桝 飛雄真

The catalytic asymmetric Friedel-Crafts/protonation of indoles and pyrroles with a-substituted nitroalkenes to give the corresponding adducts in a highly anti-selective manner was achieved by an imidazoline aminophenol (L2)-Cu complex. The anti-adducts could be successfully transformed to biochemically important alpha-substituted beta-heteroarylalkylamines.

Single crystal X-ray structures of three imidazolium salts were examined. In contrast to imidazolium salt 1 possessing an ester group which created a network of C-H center dot center dot center dot halide-anion interactions with a linear array of imidazolium and the corresponding counter anions, unique network structures were observed in imidazolium salts 2 and 3 with long alkyl chains and with carboxy moieties, respectively. Water molecules were incorporated in their H-bonding networks. Water molecules were wedged into the two neighboring halide anions to create square units which acted as a bridge to connect the two adjacent C-H center dot center dot center dot halide-anion networks of imidazolium moieties and counter anions. (C) 2011 Elsevier B.V. All rights reserved.

U-shaped N,N'-dimethyl-N,N'-diphenylureadicarboxylic acid was developed as a folding unit to fabricate an H-bonding aromatic zigzag array. Recrystallization of it with dipyridyl derivatives gave cocrystals. Zigzag-type strands were formed by pinching dipyridyl derivatives via H-bonding with two carboxy moieties. Two types of H-bonding networks, helix and zigzag, were obtained depending on the structure of dipyridyl derivatives to be included. The former afforded a triple helix and the latter gave a twisted zigzag tape with chirality.

We synthesized a series of new Ag-2(bis-NHC)(2) complexes from the corresponding bisimidazolium salts tethered with 2,7-dimethylnaphthalene-bridged bis-NHC ligands. The reaction proceeded in a selective manner, and the Ag-2(bis-NHC)(2) complexes were isolated in good to high yields. The Ag complexes were converted to the Pd-2(bis-NHC)(2) complexes efficiently. It is important to choose proper conditions for the conversion of the silver complexes to the palladium complexes, depending on the structure of the ligand: the effect of the counteranion was significant. The structures of the complexes were studied by X-ray crystallographic analyses and compared with the corresponding monodentate NHC complexes. The catalytic activity of the Pd complexes for the Mizoroki-Heck reaction was examined.

A series of adamantane-based bisphenol molecules with structurally related V-shaped skeletons were designed to examine the influence of molecular shapes and steric hindrances for the molecular association and packing of individual molecules in crystalline lattices. Single crystal X-ray analysis revealed that multiple intermolecular hydrogen bonds were formed between the hydroxyl groups of the phenol moieties. Crystallographic analysis of 1,3-bis(4-hydroxy-3,5-dimethylphenyl)adamantane (1) indicated the creation of a one-dimensional (ID) zigzag polymer through hydrogen bonds. In the crystals of 1,3bis(3-bromo-4-hydroxyphenyl)adamantane (2), infinite 1D polymers composed of cyclic frameworks were sustained by intermolecular hydrogen bonds. 1,3-Bis(3-chloro-4-hydroxyphenyl)adamantane (3) and 1,3-bis(4-hydroxyphenyl)adamantane (4) formed frameworks with channels containing chloroform molecules in the solid state. Continuous 1D polymers consisting of cyclic frameworks were generated in crystals 3a and 4a, and these ID polymers packed into two-dimensional (2D) layers with channel structures.

A simple spherical aromatic amide constructed a channel-shaped network structure by weak intermolecular interactions in the crystalline state. The channel incorporated water molecules which form a tape-like 1D chain network. Pseudopolymorphism of the spherical compound generated a different shape of the channel and incorporated acetonitrile molecules instead of water.

Tris-phenylurea-substituted calix[3]amides (3a, 3b) and tris-phenylthiourea-substituted calix[3]amides (4a, 4b) were synthesised by the reaction of amine with isocyanates and thioisocyanate, respectively. Single crystal X-ray analysis revealed that the cyclic trimers adopt a syn conformation with all of the urea groups on the same side. The binding affinities of these compounds towards anions were measured using 1H NMR titrations in DMF-d7, DMSO-d6 or CDCl3. Each receptor was observed to bind halogen anions in a 1:1 stoichiometry, exclusively through hydrogen bonding, and the anion selectivity was in the order F- Cl->> Br- I-. DFT calculations revealed that the fluoride anion is anchored in the centre of the six N-H hydrogen atoms of 3a through H center dot center dot center dot F interactions.

