Haruyasu Asahara

Chiral Recognition and Kinetic Resolution of Aromatic Amines via Supramolecular Chiral Nanocapsules in Nonpolar Solvents

Herein we report the first example of chiral recognition and kinetic resolution of aromatic amine guests using supramolecular nanocapsules assembled from cyclodextrin derivatives in nonpolar media. With these nanocapsules, an extremely high chiral recognition of 1-(1-naphthyl)ethylamine (1) in cyclohexane was achieved, with a binding selectivity of up to 41 for (S)-1 over (R)-1. In addition, kinetic resolution of 1 through enantioselective N-acylation was accomplished with an enantiomeric excess of up to 91%.

Electrophilicities of Bissulfonyl Ethylenes

Kinetics of the reactions of bissulfonyl ethylenes with various carbanions, a sulfur ylide, and siloxyalkenes have been investigated photometrically at 20 °C. The second-order rate constants have been combined with the known nucleophile- specific parameters N and s(N) for the nucleophiles to calculate the empirical electrophilicity parameters E of bissulfonyl ethylenes according to the linear free energy relationship log k(20 °C)=s(N)(N+E). Structure-reactivity relationships are discussed, and it is shown that the electrophilicity parameters E derived in this work can be employed to define the synthetic potential of bissulfonyl ethylenes as Michael acceptors.

Metal-Free α‑Hydroxylation of α‑Unsubstituted β‑Oxoesters and β‑Oxoamides

A direct metal-free α-hydroxylation of α-unsubstituted β-oxoesters and β-oxoamides was developed using m-chloroperbenzoic acid as the oxidant. This transformation enabled straightforward metal-free access to important α-hydroxy-β-dicarbonyl moieties under mild reaction conditions. Furthermore, the hydroxylated products were readily converted into vicinal tricarbonyl compounds, which are useful synthetic precursors of numerous biological targets.

Quantification and Theoretical Analysis of the Electrophilicities of Michael Acceptors

In order to quantify the electrophilic reactivities of common Michael acceptors, we measured the kinetics of the reactions of monoacceptor-substituted ethylenes (H2C═CH-Acc, 1) and styrenes (PhCH═CH-Acc, 2) with pyridinium ylides 3, sulfonium ylide 4, and sulfonyl-substituted chloromethyl anion 5. Substitution of the 57 measured second-order rate constants (log k) and the previously reported nucleophile-specific parameters N and sN for 3-5 into the correlation log k = sN(E + N) allowed us to calculate 15 new empirical electrophilicity parameters E for Michael acceptors 1 and 2. The use of the same parameters sN, N, and E for these different types of reactions shows that all reactions proceed via a common rate-determining step, the nucleophilic attack of 3-5 at the Michael acceptors with formation of acyclic intermediates, which subsequently cyclize to give tetrahydroindolizines (stepwise 1,3-dipolar cycloadditions with 3) and cyclopropanes (with 4 and 5), respectively. The electrophilicity parameters E thus determined can be used to calculate the rates of the reactions of Michael acceptors 1 and 2 with any nucleophile of known N and sN. DFT calculations were performed to confirm the suggested reaction mechanisms and to elucidate the origin of the electrophilic reactivities. While electrophilicities E correlate poorly with the LUMO energies and with Parrs electrophilicity index ω, good correlations were found between the experimentally observed electrophilic reactivities of 44 Michael acceptors and their calculated methyl anion affinities, particularly when solvation by dimethyl sulfoxide was taken into account by applying the SMD continuum solvation model. Because of the large structural variety of Michael acceptors considered for these correlations, which cover a reactivity range of 17 orders of magnitude, we consider the calculation of methyl anion affinities to be the method of choice for a rapid estimate of electrophilic reactivities.

Thermal [2+2] cycloaddition of morpholinoenamines with C60 via a single electron transfer.

The thermal reaction of C(60) with five- and six-membered morpholinocycloalkenes in refluxing toluene exclusively gave the [2+2] cycloadducts in high yields. However, a seven-membered homologue sluggishly reacted with C(60) because of the increasing steric hindrance. This cycloaddition reaction is likely to proceed via a single electron transfer (SET), a radical-coupling, and subsequent ion cyclization rather than the prior proton transfer between the radical ions.

