三野 孝

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).

The copper-catalyzed asymmetric propargylic amination of propargylic acetates 1 with amines 2 using BICMAP as a chiral ligand gave the desired products 3 in good yields and with moderate to high enantioselectivities (up to 90% ee). (C) 2013 Elsevier Ltd. All rights reserved.

Dynamic atroposelective resolution of chiral salts derived from oily racemic nicotinamides and enantiopure dibenzoyltartaric acid (DBTA) was achieved by crystallization. The absolute structures of the axial chiral nicotinamides were determined by X-ray structural analysis. The chirality could be controlled by the selection of enantiopure DBTA as a chiral auxiliary. The axial chirality generated by dynamic salt formation was retained for a long period after dissolving the chiral salt in solution even after removal of the chiral acid. The rate of racemization of nicotinamides could be controlled based on the temperature and solvent properties, and that of the salts was prolonged compared to free nicotinamides, as the molecular structure of the pyridinium ion in the salts was different from that of acid-free nicotinamides. © 2013 by the authors.

We developed a palladium-catalyzed Mizoroki-Heck type reaction of olefins with such hypervalent iodine reagents as iodobenzene diacetate in good to high yields using 2 mol% of a heterocyclic hydrazone (1b)-Pd(OAc)(2) system in NMP under air at 90 degrees C.

Optically active materials could be generated by simple solidification of achiral materials without an external chiral source. When achiral cis-3,4-diphenylsuccinimides were solidified in the presence of a catalytic amount of DBU by evaporating the solvent with stirring, optically active trans-3,4-diphenylsuccinimides were obtained quantitatively with high enantiomeric excesses. © 2013 The Royal Society of Chemistry.

Redox enzymes play a central role in generating structural complexity during natural product biosynthesis. In the postassembly tailoring steps, redox cascades can transform nascent chemical scaffolds into structurally complex final products. Chaetoglobosin A (1) is biosynthesized by a hybrid polyketide synthase-nonribosomal peptide synthetase. It belongs to the chaetoglobosin family of natural products, comprising many analogs having different degrees of oxidation introduced during their biosynthesis. We report here the determination of the complete biosynthetic steps leading to the formation of 1 from prochaetoglobosin I (2). Each oxidation step was elucidated using Chaetomium globosum strains carrying various combinations of deletion of the three redox enzymes, one FAD-dependent monooxygenase, and two cytochrome P450 oxygenases, and in vivo biotransformation of intermediates by heterologous expression of the three genes in Saccharomyces cerevisiae. Five analogs were identified in this study as intermediates formed during oxidization of 2 to 1 by those redox enzymes. Furthermore, a stereochemical course of each oxidation step was clearly revealed with the absolute configurations of five intermediates determined from X-ray crystal structure. This approach allowed us to quickly determine the biosynthetic intermediates and the enzymes responsible for their formation. Moreover, by addressing the redox enzymes, we were able to discover that promiscuity of the redox enzymes allowed the formation of a network of pathways that results in a combinatorial formation of multiple intermediate compounds during the formation of 1 from 2. Our approach should expedite elucidation of pathways for other natural products biosynthesized by many uncharacterized enzymes of this fungus.

The palladium-catalyzed asymmetric allylic alkylation of indoles with 1,3-diphenyl-2-propenyl acetate using P/N-type ligands such as N-aryl indole, C-N bond axially chiral aminophosphine (aS)-I4, gave the desired products 1 in good yields and with moderate to high enantioselectivities (up to 90% ee). (C) 2013 Elsevier Ltd. All rights reserved.

Unsymmetrical 1,3-diarylpropenes were synthesized in good to high yields by the palladium-catalyzed allylic arylation of allylic ethers, such as a cinnamyl phenyl ether, with a variety of arylboronic acids using a hydrazone 1a-Pd(OAc)(2) system in DMAc/H2O. Using this catalyst, eugenol was also synthesized from allyl phenyl ether with (4-hydroxy-3-methoxyphenyl) boronic acid pinacol ester.

