Achiral 2-pyridone and 4-aminopyridine act as chiral inducers of asymmetric autocatalysis with amplification of enantiomeric excess via the formation of chiral crystals.

Enantiomorphous crystals of achiral 2-pyridone and 4-aminopyridine served as sources of chirality, to induce the asymmetric autocatalysis of 5-pyrimidyl alkanol during the asymmetric addition of diisopropylzinc to the corresponding pyrimidine-5-carbaldehyde, that is, the Soai reaction. Following a significant amplification of enantiomeric excess through asymmetric autocatalysis, highly enantioenriched 5-pyrimidyl alkanol could be synthesized with their corresponding absolute configurations to those of chiral crystals of 2-pyridone and 4-aminopyridine.

Chiral Dinuclear EuIII , TbIII , and YIII Complexes Supported by P-Stereogenic Linear Tetraphosphine Tetraoxide.

A P-stereogenic linear tetraphosphine tetraoxide, (R,R)- or (S,S)-dpmppm(=O)4 , was synthesized to prepare C2 dinuclear M(hfa)3 complexes (M=Eu, Tb, Y) as the first example of lanthanide(III) complexes with P-chiral multidentate phosphine oxides. The mononuclear M(hfa)3 complexes (M=Eu, Y) with a P-chiral diphosphine dioxide, tpdpb(=O)2 , were also prepared, and comparison of their photophysical properties for the EuIII complexes revealed that significant chiral induction from the P-chiral centers arises on the achiral M(hfa)3 units through intramolecular π-π stacking constraint in the dinuclear system.

A Synthetic Model for the Possible FeIV2(µ-O)2 Core of Methane Monooxygenase Intermediate Q Derived from a Structurally Characterized FeIIIFeIV(µ-O)2 Complex.

A bis(µ-oxo)diiron(IV,IV) complex as a model for intermediate Q in the methane monooxygenase reaction cycle has been prepared. The precursor complex with a [FeIIIFeIV(µ-O)2] core was fully characterized by X-ray crystallography and other spectroscopic analyses and was converted to the [FeIV2(µ-O)2] complex via electrochemical oxidation at 1000 mV (vs Ag/Ag+) in acetone at 193 K. The UV-vis spectral features, Mössbauer parameters (ΔEQ = 2.079 mm/s and δ = -0.027 mm/s), and EXAFS analysis (Fe-O/N = 1.73/1.96 Å and Fe···Fe = 2.76 Å) support the structure of the low-spin (S = 1, for each Fe) [FeIV2(µ-O)2] core. The rate constants of the hydrogen abstraction reaction from 9,10-dihydroanthracene at 243 K suggest the high reactivity of these synthetic bis(µ-oxo)diiron complexes supported by simple N4 tripodal ligand.

Asymmetric Autocatalysis as an Efficient Link Between the Origin of Homochirality and Highly Enantioenriched Compounds.

Biological homochirality of essential components such as L-amino acids and D-sugars is prerequisite for the emergence, evolution and the maintenance of life. Implication of biological homochirality is described. Considerable interest has been focused on the origin and the process leading to the homochirality. Asymmetric autocatalysis with amplification of enantiomeric excess (ee), i.e., the Soai reaction, is capable to link the low ee induced by the proposed origins of chirality such as circularly polarized light and high ee of the organic compound. Absolute asymmetric synthesis without the intervention of any chiral factor was achieved in the Soai reaction.

Switching of Fluorescent Zn/Cd Selectivity in N,N,N',N'-Tetrakis(6-methoxy-2-quinolylmethyl)-1,2-diphenylethylenediamine by One Asymmetric Carbon Atom Inversion.

