Showing papers in "Advanced Synthesis & Catalysis in 2011"

Potential of Different Enzyme Immobilization Strategies to Improve Enzyme Performance

Abstract: Enzyme biocatalysis plays a very relevant role in the development of many chemical industries, e.g., energy, food or fine chemistry. To achieve this goal, enzyme immobilization is a usual pre-requisite as a solution to get reusable biocatalysts and thus decrease the price of this relatively expensive compound. However, a proper immobilization technique may permit far more than to get a reusable enzyme; it may be used to improve enzyme performance by improving some enzyme limitations: enzyme purity, stability (including the possibility of enzyme reactivation), activity, specificity, selectivity, or inhibitions. Among the diverse immobilization techniques, the use of pre-existing supports to immobilize enzymes (via covalent or physical coupling) and the immobilization without supports [enzyme crosslinked aggregates (CLEAs) or crystals (CLECs)] are the most used or promising ones. This paper intends to give the advantages and disadvantages of the different existing immobilization strategies to solve the different aforementioned enzyme limitations. Moreover, the use of nanoparticles as immobilization supports is achieving an increasing importance, as the nanoparticles versatility increases and becomes more accessible to the researchers. We will also discuss here some of the advantages and drawbacks of these non porous supports compared to conventional porous supports. Although there are no universal optimal solutions for all cases, we will try to give some advice to select the optimal strategy for each particular enzyme and process, considering the enzyme properties, nature of the process and of the substrate. In some occasions the selection will be compulsory, for example due to the nature of the substrate. In other cases the optimal biocatalyst may depend on the company requirements (e.g., volumetric activity, enzyme stability, etc).

Multi-Enzymatic Cascade Reactions: Overview and Perspectives

Abstract: Multi-enzymatic cascade reactions, i.e., the combination of several enzymatic transformations in concurrent one-pot processes, offer considerable advantages: the demand of time, costs and chemicals for product recovery may be reduced, reversible reactions can be driven to completion and the concentration of harmful or unstable compounds can be kept to a minimum. This review summarizes the developments in multi-enzymatic cascades employed for the asymmetric synthesis of chiral alcohols, amines and amino acids, as well as for CC bond formation. In addition, a general classification of biocatalytic cascade systems is provided and bioprocess engineering aspects associated with the topic are discussed.

The Growing Impact of Catalysis in the Pharmaceutical Industry

Abstract: Catalysis has become increasingly important for the pharmaceutical industry Catalysis is a critical technology that enables economical and environmentally-sound manufacturing processes The development of a viable catalytic process for industrial scales is a complex task that requires the collaboration of multiple disciplines In this article, a number of selected, noteworthy industrial examples are discussed to showcase the catalytic technologies that have been successfully practiced on large scales for active pharmaceutical ingredient (API) synthesis, involving transition metal catalysis, biocatalysis and organocatalysis In addition, several examples of potential and future catalytic transformations are included which can be utilized in pharmaceutical industry in large-scale operational settings

Coupling Chemical Modification and Immobilization to Improve the Catalytic Performance of Enzymes

Abstract: Chemical modification and immobilization of enzymes have been usually considered unrelated tools to improve biocatalyst features. However, there are many examples where a chemically modified enzyme is finally used in an immobilized form, and that exemplifies how both tools may be complementary resulting in a synergism in the final results. In this review we present some of the strategies that may give that result. For example, the chemical modification of soluble enzymes may be used to improve their immobilization (reinforcing adsorption or improving multipoint covalent attachment), or just to improve enzyme stability and facilitate the selection of the immobilization conditions. Chemical modification of previously immobilized enzymes benefits from solid-phase chemistry due to the nature of enzymes (e.g., prevention of inactivation, aggregation, etc.). The use of different targets for chemical modifications with small molecules or multifunctional polymers are also discussed: intramolecular or intersubunit cross-linking, one-point modification, generation of artificial microenvironments, etc.

