Herstellung von (Bicycloalkyl)essigsäure‐Derivaten durch zweifache nucleophile Substitution am Cyclopropan

Abstract

In (Morpholinobicyc1oalkyl)meldrurns~uren 6 kann der Morpholinrest in einer nucleophilen Substitution durch ein H-Atom oder eine Cyangruppe ersetzt werden. Die dabei erhaltenen Reaktionsprodukte 9 und 10 lassen sich durch Abbau des Meldrumsaure-Teils zusatzlich in die (Bicycloalky1)essigsaure Derivate 12-15 iiberffihren. Durch chernische Korrelation sowie durch eine Kristallstrukturanalyse von 14a folgt eine einheitliche endo-Meldrumsiure-bzw. endo-EssigsHure-Struktur der aus 6 hergestellten Derivate. Unter Einbeziehung der Synthese von 6 aus dem N,O-Acetal 1 entspricht dieser neue Zugang zu 9-15 dem Prinzip einer zweifachen nucleophilen Substitution am Cyclopropan. Die energetischen Verlnderungen bei der Addition eines Nucleophils an Methylencyclopropaneeinem wichtigen Teilschritt des hier beschriebenen Syntheseschemaswerden durch semiempirische SCF-Rechnungen (MNDO-Methode) ermittelt. Aus dem Bicycloalkanon-N,O-acetal 1 konnen mit Meldrumsaure (3) abhangig von den Reaktionsbedingungen in Schema 1 oKo 103Vc., 3 5 (I [ 21

Electrochemical carboxylation of bicyclo[n.1.0]alkylidene derivatives

“…24 Stirring of 3b with 6 M hydrochloric acid in DMSO under reflux for 30 h afforded 9 in 83% yield (Scheme 7). The melting point and spectral data of 9 supported the 7-endo-substituted-7-exo-carboxylic acid configuration of 3b.…”

“…The melting point and spectral data of 9 supported the 7-endo-substituted-7-exo-carboxylic acid configuration of 3b. 24 Usually, activated ring-fused alkylidenecyclopropanes favour nucleophilic attack from exo-direction. 25 The electrochemical carboxylation of olefinic substrates with CO 2 in aprotic solvents has already been proposed as a useful procedure for the production of mono-and dicarboxylic acids.…”

“…Evaporation of the solvent in vacuo afforded 164 mg (83%) of 7-endo-carboxymethylbicyclo[4.1.0]heptane-7-exo-carboxylic acid (9) whose spectral data are identical with reported values. 24 Mp 191 -194 8C (lit. 24 …”

Acid- and Base-Promoted Rearrangements of Cycloalkane-Fused Heterocycles

“…The ring-contraction of cyclohexane-fused 2-aminopyrazolidin-3-ones (3) on the action of HgO in the presence of Omesitylenesulfonyl-hydroxylamine (MSH) under mild conditions is an unusual synthetic route to bicyclo -lactams 4 in 30-50% yield (Scheme 2) [6,7] When dialkyl-substituted lactones were refluxed with acetic acid or p-toluenesulfonic acid (PTSA), cyclopropyl -lactones 6 were obtained in almost quantitative yield (Scheme 3). This rearrangement is strongly dependent on the substitution (R 1 and R 2 ) pattern at the bridgehead positions [8]. When unsubstituted or monomethyl -lactones were reacted with acids under the same conditions, rearrangement did not occur.…”