A quinoline-based hexadentate ligand, (S,S)-N,N,N',N'-tetrakis(6-methoxy-2-quinolylmethyl)-1,2-diphenylethylenediamine ((S,S)-6-MeOTQPh2EN), exhibits fluorescence enhancement at 498 nm upon addition of 1 equiv of Zn2+ (IZn/I0 = 12, φZn = 0.047) in aqueous DMF solution (DMF/H2O = 2:1). Addition of 1 equiv of Cd2+ affords a much smaller fluorescence increase at the same wavelength (ICd/I0 = 2.5, ICd/IZn = 21%). The trivalent metal ions such as Al3+, Cr3+, and Fe3+ also exhibit fluorescence enhancement at 395 nm (IAl/I0 = 22, ICr/I0 = 6 and IFe3+/I0 = 13). In contrast, meso-6-MeOTQPh2EN exhibits a Cd2+-selective fluorescence increase at 405 nm in the presence of 1 equiv of metal ion (ICd/I0 = 11.5, φCd = 0.022), while Zn2+ induces a smaller fluorescent response under the same experimental conditions (IZn/I0 = 3.3, IZn/ICd = 29%). In this case, the fluorescence intensities of meso-6-MeOTQPh2EN in the presence of a large amount of Zn2+ and Cd2+ become similar. This diastereomer-dependent, fluorescent metal ion specificity is derived from the Zn2+-specific intramolecular excimer formation in (S,S)-6-MeOTQPh2EN-Zn2+ complex and higher binding affinity of meso-6-MeOTQPh2EN with Cd2+ in comparison to Zn2+. The more conformationally restricted diastereomeric pair, namely, cis- and trans-TQDACHs (cis- and trans-N,N,N',N'-tetrakis(2-quinolylmethyl)-1,2-diaminocyclohexanes), both exhibit Zn2+-specific fluorescence enhancement because of the high metal binding affinity and intramolecular excimer forming property derived from the rigid DACH backbone.

Achiral amino acid glycine acts as an origin of homochirality in asymmetric autocatalysis.

Chiral crystals of the only achiral proteinogenic α-amino acid, glycine induced the asymmetric autocatalysis with amplification of enantiomeric excess (ee). The P31 crystals of γ-glycine, which display positive Cotton effect (CD) at around 215 nm, mediate the asymmetric autocatalysis to yield (R)-pyrimidyl alkanol with high ee. In contrast, the enantiomorphic P32 crystals, which display negative Cotton effect, afford (S)-alkanol after the significant amplification of ee by asymmetric autocatalysis.

Pyrophosphate-Induced Intramolecular Excimer Formation in Dinuclear Zinc(II) Complexes with Tetrakisquinoline Ligands.

Dinuclear Zn2+ complexes with HTQHPN ( N,N,N' ,N'-tetrakis(2-quinolylmethyl)-2-hydroxy-1,3-propanediamine) derivatives have been prepared, and their pyrophosphate (PPi, P2O74-) sensing properties were examined. The ligand library includes six HTQHPN derivatives with electron-donating/withdrawing substituents, an extended aromatic ring, and six-membered chelates upon zinc binding. Complexation of ligand with 2 equiv of Zn2+ promotes small to moderate fluorescence enhancement around 380 nm, but in the cases of HTQHPN, HT(6-FQ)HPN ( N,N,N' ,N'-tetrakis(6-fluoro-2-quinolylmethyl)-2-hydroxy-1,3-propanediamine), and HT(8Q)HPN ( N,N,N' ,N'-tetrakis(8-quinolylmethyl)-2-hydroxy-1,3-propanediamine), subsequent addition of PPi induced a significant fluorescence increase around 450 nm. This fluorescence enhancement in the long-wavelength region is attributed to the conformational change of the bis-(quinolylmethyl)amine moiety which promotes intramolecular excimer formation between adjacent quinolines upon binding with PPi. The structures of PPi- and phosphate-bound dizinc complexes were revealed by X-ray crystallography utilizing phenyl-substituted analogues. The zinc complex with HT(8Q)HPN exhibits the highest signal enhancement ( IPPi/ I0 = 12.5) and selectivity toward PPi sensing ( IATP/ IPPi = 20% and IADP/ IPPi = 25%). The fluorescence enhancement turned to decrease gradually after the addition of more than 1 equiv of PPi due to the removal of zinc ion from the ligand-zinc-PPi ternary complex, allowing the accurate determination of PPi concentrations at the fluorescence maximum composition. The practical application of the present method was demonstrated monitoring the enzymatic activity of pyrophosphatase.

