Gold-Catalyzed Heteroannulation of Anthranilic Acids with Alkynes: Synthesis of 3,1-Benzoxazin-4-ones.

We demonstrated a rapid and facile approach for the synthesis of various 3,1-benzoxazin-4-ones via a gold-catalyzed heteroannulation of readily available nonprotected anthranilic acids and simple aryl alkynes. Our preliminary mechanistic investigation indicated that the double incorporation of alkynes into anthranilic acids occurs through the formation of bisenamine intermediates.

Palladium-Catalyzed Heteroannulation of Salicylamides with Propargyl Carbonates: Synthesis of 1,4-Benzoxazepin-5-ones.

Herein, we report a palladium-catalyzed method to synthesize 1,4-benzoxazepin-5-ones using salicylamides and propargyl carbonates. The heteroannulation provides a wide range of products in good to excellent yields with broad functional group tolerance. In addition, H2O is used as a low-cost, abundant, and safe solvent, which is important in terms of sustainability.

Chlorobenzene-driven palladium-catalysed lactonisation of benzoic acids.

Herein, we developed a palladium-catalysed C-H cyclisation of benzoic acids in chlorobenzene without additional oxidants. The key to the success of these reactions is the use of chlorobenzene, which serves a dual role as a solvent and an oxidant, thus providing a simple and efficient method for synthesising phthalides.

Gold(I)-Catalyzed Heteroannulation of Salicylic Amides with Alkynes: Synthesis of 1,3-Benzoxazin-4-one Derivatives.

Gold(I)-catalyzed heteroannulation affords the efficient and straightforward construction of heterocyclic compounds. Herein, we developed a gold(I)-catalyzed heteroannulation of salicylic amides with alkynes producing a broad range of 1,3-benzoxazin-4-ones. The utility of this protocol was highlighted by synthesizing variously substituted benzoxazinones containing quaternary carbon centers, showing a high functional group tolerance and excellent atom economy of the thus introduced reaction course.

Site-selective iodine atom transfer in fluorinated alkyl iodides via 1,5-hydrogen atom transfer.

The direct and selective functionalization of inert C-H bonds via intramolecular hydrogen atom transfer (HAT) is an increasingly powerful tool in organic synthesis. Herein, we designed an efficient and facile iodine atom transfer in fluorinated alkyl iodides via 1,5-HAT. Our process enables site-selective iodination of unreactive C(sp3)-H bonds to afford di- and tri-fluorinated alkyl iodides in good yields. Furthermore, our process shows excellent atom economy and high functional group tolerance, including methyl, methoxy, chloro, cyano, and silyl moieties.

Nitrile Synthesis via Desulfonylative-Smiles Rearrangement.

Herein, we designed a simple nitrile synthesis from N-[(2-nitrophenyl)sulfonyl]benzamides via base-promoted intramolecular nucleophilic aromatic substitution. The process features redox-neutral conditions as well as no requirement of toxic cyanide species and transition metals. Our process shows broad scope and various functional group compatibility, affording a variety of (hetero)aromatic nitriles in good to excellent yields.

Palladium-catalyzed dehydrogenative C-H cyclization for isoindolinone synthesis.

In this paper Pd-catalyzed intramolecular dehydrogenative C(sp3)-H amidation for the synthesis of isoindolinones is described. This method features the use of a Pd/C catalyst and the addition of a stoichiometric amount of oxidant is not necessary. A mechanistic study suggested the possible formation of H2 gas during the reaction.

A solvent-dependent chirality-switchable thia-Michael addition to α,ß-unsaturated carboxylic acids using a chiral multifunctional thiourea catalyst.

An asymmetric thia-Michael addition of arylthiols to α,ß-unsaturated carboxylic acids using a thiourea catalyst that bears arylboronic acid and tertiary amine moieties is reported. Both enantiomers of the Michael adducts can be obtained in high enantioselectivity and good yield merely by changing the solvent. The origin of the chirality switch in the products was examined in each solvent via spectroscopic analyses.

