吉田 泰志

We have synthesized two boron complexes based on N,N-type bidentate imidazo[1,5-a]pyridine ligands exhibiting blue emission with good quantum yields in solution. The transient absorption and theoretical studies of the boron complexes indicated the intramolecular charge transfer nature. In addition, one specific complex, 1 a was found to work as a mitochondrial imaging agent.

Two types of imidazo[1,5-a]pyridine ligands have been reacted with divalent metals (Pd and Zn) to prepare the corresponding complexes. Single crystallographic analyses revealed that 1-(o-hydroxyphenyl)imidazo[1,5-a]pyridine and 3,3′-biimidazo[1,5-a]pyridine act as N,O-bidentate ligand for homoleptic palladium complex and N,N-bidentate ligand for zinc dichloride complex, respectively.

1,2,4-Triazole and 1,2,4-triazoline are important components of bioactive molecules and catalysts employed in organic synthesis. Therefore, the efficient synthesis of these components has received significant research attention. However, studies on their structural diversity remain lacking. Previously, we developed chiral phase-transfer-catalyzed asymmetric reactions of α-imino carbonyl compounds with α,β-unsaturated carbonyl compounds and haloalkanes. In this study, we demonstrate the formal [3 + 2] cycloaddition reaction of α-imino esters with azo compounds under Brønsted base catalysis, resulting in the corresponding 1,2,4-triazolines in high yields. The results revealed that a wide range of substrates and reactants can be applied, irrespective of their steric and electronic characteristics. The present reaction made the general preparation of 3-aryl pentasubstituted 1,2,4-triazolines possible for the first time. Furthermore, a mechanistic study suggested that the reaction proceeds without isomerization into the aldimine form.

A method for accessing pyrazole-containing helicene-like molecules from easily accessible NOBIN derivatives was developed. The reaction proceeded efficiently via diazonium salt intermediates, which provided a series of helicene-like molecular products in yields of 77%-89% regardless of their steric and electronic natures. The photophysical properties of the products were investigated. The 3,3′-disubstituted molecules showed a characteristic blue shift in their emission spectra. Product derivatizations were conducted, and interesting reactivities toward nucleophiles were observed.

We synthesized cinnamoyl amide type compounds 1 with axial chirality. We demonstrated the use of (–)-1 for chiral ligands in Pd-catalyzed asymmetric allylic substitution reactions of allylic esters with indoles (up to 97% ee).

There has been a great focus on halogen-bonding as a unique interaction between electron-deficient halogen atoms with Lewis basic moieties. Although the application of halogen-bonded atoms in organic chemistry has been eagerly researched in these decades, the development of chiral molecules with halogen-bonding functionalities and their utilization in asymmetric catalysis are still in the\ir infancy. We have previously developed chiral halonium salts with amide functionalities, which behaved as excellent catalysts albeit in only two reactions due to the lack of substrate activation abilities. In this manuscript, we have developed chiral halonium salts with an N-nitrosamine moiety and applied them to the Mannich reaction of isatin-derived ketimines with malonic esters. The study focused on our novel bromonium salt catalyst which provided the corresponding products in high yields with up to 80% ee. DFT calculations of the chiral catalyst structure suggested that the high asymmetric induction abilities of this catalyst are due to the Lewis basic role of the N-nitrosamine part. To the best of our knowledge, this is the first catalytic application of N-nitrosamines.