Point-to-Point Ultra-Remote Asymmetric Control with Flexible Linker.

An ultra-remote intramolecular (point-to-point) asymmetric control through 38 bonds (1,39-asymmetric induction) has been achieved by using the principle of direct supramolecular orientation of catalytic and reactive moieties in asymmetric autocatalysis. We found the highly stereoselective diisopropylzinc addition reaction using designed molecules possessing pyrimidine sites at each terminal of a conformationally flexible simple methylene chain.

Reversal of the sense of enantioselectivity between 1- and 2-aza[6]helicenes used as chiral inducers of asymmetric autocatalysis.

Reversal of the sense of enantioselectivity was observed between 1-aza[6]helicene 2 and 2-aza[6]helicene 3 employed as chiral inducers of asymmetric autocatalysis of pyrimidyl alkanol. In the presence of (P)-(+)-1-aza[6]helicene 2, the reaction of pyrimidine-5-carbaldehyde 1 with diisopropylzinc afforded, in conjunction with asymmetric autocatalysis, (S)-pyrimidyl alkanol 4 with high ee. Surprisingly, the reaction in the presence of (P)-(+)-2-aza[6]helicene 3 gave the opposite enantiomer of (R)-alkanol 4 with high ee. In the same manner, (M)-(-)-2 and (M)-(-)-3 afforded (R)- and (S)-alkanol 4, respectively. The sense of enantioselectivity is controlled not only by the helicity of the azahelicene derivatives but also by the position of the nitrogen atom.

Achiral Inorganic Gypsum Acts as an Origin of Chirality through Its Enantiotopic Surface in Conjunction with Asymmetric Autocatalysis.

Achiral inorganic gypsum (CaSO4 ⋅2 H2 O) triggers the asymmetric autocatalysis of pyrimidyl alkanol on its two-dimensional enantiotopic faces to give highly enantioenriched alkanol products with absolute configurations corresponding to the respective enantiotopic surfaces. This is the first example of highly enantioselective synthesis on the enantiotopic surface of an achiral mineral.

Can the analyte-triggered asymmetric autocatalytic Soai reaction serve as a universal analytical tool for measuring enantiopurity and assigning absolute configuration?

An investigation is reported on the use of the autocatalytic enantioselective Soai reaction, known to be influenced by the presence of a wide variety of chiral materials, as a generic tool for measuring the enantiopurity and absolute configuration of any substance. Good generality for the reaction across a small group of test analytes was observed, consistent with literature reports suggesting a diversity of compound types that can influence the stereochemical outcome of this reaction. Some trends in the absolute sense of stereochemical enrichment were noted, suggesting the possible utility of the approach for assigning absolute configuration to unknown compounds, by analogy to closely related species with known outcomes. Considerable variation was observed in the triggering strength of different enantiopure materials, an undesirable characteristic when dealing with mixtures containing minor impurities with strong triggering strength in the presence of major components with weak triggering strength. A strong tendency of the reaction toward an 'all or none' type of behavior makes the reaction most sensitive for detecting enantioenrichment close to zero. Consequently, the ability to discern modest from excellent enantioselectivity was relatively poor. While these properties limit the ability to obtain precise enantiopurity measurements in a simple single addition experiment, prospects may exist for more complex experimental setups that may potentially offer improved performance.

Asymmetric Induction by a Nitrogen 14 N/15 N Isotopomer in Conjunction with Asymmetric Autocatalysis.

Chirality arising from isotope substitution, especially with atoms heavier than the hydrogen isotopes, is usually not considered a source of chirality in a chemical reaction. An N2 ,N2 ,N3 ,N3 -tetramethyl-2,3-butanediamine containing nitrogen (14 N/15 N) isotope chirality was synthesized and it was revealed that this isotopically chiral diamine compound acts as a chiral initiator for asymmetric autocatalysis.

