Chiral Imines Research Articles

Asymmetric C-C Bond Formation between Chiral N-Phosphonyl Imines and Ni(II)-Complex of Glycine Schiff Base Provides a GAP Synthesis of α,β-syn-Diamino Acid Derivatives.

The GAP asymmetric synthesis of α,β-diamino acid derivatives has been achieved by reacting chiral N-phosphonyl imines with Ni(II)-complex of glycine ester-based enolate without the use of traditional purifications of chromatography and recrystallization. The successful control of synstereochemistry of vicinal diamino products complements our previous methods which afforded anti stereoisomers and enables all four individual isomers to be synthesized by simply changing enolate geometry. In contrast to our previous synthesis where required at least 5 equiv of glycine Schiff base enolate for complete conversion, the new synthesis only needs 1.1 equiv of glycine Schiff base enolate to give complete diastereoselectivity (>99% de) and yields (91% - 97%). The absolute stereochemistry has been unambiguously determined by X-ray structural analysis.

A convergent and stereoselective total synthesis of (−)-crispine A, (−)-benzo[a]quinolizidine and (−)-salsolidine

Abstract A novel strategy has been developed for the syntheses of (−)-crispine, (−)-benzo[a]quinolizidine, and (−)-salsolidine using (R)-tert-butanesulfinamide as a source of chirality. The approach involves the stereoselective addition of Grignard reagent to chiral N-sulfinyl imine followed by cyclization of the secondary amide with a tethered halide as key steps.

A Highly Stereoselective Addition of Lithiated Ynamides to Ellman–Davis Chiral N-tert-Butanesulfinyl Imines

A highly diastereoselective addition of lithiated ynamides to Ellman-Davis chiral imines is described. While additions of N-sulfonyl ynamides are highly stereoselective even without Lewis acids, the use of BF3-OEt2 completely reversed the stereoselectivity. In addition, oxazolidinone-substituted ynamides behaved differently and functioned better with BF3-OEt2, and the chirality of the oxazolidinone ring exerts no impact on the selectivity.

Enantioselective Synthesis of Both Enantio­mers of Chiral Allenes Using Chiral N‐Methylcamphanyl Piperazine Templates

AbstractThe reaction of unsubstitued camphanyl‐piperazine 4 with ZnCl2, phenylacetylene, and benzaldehyde in toluene gave the corresponding dipropargylamine (i.e., 15) with opposite configurations at the newly formed stereogenic centres, which, upon reaction with ZnI2 resulted in the formation of a racemic mixture of 1,3‐diphenyl allene in 45 % yield. N‐Methylcamphanyl‐piperazine regioisomer 5, prepared by selective N‐methylation of the NH moiety attached to the stereogenic centre with (S)‐configuration, upon reaction with ZnCl2, phenylacetylene, and benzaldehyde in toluene, gave the corresponding propargylamine in 90 % yield, with an (S)‐configuration at the newly formed stereogenic centre, and upon subsequent reaction with ZnI2, this intermediate gave (R)‐1,3‐diphenyl allene in 52 % yield and with 96 % ee. Reaction of N‐methylcamphanyl‐piperazine isomer 5 with several 1‐alkynes and aldehydes in the presence of ZnBr2 gave the corresponding (R)‐allenes in 40–75 % yield and 79–99 % ee. In contrast, regioisomeric N‐methylcamphanyl‐piperazine 6 reacted with ZnBr2 to give the corresponding (S)‐allenes in 38–71 % yield and with 79–99 % ee. The opposite chiral discriminating abilities of the two NH moieties in camphanyl‐piperazines was confirmed by single‐crystal X‐ray analysis of the propargylamines formed. The results are discussed considering mechanisms involving the in situ formation of alkynylzinc halides, followed by diastereoselective addition to chiral iminium ion derivatives to give the corresponding propargylamines, and subsequent conversion to chiral allenes by an intramolecular 1,5‐hydrogen shift.

Catalytic Ugi-Type Condensation of α-Isocyanoacetamide and Chiral Cyclic Imine: Access to Asymmetric Construction of Several Heterocycles

Several novel heterocycles have been constructed asymmetrically on the basis of a catalytic Ugi-type condensation of α-isocyanoacetamide and chiral cyclic imine. The combination of phenylphosphilic acid and trifluoroethanol is exploited to promote an Ugi-type reaction with α-isocyanoacetamide for the first time. By means of this reaction, chiral 3-oxazolyl morpholin-2-one/piperazin-2-one derivatives are synthesized with high yields and excellent stereoselectivities. As electron-rich azadienes, these condensation products are further transformed to fused tricyclic frameworks by treatment with appropriate dienophiles such as maleic anhydride and unsaturated acyl chlorides via domino processes. Moreover, a one-pot, three-component synthesis of the chiral tricyclic frameworks from isocyanoacetamide, imine, and maleic anhydride is also feasible.

