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The catalytic reactions of indoles with CO2and phenylsilane afforded indolo[3,2-b]carbazoles, where the fused benzene ring was constructed by forming two C–H bonds and four C–C bonds with two CO2molecules via deoxygenative conversions. Nine-membered cyclophanes made up of three indoles and three CO2molecules were also obtained, where the cyclophane framework was constructed by forming six C–H bonds and six C–C bonds. These multicomponent cascade reactions giving completely different carbocycles were switched simply by choosing the solvent, acetonitrile or ethyl acetate.

Tetrabutylammonium acetate (TBAA) and Cu(OAc)2worked as a binary catalytic system for the solvent-free N-formylation of amines with CO2and PhSiH3. This catalysis making C–H and C–N bonds with CO2was coupled with the C–C bond-forming reactions to achieve the one-pot synthesis of enamines, aldehydes, and nitriles. The X-ray crystal structure of a Cu(OAc)2–TBAA complex was also revealed.

Carbon dioxide (CO2) is not only a greenhouse gas but also a renewable carbon source for organic synthesis. Here we have summarized our studies on the conversions of CO2into value-added chemicals via cooperative catalysis using multifunctional catalysts. For example, bifunctional metalloporphyrin catalysts with quaternary ammonium halides were developed for the selective synthesis of cyclic carbonates or polycarbonates from epoxides and CO2. Bifunctional MgIIand ZnIIporphyrins showed high catalytic activity for the synthesis of cyclic carbonates, while bifunctional AlIIIporphyrins catalyzed the copolymerization of cyclohexene oxide and CO2to give poly(cyclohexene carbonate). The high catalytic activities resulted from the cooperative action of the central metal ion and the quaternary ammonium salts. Chiral catalysts for the kinetic resolution of terminal or internal epoxides with CO2were also developed. In addition, macrocyclic multinuclear metal complex Zn5L3, which was synthesized by the self-assembly of Zn(OAc)2and a BINOL derivative (L), catalyzed the reduction of CO2with phenylsilane to produce various useful synthetic intermediates and organic compounds.Carbon dioxide (CO2) was converted into value-added chemicals via cooperative catalysis with multifunctional catalysts. For example, bifunctional metalloporphyrins catalyzed the selective synthesis of cyclic carbonates or polycarbonates from epoxides and CO2. Macrocyclic multinuclear zinc complexes catalyzed the deoxygenative reduction of CO2with hydrosilanes to produce various useful intermediates and compounds.

Oxidation of dihydroxyhetero[7]helicenes gave dihetero[8]circulenes via the concomitant C–C coupling and dehydrative furan formation. The pristine dihetero[8]circulenes were synthesized in four steps and characterized for the first time. X-ray crystal structures and DFT-optimized structures revealed the distorted saddle-like structures, and the degree of the distortion was found to be correlated with the photophysical properties.

Catalytic CO2reduction with phenylsilane under solvent-free conditions was linked with the one-pot synthesis of 3,4-dihydropyrans from β-dicarbonyl compounds and styrenes. The synthesis includes three processes: (1) bis(silyl)acetal formation from CO2and phenylsilane and a domino reaction of (2) Knoevenagel condensation and (3) inverse-electron-demand oxa-Diels–Alder reaction. The first process was catalyzed by a pentanuclear ZnIIcomplex (0.07 mol %) to generate bis(silyl)acetals, which were hydrolyzed into formaldehyde to be used in the second step.

Light-driven ring-opening carboxylation of epoxides with CO2provided β-hydroxy acids via sequential single electron transfer (SET), followed by reaction with CO2. This reaction condition was applicable to aryl epoxides and oxetanes with (hetero)polycyclic aromatics to give the corresponding β- and γ-hydroxy acids, respectively, with high chemoselectivity.Graphical Abstractβ-Hydroxy acids were successfully synthesized by the light-driven ring-opening carboxylation of epoxides with CO2. Aryl epoxides and oxetanes with (hetero)polycyclic aromatics were converted into the corresponding β- and γ-hydroxy acids, respectively, with high chemoselectivity.