An adamantane-based bisphenol (1) assembled into three types of 2D layers with or without channels or a doubly interpenetrated 3D network bearing clathrate hydrates via hydrogen bonds. The different stoichiometries of 1 and water facilitated the formation of the diverse molecular packing structures. Infinite chains and finite triangle clusters of water were formed within the channels and cavities.

We synthesized xanthenes substituted with two different donor ligand units, N-heterocyclic carbene (NHC) and oxazoline, by the sequential coupling reaction. Silver complexes 15 and 19 were prepared by the reaction between the xanthene derivatives and Ag(2)O. Pd complexes 16 and 20 were also synthesized by the reaction of the corresponding silver complexes with Pd(PhCN)(2)Cl(2). X-ray crystallographic analysis revealed that complexes 15-PF(6), 16, and 20 adopted trans configurations, while the Ag atom of 15-Cl coordinated only to the NHC ligand.

Novel optically active axially chiral amino acid and amino acid and amino alcohols have been synthesized efficiently via lactam ring-opening, with the aid of an optically active alcohol amidoaza[5]helicene 5, which has been readily prepared by an additive-ligand-free Pd catalyzed domino coupling reaction in a single step. The stereostructures of these chiral molecules have also been clarified.

Cyclic trimers of 3-(N-alkylamino)benzoic acid (calix[3]amides) with various substituents at the meta position of the phenyl rings were synthesized and the effects of the substituents on the crystal structures and energy profiles in solution were examined. The calixamides existed in a syn conformation in the crystal state, and this was also the major conformation in solution, especially in polar solvents. The energy barrier between syn and anti conformers in the solution was not significantly affected by substituents (12.7-14.0 kcal/mol). The effect of the substituent on the temperature dependence of the syn/anti ratio are discussed. (C) 2010 Elsevier Ltd. All rights reserved.

Ligands that consist of pyridine rings linked by sulfonamide are simple and unique building blocks which form infinite polymers and networks via metal-coordination and hydrogen bonds (H-bonds). Single crystal X-ray analysis revealed that the complexation of bidentate ligands 1 and 2 bearing secondary sulfonamide with silver(I) ion results in the formation of [AgL(2)(OTf] (1a), [Ag(2)(mu-L)(2)(OTf)(2)] (2a), and [AgL(OTf](n) (2b) complexes. The complex 1a assembled into extended one-dimensional (1D) chains through H-bonds between the N-H moieties of sulfonamide and nitrogen atom of pyridyl groups. These individual chains associated into a three-dimensional (3D) network structure via C-H center dot center dot center dot O interactions between pyridyl protons and the oxygen atom of sulfonamides. The complex 2a assembled into two-dimensional (2D) sheets through H-bonds between the N H moieties of sulfonamide and H(2)O molecules. In the complex 2b, enantiopure continuous ID chain [AgL(OTf)](n) was formed. In these structures, the silver(I) centers have a T-shaped stereochemistry in which each ion is coordinated by two pyridyl groups of the ligand and a trifluoromethane sulfonate anion. In the complex of ligands 3 and 4 with an ethyl group on the nitrogen atom of sulfonamide and silver(I) ions, continuous ID homochiral chains [AgL(OTT)1 (3a) and helical polymers [AgL](n)(OTf)(n) (4a) were formed. Both 1D homochiral polymers contained a racemic mixture of right- and left-handed coordination polymers, which assemble into 2D sheets and 3D networks via Ag center dot center dot center dot Ag, Ag center dot center dot center dot O, and C-H center dot center dot center dot O interactions.

Intramolecular [2+2] photocycloaddition of aromatic chain imides possessing bis-phenanthrene moieties afforded straight and cross ring closure products. The ratio of cycloadducts was dependent on reaction time and temperature, which resulted in a reversal of regioselectivity. The reaction was proved to involve a retro cycloaddition. The cross ring closure products were formed predominantly in the early stage of the reaction at lower reaction temperature. In contrast, the straight ring closure products were predominant at higher reaction temperature with prolonged irradiation.