Catalytic Non-Enzymatic Kinetic Resolution

Abstract: While tremendous advances have been made in asymmetric synthesis, the resolution of racemates is still the most important industrial approach to the synthesis of chiral compounds. The use of enzymes for the kinetic resolution (KR) of racemic substrates to afford enantiopure compounds in high enantioselectivity and good yield has long been a popular strategy in synthesis. However, transition metal-mediated and more recently organocatalyzed KRs have gained popularity within the synthetic community over the last two decades due to the progress made in the development of chiral catalysts for asymmetric reactions. Many catalytic non-enzymatic procedures have been developed providing high enantioselectivity and yield for both products and recovered starting materials. Indeed, the non-enzymatic KR of racemic compounds based on the use of a chiral catalyst is presently an area of great importance in asymmetric organic synthesis. The goal of this review is to provide an update on the principal developments of catalytic non-enzymatic KR covering the literature since 2004. This review is subdivided into seven sections, according to the different types of compounds that have been resolved through catalytic non-enzymatic KR, such as alcohols, epoxides, amines, alkenes, carbonyl derivatives, sulfur compounds and ferrocenes. Abbreviations: Ac: acetyl; acac: acetylacetone; AQN: anthraquinone; Ar: aryl; Atm: atmosphere; BINAM: 1,1′-binaphthalenyl-2,2′-diamine; BINAP: 2,2′-bis(diphenylphosphanyl)-1,1′-binaphthyl; BINEPINE: phenylbinaphthophosphepine; BINOL: 1,1′-bi-2-naphthol; Bmim: 1-butyl-3-methylimidazolium; Bn: benzyl; Boc: tert-butoxycarbonyl; Box: bisoxazoline; BSA: bis(trimethylsilyl)acetamide; Bu: butyl; Bz: benzoyl; c: cyclo; CBS: Corey–Bakshi–Shibata; Cbz: benzyloxycarbonyl; COD: cyclooctadiene; COE: cyclooctene; Cy: cyclohexyl; Dba: (E,E)-dibenzylideneacetone; DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene; DCC: N,N′-dicyclohexylcarbodiimide; de: diastereomeric excess; DEAD: diethyl azodicarboxylate; Dec: decanyl; DHQD: dihydroquinidine; Difluorphos: 5,5′-bis(diphenylphosphino)-2,2,2′,2′-tetrafluoro-4,4′-bi-1,3-benzodioxole; DIPEA: diisopropylethylamine: DKR: dynamic kinetic resolution; DMAP: 4-dimethylaminopyridine; DMSO: dimethyl sulfoxide; DNA: deoxyribonucleic acid; DOSP: N-(dodecylbenzenesulfonyl)prolinate; DTBM: di-tert-butylmethoxy; ee: enantiomeric excess; Et: ethyl; equiv.: equivalent; Fu: furyl; Hex: hexyl; HIV: human immunodeficiency virus; HMDS: hexamethyldisilazide; KR: kinetic resolution; L: ligand; LDA: lithium diisopropylamide; MAO: methylaluminoxane; Me: methyl; Ms: mesyl; MTBE: methyl tert-butyl ether; Naph: naphthyl; nbd: norbornadiene; NBS: N-bromosuccinimide; NIS: N-iodosuccinimide; Pent: pentyl; Ph: phenyl; Piv: pivaloyl; PMB: p-methoxybenzoyl; Pr: propyl Py: pyridyl; r.t.: room temperature; s: selectivity factor; Segphos: 5,5′-bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole; (S,S′,R,R′)-Tangphos: (1S,1S′,2R,2R′)-1,1′-di-tert-butyl-(2,2′)-diphospholane; TBS: tert-butyldimethylsilyl; TBDPS: tert-butyldiphenylsilyl; TCCA: trichloroisocyanuric acid ; TEA: triethylamine; TEMPO: tetramethylpentahydropyridine oxide; THF: tetrahydrofuran; Thio: thiophene; Tf: trifluoromethanesulfonyl; TMS: trimethylsilyl; Tol: tolyl; Ts: 4-toluenesulfonyl (tosyl)