Preparation of sugar-derived 1,2-diamines via indium-catalyzed aza-Henry-type reaction: application to the synthesis of 6-amino-1,6-dideoxynojirimycin

The combination of (p-methoxyphenyl)imine, a bromonitroalkane, and zinc in the presence of catalytic indium allows straightforward access to β-nitroamine derivatives. The use of chiral sugar-derived imines furnished the corresponding β-nitroamines in high yields and stereoselectivities, from which the corresponding 1,2-diamines were easily obtained. The synthetic utility of the sugar-derived 1,2-diamines in the preparation of iminosugars was illustrated in a concise synthesis of 6-amino-1,6-dideoxynojirimycin.

Synthesis and mesomorphism of new chiral imines and copper(II) complexes

The synthesis, characterization and mesomorphic properties of a series of N-(2-hydroxy-4-n-alkyloxybenzylidene) 4′-amino-2-methylbutylcinnamate and their copper(II) complexes are reported. The imines exhibited smectic A (SmA) and chiral smectic C (SmC*) phases while their copper(II) complexes displayed SmA–SmC phase variant. The compounds have been characterized by elemental analysis and spectroscopic studies. The phase transition temperatures were detected by differential scanning calorimetry (DSC) analysis and the phases are confirmed by polarizing optical microscopy (POM). The chiral phase (SmC*) of the ligand disappeared on complexation. The unwinding of the helical superstructure of SmC* phase under the influence of electric field and the observed optical textures of SmC* phase are also discussed.

Indium‐Promoted Diastereo‐ and Regioselective Propargylation of Chiral Sulfinylimines

AbstractThe reaction of different chiral imines 3 derived from aldehydes or ketones with the silylated propargyl bromide 4b under sonication in the presence of indium metal led mainly or exclusively to the formation of protected homopropargylamines 5 in a diastereoselective manner. Of special interest are the ketimine derivatives because the new stereocenter has a quaternary configuration. The selective deprotection of the two protecting groups, the silicon and sulfinyl moieties, was easily achieved by conventional methodologies.

Towards heterogeneous organocatalysis: chiral iminium cations supported on porous materials for enantioselective alkene epoxidation

Enantiomerically pure iminium cations have been supported on a microporous support (zeolite Y) and on a mesoporous support (Al-MCM-41). These materials are effective asymmetric catalysts for the epoxidation of a range of aryl alkenes, giving high conversions quickly and with enantioselectivities similar to or in some cases even higher than are achievable using the corresponding iminium tetraphenylborates under homogeneous conditions. The catalysts can be simply recycled by filtration and washing. The methodology is illustrated in the synthesis of two natural products, (−)-(3′S)-lomatin and (+)-(3′S,4′R)-trans-khellactone, showing the general efficacy of our approach.

Lanthanide(III) Complexes of Bis‐semicarbazone and Bis‐imine‐Substituted Phenanthroline Ligands: Solid‐State Structures, Photophysical Properties, and Anion Sensing

Phenanthroline-based hexadentate ligands L(1) and L(2) bearing two achiral semicarbazone or two chiral imine moieties as well as the respective mononuclear complexes incorporating various lanthanide ions, such as La(III), Eu(III), Tb(III), Lu(III), and Y(III) metal ions, were synthesized, and the crystal structures of [ML(1)Cl(3)] (M=La(III), Eu(III), Tb(III), Lu(III), or Y(III)) complexes were determined. Solvent or water molecules act as coligands for the rare-earth metals in addition to halide anions. The big Ln(III) ion exhibits a coordination number (CN) of 10, whereas the corresponding Eu(III), Tb(III), Lu(III), and Y(III) centers with smaller ionic radii show CN=9. Complexes of L(2), namely [ML(2)Cl(3)] (M=Eu(III), Tb(III), Lu(III), or Y(III)) ions could also be prepared. Only the complex of Eu(III) showed red luminescence, whereas all the others were nonluminescent. The emission properties of the Eu derivative can be applied as a photophysical signal for sensing various anions. The addition of phosphate anions leads to a unique change in the luminescence behavior. As a case study, the quenching behavior of adenosine-5'-triphosphate (ATP) was investigated at physiological pH value in an aqueous solvent. A specificity of the sensor for ATP relative to adenosine-5'-diphosphate (ADP) and adenosine-5'-monophosphate (AMP) was found. (31)P NMR spectroscopic studies revealed the formation of a [EuL(2)(ATP)] coordination species.

The stereoselective total synthesis of (−)-dihydrotetrabenazine

A highly stereoselective synthesis of (−)-dihydrotetrabenazine has been accomplished using (R)-tert-butanesulfinamide as a chiral source. The synthesis involves the allylation of chiral N-sulfinyl imine followed by ring closure of the resulting secondary amide with a tethered halide and the Evans-Aldol reaction as key steps.

Asymmetric Addition of Alkoxy Ethynyl Anion to Chiral N-Sulfinyl Imines

The addition of lithiated ynol ethers to chiral N-sulfinyl imines proceeds in high yield and diastereoselectivity. The selectivity is completely reversed by the addition of boron trifluoride. These alkoxypropargyl sulfinamides can be reduced to afford enol ethers, selectively oxidized to busyl derivatives, or the ynol ether can be hydrolyzed to afford β-amino esters.

