Pathway from N‐Alkylglycine to Alkylisonitrile Catalyzed by Iron(II) and 2‐Oxoglutarate‐Dependent Oxygenases

N‐alkylisonitrile, a precursor to isonitrile‐containing lipopeptides, is biosynthesized by decarboxylation‐assisted ‐N≡C group (isonitrile) formation by using N‐alkylglycine as the substrate. This reaction is catalyzed by iron(II) and 2‐oxoglutarate (Fe/2OG) dependent enzymes. Distinct from typical oxygenation or halogenation reactions catalyzed by this class of enzymes, installation of the isonitrile group represents a novel reaction type for Fe/2OG enzymes that involves a four‐electron oxidative process. Reported here is a plausible mechanism of three Fe/2OG enzymes, Sav607, ScoE and SfaA, which catalyze isonitrile formation. The X‐ray structures of iron‐loaded ScoE in complex with its substrate and the intermediate, along with biochemical and biophysical data reveal that ‐N≡C bond formation involves two cycles of Fe/2OG enzyme catalysis. The reaction starts with an Fe^IV‐oxo‐catalyzed hydroxylation. It is likely followed by decarboxylation‐assisted desaturation to complete isonitrile installation.     

Self-catalyzed keto-enol tautomerization of malonic acid

We demonstrate through quantum chemical calculations that the keto-enol tautomerization of malonic acid can be catalyzed by the two tautomers of malonic acid itself. This self-catalyzed process proceeds with a relatively low barrier (Gibbs energy ca. 13 kcal/mol in gas phase, 20 kcal/mol in aqueous phase), and involves the concerted transfer of two protons between the substrate and the carboxylic acid functionality of the malonic acid catalyst. This mechanism is expected to compete with the proton relay mechanism currently favored to explain the tautomerization of malonic acid in aqueous media. Malonic acid is an important constituent of secondary organic aerosol where the present chemistry may play a role in determining chemical composition.     

Metal and organo-catalysed asymmetric hydroaminomethylation of styrenes

A new protocol that enables asymmetric hydroaminomethylation of styrenes to afford chiral amines has been developed. Catalysed by an Rh-phosphine species and a chiral phosphoric acid, styrenes are converted into β-chiral amines with good enantioselectivities under syngas in the presence of an amine and Hantzsch ester. The reaction involves two key steps, hydroformylation and reductive amination, with the former catalysed by the Rh species whilst the latter by the phosphoric acid.     

Transient Directing Groups in Metal−Organic Cooperative Catalysis

The direct functionalization of C−H bonds is among the most fundamental chemical transformations in organic synthesis. However, when the innate reactivity of the substrate cannot be utilized for the functionalization of a given single C−H bond, this selective C−H bond functionalization mostly relies on the use of directing groups that allow bringing the catalyst in close proximity to the C−H bond to be activated and these directing groups need to be installed before and cleaved after the transformation, which involves two additional undesired synthetic operations. These additional steps dramatically reduce the overall impact and the attractiveness of C−H bond functionalization techniques since classical approaches based on substrate pre-functionalization are sometimes still more straightforward and appealing. During the past decade, a different approach involving both the in situ installation and removal of the directing group, which can then often be used in a catalytic manner, has emerged: the transient directing group strategy. In addition to its innovative character, this strategy has brought C−H bond functionalization to an unprecedented level of usefulness and has enabled the development of remarkably efficient processes for the direct and selective introduction of functional groups onto both aromatic and aliphatic substrates. The processes unlocked by the development of these transient directing groups will be comprehensively overviewed in this review article.     