Molecules of macrocyclic aromatic hydrocarbon 1 assembled to form various three-dimensional (3D) structures via weak intermolecular interactions, including aromatic-aromatic interactions (1a-d). In the crystal obtained from a chloroform and acetonitrile mixture (1a), the molecules arranged in a columnar stack with a progressive helical twist between adjacent molecules due to intermolecular aromatic-aromatic interactions. The chirality of the helices was spontaneously resolved within individual single crystals. In the crystal obtained from a chloroform and nonane mixture (1b), the molecules formed a columnar stack through tilted T-shaped aromatic-aromatic interactions. Furthermore, in the crystal obtained by vapour diffusion of n-hexane or ethyl acetate into a chloroform solution, inclusion compounds (1c and 1d) were formed via van der Waals interactions between the guest molecule and the benzene ring of the biphenyl unit. The n-hexane penetrated 1 to construct [3] pseudorotaxane and an ethyl acetate molecule was trapped by 1.

The total syntheses of tetrapeptides tubulysins D (1b), U (1 c), and V (1d), which are potent tubulin polymerization inhibitors, are described. The synthesis of Tuv (2), an unusual amino acid constituent of tubulysins, includes an 1,3-dipolar cycloaddition reaction of chiral nitrone D-6 derived from D-gulose with N-acryloyl camphor sultam (-)-9 employing the double asymmetric induction, whereas the synthesis of Tup (20), another unusual amino acid, involves a stereoselective Evans aldol reaction of (Z)-boron enolate generated from (S)-4-isopropyl-3-propionyl-2-oxazolidinone with N-protected phenylalaninal and a subsequent Barton deoxygenation protocol. We accomplished the total syntheses of tubulysins U (1c) and V (1d) by using these methodologies, in which the isoxazolidine ring was used as the effective protective group for gamma-amido alcohol functionality. Furthermore, to understand the structure-activity relationship of tubulysins, we synthesized tubulysin D (lb) and cyclo-tubulysin D (le) from 2-Me and 20, and ent-tubulysin D (em-id) from eitt-2-Me and ent-20, respectively. The preliminary results regarding their biological activities are also reported.

The [6 + 2] cycloaddition reaction of 2-vinylazetidines with electron-deficient isocyanates such as tosyl Isocyanate proceeded smoothly in the absence of the catalyst at room temperature, and various cyclic ureas were isolated in good to high yields. Electron-deficient allenes also reacted with the 2-vinylazetidine, and the corresponding azocine derivatives were isolated.

Two approaches to create hydrogen-bonding (H-bonding) cyclic dimers of tethered benzoic acids in a crystalline state were examined. The cyclic dimers of the methoxy derivative 1 were generated by inclusion of aromatic guest molecules: benzene or benzonitrile, Depending on the size of the guests, the conformation of the pentylene linker of 1 took either the all-trans or 1,2- and 4,5-gauche conformation to adjust the size of the cavity for the guest. The tethered benzoic acids 2 possessing benzyloxy groups as pendants generated a poly(pseudo)rotaxane-like structure in which pendants were included in the cavity of the cyclic dimer itself. In contrast, 1 afforded a zigzag H-bonding network by recrystallization from methanol or ethanol. Incorporation of methanol in the zigzag network was observed when 1 was recrystallized from methanol.

Adamantane-based macrocycles and a cage with aromatic ring moieties have been developed and structurally revealed by X-ray crystallographic analysis. The dimerized (1) and trimerized (2) macrocycles of binary molecules based on adamantane with acetylenic aromatic ring moieties were designed and effectively synthesized. Similarly, a cryptand-like macrobicyclic cage (3) was constructed from a trisubstituted adamantane derivative. Single-crystal X-ray analysis revealed that both cyclic compounds have nearly a rectangular shape with or without a solvent molecule in the cavity. The macrobicyclic cage has an inner space and accommodates a chloroform molecule via C-H center dot center dot center dot pi interactions. Macrocycles and cage encapsulate 1,3,5-trinitrobenzene (4) as an electron-poor guest in a one-to-one complex via charge-transfer interactions in a parallel fashion, and showed the formation of molecular networks such as columns, tubes, 2D layers, and 3D networks composed of two different types through noncovalent interactions in the solid state.

We synthesized various block-like molecules based on stereochemistry of tertiary aromatic amide which prefers cis (folded) conformation and weak intramolecular interactions such as aromatic-aromatic interactions. Their crystal structures and dynamic behaviors in solution were revealed by X-ray crystallographic analysis and dynamic H-1 NMR measurement. The block-like molecules were triangular, rhombic, twisted, spherical or pinched circle in shape. Some of them aggregated into a channel-shaped network via weak intermolecular interactions.

