Pyridine Oxazoline Research Articles

Enantioselective Desymmetrization of Trifluoromethylated Tertiary Benzhydrols via Hydrogen-Acceptor-Free Ir-Catalyzed Dehydrogenative C-H Silylation: Decisive Role of the Trifluoromethyl Group.

Although the trifluoromethyl (CF3) group is one of the most important fluorinated groups owing to its significant ability to modulate pharmacological properties, constructing trifluoromethylated stereogenic centers in an enantioselective manner has been a formidable challenge. Herein, we report the development of the enantioselective desymmetrization of trifluoromethylated benzhydrols via intramolecular dehydrogenative silylation using Ir catalysts with chiral pyridine-oxazoline (PyOX) ligands. The produced benzoxasilol was transformed into several unsymmetrical benzhydrols via iododesilylation and subsequent transition-metal-catalyzed cross-coupling reactions. Moreover, the same Ir catalyst system was used for the kinetic resolution of unsymmetrical trifluoromethylated benzhydrols.

Symmetrical and Unsymmetrical Dicopper Complexes Based on Bis-Oxazoline Units: Synthesis, Spectroscopic Properties and Reactivity

Copper–oxygen adducts are known for being key active species for the oxidation of C–H bonds in copper enzymes and their synthetic models. In this work, the synthesis and spectroscopic characterizations of such intermediates using dinucleating ligands based on a 1,8 naphthyridine spacer with oxazolines or mixed pyridine-oxazoline coordination moieties as binding pockets for copper ions have been explored. On the one hand, the reaction of dicopper(I) complexes with O2 at low temperature led to the formation of a µ-η2:η2 Cu2:O2 peroxido species according to UV-Vis spectroscopy monitoring. The reaction of these species with 2,4-di-tert-butyl-phenolate resulted in the formation of the C–C coupling product, but no insertion of oxygen occurred. On the other hand, the synthesis of dinuclear Cu(II) bis-µ-hydroxido complexes based on pyridine–oxazoline and oxazoline ligands were carried out to further generate CuIICuIII oxygen species. For both complexes, a reversible monoelectronic oxidation was detected via cyclic voltammetry at E1/2 = 1.27 and 1.09 V vs. Fc+/Fc, respectively. Electron paramagnetic resonance spectroscopy (EPR) and UV-Vis spectroelectrochemical methods indicated the formation of a mixed-valent CuIICuIII species. Although no reactivity towards exogeneous substrates (toluene) could be observed, the CuIICuIII complexes were shown to be able to perform hydroxylation on the methyl group of the oxazoline moieties. The present study therefore indicates that the electrochemically generated CuIICuIII species described herein are capable of intramolecular aliphatic oxidation of C–H bonds.

Non-nucleophilic Grignard Synthesis of Bridged Pyridine–Oxazoline Ligands and Evaluation in Palladium-Catalysed Allylic Alkylation

AbstractThe synthesis of eight pyridine-oxazoline ligands, five of which have never been reported previously, is described. The ligands were prepared in two efficient steps, initially preparing 2-pyridyl alkylnitriles, followed by their conversion into oxazolines ligands using chiral amino alcohols and zinc chloride. The 2-pyridyl nitriles are prepared via a novel SNAr alkylation reaction of 2-bromopyridine with alkyl nitriles using methylmagnesium chloride as a non-nucleophilic base in conjunction with an amine mediator. This methodology allows preparation of the existing gem-dimethyl motif and its elaboration beyond previously prepared ligands in fewer steps with simplicity and scalability. The toleration of variation in the nitrile, halopyridine, and amino alcohol starting materials allows for other novel bridging substitution which gives new ligands with enhanced reactivity. The library of bridging ligands was applied to the Pd-catalysed allylic alkylation of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate and afforded conversions of up to 100% and enantioselectivities of up to 68%.