Asymmetric autocatalysis of pyrimidyl alkanol and its application to the study on the origin of homochirality.

CONSPECTUS: Amplification of enantiomeric excess (ee) is a key feature for the chemical evolution of biological homochirality from the origin of chirality. We describe the amplification of ee in the asymmetric autocatalysis of 5-pyrimidyl alkanols in the reaction between diisopropylzinc (i-Pr2Zn) and pyrimidine-5-carbaldehydes. During the reaction, an extremely low ee (ca. 0.00005% ee) can be amplified to >99.5% ee, and therefore, the initial slightly major enantiomer is automultiplied by a factor of ca. 630000, while the initial slightly minor enantiomer is automultiplied by a factor of less than 1000. In addition, pyrimidyl alkanols with various substituents at the 2-position of the pyrimidine ring, 3-quinolyl alkanol, 5-carbamoyl-3-pyridyl alkanol, and large multifunctionalized pyrimidyl alkanols also act as highly efficient asymmetric autocatalysts in the addition of i-Pr2Zn to the corresponding aldehydes. The asymmetric autocatalysis of pyrimidyl alkanol can discriminate the chirality of various compounds. Chiral substances such as alcohols, amino acids, hydrocarbons, metal complexes, and heterogeneous chiral materials can act as chiral triggers for asymmetric autocatalysis to afford pyrimidyl alkanols with the corresponding absolute configuration of the initiator. This recognition ability of chiral compounds is extremely high, and chiral discrimination of a cryptochiral quaternary saturated hydrocarbon was established by applying asymmetric autocatalysis. By using the large amplification effect of the asymmetric autocatalysis, we can link various proposed origins of chirality with highly enantioenriched organic compounds in conjunction with asymmetric autocatalysis. Thus, a statistical fluctuation in ee of racemic compounds can be amplified to high ee by using asymmetric autocatalysis. Enantiomeric imbalance induced by irradiation of circularly polarized light can affect the enantioselectivity of asymmetric autocatalysis. The asymmetric autocatalysis was also triggered by the morphology of inorganic chiral crystals such as quartz, sodium chlorate, and cinnabar. Chiral organic crystals of achiral compounds also act as chiral initiators, and during the study of a crystal of cytosine, enantioselective chiral crystal phase transformation of the cytosine crystal was achieved by removal of the water of crystallization in an achiral monohydrate crystal. Enantioselective C-C bond formation was realized on the surfaces of achiral single crystals based on the oriented prochirality of achiral aldehydes. Furthermore, asymmetric autocatalysis of pyrimidyl alkanols is a highly sensitive reaction that can recognize and amplify the significantly small effect of a chiral compound arising solely from isotope substitution of hydrogen, carbon, and oxygen (D/H, (13)C/(12)C, and (18)O/(16)O). These examples show that asymmetric autocatalysis with an amplification of chirality is a powerful tool for correlating the origin of chirality with highly enantioenriched organic compounds. Asymmetric autocatalysis using two ß-amino alcohols reveals a reversal of enantioselectivity in the addition of i-Pr2Zn to aldehyde and is one approach toward understanding the mechanism of asymmetric dialkylzinc addition, where heteroaggregates act as the catalytic species.

Crystal Structure of the Isopropylzinc Alkoxide of Pyrimidyl Alkanol: Mechanistic Insights for Asymmetric Autocatalysis with Amplification of Enantiomeric Excess.

Asymmetric amplification during self-replication is a key feature that is used to explain the origin of homochirality. Asymmetric autocatalysis of pyrimidyl alkanol in the asymmetric addition of diisopropylzinc to pyrimidine-5-carbaldehyde is a unique example of this phenomenon. Crystallization of zinc alkoxides of this 5-pyrimidyl alkanol and single-crystal X-ray diffraction analysis of the alkoxide crystals reveal the existence of tetramer or higher oligomer structures in this asymmetric autocatalytic system.