The reaction of vinyl ethers with carboxylic acids using iodine as a catalyst under solvent-free conditions was investigated. The reaction of saturated carboxylic acids with vinyl ethers gave the corresponding esters. Mechanistic studies revealed the production of the adduct of the vinyl ether with the carboxylic acid, which then rearranged to form the ester. At low temperatures, the reaction of 2-(1-hydroxycyclohexyl)acetic acid (1) and butyl vinyl ether yielded a butyl ester. However, at a reaction temperature of 80°C, both the esterification and the elimination of a water molecule occurred, yielding the unsaturated butyl ester butyl 2-cyclohexenylacetate. The reaction of 2-((1S,2S,4R)-2-hydroxy-1,7,7- trimethylbicyclo[2.2.1]heptan-2-yl)acetic acid (12) with butyl vinyl ether at low temperatures resulted in a mixture of four compounds. However, similar to the high-temperature (&gt 60°C) reaction of 1, the esterification was accompanied by the elimination of a water molecule to give the unsaturated butyl ester (E)-butyl 2-((1S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)acetate. While a g-hydrogen was abstracted to form the endo-type double bond in the reaction of 1, an α-hydrogen was abstracted to form the exo-type double bond in the reaction of 12. © 2013 by Japan Oil Chemists' Society.

The irradiation of methyl 2- and 3-chromonecarboxylate in the presence of various alkenes afforded cyclobutane type adducts, whose structures were established by X-ray structural analysis. Methyl 2-chromonecarboxylate showed higher photochemical reactivity than methyl 3-chromonecarboxylate, in which endo adducts were yielded as major products. © 2012 Springer Science+Business Media Dordrecht.

The irradiation of methyl 2- and 3-chromonecarboxylate in the presence of various alkenes afforded cyclobutane type adducts, whose structures were established by X-ray structural analysis. Methyl 2-chromonecarboxylate showed higher photochemical reactivity than methyl 3-chromonecarboxylate, in which endo adducts were yielded as major products.

The reaction of vinyl ethers with carboxylic acids using iodine as a catalyst under solvent-free conditions was investigated. The reaction of saturated carboxylic acids with vinyl ethers gave the corresponding esters. Mechanistic studies revealed the production of the adduct of the vinyl ether with the carboxylic acid, which then rearranged to form the ester. At low temperatures, the reaction of 2-(1-hydroxycyclohexyl)acetic acid (1) and butyl vinyl ether yielded a butyl ester. However, at a reaction temperature of 80°C, both the esterification and the elimination of a water molecule occurred, yielding the unsaturated butyl ester butyl 2-cyclohexenylacetate. The reaction of 2-((1S,2S,4R)-2-hydroxy-1,7,7- trimethylbicyclo[2.2.1]heptan-2-yl)acetic acid (12) with butyl vinyl ether at low temperatures resulted in a mixture of four compounds. However, similar to the high-temperature (&gt 60°C) reaction of 1, the esterification was accompanied by the elimination of a water molecule to give the unsaturated butyl ester (E)-butyl 2-((1S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)acetate. While a g-hydrogen was abstracted to form the endo-type double bond in the reaction of 1, an α-hydrogen was abstracted to form the exo-type double bond in the reaction of 12. © 2013 by Japan Oil Chemists' Society.

側鎖にメチル基のない4-oxabicyclo[4.4.0]dec-1(2)-ene(１)と、１の側鎖にメチル基を有する4-oxabicyclo[4.4.0]decane(７)のような新規二環性エーテルを合成し、これらの香気特性について検討した。さらに、６員環と７員環または８員環の組み合わせ、さらには、二重結合の有無、また側鎖メチル基の有無などで構造を変化させた１２種類の二環性エーテルを合成し、香気特性と化学構造との関連性について検討した。また、最安定化構造を、分子軌道法から計算して求め、最安定化構造と香気特性の関連性についても検討した。

The reaction of olefins with nitrites using iodine as a catalyst under solvent-free conditions was investigated. The reaction of cycloolefins, such as cyclopentene and cyclohexene, with benzonitrile using iodine as a catalyst produced both amide and heterocyclic compounds. The reaction of chiral (+)-camphene with benzonitrile produced racemic (+/-)-N-isobornylbenzamide (N-((1S,2S,4S)-1,7,7-trimethylbicyclo[2.2.1] hept-2-yl)benzamide). This indicated that skeletal rearrangement of camphene as well as amidation occurred. The optimized conditions were determined to be as follows: temperature, 90 degrees C; molar ratio of nitrile:alcohol:iodine:water, 1:5:0.2:1.0; and reaction time, 18 h. The yield was 87% under these conditions. The reaction of (+)-camphene also proceeded with the other aromatic and aliphatic nitrites to produce racemic isobornylamides. However, except for styrene, complex reactions occurred in the reactions of benzonitrile with other terpenic olefins.

3-hydroxy acids, 3-hydroxy-3,7-dimethyloct-6-enoic acid (1) and 3-hydroxy-2,2,3,7-tetramethyloct-6-enoic acid (2), were prepared from 6-methyl-5-hepten-2-one, and they were subsequently used to prepare (2,6,6-trimethyltetrahydropyran-2-ypacetic acid (3) and 2-methy1-2-(2,6,6-trimethyltetrahydropyran-2-yl)propanoic acid (4), respectively, via cyclization with an acidic catalyst such as boron trifluoride diethyl etherate or iodine. The reaction of carboxylic acids 3 and 4 with alcohols, including methanol, ethanol, and 1-propanol, produced the corresponding methyl, ethyl, and propyl esters, which all contained a tetrahydropyran ring. Reduction of carboxylic acids 3 and 4 afforded the corresponding alcohols. Subsequent reactions of these alcohols with several acyl chlorides produced novel esters. The alcohols also reacted with methyl iodide and sodium hydride to provide novel ethers. A one-pot cyclization esterification of 1 to produce esters containing a tetrahydropyran ring, using iodine as a catalyst, was also investigated.

Chiral dihydrobenzofuran-based diphosphine ligand (BICMAP) 1 was used as a ligand for the rhodium(l)catalyzed asymmetric 1,4-addition of arylboronic acids to cyclic enones up to 99% ee. We also found that the BICMAP-rhodium system was an efficient catalyst for the 1,4-addition of alkenylboronic acids to 2-cyclohexenone in good enantioselectivities. (C) 2012 Elsevier Ltd. All rights reserved.

The reaction of esters with nitriles, using iodine as a catalyst under solvent-free conditions, was investigated. For example, 1-phenylethyl acetate reacted with benzonitrile in the presence of iodine to afford the amide, N-(1-phenylethyl)benzamide. Addition of water was effective in promoting amidation. The most suitable conditions were investigated, and determined as follows: temperature = 80 degrees C, molar ratio of nitrile:alcohol:iodine:water = 1:3:0.2:1.0, and reaction time = 18 h. The amidation reactivity depended on the stability of the cationic intermediate formed from the ester. Only the reaction of 2-phenylpropan-2-yl acetate with benzonitrile gave no amide compound; rather, the cyclic compound, 1,1,3-trimethyl-3-phenyl-2,3-dihydro-1H-indene was obtained in 90% yield. The reaction of (-)-bornyl acetate with benzonitrile produced the racemic amide compound, (+/-)-exo-N-isobornylbenzamide, in 82% yield.

N,N-Diallyl-4-methyl-1-propyl-2-quinolone-3-carboxamide afforded chiral crystals of a P2(1) crystal system by spontaneous crystallization. The molecular chirality in the crystal was retained after the crystals were dissolved in a solvent at a low temperature, and the frozen molecular chirality was effectively transferred to the products by a two-step reaction involving hydrogenation and intermolecular photocycloaddition reactions.

The palladium-catalyzed synthesis of unsymmetrical 1,3-diarylpropenes from allyl esters through a MizorokiHeck-type reaction with aryl iodides followed by allyl cross-coupling with a variety of arylboronic acids was developed; the products are obtained in moderate to good yields by using a hydrazonePd(OAc)2 system.

Palladium-catalyzed Mizoroki-Heck type reaction of olefines with aryl trialkoxysilanes gave the arylation products using a catalytic amount of hydrazone Pd(OAc)(2) system with AgF at 60 degrees C in good yields. (C) 2011 Elsevier Ltd. All rights reserved.

