilide is reported. Starting from inexpensive furan-3-carboxylic acid the targeted monoterpene was obtained in 12 steps via an asymmetric cyclopropanation-lactonization cascade and a stereoselective side chain insertion at an acetal-like position.

Total Synthesis of Schilancitrilactones B and C

“…Deprotection of 26 was achieved using trifluoroacetic acid and gave the acid 27 in 93 % yield (two steps). Addition of ethyl magnesium bromide followed by acidic workup gave rise to the tricycle 28 , having an ethyl group installed stereoselectively onto the tricyclic framework 12. The absolute configuration of 28 was determined by X‐ray crystallographic analysis.…”

Catalytic Conversion of Furans and Pyrroles to Natural Products and Analogues Utilizing Donor‐Acceptor Substituted Cyclopropanes as Key Intermediates

“…By as imilar strategy,t he unnatural enantiomer 16 of the potentp latelet activation inhibitor (+)-paenolide was obtained from 4b in 11 steps and 12 %o verall yield (Scheme3). [20] Again, the stereocenters on the bridgehead positions epimerize quite easily,b eing driven by the formation of the thermodynamically favoreds tereoisomer in which the carboxylic acid group orients on the convex face of the bicycle.Apossible intermediate that rationalizes the configuration observed in the product is 15, which might form after initial ring openingt o14 by elimination of water.…”

“…In a similar way, the furan derivate 2b , having the ester group in the 3‐position, can be monocyclopropanated. However, to obtain useful enantioselectivities, bis(oxazoline) 6b and tert‐ butyl diazoacetate have to be employed to obtain 4b in 83 % ee , which again can be raised to enantiopurity upon crystallization with enantiomerically pure seed crystals of 4b .…”

Recent Applications of Cyclopropane-Based Strategies to Natural Product Synthesis

“…Finally, reductive removal of the iodine under Another elegant application of cyclopropane ring opening and lactonization chemistry is in the first enantioselective synthesis of (-)-paeonilide (142). 36 Reiser and Harrar described that asymmetric intermolecular cyclopropanation between furan-3-methyl ester 137 and tert-butyl diazoacetate in the presence of copper(I) triflate and ligand 93 generated cyclopropane 138 in moderate yield (58% based on recovery of 137) with 83% ee (Scheme 25). Selective hydrolysis followed by catalytic hydrogenation gave acid 139 in 85% overall yield.…”