Hexameric and tetrameric porphyrin nanorings, Z6·T6and Z4·T4, were synthesized in 53% and 14% yields, respectively, by the Sonogashira-type self-oligomerization of porphyrin monomer 1using hexadentate template T6and tetrapyridylporphyrin template T4. Template-free nanorings Z6and Z4were also prepared. The femtosecond transient absorption measurements revealed fast excitation energy hopping (EEH) along these nanorings with hopping rates of 2–5 ps. Treatment of Z6with chiral template CT6gave Z6·CT6showing circular dichroism (CD) and circularly polarized luminescence (CPL) in the absorption and fluorescence regions of Z6, respectively, which indicates chirality transfer from CT6to Z6.

A series of pyrenes sandwiched by axially chiral 1,1′-binaphthyls were synthesized. Among them, (R,R)-3possessing 2-hydroxy-3,3′-dimethylbinaphthyls exhibited solvent-dependent inversion of the sign of circularly polarized luminescence (CPL) without a change in emission wavelength. The (−)- and (+)-CPL were detected in nonpolar and polar solvents, respectively, with glumvalues of −0.012 and +0.012. This switching property originates from the inversion of excimer chirality caused by the presence or absence of intermolecular hydrogen bonds in the excited state. The CPL intensity was also changed by variation of the temperature and concentration.

Metal clusters in nature and artificial systems are known to exhibit excellent catalytic activities. Among various coordination systems, macrocyclic multinuclear metal complexes have unique structural features and great potential in organic synthesis. The multiple metal centers in a macrocyclic framework act as specific sites for the binding and activation of substrates, showing high catalytic activity and selectivity as a result of the cooperative effect of the multiple metal centers and robustness originating from macrocyclic skeletons. Most of them are precisely designed and synthesized, while occasionally, nice complexes also emerge from a fortuitous combination of metal ions and ligands. Here we overview the recent achievements of (i) multinuclear metal complexes with a covalently-linked macrocyclic ligand (category A), (ii) multinuclear metal complexes forming a macrocyclic skeleton (category B), and (iii) self-assembled supramolecular coordination complexes (category C). Various organic reactions catalyzed by these coordination systems are summarized here.

A series of axially chiral peri-xanthenoxanthenes (PXXs) were synthesized from 1,1′-bi-2-naphthol without optical resolution. These are the first examples of chiral PXXs. Among them, PXX 5with two naphthalene rings connected via a methylenedioxy bridge and a chiral axis displayed intense fluorescence (FL) and circularly polarized luminescence (CPL) both in solution (ΦFLof 0.72 and |glum| of 1.4 × 10–3) and in the solid state (ΦFLof 0.13 and |glum| of 4.8 × 10–3). The bridged structure of PXX 5adjusts the angle between the vectors of the electric and magnetic transition dipole moments, which is essential for showing intense CPL activity.

A versatile method for converting various fluorescent polycyclic aromatic hydrocarbons into circularly polarized luminescence (CPL) excimer dyes with high glumand ΦFLvalues is reported. This method involves the functionalization of a chiral quaternaphthyl with six fluorophores via ester linkages in the last step of the synthesis. The usefulness of this approach was demonstrated for 1-, 2-, and 4-pyrenyl, 2- and 3-perylenyl, and 2-anthryl dyes. Most of them are the first or rare examples of CPL dyes. In the ground state, the fluorophores are tightly arranged by cumulative steric and electronic effects. In the excited state, the fluorophores form a twist excimer that maintains the ground-state conformations. The local chiral excimer directly affected the CPL properties. The systematic study on the signs of the CPLs allowed us to find a rule called the excimer chirality rule: right- and left-handed excimers exhibit (+)- and (−)-CPL, respectively.

Chiral binaphthyl-strapped Zn(II) porphyrins with triazolium halide units were synthesized as bifunctional catalysts for kinetic resolution of epoxides with CO2. Several catalysts were screened by changing the linker length and nucleophilic counteranions, and the optimized catalyst accelerated the enantioselective reaction at ambient temperature to produce optically active cyclic carbonates and epoxides.

