Sels de tétraarylphosphonium : synthèse et application à
la synthèse de la (–)-coniine ;
capacité trans-directrice du groupement amide en
cyclopropanation d’oléfines

The development of new purification techniques is an important challenge for today’s academic and industrial chemists. Present methods in which a given reagent is linked to a solid support to facilitate recovery still have some issues. Indeed, the solubility properties of these supports, mainly polymers, are not always reliable. In this context, the group of Pr. Charette has recently reported the use of a tetraarylphosphonium salt (TAP) as a solubility control group. TAPs are soluble in solvents such dichloromethane and can be quantitatively precipitated by the addition of diethyl ether (Chapter 1). However, the preparation of these TAPs still remains a synthetic challenge. One of the goal of this thesis lead to the discovery of two complementary methods that are considered among the most versatile ways to access functionalized TAPs (Chapter 2). One of these methods is utilized by Soluphase Inc., which markets these salts. The efficiency of the TAP moiety as a solubility control group in the synthesis of small molecules has been demonstrated by the synthesis of (–)-coniine (Chapter 3). All of the synthetic intermediates were isolated by a simple precipitation/filtration sequence. The TAP-supported synthesis has proven to be more efficient than the unsupported one. The second part of this thesis has focused on the synthesis of different 1,1-disubstituted cyclopropanes. Such cyclopropanes are a common motif in many natural products and synthetic drugs. However, the cyclopropanation reaction between an alkene and a metal carbene bearing two acceptor groups still remains a synthetic challenge (Chapter 4). Indeed, this reaction suffers from a low level of diastereocontrol. Therefore, little data have been reported to date on the stereoselective cyclopropanation with such carbenes. Studying the Rh(II)-catalyzed cyclopropanation of alkenes, we have brought strong evidence in favor of a postulated model of this reaction (Chapter 5). This study has also led to the discovery of the «trans-directing ability» of the amide group in Rh(II)-catalyzed cyclopropanation. We have thus utilized this «trans-directing ability» of the amide group in the Rh(II)-catalyzed cyclopropanation to solve different problems observed in the literature. We first showed that it could enable the synthesis of 1,1-dicarboxy cyclopropanes (Chapter 6). Multi-step syntheses were previously necessary to access such products. We have also demonstrated that these new cyclopropanes are useful synthetic tools for the rapid synthesis of a variety of natural products and biologically active molecules. We have also used this «trans-directing ability» of the amide group in Rh(II)-catalyzed cyclopropanation to enable the synthesis of 1-cyano-1-carboxy cyclopropanes (Chapter 7). Achiral additives were found to increase the selectivity of different metal catalyzed cyclopropanation reactions. The wide scope and synthetic utility of these new cyclopropanes has been further demonstrated by several functional group transformations.

Keyphrases: Support, (–)-Coniine, Cyclopropanation, Rhodium(II), Bisabolanes, Tetraarylphosphonium, Support, (–)-Coniine, Diazo reagents, Cyclopropane, Cyclopropanation, Rhodium(II), Trans-directing ability, Bisabolanes