The asymmetric amplification of p-anisoin was studied by attrition-enhanced deracemization in the presence of chiral standard amino acids. In this reaction, p-anisoin crystallized as a conglomerate, and deracemization under basic conditions was efficiently performed in 99% ee by Viedma ripening. Although the handedness of the enantioselective crystallization cannot be controlled by spontaneous crystallization, it could be governed by the coexistence of a catalytic amount of 16 chiral amino acids except cysteine, serine, and threonine. l-Amino acids tilted the handedness of enantiomer crystals to (R)-anisoin, while d-amino acids tilted it toward (S)-isomer crystals. It was clarified that this is due to the asymmetric transformation of p-anisoin in the mother liquor by the enantiomeric amino acids. The same slight asymmetric transformation in the solution phase was observed in α-hydroxyketones such as acetoin. Though the Soai reaction for an autocatalytic and asymmetric amplification system in the presence of a variety of chiral sources is famous, the crystallization-induced dynamic deracemization of p-anisoin provides the first chirality control system to be tilted by the enantioselective crystallization derived from many chiral additives.

Annulation of N-allyl-2-ethynylaniline derivatives easily afforded the corresponding 2-substituted 3-allylindole derivatives in good to excellent yields using P,olefin ligand/palladium catalst systems.

We developed a chiral symmetry breaking method for monoacylated meso diols. The X-ray crystal structure analysis of monoacylated 1,4-anhydroerythritols, meso cyclic diols with a cis configuration, revealed that the O-(p-anisoyl) derivative crystallized as a racemic conglomerate of the P212121 crystal system. It was confirmed that the substrate racemized by intramolecular transfer of the acyl group in the presence of a catalytic amount of base. Evaporating the solvent gradually from the solution or Viedma ripening to promote crystallization-induced deracemization efficiently led to enantiomer crystals. These results provide the first successful example of asymmetric expression and amplification by deracemization of sugar derivatives without an external chemical chiral source. Furthermore, we applied this methodology to acyclic meso-1,2-diols. Three O-monoacylated substrates were successfully deracemized to 99 % ee by Viedma ripening. We also developed asymmetric desymmetrization of meso-1,2-diols by combining acylation and crystallization-induced deracemization.

We have synthesized two boron complexes of 3-(o-hydroxyphenyl)imidazo[1,5-a]pyridine exhibiting blue emission in solution. The transient absorption and theoretical studies of the complexes and their 1-(o-hydroxyphenyl) substituted isomers revealed that the phenolic substituent position in boron complex of imidazo[1,5-a]pyridine affected the excites state dynamics involved in photoluminescence (PL). Although the introduction of phenolic substituent at 1-position of the boron complex is effective to achieve the strong emission, the introduction of phenolic substituent at 3-position results in the decreasing PL quantum yield due to intersystem crossing from the singlet excited state to the triplet excited state.

Asymmetric construction of chiral N,S-acetal skeletons is important because they are widely present in natural products and pharmaceuticals. Halogen-bonding is a unique interaction that has been an organic synthesis focus, although research into chiral variants is limited. Halonium salts have been found to act as halogen-bonding catalysts and asymmetric catalysis using chiral bromonium salts under basic conditions was recently discovered by our group. Herein, we report the asymmetric syntheses of chiral N,S-acetals in good-to-excellent yields and enantioselectivities (82–97% ee) through bulky thiol additions to imines catalysed by a chiral iodonium salt under neutral conditions. The reaction mechanism was studied using NMR experiments and DFT calculations of a plausible intermediate, which revealed that the imine substrate is activated by the catalyst in a bidentate manner. The abnormal counteranion effect observed for the tetrakis[3,5-bis(trifluoromethyl)phenyl]borate anion in the present system was examined by 1H NMR spectroscopy. (Figure presented.).

Atroposelective resolution for axially chiral nicotinamides was achieved by dynamic chiral salt formation with L-DBTA using six types of nicotinamides that could not be optically resolved by the preferential crystallization method. Kinetic studies of their racemization indicated that the chiral conformation was retained for a significant period of time. Two methods of crystallization-induced asymmetric transformation were examined by dynamic diastereomeric salt formation: solvent evaporation from a supersaturated solution, and attrition-enhanced asymmetric transformation. The attrition method was more effective for asymmetric amplification of diastereomeric salts of axially chiral materials. Attrition of equimolar amount of the nicotinamide salts with L-DBTA converged to one diastereomer salts, and the corresponding enantiomers in 87–99 % ee were obtained after the chiral acid was removed. Changing the ratio of two of the nicotinamides with L-DBTA to 1 : 2 inverted the axial chirality.