Development of a new palladium catalyst supported on phenolic resin

A phenolic resin-supported palladium catalyst, in which hydroxyl groups contribute to the stabilization of palladium nanoparticles, was developed. The catalyst could be used repeatedly, and thus has a large turn over number (TON). When a composite of polyethylene terephthalate and phenolic resin was employed as a support, the catalyst was easily deformed on demand.

Kinetic Evidence for Dihapto (η2) π-Aryl Participation in Acid-Catalyzed Ring Opening of Diarylhomobenzoquinone Epoxides

The BF(3)-catalyzed ring-opening reaction of variously endo/exo m- and p-substituted diarylhomobenzoquinone epoxides proceeded through a transannular S(E)2-Ar cyclization of endo-aryl groups to give the tricyclic diketo-alcohols and cyclohexadienone spiro-linked tricyclic diketo-alcohols. Kinetics of these reactions has been investigated in CDCl(3) at 30 degrees C in order to elucidate the possible remote pi-aryl participation. The rates were significantly increased with increasing electron-donating ability of the endo-aryl substituents X (k(p-MeO)/k(p-CF3) = 8200) but only negligibly influenced by the distal exo-aryl substituents Y (k(p-MeO)/k(p-CF3) = 2.1). For the endo-X substituted series, an excellent linear free energy relationship, log k(rel)(endo) = -2.49sigma(ipso) - 1.62sigma(ortho) - 0.108 (R(2) = 0.98, n = 8), was attained using two modified site-dependent substituent parameters sigma(ipso) (using sigma(p)(+) for p-X and sigma(m) for m-X) and sigma(ortho) (using sigma(m) for p-X and sigma(p)(+) for m-X). This means that the dihapto(eta(2)) pi-coordination occurs in the pi-aryl participation, with the ipso pi-electron donation contributing 1.6 times more effectively than the ortho one. On the other hand, the distal exo-Y substituted series gave an acceptable Yukawa-Tsuno equation with small polar and resonance contributions; log k(rel)(exo) = -0.912(sigma(0) + 0.237Deltasigma(R)(+)) (R(2) = 0.96, n = 8). These kinetic substituent effects were compared with those of the acid-catalyzed pi-aryl assisted transannular S(E)2-Ar cyclization of the cyclobutene-fused diarylhomobenzoquinones. It was found that the geometrical characteristics of the vacant oxirane Walsh orbital and the cyclobutene antibonding orbital play a crucial role in the topological features of eta(2) pi-aryl participation.

Conformational effects in acid-mediated ring opening of epoxides: a prominent role of the oxirane Walsh orbital.

A kinetic study has been made of the BF(3)-mediated ring opening of two rigid conformers (alpha and beta) of m- and p-dimethyl-substituted homobenzoquinone epoxides spiro-linked with a twist-boat dibenzocycloheptene ring as compared with the conformationally mobile epoxides bearing diphenyl groups. The rates of the regioselective ring opening were dependent on the topological alignment of the dibenzocycloheptene ring as well as the substitution pattern of the quinone dimethyl groups, indicating pi-aryl participated orbital interaction with the vacant Walsh orbital of the oxirane ring.

Mechanistic evidence for remote π-aryl participation in acid-catalyzed ring opening of homobenzoquinone epoxides

The acid-induced reaction of bis(p-chlorophenyl)homobenzoquinone epoxide gave the dual ipso/ortho intramolecular S(E)2-Ar products associated with pi-aryl participated oxirane ring opening, whereas bis(p-tolyl)- and diphenyl-substituted homologues provided only the ortho products.

Synthesis of Functionalized 3-Cyanoisoxazoles Using a Dianionic Reagent

A series of 5-acylated 3-cyanoisoxazoles were efficiently synthesized by the Michael addition of dianionic cyano-aci-nitroacetate to α-chloro-α,β-unsaturated ketones followed by intramolecular nucleophilic substitution of the nitronate ion intermediate. In this process, the dianionic reagent serves as the safe synthetic equivalent of the explosive nitroacetonitrile. The 3-cyano group is sufficiently reactive toward ethanolysis and 1,3-dipolar cycloaddition with an azide to afford ethyl ester and tetrazole, respectively. A pyridine ring between the 5-acyl and the 4-aryl group was also constructed. This led to the formation of the isoxazolo[5,4-c]quinoline derivative.