三野 孝

Photodimerization of 3-arylindenones in solution and in the solid state was examined. Irradiation of 3-arylindenones in benzene exclusively gave C2-symmetric anti-HH cyclobutane dimers in good yields. In contrast, photolysis in the solid state afforded syn-HH cyclobutane dimers efficiently, which was considerably influenced by the molecular arrangement in the crystal lattice.

C2-Symmetric cyclic polyethers were conveniently provided by the photochemical dimerization of covalently-linked 2-chromonecarboxylic esters. Irradiation of polyethers possessing 2-chromonecarboxylate groups at both ends efficiently promoted intramolecular [2+2] cyclobutane formation leading to 14- to 23-membered cyclic polyethers in good chemical yields and quantum efficiencies. X-ray crystallographic analysis revealed that the stereochemistry of the cyclobutane was the C2-symmetric structure.

C2-Symmetric cyclic polyethers were conveniently provided by the photochemical dimerization of covalently-linked 2-chromonecarboxylic esters. Irradiation of polyethers possessing 2-chromonecarboxylate groups at both ends efficiently promoted intramolecular [2+2] cyclobutane formation leading to 14- to 23-membered cyclic polyethers in good chemical yields and quantum efficiencies. X-ray crystallographic analysis revealed that the stereochemistry of the cyclobutane was the C2-symmetric structure.

We found that the hydrazone-Pd-catalyzed direct intermolecular reaction of o-alkynylphenols with allylic acetates afforded the corresponding 2-substituted-3-allylbenzofuran derivatives. This reaction proceeded smoothly at room temperature using a hydrazone-Pd catalyst system.

Asymmetric synthesis involving photochemical dimerization of a prochiral flavonoid derivative in solution without any chiral source was achieved. Irradiation of ethyl 6-bromochromonecarboxylate in solution efficiently gave a C2-chiral anti-head-to-head dimer in excellent chemical yield with good quantum efficiency (Φ365 = 0.15). X-ray crystallographic analysis revealed that the dimer crystallized as a conglomerate of C2 space group. The crystalline dimer precipitated upon irradiation of the monomer in solution, and indirect racemization of the dimer through a reversible photoreaction in solution and selective crystallization simultaneously occurred to give the C2-chiral dimer in optically active form with up to 80 % ee. Optically active photoproducts could be obtained by simply irradiating achiral materials in solution without an external chiral source.

Asymmetric synthesis involving photochemical dimerization of a prochiral flavonoid derivative in solution without any chiral source was achieved. Irradiation of ethyl 6-bromochromonecarboxylate in solution efficiently gave a C-2-chiral anti-head-to-head dimer in excellent chemical yield with good quantum efficiency (phi(365) = 0.15). X-ray crystallographic analysis revealed that the dimer crystallized as a conglomerate of C2 space group. The crystalline dimer precipitated upon irradiation of the monomer in solution, and indirect racemization of the dimer through a reversible photoreaction in solution and selective crystallization simultaneously occurred to give the C-2-chiral dimer in optically active form with up to 80%ee. Optically active photoproducts could be obtained by simply irradiating achiral materials in solution without an external chiral source.

We designed and synthesized dimeric imidazo[1, 5-a]pyridines possessing various aryl groups at 1,1'-positions. The solution of these derivatives exhibited fluorescence emission in wavelength range of 487-512 nm. The fluorescence emissions were slightly red-shifted under acidic condition by addition of trifluoroacetic acid. Furthermore, the original fluorescence spectra were observed after the addition of triethylamine as a base.

© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim We have demonstrated the Mizoroki–Heck reaction of aryl iodides with aryl allyl ethers using 1.5 mol% of imidazo[1, 5-a]pyridine–Pd catalytic system. Aryl cinnamyl ethers were obtained in moderate-to-high yield under mild reaction conditions.

© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim The catalytic asymmetric umpolung reaction of ketimines is of great importance, because it can easily provide chiral amines bearing a tetrasubstituted carbon atom on its asymmetric center. Because amino acids with a tetrasubstituted carbon center are useful due to their wide applicability as pharmaceuticals and chiral building blocks, their enantioselective synthesis has great significance in organic synthesis. Herein, we demonstrate a metal-free novel phase-transfer-catalyzed highly regio- and enantioselective umpolung Michael reaction of α-imino esters, which provides amino acid derivatives in high yields with up to 98 % ee. The products are successfully converted into chiral amino acid derivative and δ-lactone with high enantiopurity.

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim We have found that Suzuki–Miyaura-type reactions of dibromoalkenes with arylboronic acids using a hydrazone–Cu catalyst system proceeded smoothly under mild conditions to afford the corresponding internal alkyne derivatives in good yields. Furthermore, we also succeeded in the synthesis of o-allyloxy(ethynyl)benzene derivatives, which are known to be effective precursors of various heterocyclic compounds, through this reaction.

Asymmetric synthesis from achiral starting materials using only crystal chirality under absolutely achiral conditions-that is, absolute asymmetric synthesis-has been investigated by many methods, including solid-state photochemical reactions, asymmetric reactions using frozen chirality, and dynamic crystallization (total spontaneous resolution). Dynamic crystallization using racemic conglomerate crystals involved that an enantiomerically enriched solid state could be achieved through crystallization from a solution in which chiral molecules could rapidly racemize. Many such examples resulted in total optical resolution by deracemization, selectively leading to single-handed molecules. Furthermore, a combined methodology for generating a chiral center from achiral materials, involving dynamic crystallization or attrition-enhanced deracemization, was recently developed. These examples demonstrate the high potential of this new category of absolute asymmetric synthesis.

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim We have found that Suzuki–Miyaura-type reactions of o-allyloxy(bromoethynyl)benzenes with arylboronic acids using a hydrazone/Cu catalyst system proceeded smoothly in iPrOH under mild conditions to afford the corresponding o-allyloxy(arylethynyl)benzene derivatives in good yields without decomposition of the allyloxy group. We have further demonstrated that annulation and enyne metathesis of the o-allyloxy(arylethynyl)benzene derivatives using transition-metal catalysts led to various heterocyclic compounds.

Irradiation of prochiral (&lt;I&gt;E&lt;/I&gt;)-aroylacrylamide with<br /> sunlight gave single-handed pyrrolinone quantitatively and<br /> with an enantiomeric excess (&lt;I&gt;ee&lt;/I&gt;) of over 99% under absolutely<br /> achiral conditions. The phenomenon was explained by<br /> photoisomerization and reversible cyclization followed by<br /> dynamic crystallization involving deracemization.

Irradiation of prochiral (E)-aroylacrylamide with sunlight gave single-handed pyrrolinone quantitatively and with an enantiomeric excess (ee) of over 99% under absolutely achiral conditions. The phenomenon was explained by photoisomerization and reversible cyclization followed by dynamic crystallization involving deracemization.

2-Propoxy-1-naphthamide possessing a chiral 2-methylpyrrolidine group exists as a mixture of four diastereomers owing to the rotation of the Ar-(C=O) and C-center dot(=O)-N bonds. The diastereomers existed in the ratio of 32:32:14:22 in CD3OD. When the MeOH solution of the mixture of diastereomers was irradiated with Pyrex filtered UV light (>290 nm) from a high-pressure mercury lamp, the ratio changed to 27:4:43:26. The diastereomeric ratio was reversibly controlled by irradiation and heat. The change was accurately reflected in the intensity of the CD spectra. Furthermore, the reversible axial chirality was transferred to the optical activity of asymmetric reaction products via the photochemical cycloaddition reaction with 9-cyanoanthracene. (C) 2015 Elsevier B.V. All rights reserved.

