Pyridyl Alcohols Research Articles

Optimized Scalable Synthesis of Chiral Iridium Pyridyl‐Phosphinite (Pyridophos) Catalysts

AbstractIridium catalysts with chiral P,N ligands have greatly enhanced the scope of asymmetric olefin hydrogenation because they do not require a coordinating group near the C=C bond like Rh and Ru catalysts. Pyridophos ligands, possessing a conformationally restricted annulated pyridine framework linked to a phosphinite group, proved to be particularly effective, inducing high enantioselectivities in the hydrogenation of a remarkably broad range of substrates. Here we report the development of an efficient scalable synthesis for the two most versatile Ir‐pyridophos catalysts, derived from 2‐phenyl‐8‐hydroxy‐5,6,7,8‐tetrahydroquinoline or the analogue with a five‐membered carbocyclic ring, respectively, by modification and optimization of the original synthetic route. The optimized route renders both catalysts readily accessible in multi‐gram quantities in analytically pure form in overall yields of 26–37 %, starting from acetophenone and cyclopentanone or cyclohexanone, respectively. A major advantage of the new synthesis is the efficient and practical kinetic resolution of the late‐stage pyridyl alcohol intermediates with commercial immobilized Candida antarctica lipase B, giving access to both enantiomers of these catalysts as essentially enantiopure compounds. The catalysts are obtained as crystalline solids, which are air‐stable and can be stored for years at −20 °C without notable decomposition.

Synthesis of 1,3‐Disubstituted Imidazo[1,5‐a]pyridines through Oxidative C‐N Bond Formation from Aryl‐2‐pyridylmethanols and Their Fluorescent Study

AbstractA simple, effortless, and efficacious protocol for the synthesis of highly fluorescing imidazo[1,5‐a]pyridines via copper catalyzed inter‐/intramolecular C−N bond formation between readily available pyridyl alcohols with either benzyl amines or amino acids has been developed. This domino reaction is involved with alcohol oxidation/condensation/oxidative amination sequence to synthesize imidazo[1,5‐a]pyridines in good to excellent yields. The fluorescence studies of these compounds indicated a bathochromic shift for the electron donating substituents, whereas a hypsochromic shift for the electron withdrawing substituents. Synthetic modification of the groups attached to the heterocyclic core showed a profound impact on the emission properties when subjected to pH and solvent polarity change.

Copper(II) complexes of a new tetradentate bis-benzimidazolyl diamide ligand with disulfanediyl linker: synthesis, characterization, and oxidation of some pyridyl, napthyl, and benzyl alcohols

The bis-benzimidazolyl diamide ligand 3,3′-disulfanediyl-bis-(N-((1H-benzo[d]imidazol-2-yl)methyl)propanamide) (L) having N, S, and O donors has been synthesized and utilized to prepare copper(II) complexes of general composition [Cu(L)X]·X·nH2O, where X is Cl– or . Ligands and complexes were characterized by elemental analysis, UV–visible, IR spectroscopy, 1H NMR, mass spectrometry, conductance, electron paramagnetic resonance, cyclic voltammetry, fluorescence, single-crystal, and PXRD. [Cu(L)(NO3)]NO3·H2O crystallizes in the monoclinic C2/c space group with one molecule in the asymmetric unit. Copper adopts a distorted octahedral geometry with four coordination sites occupied by the ligand and two sites by a bidentate nitrate. [Cu(L)(NO3)]NO3·H2O has been utilized as a catalyst to oxidize alcohols with tert-butyl hydroperoxide as an alternative source of oxygen. The oxidized products have been characterized by GCMS.

ChemInform Abstract: Chichibabin‐Type Direct Alkylation of Pyridyl Alcohols with Alkyl Lithium Reagents.

AbstractThe reaction allows a convenient and selective access to C6‐alkylated pyridyl alcohols.

Chichibabin-Type Direct Alkylation of Pyridyl Alcohols with Alkyl Lithium Reagents

Direct C(6) alkylation of pyridyl alcohols can be achieved following an initial deprotonation of the hydroxy group. This transformation, which is believed to occur by a Chichibabin-type alkylation, avoids lateral deprotonation prior to pyridine ring alkylation and gives increased regioselectivity for C(6) over C(4) alkylation.

Nickel and cationic palladium complexes bearing (imino)pyridyl alcohol ligands: Synthesis, characterization and vinyl polymerization of norbornene

A series of nickel and palladium complexes bearing (imino)pyridyl alcohol tridentate [N,N,O] ligands, 2-(ArN CMe)-6-{(HO)CR 2}C 5H 3N ( L1– L4), were synthesized and sufficiently characterized by elemental and spectroscopic analysis along with X-ray diffraction analysis. The X-ray diffraction demonstrated that five-coordinated nickel halide complexes ( 1a– 4a and 1b) and six-coordinated nickel acetate complex ( 1c) were prepared, and cationic palladium complexes ( 1d and 2d) formed with the [PdCl 4] 2− counterion. All these complexes displayed high catalytic activities up to 1.883 × 10 7 g(PNB) mol −1(cat) h −1 ( 2d) for the vinyl polymerization of norbornene on treatment with excess methylaluminoxane (MAO), affording the vinyl-type PNBs with high molecular weights and relatively narrow molecular weight distributions. The parameters of reaction conditions, the type of metals and steric effects of coordinative ligands had influences on the catalytic properties.

