A new method for the preparation of non-terminal alkynes: application to the total syntheses of tulearin†A and C.

Lactones are known to react with the reagent generated in situ from CCl4 and PPh3 in a Wittig-type fashion to give gem-dichloro-olefin derivatives. Such compounds are now shown to undergo reductive alkylation on treatment with organolithium reagents RLi to furnish acetylene derivatives bearing the substituent R at their termini (R=Me, n-, sec-, tert-alkyl, silyl); the reaction can be catalyzed with either Cu(acac)2 or Fe(acac)3 /1,2-diaminobenzene. Two alkynol derivatives prepared in this way from readily accessible lactone precursors served as the key building blocks for the total syntheses of the cytotoxic marine macrolides tulearin A (1) and C (2). The assembly of these fragile targets hinged upon ring closing alkyne metathesis (RCAM) followed by a formal trans-reduction of the resulting cycloalkynes via trans-hydrosilylation/protodesilylation.

C2-symmetric chiral disulfoxide ligands in rhodium-catalyzed 1,4-addition: from ligand synthesis to the enantioselection pathway.

A family of chiral C(2)-symmetric disulfoxide ligands possessing biaryl atropisomeric backbones has been synthesized by using the Andersen methodology. Complete characterization includes X-ray crystallographic studies of all ligands and some of their rhodium complexes. Their synthesis, optical purity, electronic properties, and catalytic behavior in the prototypical rhodium-catalyzed 1,4-addition of phenylboronic acid to 2-cyclohexen-1-one are presented through an in depth study of this ligand class. Density functional theory calculations on the step of the catalytic cycle that determines the enantioselectivity are presented and reinforce the first hypothetical explanations for the high levels of asymmetric induction observed.

Comparing the enantioselective power of steric and electrostatic effects in transition-metal-catalyzed asymmetric synthesis.

The current approach to improve and tune the enantioselective performances of transition-metal catalysts for asymmetric synthesis is mostly focused to modifications of the steric properties of the ancillary ligands of the active metal. Nevertheless, it is also known that electrostatic effects can have a remarkable role to promote selectivity in asymmetric synthesis. Using the Rh-catalyzed asymmetric 1,4-addition of phenylboronic acid to 2-cyclohexenone leading to chiral 3-phenylcyclohexanone as an example, we could show that high enantioselectivity can be indeed achieved using catalysts essentially based either on steric or electrostatic effects as the main source of enantioselective induction. In this contribution we suggest that the analysis of the surface of interaction between the catalyst and the substrate could be a useful tool to quantify the power of steric and electrostatic effects of catalysts.

Highly chemo- and enantioselective synthesis of 3-allyl-3-aryl oxindoles via the direct palladium-catalyzed alpha-arylation of amides.

A new NHC x Pd-catalyzed asymmetric alpha-arylation of amides is reported that gives direct access to synthetically valuable, allylated oxindoles with quaternary carbon centers. The reaction is made possible by the introduction of a new chiral NHC ligand. The palladium complexes derived therefrom combine excellent reactivity with high chemo- and enantioselectivity for the title transformation.

Impact of NHC ligand conformation and solvent concentration on the ruthenium-catalyzed ring-closing metathesis reaction.

Two saturated N-heterocyclic carbene ligands with substituted naphthyl side chains were used for the preparation of Blechert-type ruthenium metathesis precatalysts. The resulting conformers of the complexes were separated and unambiguously assigned by X-ray diffraction studies. All new complexes were compared in terms of activity to the original, SIMes-derived Blechert catalyst and were shown to be superior. A study on the impact of solvent concentration in RCM reactions using the most active of these new catalysts ultimately led to the ring closing of a variety of substrates at very low catalyst loadings.

Unprecedented selectivity via electronic substrate recognition in the 1,4-addition to cyclic olefins using a chiral disulfoxide rhodium catalyst.

From zero to hero? Sulfoxides are generally not considered useful ligand entities in asymmetric metal catalysis. However, a chiral disulfoxide as a chelating ligand in the rhodium-catalyzed 1,4-addition of aryl boronic acids to cyclic, alpha,beta-unsaturated ketones and esters gives impressive catalytic results, thus opening the door to future applications of this new chiral ligand class.

Matching the chirality of monodentate N-heterocyclic carbene ligands: a case study on well-defined palladium complexes for the asymmetric alpha-arylation of amides.

N-Heterocyclic carbene ligands derived from C(2)-symmetric diamines with naphthyl side chains are introduced as chiral monodentate ligands, and their palladium complexes (NHC)Pd(cin)Cl are prepared. These compounds exist as a mixture of diastereomers, and the palladium complexes can be successfully separated and their absolute stereochemistry assigned. When used in the asymmetric intramolecular alpha-arylation of amides, oxindoles with quaternary carbon centers can be obtained in high yield and selectivity when correctly matching the chirality of the NHC complexes.

Identification and characterization of a new family of catalytically highly active imidazolin-2-ylidenes.

A new class of easily accessible and stable imidazolin-2-ylidenes has been synthesized where the side chains are comprised of substituted naphthyl units. Introduction of the naphthyl groups generates C 2 -symmetric ( rac) and C s- symmetric ( meso) atropisomers, and interconversion between the isomers is studied in detail both experimentally and computationally. Complete characterization of the carbenes includes rare examples of crystallographically characterized saturated NHC structures. Steric properties of the ligands and an investigation of their stability are also presented. In catalysis, the new ligands show versatility comparable to the most widely used NHCs IMes/SIMes or IPr/SIPr. Excellent catalytic results are obtained when either the NHC salts (ring-opening alkylation of epoxides), NHC-modified palladium compounds (C-C and C-N cross-couplings), or NHC-ruthenium complexes (ring-closing metathesis, RCM) are employed. In several cases, this new ligand family provides catalytic systems of higher reactivity than that observed with previously reported NHC compounds.