Synthesis and characterization of Ni(0) complexes supported by an unsymmetric C,N ligand

Over the past decade, N-heterocyclic carbene (NHC), bipyridine (bpy), and pyridine oxazoline (PyOx) ligands have been increasingly applied in nickel catalysis, where the combination of a low-oxidation-state 3d metal and an electron-rich ligand can enable otherwise challenging bond activations. Herein we report the synthesis and characterization of two Ni(0) complexes supported by an alternative, bidentate, C,N ligand, hIMesPy (“half-IMes-pyridine” or 1-(2,4,6-trimethylphenyl)-3-(2-pyridinyl)-imidazol-2-ylidene). The unsymmetric ligand combines the strong σ-donating properties of an NHC with the π-accepting properties of pyridine to afford homoleptic [Ni(hIMesPy)2] and heteroleptic [Ni(cod)(hIMesPy)] complexes. Characterization through the combination of single-crystal X-ray diffraction analysis and NMR spectroscopy, as well as reactivity studies demonstrating reversible interconversion between the two species, provide a strong basis for future applications to overcome reactivity challenges.

Chiral pyridine oxazoline and 1,2,4-triazine oxazoline ligands incorporating electron-withdrawing substituents and their application in the Cu-catalyzed enantioselective nitroaldol reaction

Eight pyridine-containing and four 1,2,4-triazine-containing chiral oxazoline ligands incorporating electron-withdrawing substituents have been synthesized by two-step route including Buchwald–Hartwig amination. Enantio-inducing activity of the ligands has been assessed in the copper-catalyzed asymmetric nitroaldol reactions and the influence of the electron-withdrawing substituents on the ligands' activity has been investigated.Graphical abstract

Enantioselective, Copper-Catalyzed Addition of Nucleophilic Silicon to Alkenyl-Substituted Phosphine Oxides

AbstractAn enantioselective β-silylation of α,β-unsaturated phosphine oxide derivatives using a silylboronic ester as the silicon pronucleophile is reported. The reaction is catalyzed by copper salts in the presence of chiral pyridine–oxazoline (PyOx) ligands. Good to high enantioselectivities (≤95% ee) are obtained for β-aryl-substituted acceptors whereas alkyl residues in the β-position led to a lower ee value for 1° and no reaction for 2° and 3°. The new method represents another way of accessing α-chiral silanes and complements the known β-borylation.

Advances in Stereoselective Iron(II)‐Catalyzed Synthesis of Sulfilimines with N‐Mesyloxycarbamates

AbstractA stereoselective amination of thioethers to access sulfilimines using N‐mesyloxycarbamates in a catalytic system composed of iron chloride (II) and a pyridine oxazoline (PyOX) ligand, has been developed. The reaction proceeds with modest to good yields and selectivities (up to 86 : 14 d.r. and 72 : 28 e.r.). Selectivity was controlled by both the structure of the chiral ligand and the amination reagent.

Heteroaromatic N-Oxides Modified with a Chiral Oxazoline Moiety, Synthesis and Catalytic Applications

Interesting properties of N-oxides and pyridine oxazoline compounds have become the starting point to synthesize compounds connecting both groups. A multi-step synthesis of a series of chiral oxazoline substituted pyridine N-oxides, alkyl derived of pyridine N-oxides, bipyridine N-oxides, and isoquinoline N-oxides, based on amino alcohols derived from natural amino acids or other previously prepared, is presented herein. Various synthetic pathways have been designed and tested according to the properties and limitations imposed by the target products. The encountered problems related to the stability of the products were discussed. The resulting compounds (eighteen structures) were tested as catalysts in th e allylation of benzaldehyde (obtaining up to 79% ee) as well as in nitroaldol reaction (obtaining up to 48% ee).