Retention and molecular-recognition mechanisms of molecularly imprinted polymers for promazine derivatives.

Monodisperse molecularly imprinted polymers (MIPs) for promazine derivatives [promazine (PZ), methylpromazine (MPZ), chlorpromazine (CPZ) and bromopromazine (BPZ)], MIPPZ, MIPMPZ, MIPCPZ and MIPBPZ, were prepared using methacrylic acid (MAA) as a functional monomer and ethylene glycol dimethacrylate as a crosslinker by multi-step swelling and polymerization. The retention and molecular-recognition properties of the obtained MIPs were evaluated using LC in hydrophilic interaction chromatography (HILIC) and reversed-phase modes. In computational approaches, intermolecular interaction modes and energies between PZ derivatives and MAAs were evaluated at the HF/6-311G(d,p) level. The interaction energies of PZ, MPZ, CPZ and BPZ with 4 equivalents of MAAs were calculated. The results indicated that the interaction of the aliphatic amine moiety of a PZ derivative with MAA gave almost similar interaction energies at the HF/6-311G(d,p) level, and that the interaction of the sulfur atom of a phenothiazine scaffold with MAA was also the case. The third interaction of the aromatic amine of a PZ derivative with MAA was in the order of MPZ > PZ > CPZ > BPZ presumably due to the change of basicity by the electron-donating or electron-withdrawing effect of a subsituent. Furthermore, the fourth attractive modes of CPZ and BPZ were suggested to be the interaction of their halogen atoms with MAA through both halogen bonding and hydrogen bonding, while PZ and MPZ were suggested to have the weak C-H ⋅⋅⋅ π interaction with MAA. In HILIC mode, the interaction energies at the HF method had good correlation with the retention factor of a PZ derivative on each MIP, indicating that in addition to the shape recognition, the attractive electrostatic interactions would be more responsible for its retention rather than the dispersion energies. Furthermore, in addition to the shape recognition, ionic and hydrophobic interactions, and halogen bonding and hydrogen bonding (the last interaction seems to be weak) seem to work for the retention and molecular-recognition of PZ derivatives on the MIPs in reversed-phase mode.

Palladium-Catalyzed Highly Chemoselective Intramolecular C-H Aminocarbonylation of Phenethylamines to Six-Membered Benzolactams.

A palladium-catalyzed highly selective intramolecular C-H aminocarbonylation of Br-functionalized phenethylamines in the presence of CO was achieved while leaving the C-Br bond unreacted to afford six-membered benzolactams with good to high yields. The remaining C-Br group in the cyclized product was successfully used as a reactive center for further functionalization through various palladium-catalyzed coupling reactions.

Rhodium-Catalyzed Cyclization of 2-Ethynylanilines in the Presence of Isocyanates: Approach toward Indole-3-carboxamides.

Catalytic synthesis of indole-3-carboxamides from 2-ethynylanilines and isocyanates was achieved in the presence of a rhodium catalyst through a tandem-type, cyclization-addition sequence. This tandem-type process can be performed under mild reaction conditions, affording 2,3-disubstituted indoles in a one-pot manner generally in good to excellent yields. The broad substrate scope and good functional group compatibility make the method highly efficient and widely applicable, providing a facile and entirely novel route toward variously substituted indole-3-carboxamides.

Unusual O-alkylation of 2-hydroxy-1,4-naphthoquinone utilizing alkoxymethyl chlorides.

A new type of O-alkylation of 2-hydroxy-1,4-naphthoquinone with alkoxymethyl chlorides is described. The reaction course can be controlled by the choice of base and yields O-alkylated or O-alkoxymethylated products in high yield with high selectivity.

Hg2+-trapping beads: Hg2+-specific recognition through thymine-Hg(II)-thymine base pairing.

Mercury pollution poses a severe threat to human health. To remove Hg(2+) from contaminated water, we synthesized Hg(2+)-trapping beads that include oligo-thymidine functionalities that can form thymine-Hg(II)-thymine base pairs on the solid support. The beads can selectively trap Hg(2+) even in the presence of other metal cations. More interestingly, Hg(2+)-trapping efficiency was higher in the presence of the co-existing cations. Thus, the developed Hg(2+)-trapping beads can capture Hg(2+) without affecting the mineral balance of water so much. The Hg(2+)-trapping beads presented here show promise for removing Hg(2+) from environmental water.