Recent Advances in Palladium-Catalyzed Cascade Cyclizations

Abstract: The importance of palladium-catalyzed cross coupling reactions in contemporary organic synthesis is undisputed and underlined by the Nobel Prize for Chemistry in 2010. In addition to the highly efficient cross coupling reactions for single C-C bond construction, palladium-catalyzed cascade processes involving multiple bond formations have emerged in recent years as valuable tools for the rapid synthesis of complex molecular scaffolds. This review presents an overview of the most relevant developments in this field, with a focus on the generation of diverse poly- and heterocyclic scaffolds. The generally well understood reactivity of palladium has allowed the discovery of many intriguing novel cascade processes, and the creativity of the synthetic community will undoubtedly lead to many more discoveries in the future. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of Isoquinolines via Rhodium(III)-Catalyzed Dehydrative C-C and C-N Coupling between Oximines and Alkynes

Abstract: Isoquinolines have been synthesized from the redox-neutral dehydrative C―N and C—C cross-coupling between oximines and alkynes using a catalytic amount of (pentamethylcyclopentadiene)rhodium dichloride dimer {[RhCp * Cl 2 ] 2 } and cesium acetate (CsOAc), a process that involves ortho C― H activation of oximines and subsequent functionalization with alkynes. This redox-neutral catalytic isoquinoline synthesis operates under mild conditions, and is insensitive to moisture or air. A broad scope of coupling partners has been established, and a likely mechanism has been suggested.

Copper‐Catalyzed Aerobic Oxidation of Amines to Imines under Neat Conditions with Low Catalyst Loading

Abstract: The copper (I)-catalyzed direct synthesis of imines from amines under mild aerobic conditions is described. The method is applicable for the synthesis of various imines from corresponding amines such as benzylic, aliphatic, cyclic secondary, heteroaromatic species and the oxidative condensation of benzylamines with anilines extends the scope of the CuCl catalytic system. Noteworthy, solvent-free procedure, air as a benign oxidant, and the cheap and easy availability of the catalyst are the vital advantages of the method.

N‐Alkylation of Amines with Alcohols Catalyzed by a Water‐Soluble Cp*Iridium Complex: An Efficient Method for the Synthesis of Amines in Aqueous Media

Abstract: An efficient and environmentally benign catalytic system for the synthesis of various organic amines catalyzed by the water-soluble and air-stable (pentamethylcyclopentadienyl)-iridium-ammine iodide complex, [Cp * Ir(NH 3 ) 3 ][I] 2 (Cp * =pentamethyl-cyclopentadienyl), has been developed. A wide variety of secondary and tertiary amines were synthesized by the N-alkylation reactions of theoretical equivalents of amines with alcohols in water under air without a base. The synthesis of cyclic amines was also achieved by the N-alkylation of benzylamine with diols. Furthermore, the recycle use of the present water-soluble Cp * Ir catalyst was accomplished.

Recent Developments in the [5+2] Cycloaddition

Abstract: The rapid generation of molecular complexity in a relatively easy manner has made the [5+2] cycloaddition approach a highly useful tool in the synthesis of a wide number of complex natural products and important biologically active products containing seven-membered rings. Besides the common and highly efficient [5+2] cycloadditions of oxidopyrylium and oxidopyridinium ions with π-systems which offer an easy access to a wide range of novel heterocyclic seven-membered ring molecules with a oxygen or nitrogen bridge, and the less employed [5+2] photocycloadditions, the metal-catalyzed [5+2] cycloadditions have attracted a lot of attention and have become one of the most popular ways of constructing seven-membered ring products. All these cycloadducts can be synthetically manipulated easily toward a number of interesting molecular structures with high potential applications. Abbreviations: Ac: acetyl; Ar: aryl; BarF: tetrakis[3,5-bis(trifluoromethyl)phenyl]borate; BINAP: 2,2′-bis(diphenylphosphanyl)-1,1′-binaphthyl; Bn: benzyl; Boc: tert-butoxycarbonyl; Bu: butyl; Bz: benzoyl; Cbz: benzyloxycarbonyl; cod: cyclooctadiene; Cp: cyclopentadienyl; DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene; DCE: 1,2-dichloroethane; de: diastereomeric excess; DFT: density functional theory; DMF: dimethylformamide; DMSO: dimethyl sulfoxide; dppb: 1,4-bis(diphenylphosphino)butane; dppe: 1,2-bis(diphenylphosphine)ethane; dppp: 1,3-bis(diphenylphosphino)propane; ee: enantiomeric excess; Et: ethyl; HFIP: hexafluoroisopropyl alcohol; L: ligand; M: metal; Me: methyl; MOM: methoxymethyl; Ms: mesyl; Ph: phenyl; PMB: para-methoxybenzoyl; Pr: propyl; Segphos: 5,5′-bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole; TBDPS: tert-butyldiphenylsilyl; TBS: tert-butyldimethylsilyl; TEA: triethylamine; Tf: trifluoromethanesulfonyl; TFE: trifluoroethanol; THP: tetrahydropyran; TIPS: triisopropylsilyl; TMS: trimethylsilyl; Tol: tolyl; Tp: hydridotris(pyrazolyl)borate; Ts: 4-toluenesulfonyl (tosyl); VCP: vinylcyclopropane.