Preferential crystallization is a powerful tool to obtain optically active materials from racemic mixtures without any chiral source, and has been utilized widely for optical resolution on large scales for example in industrial processes.[ 1] To resolve optically active materials by crystallization efficiently, dynamic preferential crystallization involving a racemization process, a so-called total spontaneous resolution, has been developed.[2] Many efforts have been invested in new variations of this method, and the racemization processes can be classified into three groups: 1) involving an intermediate enolate anion or enol at the a-position of a carbonyl group,[3] 2) involving atropisomerism of axially chiral materials,[4] and 3) involving an equilibrium reaction via an achiral intermediate.[5-7] We have now developed a new example of total spontaneous resolution of isoindolinones that involves a combination of an intramolecular equilibrium reaction via an achiral intermediate and preferential crystallization. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

テトラヒドロピラン環を有するカルボン酸(2,6,6-trimethyltetrahydropyran-2-yl)acetic acidおよび2-methyl-(2,6,6-trimethyltetrahydropyran-2-yl)acetic acidから誘導した新規エステル、アルコール、エーテルの香気を検討した。また、分子軌道計算により最安定化構造を求め、香気との関連性についても検討した。

Crystal structures and photochemical reactions of three N,N-diallyl-2-quinolone-3-carboxamides were investigated. One quinolonecarboxamide afforded chiral crystals of a P2(1) crystal system by spontaneous crystallization, and the molecular chirality In the crystal was effectively transferred to cyclobutane in 96% ee by an intramolecular 2 + 2 photocycloaddition reaction in the solid state.

Chiral phosphine-prolineamide 1a was employed as an organocatalyst in direct asymmetric aldol reactions of various aromatic aldehydes with ketones. Cyclohexanone led to the aldol products in up to 98% ee and with good diastereoselectivity using 10 mol % of TFA and 30 mol % of prolineamide 1a in DMF at 0 degrees C. (C) 2011 Elsevier Ltd. All rights reserved.

Acyclic amines 1 were obtained by a nucleophilic aromatic substitution (SNAr) reaction and N-methylation followed by silane reduction. The optical resolution of C(aryl)-N(amine) bond atropisomers of amines 1 is described. We found that chiral acyclic amine la can be resolved by crystallization without any outside chiral source. Finally, we demonstrate the ability of chiral amines 1 as a ligand in a palladium-catalyzed asymmetric allylic alkylation (up to 93 % ee).

The Sonogashira coupling reaction of aryl bromides with a variety of terminal alkynes in DMSO at 125 degrees C gave internal arylated alkynes using low-loaded Pd(acac)(2) with hydrazone as a ligand and CuI as the co-catalyst in good yields.

Palladium-catalyzed cyanation of aryl bromides with potassium hexacyanoferrate(II) trihydrate, K(4)[Fe(CN)6]center dot 3H(2)O as the cyanide source gave benzonitrile derivatives using a catalytic amount of Pd(OCOCF(3))(2) in DMF at 110 degrees C with phosphine-free pyridyl-hydrazone ligand 2c in good yields.

N-(2-methoxy-1-naphthoyl)pyrrolidine afforded chiral crystals by spontaneous crystallization. The molecular chirality in the crystal was retained after dissolving the crystals in a cooled solvent. Kinetic resolution of racemic amines was performed using the provisional chiral molecular conformation derived from chiral crystals.

N-(2-Methoxy-1-naphthoyl)piperidine afforded chiral crystals by spontaneous crystallization, and the molecular chirality of the crystals was retained after dissolving them in a cooled solvent. An asymmetric photocycloaddition reaction with a diene was performed using the provisional chiral molecular conformation derived from these chiral crystals.

The reactions of alcohols with nitriles under solvent-free conditions, using molecular iodine as a catalyst, were investigated. The reaction of 1-phenylethanol with propanenitrile produced the amide N-(1-phenylethyl)propanamide, by dehydration and tautomerization, in 71% yield, under the following conditions: temperature = 90 degrees C, alcohol:iodine molar ratio = 1:0.2, alcohol:nitrile molar ratio = 1:5, and reaction time=5 h. The amidation reactivity depended on the stability of the cationic intermediate formed from the alcohol. The reaction of (-)-borneol with benzonitrile produced a racemic amide in 83% yield.