Catalytic asymmetric total syntheses of (+)-α-cuparenone, (+)-cuparene and (+)-herbertene

A general catalytic asymmetric route to either enantiomers of sesquiterpenes, cuparenes (1–2) and herbertenes (8–9) is disclosed from commercially available 3-methyl cyclopenten-2-one. Following a catalytic enantioselective addition of arylboronic acids to enone 15, compounds 14a-b with all carbon quaternary stereocenters are synthesized in up to 90% ee in the presence of Pd(II)-PyOx (pyridine oxazoline). Compounds 14a-b are used as precursors for the asymmetric total syntheses of (+)-cuparene (1a) (35% overall yield in 3 steps), α-(+)-cuparenone (1b) (56% overall yield in 2 steps), and (+)-herbertene (8a) (34% overall yield in 3 steps).

Cobalt-Catalyzed Asymmetric Hydrogenation of Vinylsilanes with a Phosphine–Pyridine–Oxazoline Ligand: Synthesis of Optically Active Organosilanes and Silacycles

The asymmetric hydrogenation of vinylsilanes catalyzed by a new C1-symmetric phosphine–pyridine–oxazoline cobalt complex is described. The method provides an efficient approach to chiral tertiary s...

An autonomous self-optimizing flow machine for the synthesis of pyridine–oxazoline (PyOX) ligands

A continuous flow synthesis of PyOX ligands has been developed using an autonomous self-optimizing flow reactor.

Pd(ii)-Catalyzed asymmetric 1,6-conjugate addition of arylboronic acids to Meldrum's acid-derived dienes.

A Pd(ii)-catalyzed asymmetric 1,6-addition of arylboronic acids to Meldrum's acid-derived dienes was developed. A new substituted In-Pyrox ligand was designed to enable this reaction with high enantioselectivity via a remote steric effect. A series of Meldrum's acid-derived dienes and arylboronic acids were tolerable to the reaction conditions, giving the desired adducts in moderate to high yields with good enantioselectivities (up to 96% ee). This reaction provides the first method of Pd(ii)-catalyzed asymmetric 1,6-conjugate addition of arylboron.

Palladium-Catalyzed Enantioselective Redox-Relay Heck Alkynylation of Alkenols To Access Propargylic Stereocenters.

An enantioselective redox-relay Heck alkynylation of di- and trisubstituted alkenols to construct propargylic stereocenters is disclosed using a new pyridine oxazoline ligand. This strategy allows direct access to chiral β-alkynyl carbonyl compounds employing allylic alcohol substrates in contrast to more traditional conjugate addition methods.

Palladium‐Catalyzed Enantioselective Redox‐Relay Heck Alkynylation of Alkenols To Access Propargylic Stereocenters

AbstractAn enantioselective redox‐relay Heck alkynylation of di‐ and trisubstituted alkenols to construct propargylic stereocenters is disclosed using a new pyridine oxazoline ligand. This strategy allows direct access to chiral β‐alkynyl carbonyl compounds employing allylic alcohol substrates in contrast to more traditional conjugate addition methods.

Coupling phenols and allylic alcohols

Although chemists have plenty of ways to add carbon atoms to alkenes—including the Nobel Prize-winning Heck reaction—they have fewer options when working with heteroatom nucleophiles, such as alcohols. Now, Matthew S. Sigman and his group at the University of Utah report an intermolecular oxa-Heck reaction that allows them to couple phenols with allylic alcohols in an enantioselective manner (J. Am. Chem. Soc. 2016, DOI: 10.1021/jacs.6b11486). The reaction, which is catalyzed by palladium in the presence of a chiral pyridine oxazoline ligand, creates building blocks that would be tough to make using more common synthetic reactions, such as a Michael addition (example shown). Sigman’s team selected allylic alcohols as the alkene in the reaction in order to influence which hydrogen would be removed during the β-elimination to form the chiral product. The chemists show the reaction works with a broad scope of allylic alcohols and phenols, and even successfully swaps the

ChemInform Abstract: Chain‐Walking Cycloisomerization of 1,n‐Dienes Catalyzed by Pyridine—Oxazoline Palladium Catalysts and Its Application to Asymmetric Synthesis.