Graphite Oxide as an Auto-Tandem Oxidation–Hydration–Aldol Coupling Catalyst

Abstract: Graphite oxide (GO) was found to function as an auto-tandem oxidation-hydration-aldol coupling catalyst for the formation of chalcones in a single reaction vessel. Various alkynes or alcohols were hydrated or oxidized in situ to their corresponding methyl ketones or aldehydes, respectively, which underwent a subsequent Claisen-Schmidt condensation. Each of the aforementioned reactions proceeded in the absence of metals (confirmed by inductively coupled plasma mass spectrometry, ICP-MS) and afforded a range of chalcone products in good to excellent yields from commercially available starting materials.

N‐Heterocyclic Carbene‐Catalyzed Enantioselective Annulation of Bromoenal and 1,3‐Dicarbonyl Compounds

Abstract: Highly enantioselective [3+3] annulation reactions of bromoenals and 1,3-dicarbonyl compounds are reported. In addition, both enantiomers of the resultant dihydropyranone could be easily obtained by choosing N-heterocyclic carbenes (NHCs) with the same stereocenter but different substituents under the optimized reaction conditions.

Development of a General and Practical Iron Nitrate/TEMPO-Catalyzed Aerobic Oxidation of Alcohols to Aldehydes/Ketones: Catalysis with Table Salt

Abstract: Oxidation of alcohols is a fundamental transformation related to our daily life. Traditional approaches with at least one stoichiometric amount of oxidants are expensive and cause serious environmental burdens. There are many reports on the aerobic oxidation of simple alcohols such as alkyl or phenyl carbinols and allylic alcohols, which used oxygen or air as the environmentally benign oxidant forming water as the only by-product. However, no such protocol has been reported for allenols and propargylic alcohols. Thus, it still highly desirable to develop efficient room temperature oxidations of alcohols with a wide scope including allenols and propargylic alcohols. In this paper, an efficient and clean aerobic oxidation of so far the widest spectrum of alcohols using 1 atm of oxygen or air, producing aldehydes/ketones at room temperature in fairly high isolated yields mostly within a couple of hours is described. It is interesting to observe that the reaction has been efficiently expedited by a catalytic amount of sodium chloride in easily recoverable 1,2-dichloroethane. A mechanism involving NO and NO 2 has been proposed based on the results of the control experiments and GC-MS studies of the in-situ formed gas phase of the reaction mixture.

N-Heterocyclic Carbene-Catalyzed Cyclization of Unsaturated Acyl Chlorides and Ketones

Abstract: A straightforward synthesis of optically active trifluoromethyl dihydropyranones and spirocyclic oxindole-dihydropyranones has been realized by the chiral N-heterocyclic carbenes-catalyzed cyclization of α,β-unsaturated β-methylacyl chlorides with activated trifluoromethyl ketones or isatin derivatives.