Control of Enantioselectivity with Flexible Biaryl Axes: Terpene‐Based Alkylzinc Catalysts in Enantioselective Dialkylzinc Additions

New enantiopure pyridyl alcohols are efficiently accessible through few synthetic steps from commercially available terpenes, that is, (+)-fenchone, (-)-menthone and (-)-verbenone as well as 2,6-diphenylpyridine. These chelating pyridyl alcohols exhibit flexible pyridyl-phenylene axes, which give rise to P and M conformers. Alkylzincation of the hydroxy groups eliminates equilibria of the conformers and generates alkylzinc complexes with adjusted biaryl axes, as it is demonstrated by NMR studies. These alkylzinc catalysts perform well in the addition of dimethylzinc or diethylzinc to benzaldehyde with yields up to 99% and ee's up to 95%. The adjusted pyridylphenylene conformations in the ligands now control enantioselectivities of the catalysts, which were also analysed by computations at the DFT level.

Chromatography-Free Enzymatic Kinetic Resolution of Secondary Alcohols

Racemic secondary alcohols were resolved by enzymatic esterification using Candida antarctica lipase B (CAL B). After derivatization of the unreacted enantiomer with phthalic anhydride, the resulting phthalic acid monoesters could be easily separated from the corresponding acetates by precipitation and filtration or distillation, thus avoiding laborious column chromatography, which is a major obstacle for large-scale reactions. This method has been successfully applied to the multigram synthesis of enantiopure pyridyl alcohols.

Design and synthesis of new chiral pyridine–phosphite ligands for the copper-catalyzed enantioselective conjugate addition of diethylzinc to acyclic enones

A series of new chiral pyridine–phosphite ligands have been prepared from ( R)-pyridyl alcohols and BINOL-derived chlorophosphite, and successfully employed in the copper-catalyzed enantioselective conjugate addition of diethylzinc to acyclic enones. Using the simple and inexpensive CuBr 2 as a precursor, the enantioselective additions to various substituted acyclic enones afforded products in high yields and good enantioselectivities (up to 92% ee).

Chiral Aryl Pyridyl Alcohols as Enantioselective Catalysts in the Addition of Diethylzinc to Substituted Benzaldehydes

AbstractChiral (5‐aryl‐10, 10‐dimethyl‐6‐aza‐tricyclo[7.1.1.02,7]undeca‐2(7),3,5‐trien‐8‐yl)‐diphenyl‐methanols were prepared from highly enantiopure (1R)‐(+)‐α‐pinene (> 97% ee), and applied in the enantioselective addition of diethylzinc to substituted benzaldehydes, to yield alcohols with the (S)‐configuration with an enantiomeric excess that typically ranges from 19 to 86%. Importantly, the electron‐withdrawing substituents at the meta‐position of the substituted benzaldehydes exhibited high enantioselectivity during alkylation using diethylzinc.

Pyridyl Phosphinites and Pyridyl Phosphites from Chiral Pyridyl Alcohols – A Modular Approach

On pages 4212 and 4213 of the original article,1 the characterization data (optical rotation, melting point, and 1H, 13C and 31P NMR data) for compounds 2c–BH3 and 2d–BH3 are interchanged; the correct data for 2c–BH3 are given under 2d–BH3 and vice versa. The Authors

Synthesis of Chiral Pyridyl Alcohols by Cyclotrimerization

Reported is a synthesis of chiral pyridyl alcohols by a two-step reaction. In the first step, catalyst (R,R)-A leads to the S-enantiomers while (S,S)-A results in the formation of the R-enantiomers. The enantiomeric excess of O-tri­methylsilylcyanohydrins B was retained in the final products after Co-catalyzed cyclotrimerization and desilylation.

Synthesis of Chiral Pyridyl Alcohols Using a Two-Step Catalytic Approach

Chiral pyridyl alcohols have been prepared by developing a two-step approach that uses the asymmetric cyanation of aldehydes- to give cyanohydrins and subsequent [2+2+2]-cyclotri-merization reaction with acetylene.

Kinetic Resolution of Pyridyl Alcohols by Cu(II)(Borabox)-Catalyzed Acylation

Kinetic resolution of pyridyl alcohols has been achieved using copper(II)(borabox)-catalyzed benzoylation. Selectivity factors (krel) of up to 125 have been observed and application to the synthesis of chiral pyridyl phosphine ligands is described.

