Tateshina: Swiss Inspiration!

The Tateshina conference celebrates its 20th anniversary this year. Its founder, Eiichi Nakamura, modeled the conference after the Bürgenstock conference where he was a speaker in April 2000. This short account highlights this event.

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.

Asymmetric bromine-lithium exchange: on the importance of both the diamine ligand and the organolithium reagent.

The asymmetric bromine-lithium exchange on a series of prochiral biphenyls was investigated. As in many asymmetric organolithium reactions, the chiral ligand (here a diamine) was considered to be the enantiocontrolling element. We show here that the organolithium reagent also plays an important role.

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.

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.

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.

Aza-oxindole synthesis via base promoted Truce-Smiles rearrangement.

A novel efficient NaOtBu-mediated protocol for the synthesis of 3,3-disubstituted aza-oxindoles proceeds via a Truce-Smiles rearrangement-cyclisation pathway.

An expedient approach to the total synthesis of (+)-5-epi-eudesm-4(15)-ene-1ß,6ß-diol.

The first total synthesis of (+)-5-epi-eudesm-4(15)-ene-1ß,6ß-diol has been achieved in 12 steps starting from the known (-)-cis-piperitol and by using a chelation controlled glycolate enolate Ireland-Claisen rearrangement and an intramolecular nitrile oxide dipolar cycloaddition as key steps.

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.

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.

Aza-oxindole synthesis by oxidative coupling of C(sp2)-H and C(sp3)-H centers.

A Cu(II) mediated oxidative C(sp(2))-H and C(sp(3))-H coupling protocol gives access to aza-oxindoles in good to excellent yield in the presence of NaOtBu as base and toluene as solvent.

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.

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.