Highly Active Metal-Free Catalysts for Hydrogenation of Unsaturated Nitrogen-Containing Compounds

Abstract: New highly active ansa-ammonium borate catalysts for the direct metal-free hydrogenation of imines were prepared by tuning of the basicity and steric bulkiness of their amine moieties. The highest catalytic activity among previously reported organocatalytic systems was shown for a wide range of nitrogen-containing substrates. The first example of asymmetric imine hydrogenation based on the ansa-ammonium borate concept was demonstrated. Furthermore, effective catalyst recovery by extraction of the acidic solution with an organic solvent followed by dehydration with TMSBr was elaborated. The initial findings highlight the development of more effective chiral ansa-ammonium borates for enantioselective hydrogenation. Therefore, the progress achieved in the ansa-ammonium borate concept makes it very promising for further elaboration with the aim to obtain industrially applicable catalysts.

An Easy Entry to Optically Active Spiroindolinones: Chiral Brønsted Acid‐Catalysed Pictet–Spengler Reactions of Isatins

Abstract: The first catalytic asymmetric Pictet-Spengler reaction of isatins is presented. BINOL-derived phosphoric acids were found to be competent catalysts for this transformation, giving challenging spirooxindole structures bearing a quaternary stereocentre with generally good results. The 1,2,3,4-tetrahydro-β-carboline products (spiroindolinones) are the core of some newly discovered anti-malarial agents.

Magnetite (Fe3O4) Nanoparticles‐Catalyzed Sonogashira– Hagihara Reactions in Ethylene Glycol under Ligand‐Free Conditions

Abstract: A novel application of nanoparticles of paramagnetic magnetite (Fe 3 O 4 ) as an efficient catalyst for carbon-carbon bond formation via the Sonogashira-Hagihara reaction under heterogeneous ligand-free conditions in ethylene glycol (EG) is described. By using this catalyst, arylalkynes are produced from the reaction of aryl iodides and activated heteroaryl bromides with alkynes. The results are reproducible using the catalyst, which was prepared from different sources. The catalyst is easily separated by an external magnetic field from the reaction mixture. The separated catalyst can be recycled for several consecutive runs without appreciable loss of its catalytic activity.

Stereoselectivity of Four (R)-Selective Transaminases for the Asymmetric Amination of Ketones

Abstract: Four (R)-ω-transaminases originating from Hyphomonas neptunium (HN-ωTA), Aspergillus terreus (AT-ωTA) and Arthrobacter sp. (ArR-ωTA), as well as an evolved transaminase (ArRmut11-ωTA) were successfully employed for the amination of prochiral ketones leading to optically pure (R)-amines. The first three transaminases displayed perfect stereoselectivity for the amination of all substrates tested (ee >99%). Furthermore, the transaminase AT-ωTA led in most cases to better conversion than ArR-ωTA and HN-ωTA using D-alanine as amine donor. α-Tetralone, which was the only substrate not accepted by HN-ωTA, ArR-ωTA, and AT-ωTA, was successfully transformed with perfect enantioselectivity (ee >99%) into the corresponding optically pure amine employing the variant ArRmut11-ωTA.

Effective Guanidine-Catalyzed Synthesis of Carbonate and Carbamate Derivatives from Propargyl Alcohols in Supercritical Carbon Dioxide

Abstract: The reactions of propargyl alcohols with carbon dioxide in supercritical carbon dioxide or in acetonitrile with gaseous carbon dioxide in the presence of organic bases as catalysts have been examined. Bicyclic guanidines are effective catalysts for the formation of α-methylene cyclic carbonates under mild reaction conditions. Oxoalkyl carbonates, oxoalkyl carbamates or α-methyleneoxazolidinones are obtained in high yields and good selectivities in one-step starting from propargyl alcohols and an external nucleophile (alcohols or amines) using bicyclic guanidines as catalysts in supercritical carbon dioxide. Propargylic diols under the same reaction conditions underwent a rearrangement process instead of carbon dioxide insertion whereas in the presence of an external nucleophile the formation of oxocarbonates, oxocarbamates or cyclic carbamates was achieved in satisfactory yields.