Hemisquaramide tweezers, a new family of H-bond donor organocatalysts, are reported. The catalysts could be synthesized within two steps. Among them, H8-binaphthyl-linked hemisquaramide 7markedly accelerated the synthesis of cyclic carbonates from epoxides and CO2. The reactions proceeded well under mild and solvent-free conditions. Kinetic resolution was also achieved at −20 °C (s= 3.0). The adjustable bite angle and orientation of the two NH groups of the catalysts are important for the high activity.

Chiral macrocyclic receptors 1with multiple hydrogen-bonding sites in the cavity were synthesized and used as NMR chiral solvating agents (CSAs). The Suzuki–Miyaura cross-coupling reaction gave rapid access to a series of variants 1b–pof unsubstituted parent compound 1a. Among them, 1dwith the 4-cyanophenyl group at the 3,3′-positions of the binaphthyl moiety was the most excellent CSA for a benchmark analyte compound, 2-chloropropionic acid (CPA); both of the quartet and doublet signals of CPA were split most completely in CDCl3. Binding constants (Ka) determined in CDCl3by NMR titrations indicated that (R)-1dwas the most enantioselective (Ka(S)/Ka(R) = 5.4). Interestingly, the Kavalue of (R)-1dfor (S)-CPA (5900) was greater than that of (R)-1afor (S)-CPA (3080), which strongly suggests an attractive interaction between the 4-cyanophenyl group of (R)-1dand (S)-CPA. The X-ray crystal structure of 1dindicates that one of the two H atoms meta to the cyano group is directed toward the cavity. DFT calculations suggested that this H atom of the 4-cyanophenyl group of (R)-1dforms a weak hydrogen bond with the Cl atom of (S)-CPA (C–H···Cl–C hydrogen bond).

Calix[4]pyrrole 1, calix[4]arene 2, or porphyrin 3together with tetrabutylammonium iodide (TBAI) catalyzed the conversion of epoxides and CO2into cyclic carbonates. Among them, meso-octamethylcalix[4]pyrrole 1a, which was synthesized easily in one step by the acid-catalyzed condensation of pyrrole with acetone, was found to be a very active and robust organocatalyst. DFT calculations suggested that 1aadopts a 1,3-alternate conformation to stabilize the anionic species generated during the catalysis. In the key transition state of the epoxide ring-opening step, one pyrrolic NH group and the tetrabutylammonium (TBA) cation activate the epoxide by hydrogen bonding while another NH group on the opposite side guides the I−anion, which is located away from the TBA cation, to the backside attack on the epoxide.

Tetrabutylammonium hydroxide (TBAH) and other quaternary ammonium hydroxides catalyzed the cycloaddition of CO2to epoxides under solvent-free conditions to give cyclic carbonates. When TBAH was exposed to CO2, TBAH was converted into tetrabutylammonium bicarbonate (TBABC), which was a catalytically active species. A D-labeled epoxide and an optically active epoxide were used to study the reaction mechanism, which invoked three plausible pathways. Among them, path A seemed to be predominant; the bicarbonate ion of TBABC attacks the less hindered C atom of the epoxide to generate a ring-opened alkoxide intermediate, which adds to CO2to give a carbonate ion, and the subsequent cyclization yields a cyclic carbonate. Density functional theory (DFT) calculations successfully delineated the potential energy profile for each reaction pathway, among which path A was the lowest-energy pathway in accordance with the experimental results. The tetrabutylammonium (TBA) cation carries the positive charges on the H atoms, but not on the central N atom, and the positively charged H atoms close to the central N atom form an anion-binding site capable of stabilizing various anionic transition states and intermediates.

Chemical fixation of carbon dioxide (CO2), which is an inexpensive and renewable carbon source, is becoming more and more important. The development of both new reactions and new catalysts is needed to overcome the kinetic and thermodynamic stability of CO2. Organic and metal catalysts with unique and excellent activity and selectivity have been developed for various chemical conversions of CO2. In this perspective, we provide an overview of the recent progress in this field, classifying it into several categories, where each research is concisely summarized one by one using a single reaction scheme, a representative catalyst structure, and/or a catalytic cycle.

