Synthèses diastéréo- et énantiosélectives d'acides cis-vinyl cyclopropane carboxyliques

Abstract

This work permitted us to propose new diastereo- enantioselective synthesis of cis-chrysanthemic acid strating from dimethyle dimedone. The first one involves the desymmetrization of the 3,3,6,6-tetramethyl-bicyclo[3.1.0]hexane-2,4-dione while the second one take advantage of the enantioselective reduction of the 2,2,5,5-tetramethyl-cyclohex-3-enone and the stereoselective addition on the double bond of the resulting alcohol of reagents allowing the transfert of two leaving groups on the C-3 and C-4 carbons. These allow producing the squeleton of the 3,3,6,6-tetramethyl-bicyclo[3.1.0]hexane leading to the cis stereochemistry on the cyclopropane ring and the destruction of the 5-members ring producing the vinyl cyclopropane carboxylic moity. During this work we have use the Haller-Bauer type fission and Grob fragmentation tandem reaction on ketones bearing a good leaving group in beta position allowing the concommitant formation of the carboxylate and vinylic moities on the cyclopropane ring. We have also demonstrated that wet potassium hydroxyde in dimethyle sulfoxide behave differently than dry potassium hydroxyde ("Gassman's reagent") and we have taken advantage of this fact to propose an original solution to reproductibility problems of reactions previously described in our laboratory. Finaly, we have shown that anhydrous KOH can act as a nucleophile as well as a base depending on the context and that this reagent can even act as both sequentially.

Date of Award	20 Nov 2009
Original language	French
Awarding Institution	University of Namur
Supervisor	Alain KRIEF (Supervisor), Davide BONIFAZI (Jury), Paul Knochel (Jury), Goverdhan Mehta (Jury) & BAO LIAN SU (President)