Marc Mauduit

Formation of quaternary chiral centers by N-heterocyclic carbene-Cu-catalyzed asymmetric conjugate addition reactions with Grignard reagents on trisubstituted cyclic enones.

The copper-catalyzed conjugate addition of Grignard reagents to 3-substituted cyclic enones allows the formation of all-carbon chiral quaternary centers. We demonstrate in this article that N-heterocyclic carbenes act as efficient chiral ligands for this transformation. High enantioselectivities (up to 96% ee) could be obtained for a variety of substrates.

Ring-closing metathesis in biphasic BMI·PF6 ionic liquid/toluene medium: a powerful recyclable and environmentally friendly process

Biphasic BMI[middle dot]PF(6)/toluene solvent is a remarkably suitable and clean medium for performing olefin metathesis with a new 2nd generation ionic liquid supported-ruthenium catalyst: high levels of recyclability and reusability combined with a high reactivity were obtained with a variety of di- or tri-substituted and/or oxygen-containing dienes, and very low residual ruthenium levels were detected (1 to 22 ppm) in the products.

Continuous flow homogeneous alkene metathesis with built-in catalyst separation

Continuous flow homogeneous alkene metathesis using a supported ionic liquid phase (SILP) catalyst with CO2 as a transport vector allows the self-metathesis of methyl oleate with only a slight loss of activity for at least 10 h; cross-metathesis of dimethyl maleate with methyl oleate ceases after 3 h, but the catalyst remains active for methyl oleate metathesis. The reasons for this unusual behaviour are explored and a practical system for the cross-metathesis of methyl oleate with dimethyl maleate, under batch conditions, is described.

Formation of Quaternary Stereogenic Centers by NHC–Cu-Catalyzed Asymmetric Conjugate Addition Reactions with Grignard Reagents on Polyconjugated Cyclic Enones

The copper-catalyzed conjugate addition of various Grignard reagents to polyconjugated enones (dienone and enynone derivatives) is reported. The catalyst system, composed of copper triflate and an NHC ligand, led to the unusual selective formation of the 1,4-addition products. This reaction allows for the creation of all-carbon chiral quaternary centers with enantiomeric excesses up to 99%. The remaining unsaturation on the 1,4 adducts give access to valuable synthetic transformations.

Enantioselective 1,6-Conjugate Addition to Cyclic Dienones Catalyzed by the Cu−DiPPAM Complex

In the presence of a Cu/DiPPAM catalytic system, various diorganozinc reagents realize 1,6-asymmetric conjugate addition on various cyclic five- and six-membered cyclic dienones, with complete regioselectivity and high ees (93-99%).

Highly Enantioselective and Regioselective Copper-Catalyzed 1,4 Addition of Grignard Reagents to Cyclic Enynones

In this letter we describe an unusual result in terms of regioselectivity with respect to copper-catalyzed conjugate additions of various Grignard reagents to cyclic enynones. The use of Cu(OTf)(2) and NHC ligand L1 as the catalyst combination in CH(2)Cl(2) led to the unique formation of the 1,4 adduct. This selectivity does not follow the general trend previously observed in the literature using extended Michael acceptors. Moreover these reactions allowed for the creation of a quarternary stereogenic center with enantioselectivities up to 97% ee.

Multicomponent Synthesis of Unsymmetrical Unsaturated N‐Heterocyclic Carbene Precursors and Their Related Transition‐Metal Complexes

A low-cost, modular, and easily scalable multicomponent procedure affording access in good yields and excellent selectivity (up to 93%) to a wide range of (a)chiral unsymmetrical 1-aryl-3-cycloalkyl-imidazolium salts is disclosed. Electronic and steric properties of the corresponding unsymmetrical unsaturated N-heterocyclic carbene (U2-NHC) ligands were evaluated and evidenced strong electron donor ability, high steric discrimination, and modular steric demand.

A Fast‐Initiating Ionically Tagged Ruthenium Complex: A Robust Supported Pre‐catalyst for Batch‐Process and Continuous‐Flow Olefin Metathesis

In this study, a new pyridinium-tagged Ru complex was designed and anchored onto sulfonated silica, thereby forming a robust and highly active supported olefin-metathesis pre-catalyst for applications under batch and continuous-flow conditions. The involvement of an oxazine-benzylidene ligand allowed the reactivity of the formed Ru pre-catalyst to be efficiently controlled through both steric and electronic activation. The oxazine scaffold facilitated the introduction of the pyridinium tag, thereby affording the corresponding cationic pre-catalyst in good yield. Excellent activities in ring-closing (RCM), cross (CM), and enyne metathesis were observed with only 0.5 mol % loading of the pre-catalyst. When this powerful pre-catalyst was immobilized onto a silica-based cationic-exchange resin, a versatile catalytically active material for batch reactions was generated that also served as fixed-bed material for flow reactors. This system could be reused at 1 mol % loading to afford metathesis products in high purity with very low ruthenium contamination under batch conditions (below 5 ppm). Scavenging procedures for both batch and flow processes were conducted, which led to a lowering of the ruthenium content to as little as one tenth of the original values.

Significant Asymmetric Amplification in Enantioselective Cu/DiPPAM-catalyzed 1,6- and 1,4-Conjugate Additions of Diethylzinc to (Di)enones

An unprecedented and strong positive nonlinear effect (NLE) was observed in Cu/DiPPAM-catalyzed asymmetric 1,6-conjugate addition of Et2Zn on (E)-3-(prop-1-en-1-yl)cyclohex-2-enone (71% ee reached with a 40% ee ligand). Moreover, similar behaviors were observed in Cu/DiPPAM-catalyzed 1,4-asymmetric conjugate additions of Et2Zn on both cyclohexenone and (E)-3-non-3-en-2-one (83% and 70% ee, respectively, reached with a 40% ee ligand).

Enantioselective 1,6-conjugate addition of dialkylzinc reagents to acyclic dienones catalyzed by Cu-DiPPAM complex-extension to asymmetric sequential 1,6/1,4-conjugate addition.

CC coupling: DiPPAM 1 and BINAP 2 ligands led to divergent behaviors in the asymmetric conjugate addition (ACA) of dialkylzinc reagents to linear aryldienones, which were applied to the development of a highly selective sequential asymmetric 1,6/1,4-ACA process (see scheme; Tf = triflate, DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene).