Regioselective Synthesis and Characterization of Multinuclear Convex-Bound Ruthenium-[n]Cycloparaphenylene (n = 5 and 6) Complexes.

Mono- and multinuclear complexes of ruthenium and [n]cycloparaphenylene (CPP, n = 5 and 6) were synthesized in excellent yields through ligand exchange of the cationic complex [(Cp)Ru(CH3CN)3](PF6) with CPP. In the multinuclear complexes, ruthenium selectively coordinated to alternate paraphenylene units to give bis- and tris-coordinated Ru complexes for [5] and [6]CPPs, respectively. Single-crystal X-ray analysis revealed the Ru was coordinated with η(6)-hapticity on the convex surface of CPP.

Palladium-N-heterocyclic carbene (NHC)-catalyzed asymmetric synthesis of indolines through regiodivergent C(sp3)-H activation: scope and DFT study.

Two bulky, chiral, monodentate N-heterocyclic carbene ligands were applied to palladium-catalyzed asymmetric C-H arylation to incorporate C(sp(3))-H bond activation. Racemic mixtures of the carbamate starting materials underwent regiodivergent reactions to afford different trans-2,3-substituted indolines. Although this CAr-Calkyl coupling requires high temperatures (140-160 °C), chiral induction is high. This regiodivergent reaction, when carried out with enantiopure starting materials, can lead to single structurally different enantiopure products, depending on the catalyst chirality. The C-H activation at a tertiary center was realized only in the case of a cyclopropyl group. No C-H activation takes place alpha to a tertiary center. A detailed DFT study is included and analyses of methyl versus methylene versus methine C-H activation is used to rationalize experimentally observed regio- and enantioselectivities.

Catalysis with complexes containing stereogenic metal centers.

Alfred Werner, one of the founders of the Swiss Chemical Society and its first president and the first Nobel Prizewinner for Chemistry in Switzerland, established the stereochemistry of coordination complexes. As an important element in the verification of his hypothesis he demonstrated the existence of two enantiomeric forms of [Co(ethylenediamine)3][Cl3]. The present article briefly examines the question of the use in asymmetric catalysis of catalysts possessing a stereogenic metal center.

Synthesis of 3,3-Disubstituted Oxindoles by Palladium-Catalyzed Asymmetric Intramolecular α-Arylation of Amides: Reaction Development and Mechanistic Studies.

Palladium complexes incorporating chiral N-heterocyclic carbene (NHC) ligands catalyze the asymmetric intramolecular α-arylation of amides producing 3,3-disubstituted oxindoles. Comprehensive DFT studies have been performed to gain insight into the mechanism of this transformation. Oxidative addition is shown to be rate-determining and reductive elimination to be enantioselectivity-determining. The synthesis of seven new NHC ligands is detailed and their performance is compared. One of them, L8, containing a tBu and a 1-naphthyl group at the stereogenic centre, proved superior and was very efficient in the asymmetric synthesis of fifteen new spiro-oxindoles and three azaspiro-oxindoles often in high yields (up to 99 %) and enantioselectivities (up to 97 % ee; ee=enantiomeric excess). Three palladacycle intermediates resulting from the oxidative addition of [Pd(NHC)] into the aryl halide bond were isolated and structurally characterized (X-ray). Using these intermediates as catalysts showed alkene additives to play an important role in increasing turnover number and frequency.

Copper(ii) chloride mediated (aza)oxindole synthesis by oxidative coupling of Csp(2)-H and Csp(3)-H centers: substrate scope and DFT study.

A CuCl2 mediated direct intramolecular oxidative coupling of Csp(2)-H and Csp(3)-H centers gives access to 3,3-disubstituted oxindoles containing aromatic, heteroaromatic and alkyl substituents as well as a heteroatom at the quaternary center in good to excellent yields. The reaction is carried out in the presence of NaOtBu and CuCl2 in DMF at 110 °C. The key step of this reaction is the formation of an amidyl radical by one electron oxidation of amide enolate followed by an intramolecular radical cyclization reaction (homolytic aromatic substitution reaction). A detailed DFT study shows that the cyclization of the amidyl radical is the rate-limiting step in the oxindole synthesis, whereas the second single electron transfer (SET) becomes the rate-determining step in the aza-oxindole formation. Computational data are in agreement with the experimentally observed relative reactivity and regioselectivity.

Desymmetrisation of meso-diols mediated by non-enzymatic acyl transfer catalysts.

Complementary to enzymatic methods, catalytic enantioselective desymmetrisation of meso-diols (EDMD) by small molecule catalysts has emerged as a powerful tool that provides highly enantioenriched materials of considerable value in organic synthesis. This review traces the evolution of easily accessible catalysts used in the EDMD and compares their performance with the existing enzymatic methods.

Electronic effects in 1,3-dipolar cycloaddition reactions of N-alkyl and N-benzyl nitrones with dipolarophiles.

1,3-Dipolar cycloadditions afforded fast access to isoxazolidines bearing N-alkyl or N-benzyl substituents. The electronic properties of the substituents in the nitrones define the activity of the dipoles and modulate diastereoselectivity in the non-catalyzed reactions. Using a chiral one-point binding ruthenium Lewis acid catalyst, products were obtained in good yields and with excellent regio-, diastereo-, and enantioselectivity.

Asymmetric synthesis of (+)-vertine and (+)-lythrine.

The total syntheses of the Lythracea alkaloids (+)-vertine and (+)-lythrine are described. Enantioenriched pelletierine is used as a chiral building block and engaged into a two step pelletierine condensation leading to two quinolizidin-2-one diastereomers in a 8 : 1 ratio. The major product is used in the synthesis of (+)-vertine via aryl-aryl coupling and ring closing metathesis to provide a Z-alkene α to the lactone carbonyl function. The same procedure was used for (+)-lythrine after base induced epimerization of the main quinolizidin-2-one diastereomer. Alternative classical ring closure strategies like macrolactonisation or aryl-aryl coupling failed.

Palladium-NHC catalyzed enantioselective synthesis of fused indolines via inert C(sp(3))-H activation.

New sterically hindered chiral N-heterocyclic carbene (NHC) ligands were used in palladium catalysis to bring about a highly enantioselective C(sp(3))-H activation on the methylene site of a cycloalkane moiety. The intramolecular coupling reaction of a prochiral N-aryl-N-cycloalkyl methyl carbamate required high temperatures (140-160 °C) and afforded highly enantioenriched trans-2,3-fused indolines.

Intramolecular Diels-Alder reactions using chiral ruthenium Lewis acids and application in the total synthesis of ent-ledol.

One-point binding chiral ruthenium Lewis acids incorporating the C(2)-symmetric electron-poor bidentate phosphinite ligand BIPHOP-F and a Cp or an indenyl 'roof' can efficiently catalyze asymmetric intramolecular Diels-Alder reactions of trienes to form bicyclic adducts with good to excellent asymmetric induction. This reaction forms the key step in a total synthesis of ent-ledol in 96% ee. The synthesis also helps to clarify the stereochemical assignment of ledol and inconsistencies in the measured optical rotation.

Enantiopure Ti(IV) amino triphenolate complexes as NMR chiral solvating agents.

Enantiopure Ti(IV) complexes bearing pseudo-C(3) amino triphenolate ligands have been synthesized and characterized. The complexes bearing ortho phenyl groups act as (1)H NMR chiral solvating agent (CSA) for the stereochemical analysis of a series of sulfoxides. The coordination of a Lewis base coligand (sulfoxide) and the presence of aromatic rings are the key structural factors for the efficiency of the CSA.

Asymmetric intramolecular Diels-Alder reactions of trienals catalyzed by chiral ruthenium Lewis acids.

Chiral single-point binding ruthenium Lewis acid catalysts [Ru(acetone)((S,S)-BIPHOP-F)(Cp)][SbF6] ((S,S)-1a) and [Ru(acetone)((S,S)-BIPHOP-F)(indenyl)][SbF6] ((S,S)-1b) efficiently catalyze intramolecular Diels-Alder (IMDA) reactions of trienals under mild conditions to afford the endo cycloaddition products as the major products in good yields with high diastereo- and enantioselectivities.

New chiral N-heterocyclic carbene ligands in palladium-catalyzed alpha-arylations of amides: conformational locking through allylic strain as a device for stereocontrol.