As a new supramolecular tecton based on hydrogen bonding for crystal engineering, benzoic acid derivatives possessing two hydroxymethyl groups were developed and their crystal structures were investigated by single crystal X-ray analysis. The hydrogen-bonded dimer of the acid which possesses four hydrogen-bonding sites creates two types of networks, a zigzag and a straight hydrogen-bonded network. Zigzag hydrogen-bonded networks were created with methoxy (1) and benzyloxy (2) derivatives. It was found that the ladder structure was created via a straight hydrogen-bonded network when 2 included either methanol or ethanol in its cavity. The introduction of a long alkoxy group (hexyloxy) (3) resulted in the formation of an alternate hydrogen-bonded network. Ethyl benzoate derivative (4) also formed a hydrogen-bonded network in a zigzag manner.

Synthetic studies of two components of tubulysins, tubulin polymerization inhibitors are described. The highly stereoselective synthesis of tubuvaline methyl ester (2) was accomplished by 1,3-dipolar cycloaddition of nitrone D-6 and acrylic acid derivatives 7 as a key step. The synthesis of tubuphenylalanine (3) was conducted by an aldol reaction of a boron enolate of (S)-4-isopropyl-3-propionyl-2-oxazolidinone (13) with aldehyde 14, readily prepared from phenylalanine, followed by Barton deoxygenation under radical conditions. (c) 2009 Elsevier Ltd. All rights reserved.

The nickel-catalyzed [3 + 2 + 2] cycloaddition of ethyl cyclopropylideneacetate and conjugated enynes proceeded smoothly and divinylcycloheptadienes were isolated in high yields. The three-component cocyclization of ethyl cyclopropylideneacetate, conjugated enynes, and (trimethylsilyl)acetylene also proceeded in a highly selective manner to afford vinylcycloheptadienes, which were reacted with various dienophiles. This study provided a new, short-step synthesis of polycyclic compounds with cycloheptane skeleton.

The crystal structures and dynamic behavior in solution of aromatic amides containing terphenyl groups were revealed by X-ray crystallographic analysis and VT-NMR measurements. Controlling the synthetic yield and molecular shape of the macrocycles with intramolecular aromatic-aromatic interactions was successfully achieved. N,N'-Diethyl-N,N-diterphenyl-1,3-benzenedicarboxamide (2) exists in the syn conformation and two terphenyl groups are on the same side of the plane of the central benzene ring due to attractive aromatic-aromatic interactions between the two terphenyl moieties. The yield of the macrocyclization reaction of 1,3-benzenedicarboxylic acid with bis(ethylamino)terphenyl (4) was relatively high (55% yield) because an intermediate in the macrocyclization reaction was preorganized in the syn conformation, which is similar to the diamide 2. On the other hand, N,N'-diethyl-N,N'-diterphenyl-1,4-benzenedicarboxamide (3) exists in the anti conformation and two terphenyl groups are positioned on opposite sides of the plane of the central benzene ring. In contrast to the 1,3-derivative, the yield of the macrocyclization reaction of the 1,4-benzenedicarboxylic acid with the diamine 4 was low (19% yield). Although macrocycle 5 exists in a planar conformation in the crystal and in solution, macrocycle 6 exists in a twisted conformation. A deformation of the twist was induced by a tilted T-shaped aromatic-aromatic interaction between the central phenylene rings of the macrocycle.

The Ni-catalyzed [3+2+2] cocyclization between ethyl cyclopropylideneacetate (1) and 1,3-diynes afforded cycloheptadiene derivatives. The three-component reaction of 1, 1,3-diynes, and alkynes proceeded with good yield and high selectivity. Scope of the substrates was studied, and the origin of chemo- and regioselectivity of the reaction is discussed. (C) 2008 Elsevier Ltd. All rights reserved.