Chiral diporphyrin receptor 1, which has a macrocyclic cavity for the intercalation of aromatic guest molecules, was designed and synthesized from pyrrole in five steps. The binding constants (Ka) revealed the greater affinity of 1for more electron-deficient aromatic guests. The complexation between 1and 1,3,5-trinitrobenzene (G8) (Ka= 1850 M-1) was much stronger than that between porphyrin monomer 3and G8(Ka= 50 M-1). This result strongly suggests that G8was intercalated into the cavity of 1via cooperative double p–p stacking. Interestingly, 1enabled the naked-eye detection of an aromatic explosive G8; a dark-red solution of 1in CHCl3turned into a colloidal suspension upon addition of G8, and the light was scattered. Fluorescence spectroscopy was also useful for the selective detection of G8; fluorescence of 1was quenched by complexation with G8, which was visible with the naked eye. Despite modest binding constants for dinitrobenzene derivatives, 1showed a good ability to discriminate the enantiomers of twelve chiral compounds bearing a dinitrophenyl group by NMR spectroscopy. The MM calculations with the MM3 force field reproduced inclusion complexes between 1and nitroaromatic compounds. The mechanism of chiral discrimination is proposed.

Chemical modifications of the I287C mutant of a Burkholderia cepacialipase afforded various I287C-X conjugates, among which I287C-PAA bearing an N-phenylacetamide (PAA) moiety showed excellent enantioselectivity and catalytic activity for secondary alcohols. Site-directed chemical modifications are powerful tools to control enantioselective biocatalysis.

Methyl Rochloromandelate R1, which is an intermediate for a platelet aggregation inhibitor named clopidogrel, was obtained in >99% eeby the asymmetric reduction of methyl ochlorobenzoylformate 2 with recombinant Escherichia colioverproducing a versatile carbonyl reductase. A remarkable temperature effect on productivity was observed in the wholecell reduction of 2, and the optimum productivity as high as 178gL was attained at 20 °C on a 2g scale 1.0 M. The optimized reaction could be scaled up easily to transform 20g of 2in 100mL of buffer. Three synthetic methods for 2are compared.

A molecular tweezer having two bidentate pentafluorophenyl (C6F5) groups was synthesized, and the π–π stacking ability of the C6F5groups toward benzene derivatives in a polar organic solvent was evaluated. The structure of the molecular tweezer was revealed to be dimeric in the crystalline state by X-ray analysis. Association constants (Ka) between the molecular tweezer and aromatic guests in THF were found to be roughly correlated with the quadrupole moment (Qzz) of the guests, suggesting that the quadrupole–quadrupole contribution plays a significant role in the π–π interaction even in a polar organic solvent.

Lipases are biocatalysts most widely used in organic synthesis. Unusual but attractive feature of lipases is that, in addition to high catalytic activity and thermostability in organic solvents, lipases show high enantioselectivity and broad substrate specificity simultaneously. They show excellent enantioselectivity especially toward a wide range of secondary alcohols. The mechanistic details of stereoselective organic reactions are relatively well understood, and knowledge has been used to develop new chemical reagents. In contrast, biocatalysts are behind chemical reagents in rational design approaches, which is partly due to the mechanistic ambiguity of enzymatic reactions. The mechanistic aspects of enantioselective biocatalysts are nevertheless becoming clear. This review provides an overview of the studies aimed at understanding the mechanisms of enantioselectivity of synthetically useful hydrolases such as lipases, subtilisins and chymotrypsins toward unnatural chiral substrates. Several methods for addressing the mechanism are introduced: (i) substrate mapping, (ii) X-ray crystallographic analysis, (iii) computational calculations, (iv) kinetic analysis, (v) thermodynamic analysis, (vi) site-directed or random mutagenesis, (vii) spectroscopic methods such as fluorescence, ESR, and mass spectroscopy. Different models and mechanisms proposed so far are selected and explained. The chemical principles revealed by the mechanistic studies will be useful for (i) using the enzymes in organic synthesis efficiently, (ii) altering the features of the enzymes rationally, (iii) utilizing them as a tool for determining the absolute stereochemistry of molecules, and (iv) designing new artificial catalysts mimicking the catalytic machinery of the enzymes.