New Enders/Herrmann-type chiral N-heterocyclic carbene (NHC) ligands have been developed and applied in asymmetric palladium-catalyzed intramolecular alpha-arylations of amides. The best ligands feature the bulky tert-butyl group and ortho-substituted aryl groups at the stereogenic centers. Aryl bromides readily react at room temperature and aryl chlorides at 50 degrees C. The highly enantiomerically enriched (up to 96% ee) 3-alkyl-3-aryloxindole products were obtained in generally high yields (>95%) except in cases of steric congestion. The critical roles both of the bulky alkyl group and of the ortho-aryl substituent at the stereogenic center of the ligand were revealed in the crystal structure of a [Pd(eta(3)-allyl)(NHC-L*)(I)] complex. The ligand aryl location and orientation is fixed by conformational locking that minimizes A(1,3)-strain and enables optimal transfer of chiral information.

Asymmetric catalytic hydrogenolysis of aryl-halide bonds in fused arene chromium and ruthenium complexes.

Access to highly enantioenriched planar chiral [Cr(5-bromonaphthalene)(CO)(3)] (6), [Ru(eta(5)-C(5)R(5))(5-bromonaphthalene)][PF(6)] (42) and [Ru(eta(5)-C(5)R(5))(4-bromoindene)] (44) was sought using asymmetric hydrogenolysis of [Cr(5,8-dibromonaphthalene)(CO)(3)] (5), [Ru(eta(5)-C(5)R(5))(5,8-dibromonaphthalene)] (39) and [Ru(eta(5)-C(5)R(5))(4,7-dibromoindene)] (40), respectively. Initial efforts focused on the chromium complex 5. Pd(0) catalysts with dimethoxyethane as the solvent and LiBH(4) or NaBH(3)CN as a hydride source worked best. Nineteen chiral bidentate phosphorus ligands were screened in this reaction. Asymmetric induction was low to modest with product ee's in the range of 4 to 52% and yields of 6 of up to 70%. Chiral phosphoramidite ligands proved superior and a bulky ligand derived from a Whitesell amine and 3,3'-diphenyl-binaphtol afforded 6 with an ee of 97%. The high enantioselectivity is largely due to the initial desymmetrization reaction though kinetic resolution also plays an important role as shown by the determination of a selectivity factor s=8.5 at -10 degrees C. Initially high ligand loadings (4 equiv/Pd) were necessary to achieve good asymmetric induction. This could be traced to the trapping of the chiral ligand by borane formed in the reaction. Addition of 1,4-diazabicyclo[2.2.2]octane (DABCO) suppressed this, and its addition led to the use of Pd and chiral ligand in a 1:1.2 ratio. Asymmetric hydrogenolysis of cationic dibromonaphthalene and neutral dibromoindenyl complexes of Ru cyclopentadienyl complexes was investigated and afforded the following results: [RuCp(5-bromonaphthalene)][PF(6)] (39a; 75%, 90% ee), [RuCp*(5-bromonaphthalene)] [PF(6)] (39b; 88%, 99% ee), [RuCp(4-bromoindenyl)] (44a; 72%, 96% ee), and [RuCp*(4-bromoindenyl)] (44b; 62%, 68% ee).

Asymmetric ruthenium-catalyzed 1,4-additions of aryl thiols to enones.

Well defined, stable, one-point binding ruthenium complexes and selectively bind and activate alpha,beta-unsaturated carbonyl compounds for cycloaddition reactions. These mild Lewis acids catalyze asymmetric 1,4-addition reactions of aryl thiols to enones with product selectivities up to 87% ee. (31)P NMR experiments provide an insight into the intricate equilibria governing the reaction mechanism. The absolute configuration of the major products indicates enones to react in the syn-s-trans orientation. Models based on X-ray structures of the Ru complexes can be used to rationalize selectivity.

An efficient entry to planar chiral organometallic complexes via Pd-catalyzed asymmetric hydrogenolysis.

Planar chiral chromium- and ruthenium-based arene complexes were prepared with high levels of enantioselectivity via a Pd-catalyzed asymmetric hydrogenolysis reaction using a bulky chiral phosphoramidite ligand. Key elements for the efficiency of the process are the use of DABCO as borane-trapping reagent as well as substantial kinetic resolution, which was found to enhance the stereochemical outcome of the reaction.