A cyclic trimer and a cyclic tetramer of m-aminobenzenesulfonic acid were obtained by one-pot synthesis using dichlorotriphenylphosphorane as a coupling reagent. Single crystal X-ray analysis revealed that all sulfonamide moieties of the cyclic sulfonamides adopted a synclinal conformation, and that multiple intermolecular hydrogen bonds were formed between the sulfonamide protons and the suffonyl oxygens on the adjacent molecules. The cyclic trimer has three types of pseudopolymorph containing water, methanol, or acetonitrile molecules. The molecule in each crystal was bowl-shaped, and the enantiomeric pair of molecules existed in a discrete dimeric structure with or without a guest molecule in the cavity. Furthermore, the cyclic tetramer existed in a 1,3-alternate conformation with pseudo-S(4)-symmetry, and formed an infinite network structure through intermolecular hydrogen bonds.

Treatment of 6-amino-2-naphthoic acid with dichlorotriphenylphosphorane afforded a new naphthalene ring-based calix[3]amide in moderate yield. The macrocyclic calix[3]amide exists in an anti-form in the crystalline state and forms a channel structure along its b axis. In CDC13 solution it exists in equilibrium between the syn- and anti-forms in solution (100:57). The energy barrier between the anti- to syn-forms was calculated to be 17.8 +/- 0.2 kcal/mol. (C) 2008 Elsevier B.V. All rights reserved.

A series of new bidentate bis(N-heterocyclic carbene)-palladium complexes 4a-e and 6 with xanthene framework was synthesized. The X-ray analyses of the complexes revealed that the complexes have conformational chirality. Homochiral crystals of 4a and 6 were obtained by recrystallization from THF or 1,4-dioxane as solvent. The energy barriers for racemization of the complexes were calculated from dynamic NMR spectroscopy. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

1,2-Bis(N-p-fluorobenzoyl-N-methylamino)benzene (1) afforded 13 types of crystals upon crystallization from various solvents. Eleven of them are pseudopolymorphs that have crystallizing solvents in the crystalline lattice, whereas the others are polymorphs. Both the polymorphs and pseudopolymorphs included conformational polymorphs based on cis/trans isomerization of the amide bonds. Three of the pseudopolymorphs showed spontaneous resolution (total asymmetric transformation), belonging to the chiral space group P3(1) or P3(2). The absolute configuration of each chiral crystal was determined by single crystal X-ray analysis. Solid-state CD spectrum was also measured in the KBr matrix for the same crystal used for X-ray analysis. Phase transition between the polymorphs and pseudopolymorphs was observed by simultaneous measurement of DSC and X-ray powder diffraction.

Base-promoted self-condensation reactions of trans-stilbene and diphenylacetylene monomers bearing 4-alkylamino and 4'-methoxycarbonyl groups were investigated. Reactions of N-propyl monomers under pseudohigh-dilution conditions (a THF solution of monomer was added dropwise to a THF solution of LiHMDS) afforded the corresponding cyclic triamides in good yields. X-ray crystallographic analysis showed that these cyclic triamides possessed an almost equilateral triangle structure with a cavity surrounded by tilted benzene rings.

A novel chiral spherical molecule composed of aromatic amide was synthesized in short steps. The molecule is constructed from four benzene rings connected by six amide bonds and has multiple functionalizable points and an asymmetric structure. The racemic spherical molecule constructed channel network structures in the crystalline state.

Enantioselective C-C bond formation at an a-position of a nitrite group with an external electrophile can be realized, although in modest ee, with the aid of both the concerted process of an epoxysilane rearrangement and a carbamoyl group. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).

A biphenanthryl ether with substituents in the bay regions was efficiently synthesized for the first time. The unique stereostructure of 1 was clarified. Its twisted conformation and optical behavior as well as its characteristic supramolecular helical structure, which is constructed through a C-H center dot center dot center dot F hydrogen bonding network in the solid state, are discussed. (C) 2008 Elsevier Ltd. All rights reserved.

Four-component synthesis of nitroimine derivatives (3) via double nitro-Mannich reaction was carried out in which nitroalkane, two moles of aldehyde, and lithium hexamethyldisilazide (LHMDS) were coupled in one-pot. In situ generated N-trimethylsilylaidimine was reacted with nitroalkane dianion followed by the second addition of the resulting nitrogen anion to the aldimine and the subsequent elimination of bistrimethylsilylamine furnished nitoroimine. The reaction was proceeded with erythro selectivity. (c) 2007 Elsevier Ltd. All rights reserved.