1,2-Bis(pentafluorophenyl)ethane-1,2-diamine (1) was synthesized by the imino pinacol coupling of 4-methoxy-N-(pentafluorobenzylidene)benzylamine using a Zn–Cu couple and p-TsOH·H2O. The optical resolution of (±)-1by means of chiral HPLC gave enantiomerically pure (R,R)- and (S,S)-1. The pKavalue of 1was estimated by a titration experiment and ab initio calculations, showing that 1has a basicity comparable to aniline derivatives.

For the enhancement of enantioselectivity and acceleration of the reaction rate in the lipase-catalyzed resolution of primary alcohols, the use of a very low reaction temperature (−30 °C) and an immobilized lipase on organic bridges-coated porous ceramic support was found to be highly effective. Furthermore, the structure of the organic bridges greatly influenced the temperature effect between ln Eand 1/Tas well as the reaction rate. Among the organic bridges examined in the resolution of (±)-2-hydroxymethyl-1,4-benzodioxane, the 6-(2-methylpropanoyloxy)hexylsilanetrioxyl bridge was the best choice for both the Evalue and the reaction rate at −30 °C.

In the subtilisin-catalyzed transesterifications of a variety of secondary alcohols, the ( S)-enantiomers were acylated faster. Kinetic measurements indicated that the enantioselectivity originates from chiral discrimination in the transition state. A transition-state model capable of explaining the S-preference of subtilisin toward secondary alcohols has been proposed.

Low-temperature method (−40 °C at best) for enhancement of the enantioselectivity in a lipase-catalyzed transesterification was proved to be widely applicable to primary and secondary alcohols and enabled theoretical prediction of the course of enhancement of the enantioselectivity physicochemically.

Efficient kinetic resolution of racemic 3-hydroxy-3-(pentafluorophenyl)- propionitrile (±)- 1by a lipase-catalyzed transesterification gave optically pure ( S)-3-hydroxy-3-(pentafluorophenyl)-propionitrile (S)- 1and (R)-(+)-3- acetoxy-3-(penta-fluorophenyl)propionitrile(R)- 1[>99% ee, respectively, E= 1057], the former of which was further transformed into ( S)-(−)-3-amino-1-(pentafluorophenyl)-1-propanol (S)- 7in four steps.

Bakers' yeast reduction of 1-chloro-2,4-alkanediones 1aafforded 1-chloro-2-hydroxy-4-alkanones 2aregioselectively with low optical purities. Application of inhibitors and heat-treatment of bakers' yeast enhanced the optical purities toward the Senantiomer (88–91% ee). Organic solvents added in small amounts were also found to enhance the Sselectivity significantly. High optical purities of 94–96% ee were achieved by the combined action of the inhibitor, heat-treatment, and organic solvent. © 1997 Elsevier Science Ltd.

Large secondary alcohols, 5-[4-(1-hydroxyethyl)phenyl]-10,15,20-triphenylporphyrin ( 1a) and the zinc complex 1b, designed on the basis of the transition-state model recently proposed by us, were subjected to the lipase-catalyzed transesterifications. The alcohols were resolved using lipases from Pseudomonas cepacia(lipase PS), Candida antarctica(CHIRAZYME L-2), Rhizomucor miehei(CHIRAZYME L-9), and Pseudomonas aeruginosa(lipase LIP) with high enantioselectivities ( E> 100).

The lipase-catalyzed kinetic resolution of (±)-2-acyloxy-2-(pentafluorophenyl)acetonitrile (±)- 1gave optically active cyanohydrin (S)- 2and its antipodal ester (R)- 1( E= 211), the former of which was transformed (TBSOTf, DMAP) into its TBS-ether (S)- 3, a new fluorinated chiral building block, and into naproxen ester 4for X-ray analysis to determine the absolute configuration.