Catalytic asymmetric aziridination with borate catalysts derived from VANOL and VAPOL ligands: scope and mechanistic studies

An extended study of the scope and mechanism of the catalytic asymmetric aziridination of imines with ethyl diazoacetate mediated by catalysts prepared from the VANOL and VAPOL ligands and triphenylborate is described. Nonlinear studies with scalemic VANOL and VAPOL reveal an essentially linear relationship between the optical purity of the ligand and the product suggesting that the catalyst incorporates a single molecule of the ligand. Two species are present in the catalyst prepared from B(OPh)(3) and either VANOL or VAPOL as revealed by (1)H NMR studies. Mass spectral analysis of the catalyst mixture suggests that one of the species involves one ligand molecule and one boron atom (B1) and the other involves one ligand and two boron atoms (B2). The latter can be formulated as either a linear or cyclic pyroborate and the (11)B NMR spectrum is most consistent with the linear pyroborate structure. Several new protocols for catalyst preparation are developed which allow for the generation of mixtures of the B1 and B2 catalysts in ratios that range from 10:1 to 1:20. Studies with catalysts enriched in the B1 and B2 species reveal that the B2 catalyst is the active catalyst in the VAPOL catalyzed asymmetric aziridination reaction giving significantly higher asymmetric inductions and rates than the B1 catalyst. The difference is not as pronounced in the VANOL series. A series of 12 different imines were surveyed with the optimal catalyst preparation procedure with the finding that the asymmetric inductions are in the low to mid 90s for aromatic imines and in the mid 80s to low 90s for aliphatic imines for both VANOL and VAPOL catalysts. Nonetheless, the crystallinity of the N-benzhydryl aziridines is such that nearly all of the 12 aziridine products screened can be brought to >99 % ee with a single recrystallization.     

Asymmetric Triple Relay Catalysis: Enantioselective Synthesis of Spirocyclic Indolines through a One‐Pot Process Featuring an Asymmetric 6π Electrocyclization

A rare example of a one‐pot process that involves asymmetric triple relay catalysis is reported. The key step is an asymmetric [1,5] electrocyclic reaction of functionalized ketimines. The substrates for this process were obtained in situ in a two‐step process that involved the hydrogenation of nitroarenes with a Pd/C catalyst to yield aryl amines and their subsequent coupling with isatin derivatives in a Brønsted acid catalyzed ketimine formation reaction. The electrocyclization was catalyzed by a bifunctional chiral Brønsted base/hydrogen bond donor catalyst. The one‐pot process gave the desired products in good yields and with excellent enantioselectivity.     

Production of Diethyl Terephthalate from Biomass‐Derived Muconic Acid

We report a cascade synthetic route to directly obtain diethyl terephthalate, a replacement for terephthalic acid, from biomass‐derived muconic acid, ethanol, and ethylene. The process involves two steps: First, a substituted cyclohexene system is built through esterification and Diels–Alder reaction; then, a dehydrogenation reaction provides diethyl terephthalate. The key esterification reaction leads to improved solubility and modulates the electronic properties of muconic acid, thus promoting the Diels–Alder reaction with ethylene. With silicotungstic acid as the catalyst, nearly 100 % conversion of muconic acid was achieved, and the cycloadducts were formed with more than 99.0 % selectivity. The palladium‐catalyzed dehydrogenation reaction preferentially occurs under neutral or mildly basic conditions. The total yield of diethyl terephthalate reached 80.6 % based on the amount of muconic acid used in the two‐step synthetic process.     

Efficient and Convenient Synthesis of Diethers from Furoin Under Ultrasound and Solid-liquid Phase Transfer Catalysis Conditions

Introduction Compounds having an active hydroxy group, such as, acyloins can be easily alkylated by alkyl halides in the presence of a phase transfer catalyst (PTC). The reaction is usually carried out in the presence of concentrated aqueous sodium or potassium hydroxide and a phase transfer catalyst, such as, quaternary ammonium salts[1-3], which facilitate the interphase transfer of species, making reactions between reagents in two immiscible phases possible. The reaction involves a series of equilibrium and mass-transfer steps.     

The mechanism of ring-opening polymerization of L-lactide by ICl3 catalysts: Halogen bond catalysis or participating in reactions?

The mechanism of ring-opening polymerization of L-lactide by iodine trichloride (ICl₃) catalyst has been explored by using density functional theory (DFT) calculations and three catalytic pathways were proposed. The first and second pathways belong to the halogen bond catalysis, and the third pathway involves the ICl₃ catalysts participating in reactions. When the carbonyl group was maintained involved in the reaction and activated catalytically by the halogen bond, there are two possible pathways. The first pathway involves only one transition state, and the second pathway requires two transition states. There is another pathway in which ICl₃ directly participates in the reaction, it is named the third pathway. Two different transition states of the four-membered rings are generated successively, the transfer of I─O bonds determined the progress of the reaction. Theoretical calculations in this work provide the most basic understanding of ring-opening polymerization of L-lactide by ICl₃ catalysts. © 2019 Wiley Periodicals, Inc.     