Organocatalyzed Dynamic Kinetic Resolution

Abstract: In the last decade, the first examples of organocatalyzed dynamic kinetic resolution (DKR) processes have been described, considerably expanding the synthetic scope of this powerful process which allows the resolution of racemic compounds with up to 100% yield. Today, a significant number of chiral organocatalysts are available that afford excellent levels of stereocontrol in various reactions evolving through DKR that could only previously be achieved using biocatalysts. The goal of the present review is to cover the works dealing with organocatalytic reactions evolving through DKR. This review is subdivided into four sections, according to the different types of organocatalysts employed in these reactions, such as Cinchona alkaloid catalysts, catalysts derived from amino acids, hydroxy acid catalysts, and miscellaneous organocatalysts. Abbreviations: Ac: acetyl; Ar: aryl; BINOL: 1,1′-bi-2-naphthol; Bn: benzyl; Bu: butyl; c: cyclo; Cbz: benzyloxycarbonyl; CPME: cyclopentyl methyl ether; Cy: cyclohexyl; DABCO: 1,4-diazabicyclo[2.2.2]octane; de: diastereomeric excess; DKR: dynamic kinetic resolution; DMF: dimethylformamide; Dmpe: 1,2-bis(dimethylphosphino)-ethane; DMSO: dimethyl sulfoxide; DYKAT: dynamic kinetic asymmetric transformation; ee: enantiomeric excess; Et: ethyl; Fmoc: 9-fluorenylmethoxycarbonyl; Fu: furyl; Me: methyl; MTBE: methyl tert-butyl ether; Naph: naphthyl; Pent: pentyl; Ph: phenyl; PMP: p-methoxyphenyl; Pr: propyl; TBHP: tert-butyl hydroperoxide; TEA: triethylamine; THF: tetrahydrofuran; Thio: thiophene; TMS: trimethylsilyl; Tol: tolyl.

Grignard‐Type Arylation of Aldehydes via a Rhodium‐Catalyzed CH Activation under Mild Conditions

Abstract: An efficient Grignard-type arylation of aldehydes via aryl C―H activation was achieved under mild conditions catalyzed by rhodium. The reaction provides an easy access to a wide variety of benzyl alcohols and can tolerate various functional groups as well as air and water.

Organocatalytic Enantioselective Michael‐Addition of Malonic Acid Half‐Thioesters to β‐Nitroolefins: From Mimicry of Polyketide Synthases to Scalable Synthesis of γ‐Amino Acids

Abstract: Highly enantioselective biomimetic Michael addition reactions of malonic acid half thioesters (MAHTs) to a variety of nitroolefins, affording the optically active γ-amino acid precursors, were developed by employing the Cinchona-based squaramides (up to >99% ee). Remarkably, this biomimetic process is enantioconvergent, a highly desirable feature of a catalytic asymmetric reaction, whereby E/Z-isomers of the nitroolefins afford the same product enantiomer. The synthetic utility of this organocatalytic protocol was also demonstrated in the formal synthesis of pharmaceutically important γ-amino acids such as baclofen. Moreover, a quantum chemical analysis of the catalyst-substrate complexes is shown to give a detailed and instrumental insight into the origin of the observed catalytic activity.

Iron‐Catalyzed CH Fuctionalization of Indoles

Abstract: An easily available iron catalyst was de- veloped to accomplish the CH functionalization of indoles with a-aryl-a-diazoesters in high yields under mild conditions. The asymmetric CH func- tionalization of indoles was also realized by using iron complexes of chiral spiro bisoxazolines with up to 78% ee.

Iron-Facilitated Iodine-Mediated Electrophilic Annulation of N,N-Dimethyl-2-alkynylanilines with Disulfides or Diselenides

Abstract: An efficient synthesis of N-methyl-3-chalcogeno-indoles has been developed via iodine-mediated electrophilic annulation reactions of 2-alkynylaniline derivatives with disulfides or diselenides In the presence of iodine and iron, a variety of 2-alkynylanilines selectively underwent the electrophilic annulation with numerous disulfides or diselenides leading to the corresponding 3-sulfenylindoles and 3-selenenylindoles in moderate to excellent yields It is noteworthy that iron can promote the reaction

Palladium(II)‐Catalyzed Direct ortho‐C ? H Acylation of Anilides by Oxidative Cross‐Coupling with Aldehydes using tert‐Butyl Hydroperoxide as Oxidant

Abstract: An efficient palladium-catalyzed CH acylation with aldehydes using tert-butyl hydroperoxide (TBHP) transforms various anilides into synthetically useful 2-aminobenzophenone derivatives under mild conditions (40 °C, 3 h). The acylation reaction exhibits excellent regioselectivity and functional group tolerance, and simple aromatic aldehydes, functionalized aliphatic aldehydes and heteroaromatic aldehydes are effective coupling partners. The acylation reaction is probably initiated by a rate-limiting electrophilic CH cyclopalladation (kH/kD=3.6; ρ+=−0.74) to form an arylpalladium complex, followed by acyl radical functionalization.