1,2-Addition reactions using organoboron compounds are one of the useful syntheses of various functionalized alcohols, but they generally require a large quantity of bases. In this study, we attempted to solve this problem by synthesizing unsymmetrical 1,3-diarylimidazoline-type N-heterocyclic carbene (NHC)-coordinated C^C* cyclometalated palladium(II) complexes with bridging hydroxide ligands (CYPOHs) in two steps and one pot from the corresponding Cl bridged dimer and using them as catalysts. 2,6-di(pentan-3-yl)aniline (IPent)-based NHC coordinated PhS-IPent-CYPOH acted as a highly efficient catalyst for the 1,2-addition of (hetero)arylboronates to a large number of aldehydes and ketones, including unactivated ketones, under base-free conditions.

Asymmetric synthesis was performed by combining the photochemical reaction of an achiral substrate followed by crystallization-induced deracemization. The results indicated that a fused indoline produced by photochemical intramolecular δ-hydrogen abstraction and cyclization of N-(5-chloro-2-methylphenyl)phthalimide crystallized as a racemic conglomerate. Since this substrate has an aminal skeleton, racemization involving a ring-opening and ring-closing equilibrium process occurred under suitable conditions. Efficient racemization was observed in acetone containing a catalytic base, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Crystallization-induced dynamic deracemization by Viedma ripening from racemic indoline was performed with an excellent enantioselectivity of 99 % ee. Furthermore, one-pot asymmetric synthesis of the indoline was achieved by the photochemical reaction of achiral phthalimide followed by continuous attrition-enhanced deracemization converging to 99 % ee of enantiomeric crystals. This is the first example of asymmetric expression and amplification by photochemical hydrogen abstraction and crystallization-induced dynamic deracemization.

Chiral symmetry breaking of 3-phenylsuccinimides by crystallization-induced dynamic deracemization was performed. We found that N-propyl and N-(3-methoxyphenyl)-3-phenylsuccinimides crystallized as racemic conglomerates, and their crystal structures were determined by single-crystal X-ray structure analysis. Their rapid racemization via enolate ions under basic conditions was confirmed. Crystallization of a small amount of racemic substrates from the solution by evaporating solvent with stirring promoted deracemization from 55% to 98% ee. On the other hand, attrition-enhanced deracemization (Viedma ripening) was applied to deracemization experiments on a larger scale converging to enantiomeric crystals with >99% ee.

Bromonium salts, which are hypervalent bromine reagents, have been explored as being strong electrophiles owing to their extremely high nucleofugalities. Only one example of their catalytic application has been reported by our group; however, their chiral versions have not yet been researched. Halogen-bonding (XB) has been widely applied in chemistry; however, its successful application to highly enantioselective Lewis acid catalysis has not yet been achieved. Herein, we report the design and development of chiral cyclic diarylbromonium salts. These catalysts enabled a highly enantioselective Lewis acid XB catalysis, giving products with up to 96% ee.

We have synthesized a cyan fluorescent benzothiazole–pyridinium salt composite based on D–π–A architecture. This salt was found to work as not only a two- and three-photon excitable fluorophore but also a degradation agent against amyloid fibrils under LED irradiation conditions.

We have synthesized a cyan fluorescent boron complex based on a tridentate imidazo[1,5-a]pyridine ligand. The boron complex was found to have potential applications as not only a chiroptical material but also a heavy-atom-free mitochondria-targeted photosensitizer for cancer treatment.