Conformation of aromatic foldamers possessing three aromatic rings in a sequence of anthracene - phenylene - anthracene linked with iminodicarbonyl was examined. Their folding structures were confirmed by single crystal X-ray analysis. Two conformations, straight-zigzag and helically-zigzag conformations, were found depending on the substituents at the imide nitrogen atom. Induced circular dichroism originated in the interaction of the upper and bottom anthracene moieties was observed both in solution and in the solid state. (c) 2007 Elsevier Ltd. All rights reserved.

Anthracene derivatives possessing pentafluorobenzoyloxy moieties at 9- and 10-positions showed polymorphism affording two types of fluorescent crystals with blue and bluish green fluorescence in their crystalline state, respectively. Their single crystal X-ray structures showed that the degree of overlap of anthracene moieties was responsible for the difference in fluorescence. Fluorescence in the crystalline state originated in the dimer emission deduced from their excitation spectra. (C) 2007 Elsevier Ltd. All rights reserved.

We constructed a novel molecular conformational alteration system with an N-aryl-N-phenylacetamide structure, in which the N-aryl group consists of a hydroquinone-p-quinone system as a redox-dependent aromatic trigger. The amide conformation depended on-the oxidation state of the aryl group, and the two states (compounds 2 and 3) were reversibly converted to each other by redox reactions. Such compounds would be applied as useful structural units for external stimulus-responsive control on the shape and function of large molecules or supramolecules.

Discotic helical macrocycle constructed by aromatic tertiary amide was effectively synthesized using dichlorotriphenylphosphorane as the condensation reagent. The yield was significantly higher when meta-substituted diaminobenzene was used as the linkage for a two 1,3,5-tris(4-carboxyphenyl)benzene moiety than when para-substituted diaminobenzene was used. The yield is thus dependent on whether the pre-organized partial diamide structure suits the construction of the macrocyclic structure. (c) 2007 Elsevier Ltd. All rights reserved.

Aromatic chain imides possessing chromophores connected by iminodicarbonyl linkers were synthesized as novel aromatic foldamers. In these molecules chromophores face each other and form the helical folding structures both in solution and in solid state. Their folding structures were investigated by single crystal X-ray analysis and H-1 NMR spectroscopy. A circular dichroism (CD) spectral study on the chiral aromatic chain imides with bulky N-substituents showed that their helically chiral conformation based on folding remained for a reasonably long time without racemization in solution. As the number of folded chromophores increased, their absorption and fluorescence spectra were red-shifted, and induced CD signals were increased. This remarkable change is based on the intramolecular interaction between folded chromophores. As an application of these aromatic chain imides, a chiral photochromic system was investigated by utilizing the intramolecular photo [4+4] cycloaddition and thermal cycloreversion of anthracene and naphthalene chromophores connected by iminodicarbonyl linkers.

The structural features and conformational conversion of the N-methyl pyridyl amide oligomer bearing 2,6-disubstituted pyridines were investigated. H-1 NMR and X-ray crystallography revealed that the environment-responsive type of conformational control can be performed. The amide bond switching together with intramolecular hydrogen-bonding effects caused dynamic protonation-associated conformational conversion from layered to spiral and then flat.

Aromatic N-methyl amides containing N-(2-pyridyl) and 2-pyridinecarboxamide or 2,6-pyridinedicarboxamide moieties switch their conformation from cis to trans depending upon the addition of acid. (c) 2006 Elsevier Ltd. All rights reserved.

C-2v-symmetrical cyclic tetramers of aromatic amides were simply synthesized in moderate yield by condensation reaction of N,N'-dimethyl-1,3-phenylenediamine and isoplithalic acid derivatives using dichlorotriphenylphosphorane. The calix[4]amides exist in 1,3-alternate structure with cis conformation of tertiary aromatic amides, which were shown to be a versatile scaffold leading to a bowl-shaped macrocyclic compound possessing a anomalously strained structure, a bent hinge angle between two aromatic ring planes of biphenyl moiety, via an intramolecular ligation reaction. (c) 2006 Elsevier Ltd. All rights reserved.

An effective screening method combining parallel synthesis and solid-state CD measurements was established to identify achiral aromatic sulfonamides that show spontaneous resolution with rapidity. We found that 4 of the 12 achiral sulfonamides crystallized as chiral crystals through this method. The chirality of each sulfonamide was discriminated by solid-state CD spectra and Flack parameter in an X-ray analysis. Correspondence between the observed Cotton effect and the absolute configuration could be confirmed by time-dependent DFT calculations.