Chiral Squaramide-Catalyzed Highly Enantioselective Michael Addition of 2-Hydroxy-1,4-naphthoquinones to Nitroalkenes

Abstract: A chiral squaramide-organocatalyzed, highly enantioselective Michael addition of 2-hydroxy-1,4-naphthoquinones to nitroalkenes has been developed. This reaction afforded the chiral naphthoquinones in excellent yields (up to 99%) and excellent enantioselectivity (up to 98% ee) under very low catalyst loading (0.25 mol%). This organocatalytic asymmetric Michael addition provides an efficient alternative route toward the synthesis of chiral functionalized naphthoquinones.

Enzymatic Asymmetric Synthesis of Enantiomerically Pure Aliphatic, Aromatic and Arylaliphatic Amines with (R)-Selective Amine Transaminases

Abstract: Seven (R)-selective amine transaminases (R-ATAs) recently discovered by an in silico-based approach in sequence databases were produced recombinantly in Escherichia coli and subjected to partial purification by ammonium sulfate precipitation. A range of additives and various buffers were investigated to identify best conditions to ensure good storage stability and stable activity during biocatalysis. All enzymes show pH optima between pH 7.5―9. These R-ATAs were then applied in the asymmetric synthesis of twelve aliphatic, aromatic and arylaliphatic (R)-amines starting from the corresponding prochiral ketones using a lactate dehydrogenase/glucose dehydrogenase system to shift the equilibrium. For all ketones, at least one enzyme was found that allows complete conversion to the corresponding chiral amine having excellent optical purities >99% ee. Variations in substrate profiles are also discussed based on the phylogenetic relationships between the seven R-ATAs. Thus, we have identified a versatile toolbox of (R)-amine transaminases showing remarkable properties for application in biocatalysis.

Visible‐Light‐Induced Metal‐Free Allylic Oxidation Utilizing a Coupled Photocatalytic System of g‐C3N4 and N‐Hydroxy Compounds

Abstract: Graphitic carbon nitride (g-C 3 N 4 ) and N-hydroxy compounds can function as a non-metal photocatalytic system to activate O 2 for the selective allylic oxidation under mild conditions, avoiding the employment of any metal derivative or organic oxidizing agents. Interestingly, the novel photocatalytic system affords a remarkably high selectivity towards the formation of aldehydes, especially in the oxidation of toluene. By combining the unique nature of g-C 3 N 4 (surface basicity, semiconductor features, high stability) and the remarkable catalytic oxidation reactivity of nitroxyl radicals, this photocatalytic system opens up a mild and efficent access for C―H bond activation.

Aryl Diazonium versus Iodonium Salts: Preparation, Applications and Mechanisms for the Suzuki–Miyaura Cross-Coupling Reaction

Abstract: This review gives an overview of the use of unusual diazonium and iodonium salts as electrophiles for the Suzuki–Miyaura reaction. The discussion mainly focuses, with a critical view, on catalytic systems developed with these electrophiles. The review also discusses their general properties and preparation as well as mechanistic aspects. A last and brief comparison of diazonium versus iodonium salts, by highlighting advantages and drawbacks of both, gives the reader an understandable resume.

Current Trends in Asymmetric Synthesis with Aldolases

Abstract: The work developed in our research group was supported by the Spanish MICINN (CTQ2009-07359 and CTQ2009- 08328), Generalitat de Catalunya (2009 SGR 00281), and ESF project COST CM0701. X. Garrabou acknowledges the CSIC for the I3P predoctoral scholarship.