Unprecedented absolute asymmetric synthesis was carried out using frozen chirality derived from chiral crystals of achiral coumarin-3-carboxamide and carbenoids. An enantioselective cycloaddition reaction with a sulfur ylide gave an optically active cyclopropane up to 97% ee. Furthermore, a cycloaddition reaction with dichlorocarbene gave dihydrofuran in 93% ee. Nucleophilic addition of ylide or carbene occurs from the side of the carbonyl oxygen atom to avoid steric hindrance of substituents on the nitrogen atom.

Single-handed -amino acid derivatives were generated from achiral precursors without an external chiral source. Conjugate addition of phenethylamine to an achiral aroyl acrylamide under homogeneous conditions gave the -amino amides in quantitative yields, which crystallized as a conglomerate of a P2(1) crystal system. Dynamic preferential crystallization or attrition-enhanced deracemization resulted in the formation of enantiomorphic crystals of 99% ee.

Amino acid-derived novel chiral hypervalent iodine(V) reagents were synthesized from the corresponding chiral iodoarenes through DMDO oxidations. Their oxidation states were determined by the C-13 NMR chemical shifts of the ipso-carbon of the iodine atom, HRMS analysis, and elemental analyses. They were applied to the enantioselective hydroxylative dearomatization/[4+2]-dimerization cascade reactions of phenol derivatives to afford the desired products with up to 58% ee. (C) 2016 Elsevier Ltd. All rights reserved.

A chiral aluminum catalyst was used for the kinetic resolution of citronellal analogues. Racemic 3-alkyl-citronellals gave optically active 5-alkylisopulegols with high enantioselectivity. Unreacted 3-alkyl-citronellal analogues were obtained with low enantioselectivity. The two main diastereoisomers of the product were opposite to each other. The scents of 5-substituted isopulegols were evaluated. The chiral recognition of the catalysts and their effects on the kinetic resolutions are also discussed. (C) 2016 Elsevier Ltd. All rights reserved.

The annulation of 1-cinnamyloxy-2-ethynylbenzene derivatives using a hydrazone-palladium catalyst system proceeded smoothly and gave the corresponding 2-substituted-3-cinnamylbenzofurans in good-to-excellent yields.

The annulation of 1-cinnamyloxy-2-ethynylbenzene derivatives using a hydrazone-palladium catalyst system proceeded smoothly and gave the corresponding 2-substituted-3-cinnamylbenzofurans in good-to-excellent yields.

Single-handed α-amino acid derivatives were generated from achiral precursors without an external chiral source. Conjugate addition of phenethylamine to an achiral aroyl acrylamide under homogeneous conditions gave the α-amino amides in quantitative yields, which crystallized as a conglomerate of a P21crystal system. Dynamic preferential crystallization or attrition-enhanced deracemization resulted in the formation of enantiomorphic crystals of 99 % ee.

© 2016 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim We designed a new class of N-type ligands bearing an imidazo[1,5-a]pyridine moiety and synthesized seven imidazo[1,5-a]pyridine derivatives. The palladium-catalyzed Mizoroki–Heck reaction of aryl bromides and chlorides with alkenes using our imidazo[1,5-a]pyridine-PdCl2system afforded the desired products in good-to-high yields with the low palladium loadings and short reaction times.

Such chiral phosphine-internal olefin hybrid type ligands as N-1-adamantyl-N-cinnamylaniline derivatives 1 with C(aryl)-N(amine) bond axial chirality were synthesized and utilized for the palladium-catalyzed asymmetric allylic alkylation of indoles to afford the desired products in high enantioselectivities (up to 98% ee).