The stereoelectronic considerations and the molecular modeling using an X-ray structure of Rhizomucor mieheilipase suggested that the lipase-catalyzed reactions proceed under the stereoelectronic control. This suggestion was supported by the semiempirical MO (MNDO-PM3) calculations carried out on the imidazole-catalyzed transesterification as a model reaction. The stereoelectronic effect operates at the transition state (TS) more effectively than at the tetrahedral intermediate (THI). The stabilization energy due to the stereoelectronic effect operating at the TS was estimated to be ca. 5 kcal mol−1. The enantioselectivities for 1-phenylethanol, 1-phenyl-2-propanol, and 1-cyclohexylethanol were estimated in terms of the lipase-induced strain caused at the TS. A TS model generally applicable to chiral secondary alcohols is proposed. The kinetic study supported the TS model. The result that the enantioselectivity in the lipase-catalyzed transesterifications arises from the difference in Vmaxbetween the two enantiomers rather than from the difference in Kmindicates that the ability of lipases to discriminate between the enantiomers at the TS is high, while the ability to recognize the chirality in the binding step is poor. Furthermore, the difference in Vmaxbetween the enantiomers was found to result not from the enhanced reactivity of the (R)-enantiomers but from the reduced reactivity of the (S)-enantiomers.

Bifunctional macrocycle 1with C2symmetry was newly synthesized. NMR studies demonstrated that receptor 1functions as a chiral shift reagent (solvating agent) that is highly effective for a wide range of chiral compounds having a carboxylic acid, oxazolidinone, lactone, alcohol, sulfoxide, sulfoximine, isocyanate, or epoxide functionality. Binding constants were determined to investigate the binding behavior of 1.

A synthetically useful primary alcohol, 3-phenyl-2H-azirine-2-methanol, was resolved efficiently by a reaction at −40 °C with a lipase immobilized on the porous ceramic (Toyonite) and vinyl butanoate in ether (Evalue of 130 and TTN/h value of 7800).

Bulky alcohol, 5-[4-(1-hydroxyethyl)phenyl]-10,15,20-tris(pentafluorophenyl)porphyrin (1b), was synthesized, and enantiomerically pure alcohol 1band ester 2bwere obtained by a single kinetic resolution catalyzed by Candida antarcticalipase in i-Pr2O and in [bdmim][PF6].

The enantioselectivity of a Burkholderia cepacialipase toward secondary alcohols could be both increased and decreased rationally by introducing only a single mutation on the basis of the mechanism proposed previously.

Thermodynamic parameters for subtilisin-catalyzed kinetic resolutions of secondary alcohols were determined, and a compensation effect between ΔΔH‡and ΔΔS‡was found. These data are explained in terms of the transition-state model.

Insertion of zinc to a cationic porphyrin in water was accelerated by the addition of catechols and related compounds 2-5, while decelerated by the addition of pyridine derivatives 6-7. Complexes between zinc and 2-7with different stoichiometric ratios showed different activity toward the zinc insertion reaction. The reaction becomes slower as the ionic strength is higher in the presence of tiron, indicating that electrostatic force plays an important role in the catalysis.

An asymmetric reduction of ethyl pyruvate was carried out using bakers’ yeast cell free extract with addition of NADPH in catalytic amounts and glucose as a hydride source. The total turnover number of NADPH reached 7680. The efficiency of the cell free extract is discussed.

Optically active dimeric porphyrin covalently linked by a chiral cyclophane was synthesized; the two porphyrin chromophores were disposed in a slipped cofacial fashion, which was found to be tunable by cooperative coordination of diamines with various chain lengths.

The catalyst can be easily recovered and reused at least 5 times with only slight decay of activity.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

For Abstract see ChemInform Abstract in Full Text.

For Abstract see ChemInform Abstract in Full Text.

For Abstract see ChemInform Abstract in Full Text.