Catalytic asymmetric synthesis of the alkaloid (+)-myrtine

A new protocol for the asymmetric synthesis of trans-2,6-disubstituted-4-piperidones has been developed using a catalytic enantioselective conjugate addition reaction in combination with a diastereoselective lithiation–substitution sequence; an efficient synthesis of (+)-myrtine has been achieved via this route.

Copper-catalyzed asymmetric conjugate addition to various Michael acceptors : construction of all-carbon quarternary chiral centres

L'emploi des ligands de type phosphoramidite pour l'Addition Conjuguée Asymétrique (A.C.A.) catalysée par le cuivre d'espèces organozinciques (R₂Zn) ou organoaluminiques (R₃AI) sur des substrats disubstitués, cycliques ou acycliques, de géométrie exclusivement E ou Z, conduit à la formation d'adduits chiraux avec d'excellentes énantiosélectivités atteignant 99%. En outre, le caractère acide de Lewis de R₃AI permet une activation suffisante des substrats 2- ou 3-trisubstitués, et ainsi, l'obtention d'adduits cycliques possédant un centre quaternaire chiral avec une induction asymétrique atteignant 98% via l'A.C.A. catalysée par le cuivre. L'utilisation des énolates métalliques énantio-enrichis est étudiée aussi bien pour les systèmes di- que trisubstitués, avec notamment la formation d'acétates d'énol chiraux comme alternative à la synthèse d'éthers d'énol silylés. Enfin, l'utilisation ultérieure des adduits possédant un centre quaternaire chiral est envisagée afin de trouver diverses applications à la méthodologie développée, alors qu'une nouvelle réaction tandem d'hydroalumination-A.C.A. est mise au point

Tandem asymmetric conjugate addition-enolacetates formation of enantiomerically enriched zinc and aluminium enolates

The metal enolates, resulting from the copper-catalyzed enantioselective conjugate addition of organometallic reagents (Et2Zn or R3Al) to cyclic and acyclic enones are quantitatively trapped as enolacetates with acetic anhydride

Copper catalysed asymmetric conjugate addition of trialkylaluminuim reaggents to trisubstituted enones: construction of chiral quaternary centers

The Cu-catalyzed enantioselective conjugate addition of dialkylzinc to bis-alpha,beta-unsaturated carbonyl compounds followed by the intramolecular trapping of the zinc enolate in the presence of chiral phosphoramidite ligands was investigated. Cyclic and heterocyclic compounds with multichiral centers were formed as a mixture of two diastereomers with excellent diastereoselectivities (up to 99:1) and enantioselectivities (up to 94 % ee, ee=enantiomeric excess). The stereochemistry was determined to be trans,trans for the major products and trans,cis for the minor products. The absolute configuration of the cyclic compounds was assigned by comparison with the analogous adduct derived from trans-3-nonen-2-one and Et(2)Zn or the adduct obtained through conjugate addition of Me(2)Zn to trans-1-phenyl-non-2-en-1-one. Further transformation of these cyclic products into more complex compounds is under investigation in our laboratory

Enantioselective copper catalysed conjugate addition to 2- or 3- substituted cyclopent-2-ene-1-ones: Construction of stereogenic quaternary carbon centers

Trimethyl- and triethylaluminum undergo enantioselective conjugate addition to 2- and 3-substituted cyclopent-2-en-1- ones in the presence of catalytic amount of a copper salt and a phosphoramidite or a diphosphite ligand. Thus, chiral quaternary centers can be built with up to 93% ee

Regiodivergent 1,4 versus 1,6 asymmetric copper-catalysed conjugate addition

A highly regiodivergent copper-catalyzed asymmetric conjugate addition to, and, Michael acceptors is described. Zinc and aluminum reagents afford the 1,6 adduct with good to moderate enantioselectivity in the presence of ligand 1. In contrast, Grignard reagents used with hydroxy imidazolium ligand 2 afforded the 1,4 adduct with excellent ee values