Mechanism of nucleophilic fluorination promoted by bis‐tert‐alcohol‐functionalized crown‐6‐calix[4]arene

Theoretical calculations were performed to elucidate the ability of the recently reported bis‐tert‐alcohol‐functionalized crown‐6‐calix[4]arene (BACCA) molecule to promote nucleophilic fluorination of alkyl mesylates with cesium fluoride reagent. It was found that a similar structure, named BACCAt, can separate the cesium fluoride ion pair in tert‐butanol solution. This separation has a free energy cost, even considering the double hydrogen bonds with the fluoride ion. The solvent has an important effect on the stabilization of this complex, due to interaction with the high dipole moment of the separated ion pair. The observed rate acceleration effect involves a structure with double hydrogen bonds between the BACCAt and the centers of negative charges of the S_N2 transition state. The predicted free energy barrier of 27.3 kcal mol⁻¹ is in excellent agreement with the estimated experimental value of 26.2 kcal mol⁻¹.     

Control over Electrochemical Water Oxidation Catalysis by Preorganization of Molecular Ruthenium Catalysts in Self‐Assembled Nanospheres

Oxygen formation through water oxidation catalysis is a key reaction in the context of fuel generation from renewable energies. The number of homogeneous catalysts that catalyze water oxidation at high rate with low overpotential is limited. Ruthenium complexes can be particularly active, especially if they facilitate a dinuclear pathway for oxygen bond formation step. A supramolecular encapsulation strategy is reported that involves preorganization of dilute solutions (10^?5 m ) of ruthenium complexes to yield high local catalyst concentrations (up to 0.54 m ). The preorganization strategy enhances the water oxidation rate by two‐orders of magnitude to 125 s^?1, as it facilitates the diffusion‐controlled rate‐limiting dinuclear coupling step. Moreover, it modulates reaction rates, enabling comprehensive elucidation of electrocatalytic reaction mechanisms.     

Highly Enantioselective Bromocyclization of Allylic Amides with a P/P=O Double‐Site Lewis Base Catalyst

The enantioselective bromocyclization of allylic amides catalyzed by phosphorus‐containing Lewis bases was examined in detail. A series of control experiments and NMR studies showed that a partially oxidized bis‐phosphine generated in situ serves as the actual enantioselective catalyst. The reaction mechanism involves distinct roles of two Lewis basic sites, P and P=O, with P⁺Br serving as a fine‐tuning element for substrate fixation in the chiral environment, and P⁺OBr as the Br⁺ transfer agent to the olefin. Catalyst loading could be reduced to as little as 1 mol %, and the reaction affords enantioenriched oxazolines with up to >99.5 % ee.     

Gold‐Catalyzed [2+2+1] Cycloaddition of 1,6‐Diyne Carbonates and Esters with Aldehydes to 4‐(Cyclohexa‐1,3‐dienyl)‐1,3‐dioxolanes

A synthetic method to stereoselectively prepare 4‐(cyclohexa‐1,3‐dienyl)‐1,3‐dioxolanes in good to excellent yields by gold(I)‐catalyzed [2+2+1] cycloaddition of 1,6‐diyne carbonates and esters with aldehydes is described. The cascade process involves 1,2‐acyloxy migration followed by cyclopropenation and cycloreversion. This leads to an unprecedented [2+2+1] cycloaddition of the resulting alkenylgold carbenoid species, examples of which are extremely rare, with two aldehyde molecules at catalyst loadings as low as 1 mol %. The usefulness of this cycloisomerization chemistry was further demonstrated by the transformation of one example to the corresponding phenol.     