Molecular structures of dinuclear zinc(II) complexes of chiral tridentate imine and amine ligands: Effect of ligand geometry on diastereoselectivity

Racemic mixtures of Schiff bases (L1H and L2H) were reduced to respective amines (L1′H and L2′H). Compounds of composition [Zn2(L1)2(NCO)2] (1), [Zn(L1)N3]n (2), [Zn2(L2)2(NCO)2] (3), [Zn2(L1′)2(NCO)2] (1′), [Zn2(L1)2(N3)2]·2DMF (2′·2DMF) and [Zn2(L2′)2(NCO)2]·DMF (3′·DMF) were synthesized using these ligands, Zn(NO3)2·6H2O and NCO− or N3− ions. Molecular structures of all six compounds have been established. Both imine and amine ligands have N2O donor set, but coordinate, respectively, in meridional and facial fashions. First four complexes are monochelates and last two are bis-chelates. The Zn2O2 unit in 1–3 has RS combination of imine where as in 1′ has RR(SS) combinations of amine. In 2′ and 3′, zinc(II) bis-chelates have cis,cis,trans-(OP)2(NA)2(NY)2 stereochemistry and cis-(OP)2 disposition further coordinate to tetrahedral zinc. Compound 1′ exhibits 1D hydrogen-bonded polymer by enantioselective H-bonding interaction. In 2′, DMF molecules assemble RR and SS bis-chelates through N–H⋯O interactions.

Organocatalytic Asymmetric Synthesis of β‐Aryl‐β‐isocyano Esters

AbstractThe asymmetric addition of malonates to in situ generated N‐formylimines of aromatic aldehydes was achieved under phase‐transfer catalysis using Cinchona alkaloids‐derived quaternary ammonium salts. The resulting β‐formamidomalonates have been efficiently converted into β‐aryl‐β‐isocyano esters. Their utility in the multicomponent Ugi reaction with chiral cyclic imines has been demonstrated.

An Ugi-Type Condensation of α-Isocyanoacetamide and Chiral Cyclic Imine under a New Catalytic System

A new catalytic Ugi-type condensation of α-isocyanoacetamide and chiral cyclic imine is developed, where the combination of phenyl phosphilic acid and trifluoroethanol is exploited to promote the Ugi-type condensation with α-isocyanoacetamide for the first time. Under this new catalytic system, the reaction using the cyclic imines as relatively inertial substrates proceed well, and chiral 3-oxazolyl-morpholin/piperazine-2-one derivatives are synthesized with high yield and stereoselectivity. Furthermore, transformation of the condensation product to a novel fused tricyclic structure is attempted initially by treatment with maleic anhydride.

Stereocontrolled synthesis of piperidine alkaloids, (−)-241D and (−)-isosolenopsin

Highly diastereocontrolled synthesis of alkaloids, (−)-241D and (−)-isosolenopsin was achieved in 7.7% and 5.3% yields, respectively, using a Barbier-type allylation of a chiral imine and d-proline catalyzed aldol addition reaction of a β-amino aldehyde with acetone as the key steps. The synthesis involves a nine-step sequence using (S)-valinate imine in a Barbier-type allylation for the first time.

Vibrational and electronic circular dichroism monitoring of copper(II) coordination with a chiral ligand

Novel copper(II) coordination compounds with chiral macrocyclic imine ligands derived from R-/S-camphor were asymmetrically synthesized and characterized with the aid of chiroptical spectroscopies. Crystal structures of both enantiomers were determined by single crystal X-ray diffraction analysis. Circular dichroism (CD) spectra were analyzed using a simplified exciton model as well as quantum chemical computations. The absolute configuration of the copper(II) coordination compounds determined from CD was found consistent with the crystal data. The copper(II) complexes were further investigated by vibrational CD (VCD) measurement combined with density functional theory calculation. The complex formation was evidenced by spectral shifts of the characteristic bands in the CD and VCD spectra.

ChemInform Abstract: An Asymmetric Ugi Three‐Component Reaction Induced by Chiral Cyclic Imines: Synthesis of Morpholine— or Piperazine—Ketocarboxamide Derivatives.

AbstractTreatment of chiral cyclic imines like (I) and (VII) with acids and isocyanides allows an efficient and stereoselective access to novel morpholines.

The first report of [2+2] ketene–imine cycloaddition reactions (Staudinger) on carbon nanotubes

Several new carbon nanotube-functionalized β-lactams have been synthesized from chiral imines derived from β-d-glucopyranosylamine and a ketene from carbon nanotube-based oxyacetic acid via a [2+2] cycloaddition reaction. The cycloadducts were characterized by thermogravimetric analysis, Raman spectrometry, IR, and N2 adsorption processes.

β-Peptoids: synthesis of a novel dimer having a fully extended conformation

Chiral imines 1a,b, already synthesized in our laboratory, were converted in good yield by reduction into the corresponding N-benzyl-γ-lactams 2a,b. Desilylation followed by oxidation of the hydroxymethyl functionality gave the N-benzyl-β-amino acids 5a,b in good yield and high purity. Starting from compound 6a, the corresponding β-peptoid dimer 8 was prepared, together with its derivatives 9 and 10, these latter displaying conformational restriction about the peptide bond, as evidenced by NMR data.