Arimasa Matsumoto

Iron-Catalyzed Direct Arylation through Directed C−H Bond Activation

An iron-catalyzed C-C bond formation reaction of a nitrogen-containing aromatic compound with an arylzinc reagent takes place at 0 degrees C in a good to quantitative yield. The reaction involves a C-H bond activation directed by a neighboring nitrogen atom. The important additives in this reaction are 1,10-phenanthroline, tetramethylethylenediamine, and 1,2-dichloro-2-methylpropane, in the absence of which a very low product yield was observed.

β-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 β-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.

Iron‐Catalyzed Chemoselective ortho Arylation of Aryl Imines by Directed CH Bond Activation

No Fe-ar: Iron catalyzes an imine-directed C-H bond activation to introduce an ortho-aryl group to an acetophenone-derived imine using a diarylzinc reagent (see scheme), whereas palladium catalyzes the conventional substitution reaction . The title reaction features mild and selective C-H bond activation in the presence of aryl bromide, chloride, or sulfonate groups, and 1,2-dichloroisobutane is essential to achieve such selectivity.

Iron-Catalyzed C−C Bond Formation at α-Position of Aliphatic Amines via C−H Bond Activation through 1,5-Hydrogen Transfer

C-C bond formation reactions that take place through organoiron species sometimes exhibit radical-like character. The reaction of N-(2-iodophenylmethyl)dialkylamine with a Grignard or diorganozinc reagent in the presence of a catalytic amount of Fe(acac)(3) gives the product resulting from arylation, alkenylation, or alkylation of the sp(3) C-H bond next to the amine group in good to excellent yield. Mechanistic studies including labeling experiments indicate that the reaction involves radical translocation triggered by the formation of a radical-like species by removal of the iodide group.

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 β-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.

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.

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.

Asymmetric autocatalysis initiated by achiral nucleic acid base adenine: implications on the origin of homochirality of biomolecules

Enantiomorphous crystals of adeninium dinitrate acted as the source of chirality in asymmetric autocatalysis producing highly enantioenriched (S)- and (R)-5-pyrimidyl alkanols, with the absolute configurations corresponding to that of crystals.

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.

Asymmetric Autocatalysis Initiated by Finite Single-Wall Carbon Nanotube Molecules with Helical Chirality

An asymmetric autocatalysis reaction was initiated by a finite single-wall carbon nanotube molecule with helical chirality. The asymmetric induction was initiated by the chiral environment arising from the planar chirality of the tubular polyaromatic hydrocarbons.