Preparation of a Privileged Silicon‐Stereogenic Silane: Classical versus Kinetic Resolution

AbstractThe cyclic silicon‐stereogenic silane (SiR)‐5 decorated with three different substituents of distinct steric demand is an exceptionally useful chiral reagent in asymmetric organosilicon chemistry. Several approaches for its large‐scale preparation in optically pure form have been investigated. These hinge upon the resolution of racemic silane rac‐5 which, in turn, is accessible in multi‐gram quantities by a straightforward one‐pot two‐step reaction sequence. For this, a classical as well as a novel kinetic resolution via its diastereomeric silyl ethers derived from enantiopure secondary alcohols as resolving agents has been elaborated: (1) the use of (−)‐menthol [(−)‐7] allowed for a quantitative separation of silyl ethers (SiS)‐10 and (SiR)‐10 by practical fractional crystallization and (2) a diastereoselective copper‐catalyzed dehydrogenative silicon‐oxygen coupling using pyridyl alcohols (S)‐16 or (R)‐16 capable of two‐point binding has been devised and assessed as a novel kinetic resolution strategy for the synthesis of a silane with silicon‐centered chirality. Subsequent stereospecific reductive cleavage of the silicon‐oxygen bond enabled the preparation of (SiR)‐5 and (SiS)‐5 in excellent enantiomeric excesses of up to 99 % ee.

Kinetic Resolution of Diols and Pyridyl Alcohols

Kinetic Resolution of Diols and Pyridyl Alcohols

Synthesis of Boron-Bridged Anionic C2-Symmetric Bisoxazolines and Their Application in Asymmetric Catalysis

Anionic boron-based chiral bisoxazoline ligands, the borabox ligands, are readily prepared from amino alcohols and haloboranes. The highly modular nature of these ligands allows both for electronic and steric tuning of the structure. The high enantioselectivities obtained in various Cu-catalyzed asymmetric reactions and especially in the kinetic resolution of pyridyl alcohols where bisoxazoline ligands exhibit almost no selectivity, point to a considerable potential of borabox ligands in asymmetric catalysis.

Kinetic Resolution of Diols and Pyridyl Alcohols by Cu(II)(borabox)-Catalyzed Acylation

[reaction: see text] Boron-bridged bisoxazoline (borabox) ligands have been used in the copper(II)-catalyzed benzoylation of pyridyl alcohols and 1,2-diols. Efficient kinetic resolution of 1,2-diols was achieved using both borabox and bisoxazoline (box) ligands. Borabox ligands induced high selectivities in the benzoylation of suitable pyridyl alcohols, where they outperformed bisoxazolines. In addition, highly enantioselective Cu(II)(borabox)-catalyzed benzoylation has been used for the synthesis of both enantiomers of a pyridyl alcohol.

Synthesis, Structure and Reactivity in Styrene Polymerization by Heterocyclic Alkoxy‐ and Thiolatotitanium(IV) Complexes

AbstractThe reaction of [Ti(OiPr)4] or [TiCl4(THF)2] with two equivalents of pyridyl alcohols or pyridyl or pyrimidinyl thiols has proven to be a good preparative method to obtain a variety of non‐metallocene diisopropoxo‐ or dichlorotitanium(IV) complexes. The complexes [Ti(X)2{2‐(OCH2)‐6‐R‐(C5H3N)}2] were found to be dynamic at room temperature, with the heterocyclic alkoxy ligand dissociating and recoordinating in a κ2‐N,O chelate fashion, as revealed by a single‐crystal X‐ray analysis of [Ti(OiPr)2{2‐(OCH2)(C5H4N)}2] (1). The dynamic behavior of some of the resulting thiolato complexes was also studied and the single‐crystal X‐ray analysis of [Ti(OiPr)2{2‐S‐4,6‐Me2‐(C4HN2)}2] (5) revealed a κ2‐N,S system for these complexes. These complexes show catalytic activity in the polymerization of styrene upon activation with methylaluminoxane. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Bifunctional pyridyl alcohols with the bicyclo[3.3.0]octane scaffold in the asymmetric addition of diethylzinc to aldehydes

Some new pyridyl alcohols with the cis-bicyclo[3.3.0]octane scaffold were synthesized and used as chiral ligands for the enantioselective addition of diethylzinc to aldehydes. Ligands 4 were found to be far superior to the C 2-symmetric ligands 2 in terms of enantioselectivities. Quantitative yields and enantiomeric excesses of up to 92% were obtained when the ligand 4 was used. The carbonyl function in 4 proved to be beneficial for the high enantioselectivities in the addition of diethylzinc to aldehydes. Conversion of the carbonyl group into oxime or oxime ether group led to a sort of more active ligands, which catalyzed the same reaction with rate acceleration.