Understanding enzymatic Diels-Alder (DA) reactions that can form complex natural product scaffolds is of considerable interest. Sch210972 1, a potential anti-HIV fungal natural product, contains a decalin core that is proposed to form through a DA reaction. We identified the gene cluster responsible for the biosynthesis of 1 and heterologously reconstituted the biosynthetic pathway in Aspergillus nidulans to characterize the enzymes involved. Most notably, deletion of cghA resulted in a loss of stereoselective decalin core formation, yielding both an endo (1) and a diastereomeric exo adduct of the proposed DA reaction. Complementation with cghA restored the sole formation of 1. Density functional theory computation of the proposed DA reaction provided a plausible explanation of the observed pattern of product formation. Based on our study, we propose that lipocalin-like CghA is responsible for the stereoselective intramolecular [4+2] cycloaddition that forms the decalin core of 1.

Rhodium(I)-catalyzed asymmetric 1,4-addition of arylboronic acids 2 to coumarins 1 using (S)-BICMAP as a chiral ligand gave the desired 4-arylchroman-2-one derivatives 2 in good yields and with high enantioselectivities (up to 99% ee). (C) 2015 Elsevier Ltd. All rights reserved.

A new class of C-2 chiral materials was easily prepared by the photodimerization reaction of (R)-N-phenethy1-2-chromonecarboxamide followed by recrystallization. Reduction of the photodimer gave the corresponding alcohol stereoselectively. Both C-2 chiral materials worked effectively as ligands for enantioselective ethylation of arylaldehydes using diethylzinc. (C) 2015 Elsevier Ltd. All rights reserved.

We found that N-(tert-butyl)-N-methylanilines 1 have C(aryl)-N(amine) bond axial chirality and succeeded the optical resolution of C-N bond atropisomers of amines I by a chiral palladium resolving agent and/or a chiral HPLC method. Finally, we demonstrated the ability of chiral amines 1 as a ligand in palladium-catalyzed asymmetric allylic alkylation of allylic esters with malonates (up to 95% ee). (C) 2015 Elsevier Ltd. All rights reserved.

Crystallization-induced asymmetric transformation (CIAT) of axially chiral materials is summarized on the basis of our studies. CIAT can be classified into two categories, Crystallization-Induced Enantiomer Transformation (CIET) and Crystallization-Induced Diastereomer Transformation (CIDT). Racemic mixtures or diastereomixtures that exist as a mixture of stereoisomers in solution converge on a single stereoisomer by dynamic crystallization. Many axially chiral materials, such as N-arylpyrimidine-2-(1H)-ones and -thiones, were crystallized as conglomerates, and total resolution was performed with high enantiomeric purities from the solution by CIET. Dynamic resolution of aromatic amides, such as 2-alkoxy-1-naphthamides, 2-quinolone-3-carboxamide, coumarin-3-carboxamide, and nicotinamides, was also successfully achieved by crystallization from the melt with high ees. Furthermore, optically active materials tend to crystallize in a chiral fashion, and CIDT is useful to obtain single diastereomers from a mixture of many diastereomers. Many types of aromatic amides with chiral auxiliaries were crystallized in a chiral fashion and were easily resolved by dynamic crystallization from the melt. Salt formation of oily racemic nicotinamides with enantiopure acid involving racemization during salt formation also gave diastereopure salts. The optical activity of the materials resolved by dynamic crystallization was effectively transferred to the products by many kinds of asymmetric reactions.

We report a highly selective asymmetric ring-closing ene reaction catalysed by aluminum complexes with chiral BINOL. This reaction yields optically active 6-membered cyclized alcohols from unsaturated aldehydes, with good diastereo- and enantioselectivities. Asymmetric amplification of this reaction was investigated by varying the ee of the BINOL employed in the catalyst.

Annulation of 1-allyl-2-bromobenzene derivatives with internal alkynes using a hydrazone-palladium catalyst system proceeded smoothly and gave the corresponding polysubstituted naphthalene derivatives in good to high yields.