Reactions of α-vinylbenzyl alcohol with other alcohols using iodine as a catalyst were investigated. The corresponding cinnamyl ethers were obtained as products. This suggested that α-vinylbenzyl alcoholwas converted to cinnamyl ethers via 1-phenylallyl cation. Cinnamyl ethyl ether was obtained in 75% yield by the reaction of α-vinylbenzyl alcohol and ethanol in acetonitrile with iodine under the following conditions: temperature = 50 °C, molar ratio of α-vinylbenzyl alcohol:ethanol:iodine = 1:3.0:0.2, and time period = 6 h. Generally, the yields of the reactions using primary alcohols were higher than those using secondary and tertiary alcohols. Ether interchange also occurred by the reaction of α-vinylbenzyl alcohol and iodine, but proceeded smoothly only when an allyl group was used as the other substituent of the starting ether. © 2010 by Japan Oil Chemists' Society.

Many examples of solid-state photoreactions using chiral crystals composed of achiral materials and leading to optically active products have been successfully demonstrated and recognized as absolute asymmetric synthesis. Recently, we have discovered a new methodology for asymmetric synthesis using the molecular chirality in crystal as a source of homochirality in fluid media. The chirality can be effectively transferred to optically active products by asymmetric reactions involving nucleophilic reactions and an intermolecular photochemical reaction, and which had so far not been achieved in solid state reactions.

The irradiation of chromone-2-carboxylic esters resulted in the stereo- and regioselective formation of C(2) chiral anti-HR dimers from the triplet excited state. On the contrary, photolysis in the solid-state gave anti-HT dimers exclusively controlled by molecular arrangement in the crystal

N-Aryl indole-derived C-N bond axially chiral phosphine ligands 2a-c were obtained by DDQ oxidation of N-aryl indoline-derived phosphine oxide followed by silane reduction. Resolution of C-N bond atropisomers was achieved by chiral HPLC. The investigation of the rotation barrier for the C-N bond axial stability of phosphines and the determination of the absolute configuration of 2c are described. Finally, the ability of the chiral ligand 2c was demonstrated in a palladium-catalyzed asymmetric allylic alkylation (up to 99% ee). (C) 2010 Elsevier Ltd. All rights reserved.

X-Ray crystallographic analysis of N-(1-naphthyl)-2(1H)-pyrimidinethione revealed that the space group was tetragonal and chiral P4(3). The rate of racemization due to the C-N bond rotation was considerably influenced by the solvent properties. A nonpolar solvent lowers the Delta G(double dagger) value by about 3.0 kcal mol(-1) relative to the value in a polar or a protic solvent. The crystallization of racemic axially chiral pyrimidinethione at high temperature led to the chiral breaking of symmetry up to 91% e.

Palladium-catalyzed Mizoroki-Heck reaction of allyl aryl ethers with aryl iodides gave aryl cinnamyl ethers using a catalytic amount of Pd(OAc)(2) in DMF at 50 degrees C with phosphine-free hydrazone as a ligand in good yields. (C) 2009 Elsevier Ltd. All rights reserved.

Copper-catalyzed C-C coupling reaction of aryl iodides with diethylmalonate in toluene at 90 degrees C gave arylated malonates using 5 mol% of Cul with hydrazone 1a as a ligand in good yields under an aerobic atmosphere. We also found Cul/hydrazone 1b in toluene to be an efficient catalytic system for C-O Coupling reactions of aryl bromides with phenols to give aryl ethers ill good yields at 110 degrees C under an aerobic atmosphere.

Intramolecular etherification of 1,3-diols was investigated using iodine as a catalyst under solvent-free conditions. The reaction proceeded to completion in a heterogeneous system. Five-membered cyclic ethers were obtained by intramolecular cyclization of 1,3-diols with dehydration. A propella ether (11-oxatricyclo[4.4.3.0(1,6)] tridecane) was conveniently synthesized from a 1,3-diol (6-(2-hydroxyethyl)spiro[4.5]decan-6-ol) in 86% yield with carbon skeleton rearrangement under the following conditions: a temperature of 60 degrees C, a molar ratio of 1,3-diol:iodine = 1:0.2, and a time period of 3 h. Bicyclic ethers were also obtained from the corresponding 1,3-diols, but spiro, ethers were obtained in lower yield. Terpenic cyclic ethers were efficiently synthesized from the corresponding 1,3-diols, derived from (+)-camphor and (-)-fenchone. In the case of etherification with a mechanism of carbon skeleton rearrangement, the yield of the solvent-free reaction was as high as that of the corresponding reaction in solution. Etherification reactions with carbon skeleton rearrangement proceeded more smoothly than those with hydride shift.