The study of chirogenesis of organic molecules is important to elucidate the origin of the homochirality of biomolecules on Earth. Here, we have accomplished chiral symmetry breaking from a racemate using optical vortices with orbital angular momentum and a helical wavefront. We propose a new methodology of asymmetric transformation by the combination of enantioselective crystal nucleation by irradiation with optical vortices and crystallization-induced dynamic optical resolution of conglomerate crystals. Chiral green vortices generated using a spiral phase plate (SPP) with a 532 nm CW-laser were used to irradiate a supersaturated solution of a racemic isoindolinone, leading to crystal nucleation. The handedness of the crystals were controlled by the winding direction of the chiral optical vortices. The molecular chirality of the isoindolinone was then amplified by dynamic crystallization.

The highly enantioselective synthesis of p-anisoin was achieved via the benzoin condensation of a prochiral p-anisaldehyde using achiral NHC catalysts such as vitamin B1. In this reaction, p-anisoin crystallized as a conglomerate, and the deracemization of racemic p-anisoin under basic conditions was efficiently performed by Viedma ripening. Although the handedness of the enantioselective crystallization could not be controlled by spontaneous crystallization, it could be controlled by the coexistence of a catalytic amount of optically active valine. It was clarified that this is due to the asymmetric transformation of p-anisoin with enantiomeric valine in the mother liquor.

We synthesized a series of phosphine-olefin-type chiral aminophosphines, and we confirmed that these each exists as two rotamers at the C(aryl)-N(amine) bond. We also investigated the ability of these aminophosphines to act as chiral ligands for Pd-catalyzed asymmetric allylic substitution reactions, such as the alkylation of allylic acetates with malonates or indoles, and we found they gave high enantio-selectivities (up to 98% ee).

Bromonium salts have been typically but infrequently used in various reactions as good leaving groups or as aryl or vinyl transfer reagents owing to their extremely high nucleofugality. Herein, we report the synthesis of novel, stable bromonium salts and their first catalytic application to the Michael reaction, with excellent product yield (up to 96%).

<p>α-Tetrasubstituted-α-amino thioesters were synthesised through chiral phase-transfer catalysed Michael reaction of imino thioesters in up to 97% yield with up to 81% ee.</p>

Longer cumulenes have come to draw considerable attention due to their unique properties and reactivities, leading to various hydrocarbons. In this manuscript, we describe the reaction of tetrakis(p-methoxyphenyl)[5]cumulene with iodine...

We found that the reaction of tetraaryl[3]cumulenes with N-iodosuccinimide afforded the corresponding iodinated triarylbenzofulvenes with high yields under mild reaction conditions. Unsymmetrical tetraaryl[3]cumulenes underwent regioselective reactions to give a single isomer of benzofulvenes depending on the aryl substituents. The obtained iodinated benzofulvene was successfully used as aryl iodide for common cross-coupling reactions, and the corresponding tetrasubstituted benzofulvenes was easily accessed via Suzuki-Miyaura and Sonogashira cross-coupling reactions, respectively.

We have synthesized and characterized an acceptor-pi-donor-pi-acceptor type pyridinium salt. The salt exhibited yellow emission with large Stokes shift in solution and was successfully excited by NIR irradiation via two-photon absorption process. In addition, it was found that the usage of the salt as a bioimaging agent for HeLa cells visualizes cell death. The combined use of the salt and a commercially available green fluorescent dye for the detection of live cell viability realized the one-shot fluorescence imaging of live and dead HeLa cells under the single blue excitation.

We have synthesized a series of quaternized imidazo[1,2-a]pyridines in three steps from commercially available reagents. These compounds exhibit blue fluorescence emission at around 425 nm with good quantum yields. In addition, one specific compound was found to work as not only a two- and three-photon excitable mitochondria imaging agent, but also a therapeutic agent upon continuous irradiation conditions.