Crystallization-induced asymmetric transformation (CIAT) of axially chiral materials is summarized on the basis of our studies. CIAT can be classified into two categories, Crystallization-Induced Enantiomer Transformation (CIET) and Crystallization-Induced Diastereomer Transformation (CIDT). Racemic mixtures or diastereomixtures that exist as a mixture of stereoisomers in solution converge on a single stereoisomer by dynamic crystallization. Many axially chiral materials, such as N-arylpyrimidine-2-(1H)-ones and -thiones, were crystallized as conglomerates, and total resolution was performed with high enantiomeric purities from the solution by CIET. Dynamic resolution of aromatic amides, such as 2-alkoxy-1-naphthamides, 2-quinolone-3-carboxamide, coumarin-3-carboxamide, and nicotinamides, was also successfully achieved by crystallization from the melt with high ees. Furthermore, optically active materials tend to crystallize in a chiral fashion, and CIDT is useful to obtain single diastereomers from a mixture of many diastereomers. Many types of aromatic amides with chiral auxiliaries were crystallized in a chiral fashion and were easily resolved by dynamic crystallization from the melt. Salt formation of oily racemic nicotinamides with enantiopure acid involving racemization during salt formation also gave diastereopure salts. The optical activity of the materials resolved by dynamic crystallization was effectively transferred to the products by many kinds of asymmetric reactions.

We report a highly selective asymmetric ring-closing ene reaction catalysed by aluminum complexes with chiral BINOL. This reaction yields optically active 6-membered cyclized alcohols from unsaturated aldehydes, with good diastereo- and enantioselectivities. Asymmetric amplification of this reaction was investigated by varying the ee of the BINOL employed in the catalyst.

Annulation of 1-allyl-2-bromobenzene derivatives with internal alkynes using a hydrazone-palladium catalyst system proceeded smoothly and gave the corresponding polysubstituted naphthalene derivatives in good to high yields.

シンナミル構造またはプレニル構造を有する新規エーテル類を合成し、これらの香気について検討した。また、これらの最安定化構造をGaussian 09プログラムによる量子化学計算にて求め、立体構造が香気に与える影響についてさらに検討した。

A highly reactive catalytic ring-closing ene reaction is discussed. This reaction is catalyzed via novel optically active aluminum BINOL and TADDOL complexes. The kinetic resolution of the racemic analogs of citronellal was affected by these Al catalysts. The BINOL-Al catalyst afforded 68% ee of a diastereomer of isopulegol and 62% ee of citronellal at 47% conversion. The reaction mechanism proposed assumes that the optically active catalyst possesses a metal center between two parallel aromatic rings. We postulate that the edge of the aromatic rings can recognize the methyl group at the 3-position of citronellal, as the rings are oriented in a pseudoparallel orientation. We utilized the kinetic resolution for the synthesis of l-menthol from citral.

We report a new catalyst system, morpholine-NiCl2, for the Suzuki-Miyaura coupling of aryl chlorides with aryl-or alkenylboronic acids to give biaryl compounds. This catalyst system is easy to apply on a large scale because of its easy preparation and the use of inexpensive reagents. In addition, analysis of the residual nickel shows only 9.7 ppm remaining after normal work-up. This catalyst system has been applied to 26 compounds to give a variety of biaryl products, including hetero-biaryl compounds.

An asymmetric photoreaction by using chirality provided by<br /> dynamic chiral salt formation was demonstrated. Crystallization<br /> of racemic 2-quinolone-3-carboxamide and 2-quinolone-<br /> 4-carboxamide with enantiopure L-dibenzoyltartaric<br /> acid led to deracemization and gave high diastereomeric excess<br /> values of the crystalline salts in almost quantitative yield. The axial chirality was retained for a long period of<br /> time after the salts were dissolved in cooled solvent. The frozen<br /> chirality derived from the chiral salts was effectively<br /> transferred to the products by using a typical [2+2] photocycloaddition<br /> reaction with alkenes.