ChemInformVolume 47, Issue 37 Preparative Organic Chemistry ChemInform Abstract: Chain-Walking Cycloisomerization of 1,n-Dienes Catalyzed by Pyridine—Oxazoline Palladium Catalysts and Its Application to Asymmetric Synthesis. Taro Hamasaki, Taro Hamasaki Dep. Chem., Fac. Sci. Technol., Keio Univ., Kohoku, Yokohama 223, JapanSearch for more papers by this authorFumitoshi Kakiuchi, Fumitoshi Kakiuchi Dep. Chem., Fac. Sci. Technol., Keio Univ., Kohoku, Yokohama 223, JapanSearch for more papers by this authorTakuya Kochi, Takuya Kochi Dep. Chem., Fac. Sci. Technol., Keio Univ., Kohoku, Yokohama 223, JapanSearch for more papers by this author Taro Hamasaki, Taro Hamasaki Dep. Chem., Fac. Sci. Technol., Keio Univ., Kohoku, Yokohama 223, JapanSearch for more papers by this authorFumitoshi Kakiuchi, Fumitoshi Kakiuchi Dep. Chem., Fac. Sci. Technol., Keio Univ., Kohoku, Yokohama 223, JapanSearch for more papers by this authorTakuya Kochi, Takuya Kochi Dep. Chem., Fac. Sci. Technol., Keio Univ., Kohoku, Yokohama 223, JapanSearch for more papers by this author First published: 25 August 2016 https://doi.org/10.1002/chin.201637021Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume47, Issue37August, 2016 RelatedInformation

ChemInform Abstract: Enantioselective Dehydrogenative Heck Arylations of Trisubstituted Alkenes with Indoles to Construct Quaternary Stereocenters.

An enantioselective, intermolecular dehydrogenative Heck arylation of trisubstituted alkenes to construct remote quaternary stereocenters has been developed. Using a new chiral pyridine oxazoline ligand, good to high enantioselectivity is achieved for various combinations of indole derivatives and trisubstituted alkenes. However, some combinations of substrates led to lower enantioselectivity, which provided the impetus to use structure enantioselectivity correlations to design a better performing ligand.

Chain-walking Cycloisomerization of 1,n-Dienes Catalyzed by Pyridine–Oxazoline Palladium Catalysts and Its Application to Asymmetric Synthesis

Palladium catalysts possessing pyridine–oxazoline ligands were found to catalyze the chain-walking cycloisomerization of 1,n-dienes to form five-membered rings and were particularly effective for t...

Enantioselective Dehydrogenative Heck Arylations of Trisubstituted Alkenes with Indoles to Construct Quaternary Stereocenters.

An enantioselective, intermolecular dehydrogenative Heck arylation of trisubstituted alkenes to construct remote quaternary stereocenters has been developed. Using a new chiral pyridine oxazoline ligand, good to high enantioselectivity is achieved for various combinations of indole derivatives and trisubstituted alkenes. However, some combinations of substrates led to lower enantioselectivity, which provided the impetus to use structure enantioselectivity correlations to design a better performing ligand.

Pyridine–oxazoline and quinoline–oxazoline ligated cobalt complexes: Synthesis, characterization, and 1,3-butadiene polymerization behaviors

A series of cobalt complexes supported by pyridine–oxazoline (Pyox) and quinoline–oxazoline (Quox) were synthesized. Determined by single crystal X-ray crystallography, complexes 6a and 7c adopted distorted octahedron and trigonal bipyramid geometries, respectively, while complex 6b existed as an ion pair comprised of [CoL2]2+ and [CoCl4]2−, in which the cationic and anionic moieties displayed distorted octahedron and tetrahedral geometries, respectively. Upon activation with ethylaluminium sesquichloride (EASC), these cobalt complexes exhibited high catalytic activity and cis-1,4-selectivity toward 1,3-butadiene polymerization. The selectivity of the catalytic system could be switched from cis-1,4 to 1,2-fashion via the addition of PPh3. The effects of ligand environment, polymerization temperature, and [Al]/[Co] ratio on the polymerization were investigated in detail.