Seven racemic 5,7-dimethoxyflavanones afforded conglomerate crystals upon recrystallization from a solvent. Three methodologies were investigated to achieve asymmetric transformation based on dynamic crystallization of the chiral conglomerate system. The first was chiral symmetry breaking of racemic flavanones by attrition-enhanced deracemization. Continuous suspension of racemic flavanones in a small amount of propanol in the presence of a base (1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)) and glass beads promoted chiral symmetry breaking and converted the flavanones to crystals of (+)- or (-)-enantiomers with 78 to 99% ee. The second method involved cyclization of the intermediate aldol product to give optically active flavanone with 90% ee involving a reversible oxa-Michael addition reaction with attrition-enhanced deracemization. The third was a reaction starting from prochiral 2-hydroxy-4,6-dimethoxyacetophenone and 2-naphthaldehyde under basic conditions, which gave the corresponding flavanone in 89% ee.

Chiral symmetry breaking of thiohydantoins by attrition-enhanced deracemization was performed. It was found that three thiohydantoins afforded conglomerate crystals, and their absolute structures were determined by single crystal X-ray structure analysis. The effect of substituents on the racemization rate via a ring-opening and -closing reaction was investigated experimentally and computationally. Attrition of the crystals of racemic thiohydantoins in the presence of a catalytic amount of base promoted deracemization, leading to optically active thiohydantoins with excellent enantiomeric purity (94-96% ee) without any external chiral source.

A series of novel polychlorinated compounds were synthesized with using o-chloranil (1) as a source substrate and the detailed structures of the products were elucidated by X-ray analysis. Chemoselective formations of several polychlorinated compounds were achieved by choosing reaction condition, particularly, a kind of mixed solvent. In a mixed solvent of 1,4-dioxane and H2O, three component coupling reaction of 1 gave nonachloro compound, 2-Cl9, through two kinds of oxidative reactions. In the case of a mixed solvent of MeOH and H2O, another coupling reaction of 1 along with addition of the solvent, MeOH, proceeded to afford hexachloro compound, 3-Cl6. The MeO group of 3-Cl6 could be eliminated by heating at 80 degrees C in a solution of H2O/1,4-dioxane to eventually give a hexachloro dibenzodioxindiol, 4-Cl6OH2. (C) 2020 Elsevier Ltd. All rights reserved.

© 2020 by the authors. Efficient generation and amplification of chirality from prochiral substrates in the Diels-Alder reaction (DA reaction) followed by dynamic crystallization were achieved without using an external chiral source. Since the DA reaction of 2-methylfuran and various maleimides proceeds reversibly, an exo-adduct was obtained as the main product as the reaction proceeded. From single crystal X-ray structure analysis, it was found that five of ten exo-adducts gave conglomerates. When 2-methylfuran and various maleimides with a catalytic amount of TFA were reacted in a sealed tube, the exo-DA adducts were precipitated from the solution, while the reaction mixtures were continuously ground and stirred using glass beads. Deracemization occurred and chiral amplification was observed for four of the substrates. Each final enantiomeric purity was influenced by the crystal structure, and when enantiomers were included in the disorder, they reached an enantiomeric purity reflecting the ratio of the disorder. The final ee value of the 3,5-dimethylphenyl derivative after chiral amplification was 98% ee.

Efficient generation and amplification of chirality from prochiral substrates in the Diels-Alder reaction (DA reaction) followed by dynamic crystallization were achieved without using an external chiral source. Since the DA reaction of 2-methylfuran and various maleimides proceeds reversibly, anexo-adduct was obtained as the main product as the reaction proceeded. From single crystal X-ray structure analysis, it was found that five of tenexo-adducts gave conglomerates. When 2-methylfuran and various maleimides with a catalytic amount of TFA were reacted in a sealed tube, theexo-DA adducts were precipitated from the solution, while the reaction mixtures were continuously ground and stirred using glass beads. Deracemization occurred and chiral amplification was observed for four of the substrates. Each final enantiomeric purity was influenced by the crystal structure, and when enantiomers were included in the disorder, they reached an enantiomeric purity reflecting the ratio of the disorder. The final ee value of the 3,5-dimethylphenyl derivative after chiral amplification was 98% ee.