An asymmetric photoreaction by using chirality provided by dynamic chiral salt formation was demonstrated. Crystallization of racemic 2-quinolone-3-carboxamide and 2-quinolone-4-carboxamide with enantiopure L-dibenzoyltartaric acid led to deracemization and gave high diastereomeric excess values of the crystalline salts in almost quantitative yield. The axial chirality was retained for a long period of time after the salts were dissolved in cooled solvent. The frozen chirality derived from the chiral salts was effectively transferred to the products by using a typical [2+2] photocycloaddition reaction with alkenes.

Allylic arylation of cinnamyloxyphenylboronic acid pinacol esters 3, which have arylboronic acid moiety and allylic ether moiety, using a hydrazone 1d-Pd(OAc)(2) system proceeded and gave the corresponding 1,3-diarylpropene derivatives 4 with a phenolic hydroxyl group via a selective coupling reaction of the pi-allyl intermediate to the boron-substituted position of the leaving group.

We report a new catalyst system, a morpholine-Pd(OAc)2 complex, for Suzuki-Miyaura coupling of aryl tosylates or mesylates with arylboronic acids to give biaryl compounds. The morpholine-Pd(OAc)2 catalyst system is proposed to be a precursor of the catalytically active species in the coupling reaction. Aryl chlorides and aryl triflates can also be used in this coupling reaction. Altogether, 22 biaryl compounds were obtained using this catalyst system.

Palladium-catalyzed decarboxylative coupling of benzoic acid derivatives with arylboroxins gave biaryls using a catalytic amount of Pd(TFA)(2)-hydrazone Id system with Ag2CO3 at 80 degrees C in good yields. We also found that decarboxylative coupling with aryl(trialkoxy)silanes gave biaryls using a Pd(TFA)(2)-hydrazone 1g system with AgF in good yields. 2014 Elsevier Ltd. All rights reserved.

As dimeric natural products frequently exhibit useful biological activities, identifying and understanding their mechanisms of dimerization is of great interest. One such compound is (-)-ditryptophenaline, isolated from Aspergillus flavus, which inhibits substance P receptor for potential analgesic and anti-inflammatory activity. Through targeted gene knockout in A. flavus and heterologous yeast gene expression, we determined for the first time the gene cluster and pathway for the biosynthesis of a dimeric diketopiperazine alkaloid. We also determined that a single cytochrome P450, DtpC, is responsible not only for pyrroloindole ring formation but also for concurrent dimerization of N-methylphenylalanyltryptophanyl diketopiperazine monomers into a homodimeric product. Furthermore, DtpC exhibits relaxed substrate specificity, allowing the formation of two new dimeric compounds from a non-native monomeric precursor, brevianamide F. A radical-mediated mechanism of dimerization is proposed.

A highly reactive catalytic ring-closing ene reaction is discussed. This reaction is catalyzed via novel optically active aluminum BINOL and TADDOL complexes. The kinetic resolution of the racemic analogs of citronellal was affected by these Al catalysts. The BINOL-Al catalyst afforded 68% ee of a diastereomer of isopulegol and 62% ee of citronellal at 47% conversion. The reaction mechanism proposed assumes that the optically active catalyst possesses a metal center between two parallel aromatic rings. We postulate that the edge of the aromatic rings can recognize the methyl group at the 3-position of citronellal, as the rings are oriented in a pseudoparallel orientation. We utilized the kinetic resolution for the synthesis of L-menthol from citral.

Irradiation of three chromone-2-carboxamides with a chiral auxiliary resulted in diastereoselective formation of a C-2-chiral anti-HH dimer scaffold. Selection of the solvent polarity and decreasing the temperature resulted in asymmetric induction with up to 84% diastereomeric excess (de).

An aluminium complex bearing 2-cyclohexyl-6-phenylphenol afforded (5R)-n-isopulegol from (R)-citronellal via the intermolecular Prins reaction with an exceptionally high diastereoselectivity. Using this reaction, L-menthol was obtained with an excellent diastereoselectivity.