Stereoselective Synthesis of Cyclopropanes via Homoallylic Participation

Abstract

A facile method for synthesizing trans-disubstituted cyclopropanes is described. γ,γ-Dimethyl homoallyl alcohols, upon conversion to the corresponding triflate, undergo smooth cyclization to give cyclopropanes in a stereoselective manner (trans) and in a stereospecific manner (inversion of configuration at the chiral center). Various functionalities could be introduced at the α-position of the newly formed cyclopropane ring by treating the cyclization mixture with hetero as well as carbon nucleophiles. Alternatively, treatment of the reaction mixture with triethylamine effects the clean elimination of a triflic acid to give high yields of the cyclopropanes with a 2-propenyl group, which are convertible to the corresponding cyclopropyl methyl ketones by ozonolysis in high yields. Also described is an application of the method to a short-step synthesis of a cyclopropane-containing eicosanoid, related to marine prostanoid biosynthesis.

Synthesis of Isopropenylcyclopropanes − Revision of the Relative Configuration of Cyclopropyl Ketones Obtained by 1,3-Elimination of γ-Epoxy Ketones

“…Furthermore, the spectral data of 17 and 18 are in agreement with those recently reported for the trans diastereomers prepared by a different route 15. Ketone 18 was olefinated under standard Wittig conditions to give the trans ‐isopropenylcyclopropane 20 (86%), which was clearly different from the cis ‐isopropenylcyclopropane 11 16. Therefore, cyclopropyl ketones 16 and 18 must have a trans relative configuration.…”

Scalable C–H Oxidation with Copper: Synthesis of Polyoxypregnanes

“…$3/gram), which is transformed to Δ 6 - i -diene via triflation and elimination (35%). 19 The remaining mass balance was accounted for by an ammonium adduct by the attack of triethylamine into the allylic triflate (see SI for structure). Next, the Cu-mediated C–H oxidation was employed on gram-scale as discussed above to deliver 12 in 40% yield.…”

Anti-addition of Dimethylsulfoxonium Methylide to Acyclic α,β-Unsaturated Ketones and Its Application in Formal Synthesis of an Eicosanoid

“…Although benzyl-protected enone 15 only gave a 1.4:1 diastereomeric ratio of cyclopropane adducts (entry 12), the 1 H NMR of the major diastereomer is consistent with the spectroscopic data of the reported anti- 15C , in which the cyclopropane was derived from the cyclization of a chiral, homoallylic triflate and supported by X-ray crystallography. 21 Compound 11C , prepared in this study, was also converted to the same anti- 15C after the removal of its TBS group and the following benzylation (eq 2), which provides a solid basis to support the antistereochemical assignment.This method was applied to our formal synthesis of cyclorpoyl-containing eicosanoid 16 , which was isolated by the incubation of arachidonic acid with an acetone powder of the Caribbean soft coral Plexaura homomalla and showed an inhibitory activity to lipoxygenases. 22,23 These properties of 16 stimulated several synthetic studies on this compound.…”