Crystallization-induced diastereomer transformation of valuable thiohydantoin derivatives was developed for the first time. Three thiohydantoins synthesized from three (R)-N-phenethylthioureas and benzoylformyl chloride were obtained as diasteromeric mixtures. These thiohydantoins have aminal carbons at the chiral center which could be epimerized via ring-opening and -closing reactions under suitable conditions. The suspension of the diastereomixture of thiohydantoins in a small amount of solvent selectively converged to crystals composed of a single diastereomer in a quantitative fashion. Stereoselective switching of diastereoselectivity by CIDT of one thiohydantoin was achieved with a suitable solvent. (C) 2020 Elsevier Ltd. All rights reserved.

We have designed and synthesized an iridium(III) complex of pincer type imidazo[1,5-a]pyridine ligand. The complex has a broad absorption band and shows the yellow emission in solution. When the complex was used as a photocatalyst in the visible-light-induced oxidative coupling reaction of benzylic amines, the corresponding imines were obtained in quantitative yields. (C) 2020 Elsevier Ltd. All rights reserved.

Attrition-enhanced deracemization of two axially chiral nicotinamides, crystallizing as a conglomerate of a P2(1) crystal system, was performed. N,N-Dialkylnicotinamides with substituents on the 2- and 4-positions of the pyridine ring exhibited stable axial chirality due to rotationally restricted scaffolds for the Ar-C(=O)N bond. Crystallization of the racemic mixtures from the melt or attrition-enhanced deracemization led to the chiral breaking of symmetry to give 95-96 % ee of enantiomorphic crystals.

The asymmetric synthesis of an aspartic acid derivative, N-succinopyridine, from prochiral starting materials involving dynamic enantioselective crystallization was accomplished without using any external chiral source. The aza-Michael addition reaction of prochiral maleic acid and pyridine afforded racemic conglomerate N-succinopyridine in water. Continuous stirring of the suspension of the reaction mixture with acetic acid promoted gradual deracemization to afford a crystal with an excellent optical purity of 99% in 71% yield.

Chiral functionalized aminals are important core structures of natural products and pharmaceuticals. Their chemo- and regioselective catalytic, asymmetric synthesis has been realized through the umpolung reaction of alpha-imino amides using a catalyst we originally developed. Functionalized aminals were prepared with high chemoselectivity by treating a hemiaminal intermediate with pyridine in butanol. Evaluation of substrate scope revealed that this transformation could be achieved with a wide range of alpha-imino amides to produce the desired products in high yields with up to 97 % ee. A mechanistic study suggested that aminal formation proceeded through the ring opening/ring closing equilibrium of the hemiaminal skeleton.

Dynamic enantioselective crystallization enabled the chiral symmetry breaking of two spiropyrans and one spirooxazine. The three spiro compounds afforded racemic conglomerate crystals, and easily racemized in alcoholic solution without irradiation. Optically pure enantiomorphic crystals were obtained by vapor-diffusion crystallization or attrition-enhanced deracemization (Viedma ripening). Their absolute configurations were determined by single-crystal X-ray analysis and each enantiomorphic crystal was correlated with its solid-state circular dichroism (CD) spectrum.

A new class of flavonoids bearing cyclic polyethers involving a phenyl ring was conveniently provided by the intramolecular photochemical dimerization of 2-chromonecarboxylic esters. Irradiation of 2-chromonecarboxylate with a polyether tethered at both ends promoted intramolecular [2 + 2] cyclobutane formation leading to 14- to 27-membered cyclic polyethers. The efficiency depended on the substituted position of the phenyl ring, with ortho- and meta-substituted derivatives giving cycloadducts in good chemical yields and quantum efficiencies, whereas the para-derivatives were inert toward photolysis. X-ray crystallographic analysis revealed that the stereochemistry of the macrocyclic cycloadducts exhibited C-2-symmetry. (C) 2019 Elsevier Ltd. All rights reserved.

