Kei Takeda

Regio- and stereoselective multisubstituted enol ester synthesis.

Regio- and stereoselective cohalogenation of alkynes with NXS (X = Br, I) was achieved, and the stereoselectivity of the resulting alkenes was dependent on the substituent on the alkyne. Cohalogenation and successive cross-coupling gave multisubstituted enol esters in a one-pot process.

Platinum-catalyzed, one-pot tandem synthesis of indoles and isoquinolines via sequential rearrangement of amides and aminocyclization.

By using platinum(II) chloride as a Lewis acid catalyst, concise and efficient syntheses of indole carbamates, 1,2-dihydroisoquinoline carbamates, macrocyclic indole carbamates, indole ureas, and indole phosphoranes have been achieved via tandem Hofmann-type rearrangement of 2-alkynylbenzamides and 2-alkynylbenzylamides, nucleophilic addition of alcohols and amines to the isocyanate intermediates, and intramolecular aminocyclization of the thus-formed carbamates and ureas to 2-alkynyl functions. A variety of nucleophiles such as alcohols, amines, and stable Wittig reagents could be introduced to the highly electrophilic carbon of the isocyanate intermediates derived from amides. We observed enhancement of the reaction rates when the reactions were run under microwave irradiation.

Design and Synthesis of a Stable Supramolecular Trigonal Prism Formed by the Self-Assembly of a Linear Tetrakis(Zn2+-cyclen) Complex and Trianionic Trithiocyanuric Acid in Aqueous Solution and Its Complexation with DNA (Cyclen =1,4,7,10-Tetraazacyclododecane)

A new supramolecular complex, {(Zn(4)L(4))(3)-(TCA(3-))(4)}(12+), was designed and synthesized by the 3:4 self-assembly of a linear tetrakis(Zn(2+)-cyclen) complex (Zn(4)L(4))(8+) and trianionic trithiocyanurate (TCA(3-)) in aqueous solution (cyclen = 1,4,7,10-tetraazacyclododecane). The {(Zn(4)L(4))(3)-(TCA(3-))(4)}(12+) complex, which should have a trigonal prism configuration, was found to be very stable in aqueous solution at neutral pH and 25 degrees C, as evidenced by (1)H NMR titration, potentiometric pH and UV titrations, and MS measurements. The complex does not dissociate into the starting building blocks in the presence of Zn(2+)-binding anions such as phosphates and double-stranded DNA. The results of the competitive binding assays with ethidium bromide and calf-thymus DNA, thermal melting experiments, gel mobility shift assays, and dynamic light-scattering data strongly indicated that the trigonal prism functions as a polycationic template to induce the aggregation of double-stranded DNA.

One-pot approach to 2,3-disubstituted-2,3-dihydro-4-quinolones from 2-alkynylbenzamides.

Concise and efficient syntheses of various trans-2,3-disubstituted-2,3-dihydro-4-quinolones have been achieved via tandem Hofmann-type rearrangement of 2-alkynylbenzamides, nucleophilic addition of alcohols to the isocyanate intermediates, intermolecular [2+2]-cycloaddition with carbon-carbon triple bonds and aldehydes, and intramolecular aminocyclization of nitrogen of carbamates to the α,β-unsaturated ketones.

Reaction of silyl thioketones with lithium diethylphosphite : First observation of thia-brook rearrangement

Abstract Reaction of silyl thioketone 7 with lithium diethylphosphite at −98°C afforded a S-attack product 8 and formal C-attack products 10 and 11, which were formed by S-to-C migration of the phosphoryl group in the S-adduct followed by C-to-S migration of the silyl group (Thia–Brook rearrangement), in a ratio depending on the conditions. The relative facility of the Thia–Brook rearrangement was compared with that of the Brook rearrangement using the (t-butyldimethylsilyl)diphenylmethyl derivatives 22 and 23.

Formation of 2-Cyano-2-siloxyvinylallenes via Cyanide-Induced Brook Rearrangement in γ-Bromo-α,β,γ,δ-unsaturated Acylsilanes.

Reactions of γ-bromo-α,β,γ,δ-unsaturated acylsilanes with KCN under phase-transfer catalyst conditions using n-Bu4NBr afforded 2-cyano-2-siloxyvinylallenes via a tandem process that involves a nucleophilic attack of a cyanide ion and a Brook rearrangement induced conjugate vinylic 1,4-elimination. Use of a chiral cyanide ion source, derived from KCN and quaternary ammonium bromide derived from cinchona alkaloids, provided nonracemic allene derivatives. Based on this result and the reaction using a chiral hydride ion source, we propose a reaction pathway in which a Brook rearrangement mediated vinylic conjugate 1,4-elimination occurs in a syn alignment between the C-Br bond and C-Si bond in the silicate intermediate.

Spontaneous Oxygenation of Siloxy-N-silylketenimines to α-Ketoamides

Siloxy-N-silylketenimines generated in situ from O-silyl cyanohydrins were converted to α-ketoamides by brief exposure to air or oxygen. Oxidation under extremely mild conditions can be explained by assuming the intermediacy of a 3-imino-1,2-dioxetane derivative generated via triplet-singlet intersystem crossing after the reaction of siloxy-N-silylketenimines with triplet oxygen.

Transnitrosation of non-mutagenic N-nitrosoproline forms mutagenic N-nitroso-N-methylurea.

N-Nitroso-N-methylurea (NMU) is a potent carcinogen and suspected as a cause of human cancer. In this study, mutagenic NMU was detected by HPLC after the transnitrosation of non-mutagenic N-nitrosoproline (NP) to N-methylurea in the presence of thiourea (TU) under acidic conditions. The structure of NMU was confirmed by comparing (1)H NMR and IR spectra with that of authentic NMU after fractionation by column chromatography. Furthermore, a fraction containing NMU formed by transnitrosation was mutagenic in Salmonella typhimurium TA1535. NMU was formed in the reaction of NP and N-methylurea in the presence of 1,1,3,3-tetramethylthiourea (TTU) or 1,3-dimethylthiourea in place of TU as an accelerator. The reaction rate constants (k) for NMU formation were correlated with their nucleophilicity of sulfur atom in thioureas. The N-methylurea concentration did not affect the NMU formation, whereas the rate of NMU formation correlated linearly with concentrations of NP, TTU and oxonium ion. The observed kinetics suggests a mechanism by which the nitroso group was transferred directly from the protonated NP to the thiourea then to N-methylurea to form NMU. The rate-determining step was the formation of the complex with the protonated NP and thiourea.