Intertwined Analytical, Experimental and Theoretical Studies on the Formation and Structure of a Copper Dienolate.

The reaction of a silyl dienolate, a Cu(II) salt and TBAT yielding the corresponding copper dienolate is addressed. A combined NMR and cyclic voltammetry analysis first highlight the role of TBAT in the Cu(II) to Cu(I) reduction and the structure of the precatalytic species. From these first results a second set of NMR and theoretical studies enable the determination of the structure and the mechanism of formation of the copper dienolate catalytic species. Finally, we showed that that the copper catalyst promote the E/Z s-cis/s-trans equilibration of the silyl dienolate precursor through a copper dienolate intermediate. All of these results unveil some peculiarities of the catalytic and asymmetric vinylogous Mukaiyama reaction.

Copper-catalyzed asymmetric conjugate addition to challenging Michael acceptors and synthesis of relevant target molecules.

We report herein the enantioselective Cu-catalyzed conjugate addition of organometallic reagents to sensitive Michael acceptors and their application to the synthesis of relevant target molecules. This is one of the most important methodologies to form a C-C bond in an enantioselective manner. A wide range of α,ß-unsaturated aldehydes and ß,γ-unsaturated-α-ketoesters has been successfully used. Reactivity, regio- and enantioselectivities were strongly dependent on the reaction conditions, therefore moderate to very good results were obtained. Furthermore, γ-substituted-α-ketoesters were used as chiral building blocks for further derivatization with complete retention of the chiral information to obtain key compounds.

Copper-catalyzed enantioselective 1,4-addition to alpha,beta-unsaturated aldehydes.

The first asymmetric Cu-catalyzed conjugate addition of dialkylzinc zinc reagents to a large scope of enals in presence of phosphoramidite, SimplePhos, or (R)-BINAP ligands with enantiomeric excesses up to 90% is reported. Moreover, ACA of Grignard reagents afforded moderate to good 1,4-regioselectivities with enantioselectivities up to 90%.

Copper-catalysed ring opening of polycyclic meso-hydrazines with trialkylaluminium reagents and SimplePhos ligands.

meso-Hydrazines could be desymmetrised by ring-opening reactions by using various metal catalysts to form substituted cyclopentenes, which have a high synthetic potential. Herein, we report the asymmetric copper-catalysed ring opening of a range of polycyclic hydrazines with trialkylaluminium reagents and SimplePhos ligands with both high isolated yields and enantioselectivities of up to 95 %.

Copper-catalyzed asymmetric conjugate addition with chiral SimplePhos ligands.

SimplePhos ligands represent a novel class of monodentate chiral ligands based on a chiral amine moiety and flexible diaryl groups on the phosphorous atom. They can be easily prepared by two different pathways and they can be highly functionalised. Herein we report the copper-catalysed asymmetric conjugate addition of diethyl zinc and trialkylaluminium reagents with SimplePhos ligands, which gives high enantioselectivity with cyclic enones, acyclic enones and nitro-olefins, with up to 98.6% ee. Of particular interest is the reaction of trialkylaluminium reagents with a wide range of 3-substituted enones, thus allowing the formation of stereogenic quaternary carbon centres.