Direct condensation of functionalized sp(3) carbons with formanilides for enamine synthesis using an in situ generated HMDS amide catalyst.

The efficient synthesis of functionalized enamines including ß-enaminoesters was effectively accomplished by the direct condensation of functionalized sp(3) carbanions such as acetates with formamides using in situ generated HMDS base from catalytic cesium fluoride and stoichiometric tristrimethylsilylamine.

Synthesis of heterocyclic compounds through palladium-catalyzed C-H cyclization processes.

Herein, we describe our development of synthetic methods for heterocyclic compounds based on the palladium-catalyzed carbon-hydrogen bond (C-H) functionalization/intramolecular carbon-heteroatom (nitrogen or sulfur) bond formation process. By this C-H cyclization method, we efficiently prepared various N-heterocycles, including indazoles, indoles, and 2-quinolinones, as well as S-heterocycles such as benzothiazoles and benzo[b]thiophenes. Yields are typically good to high and good functional-group tolerance is observed for each process, thereby indicating that the method provides a novel, highly applicable synthetic route to the abovementioned biologically important heterocyclic frameworks. As an application of this approach, an auto-tandem-type, one-pot process involving the oxidative Heck reaction and subsequent C-H cyclization using cinnamamides and arylboronic acids as starting materials in the presence of a palladium catalyst was also developed for the rapid construction of the 2-quinolinone nucleus.

Ruthenium-catalyzed carbonylative C-H cyclization of 2-arylphenols: a novel synthetic route to 6H-dibenzo[b,d]pyran-6-ones.

Catalytic carbonylative C-H cyclization of 2-arylphenols can be achieved in the presence of a ruthenium-based catalytic system. The process proceeds efficiently under balloon pressure of CO and produces variously substituted 6H-dibenzo[b,d]pyran-6-one compounds, typically in good to high yields. Functional groups such as the alkoxycarbonyl and acetyl groups as well as halogen atoms (F, Cl, and Br) are well tolerated during the reaction.

Organocatalytic functionalization of heteroaromatic N-oxides with C-nucleophiles using in situ generated onium amide bases.

Organocatalytic functionalization of heteroaromatic N-oxides was investigated using in situ generated onium amide bases, and C-nucleophiles were efficiently introduced by the sequential addition-elimination reaction under metal-free conditions, affording 2-substituted nitrogen heteroaromatics generally in good to high yields.

Carboxylation of alkynylsilanes with carbon dioxide mediated by cesium fluoride in DMSO.

The facile syntheses of a variety functionalized propiolic acids were achieved by carboxylation of alkynylsilanes with carbon dioxide mediated by cesium fluoride under ambient conditions.

Organocatalytic deprotonative functionalization of C(sp2)-H and C(sp3)-H bonds using in situ generated onium amide bases.

Onium amides, generated in situ from the combination of aminosilanes and onium fluorides (R(4)PF, R(4)NF), are employed for the first time as bases for catalytic deprotonative functionalization of C(sp(2))-H and activated C(sp(3))-H bonds under mild conditions.

Synthesis of 3-carboxylated indoles through a tandem process involving cyclization of 2-ethynylanilines followed by CO2 fixation in the absence of transition metal catalysts.

In this study, a facile synthesis of 3-carboxylated indoles involving a tandem-type cyclization of 2-ethynylanilines and subsequent CO2 fixation at the 3-position of the indole ring is realized. The reaction proceeds efficiently at 65 °C under 10 atm of CO2, giving rise to variously substituted 3-carboxylated indoles, generally in high yields. An inorganic base, such as K2CO3, is the only reagent required, and the addition of transition metal catalysts is not necessary. The method provides a novel, simple, and promising strategy for CO2 fixation in the research field of heterocyclic chemistry.