Novel optically active hypervalent iodine(V) reagents with planar chiral crown ether backbones were synthesized using the intramolecular Huisgen reaction as a key step and L-methyl lactate as the source of chirality. The relative configurations of these reagents and stabilities of planar chiralities were determined by DFT calculations. These planar chiral reagents were applied to the hydroxylative dearomatization/[4 + 2]-dimerization reactions of phenols to afford bisthymol and biscarvacrol, a natural product, with moderate enantioselectivities. (C) 2019 Elsevier Ltd. All rights reserved.

The efficient chemo- and regioselective catalytic asymmetric syntheses of enamides, which are important core structures of bioactive natural products, have been achieved through the first umpolung organocascade reaction of alpha-imino amides. A variety of enamides have been synthesized enantioselectively in high yields with up to 99% ee. Notably, both enantiomers of the products can be selectively prepared by the simple pretreatment of the substrate. Mechanistic studies reveal that E/Z-geometry information from the substrate is transferred to the product. The present method can be applied to a wide range of alpha-imino amides, irrespective of the electronic nature of the substituents.

Dynamic enantioselective crystallization enabled the chiral symmetry breaking of two spiropyrans and one spirooxazine.<br /> The three spiro compounds afforded racemic conglomerate crystals, and easily racemized in alcoholic solution<br /> without irradiation. Optically pure enantiomorphic crystals were obtained by vapor-diffusion crystallization or<br /> attrition-enhanced deracemization (Viedma ripening). Their absolute configurations were determined by single-crystal Xray<br /> analysis and each enantiomorphic crystal was correlated with its solid-state circular dichroism (CD) spectrum.

We synthesized N-trans-cinnamyl-N-cyclohexylaniline type aminophosphine 2 and a series of N-2-adamantyl-N-trans-cinnamylaniline type aminophosphines 3. Although aminophosphine 2 failed to find the existence of axial chirality, aminophosphines 3, which exist in the axial chirality in a C(aryl)-N(amine) bond by chiral HPLC analysis as 1-adamantyl type chiral ligands 1. Enantiomeric isomers of 3b, 3c, and 3d were obtained in an enantiomerically pure form. We also identified the palladium-catalyzed asymmetric allylic substitution of 1,3-diphenyl-2-propenyl acetate with indoles using aminophosphines 3b-d as effective chiral ligands in high enantioselectivities (up to 96% ee).

The 7-allylated benzofuran derivatives were synthesized via a continuous reaction of Claisen rearrangement and annulation using o-allyloxyetynylbenzene as starting material. In addition, it was observed that annulation of o-alkynylphenol proceeded under mild conditions when carried out in the presence of a catalytic amount of TBAF. Furthermore, these continuous reactions could be achieved in a one-pot reaction and afforded not only 7-allylbenzofurans but also 7-alkenylbenzofurans by controlling the reaction temperature and time of the annulation. Finally, we demonstrated that 7-allylbenzofuran and 7-alkenylbenzofuran could be converted into 7-(2-formylvinyl)benzofuran and 7-formylbenzofuran derivatives, respectively. Therefore, various 7-substituted benzofuran derivatives could be synthesized according to this synthetic strategy.

A novel regioselective cyclization reaction of N-cinnamoylthioureas leading to six- or five-membered heterocyclic compounds was developed. N-Cinnamoylthioureas in the presence of trifluoroacetic acid (TFA) underwent the well-established intramolecular cycloaddition reaction to give 2-imino-2,3,5,6-tetrahydro-4H-1,3-thiazin-4-ones in good yields. On the other hand, the reaction with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) proceeded in an unprecedented umpolung cyclization fashion to afford five-membered 2-imino-1,3-thiazolidin-4-ones and/or 2-thioxoimidazolidine-4-ones. The reaction was considered to occur via a cycloadduct of DBU with the cinnamoyl moiety followed by intramolecular attack of the thiourea group.