A new atropisomeric dihydrobenzofuran-based bisphosphine ligand I was easily prepared from 1,4-dibromo-2-fluorobenzene. This racemic bisphosphine (+/-)-1 was used as a ligand for the palladium-catalyzed Suzuki-Miyaura reaction of aryl chloride with arylboronic acids and Hartwig-Buchwald amination of aryl bromides with aniline derivatives. The optical resolution of (+/-)-1 was also carried out by HPLC with a chiral stationary phase column. (C) 2009 Elsevier Ltd. All rights reserved.

Zinc-finger-FokI nucleases (ZFNs) are useful for manipulating genomic DNA, but two ZFNs are required to cleave one site of double-stranded DNA (dsDNA), which limits the choice of targets. To refine ZFN technology, we constructed artificial zinc-finger nucleases containing an artificial zinc-finger protein (AZP) and a single-chain FokI dimer with nine different peptide linkers between two FokI molecules (designated AZP-scFokI). DNA cleavage assays revealed that the AZP-scFokI variant possessing the longest peptide linker cleaved dsDNA with equal or greater reactivity than the corresponding AZP-FokI dimer. The DNA cleavage pattern of AZP-scFokI suggests that the enhanced dsDNA cleavage was due to increased formation of FokI dimer in AZP-scFokI. Furthermore, we demonstrated that AZP-scFokI site-specifically cleaved its target DNA due to the AZP moiety discriminating one base pair difference. Thus, a single AZP-scFokI molecule is able to cleave dsDNA efficiently and site-specifically, and enhances the usefulness of the ZFN approach. © 2009 Elsevier B.V. All rights reserved.

Irradiation of the simple chromone (benzo-gamma-pyrone) resulted in the formation of two types of dimers, anti-HT (head-to-tail) and trans-fused HT isomers, whose structures were established by X-ray structural analysis.

Chiral allylic esters, such as (R)-1,3-diphenyl-2-propenyl acetate (R)-2a, were synthesized by kinetic resolution in a palladium-catalyzed asymmetric allylic alkylation using N-aryl indoline type C-N bond axially chiral aminophosphines (S)-1 as ligands. © 2008 Elsevier Ltd. All rights reserved.

Palladium-catalyzed allyl cross-coupling reaction of allylic acetates with a variety of boronic acids at room temperature using a catalytic amount of Pd(OAc)2 with phosphine-free hydrazone as a ligand gave the allylbenzene derivatives in good yields.

Palladium-catalyzed allyl cross-coupling reaction of allylic acetates with a variety of boronic acids at room temperature using a catalytic amount of Pd(OAc)(2) with phosphine-free hydrazone as a ligand gave the allylbenzene derivatives in good yields.

Intramolecular cyclic etherification of 1,3-diols was investigated using iodine as a catalyst under solution reaction conditions. Compounds containing five-membered ether rings were obtained. Propella ether (11-oxatricyclo[4.4.3.0(1.6)]tridecane) was conveniently synthesized from 1,3-diol (6-(2-hidroxyethyl)spiro[4.5]decan-6-ol) in 97% yield via carbon skeleton rearrangement. Spiroethers and bicyclic ethers were also obtained from the corresponding 1,3-diols in yields of over 77%. The most suitable reaction conditions were a temperature of 80 degrees C, a 1:0.2 molar ratio of 1,3-diol:iodine, and a time period of 8 h. In addition, terpenoic ethers were efficiently synthesized from the corresponding 1,3-diols, derived from (+)-camphor and (-)-fenchone, via skeleton rearrangement. In particular, the reaction of the 1,3-diol derived from (+)-camphor proceeded smoothly at room temperature with a yield of 91%. The yield of the cyclic ether using iodine as a catalyst was comparable to the method using sulfuric acid.

Optically active β-lactams were synthesized via photochemical intramolecular γ-hydrogen abstraction reaction of thioimides involving a highly-controlled chiral-memory effect. © The Royal Society of Chemistry.