Partenaires et organisations internationales
(Anglais)
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A, B, HR, CZ, DK, F, D, H, IRL, I, LV, NL, N, PL, P, RO, SI, E, S, CH, GB
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Résumé des résultats (Abstract)
(Anglais)
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Our group focussed on two aspects of asymmetric organocopper chemistry: the conjugate addition and the allylic substitution. The conjugate addition is performed with dialkyl zinc as primary organometallic reagent, copper (II) triflate or carboxylate (0.5 to 2%) associated with a chiral ligand (1 to 4%), and toluene or diethyl ether as solvent. We have found that Cu(OAc)2 and Et2O are the optimum conditions for high enantioselectivity. The chiral ligand is a trivalent organophosphorus compound, usually derived from TADDOL or binaphthol. We have found that biphenol-based ligands, with induced atropoisomerism, are cheaper and more efficient. A new class of ligands has also been disclosed: chiral diaminocarbenes. The reaction is wide in scope of of Michael acceptors: cyclic and acyclic enones, nitro-olefins, alkylidene malonates, all undergo conjugate addition with high enantioselectivities (90-99%). We have also studied the reactivity of the resulting zinc enolate, by reactions with acetals, ketal and silylating agents, thus widening considerably the scope of the reaction.The allylic substitution reaction poses two problems : the g-selectivity, and the enantioselectivity. As typical substrate we choose cinnamyl chloride. Screening of various organometallic reagents (RZnX, R2Zn, RMgX, RLi, R3Al ….) showed that Grignard reagents (R-MgCl or R-MgBr) were the most appropriate. The best solvent in this case is dichloromethane, and the best copper salt is CuCN or copper thiophene-2-carboxylate (CuTC). Under these conditions almost exclusive SN2' product is obtained. Screening of 36 chiral phosphorus ligands revealed a derivative of TADDOL and Ephedrine as the best one with up to 86% enantioselectivity. Biphenol-type ligands are even more versatile, as they allow the reaction to be performed efficiently with a larger variety of allylic substrates. Finally, we have shown that the allylation may be followed, in situ, by a Ru-catalyzed intra-or intermolecular metathesis.
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