The origins of homochirality examined by using asymmetric autocatalysis.

Pyrimidyl alkanol was found to act as an asymmetric autocatalyst in the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde. Asymmetric autocatalysis of 2-alkynylpyrimidyl alkanol with an extremely low enantiomeric excess (ca. 0.00005% ee) exhibits enormous asymmetric amplification to afford the same compound with >99.5% ee. This asymmetric autocatalysis with amplification of ee has been employed to examine the validity of proposed theories of the origins of homochirality. Circularly polarized light, quartz, sodium chlorate, cinnabar, chiral organic crystals and spontaneous absolute asymmetric synthesis were considered as possible candidates for the origin of chirality; each could act as a chiral source in asymmetric autocatalysis. Asymmetric autocatalysis can discriminate the isotope chirality arising from the small difference between carbon (carbon-13/carbon-12) and hydrogen (D/H) isotopes. Cryptochiral compounds were also discriminated by asymmetric autocatalysis.

Self-replication and amplification of enantiomeric excess of chiral multifunctionalized large molecules by asymmetric autocatalysis.

Self-replication of large chiral molecular architectures is one of the great challenges and interests in synthetic, systems, and prebiotic chemistry. Described herein is a new chemical system in which large chiral multifunctionalized molecules possess asymmetric autocatalytic self-replicating and self-improving abilities, that is, improvement of their enantioenrichment in addition to the diastereomeric ratio. The large chiral multifunctionalized molecules catalyze the production of themselves with the same structure, including the chirality of newly formed asymmetric carbon atoms, in the reaction of the corresponding achiral aldehydes and reagent. The chirality of the large multifunctionalized molecules controlled the enantioselectivity of the reaction in a highly selective manner to construct multiple asymmetric stereogenic centers in a single reaction.

ß-Arylation of carboxamides via iron-catalyzed C(sp3)-H bond activation.

A 2,2-disubstituted propionamide bearing an 8-aminoquinolinyl group as the amide moiety can be arylated at the ß-methyl position with an organozinc reagent in the presence of an organic oxidant, a catalytic amount of an iron salt, and a biphosphine ligand at 50 °C. Various features of selectivity and reactivity suggest the formation of an organometallic intermediate via rate-determining C-H bond cleavage rather than a free-radical-type reaction pathway.

Asymmetric autocatalysis triggered by oxygen isotopically chiral glycerin.

Chiral (S)- and (R)-(18)O-glycerin induces enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde, and the subsequent asymmetric autocatalysis affords (R)- and (S)-pyrimidyl alkanol with high enantiomeric excess, respectively.

Phenanthrene synthesis by iron-catalyzed [4+2] benzannulation between alkyne and biaryl or 2-alkenylphenyl Grignard reagent.

The [4+2] benzannulation reaction of internal or terminal alkynes with 2-biaryl, 2-heteroarylphenyl, or 2-alkenylphenyl Grignard reagents in the presence of Fe(acac)(3), 4,4'-di-tert-butyl-2,2'-bipyridyl, and 1,2-dichloro-2-methylpropane takes place at room temperature in 1 h to give 9-substituted or 9,10-disubstituted phenanthrenes and congeners in moderate to excellent yields. The reaction tolerates sensitive functional groups such as bromide and olefin. When applied to a 1,3-diyne, the annulation reaction takes place on both acetylenic moieties to give a bisphenanthrene derivative.

Chiral approach to investigate mechanism of highly efficient thermally activated delayed fluorescence.

A chiral chromophore with thermally activated delayed fluorescence characteristics is designed. A model describing vibrations of the dihedral angle between donor and acceptor units allowed at room temperature explains the enhanced fluorescence rate of the molecule, including a nearly 100% photoluminescence quantum yield and the absence of circularly polarized emission characteristics from enantiomers of the chromophore.