Brønsted Acid versus Phase-Transfer Catalysis in the Enantioselective Transannular Aminohalogenation of Enesultams

We have studied the enantioselective transannular aminohalogenation reaction of unsaturated medium-sized cyclic benzosulfonamides by using both chiral Brønsted acid and phase-transfer catalysis. Under optimized conditions, a variety of bicyclic adducts can be obtained with good yields and high enantioselectivities. The mechanism of the reaction was also studied by using computational tools; we observed that the reaction involves the participation of a conformer of the nine-membered cyclic substrate with planar chirality in which the stereochemical outcome is controlled by the relative reactivity of the two pseudorotational enantiomers when interacting with the chiral catalyst.     

Synergistic Catalysis: Enantioselective Addition of Alkylbenzoxazoles to Enals

A novel catalytic enantioselective methodology based on synergistic catalysis is reported. The strategy involves: 1) the metal‐Lewis‐acid activation of alkylazaarenes, and 2) the secondary‐amine activation of enals. Consequently, highly functionalized chiral alkylazaarenes were obtained in good yields and with reasonable stereoselectivity.     

Calcium‐Catalyzed Formal [2+2+2] Cycloaddition

A formal intermolecular [2+2+2] cycloaddition reaction of enynes to aldehydes is presented, which can be realized in the presence of a simple and benign calcium catalyst. The reaction proceeds with excellent chemo, regio‐ and diastereoselectivity and leads to a one‐step assembly of highly interesting bicyclic building blocks containing up to three stereocenters from simple precursors via a new type of skeletal rearrangement of enynes. The observed diastereoselectivity is accounted for by two different mechanistic proposals. The first one engages mechanistic prospects arising from a gold catalyzed reaction in the absence of the stabilizing gold substituent. The second proposal involves an unprecedented cyclization–carbonyl allene ene reaction–hydroalkoxylation cascade.     

Efficient Reduction of Esters to Aldehydes through Iridium-Catalyzed Hydrosilylation

Trumping DIBALH: A new method for reduction of esters to aldehydes through silyl acetal intermediates involves a single-step hydrosilylation catalyzed by a readily available iridium complex, [{Ir(coe)(2) Cl}(2) ] (see scheme; coe=cyclooctene). The low catalyst loading, mild reaction conditions, high conversions, and broad substrate scope make this method a superior alternative to ester reduction using DIBALH.     

Water-insoluble Ag-U-organic assemblies with photocatalytic activity

Two metal-organic coordination polymers [Ag(bipy)(UO(2))(bdc)(1.5)] (bipy=2,2'-bipyridyl, bdc=1,4-benzenedicarboxylate) and [Ag(2)(phen)(2)UO(2)(btec)] (phen=1,10-phenanthroline, btec=1,2,4,5-benzenetetracarboxylate) were obtained by hydrothermal assembly of the d(10) metal silver and the 5f metal uranium with mixed ligands. Both compounds form two-dimensional networks with pi-pi overlap interactions between the aromatic fragments in the neighboring layers. In aqueous suspension the two water-insoluble materials show photocatalytic degradation performance superior to that of commercial TiO(2) (Degussa P-25) when tested on nonbiodegradable rhodamine B (RhB) as model pollutant. The relationship between the structure of the photocatalysts and the photocatalytic activity was also elucidated. On the basis of the monitored intermediate species and the final mineralized products, it is proposed that the possible reaction mechanism for the photodegradation (oxidation) of RhB in aqueous solution catalyzed by the two assembly compounds involves photoexcitation of uranyl centers and molecular oxygen.     

Chiral model complexes for methane monooxygenase and their asymmetric catalysis of styrene epoxidation

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Enzymatic Ring-Opening Polymerization of Lactones by Lipase Catalyst: Mechanistic Aspects

Mechanistic aspects of lipase-catalyzed ring-opening polymerization (ROP) of lactones to give polyesters are discussed from accumulated experimental data and new insight. Comparison of the ROP reactivity by lipase catalyst with the anionic ROP reactivity by a metal-catalyst clearly demonstrates the characteristics of lipase catalysis; the larger ring-sized monomers with lower ring strain showed higher polymerizability than medium ring-sized ones, in contrast to the anionic ROP showing the reverse direction where the ring strain of monomer is operative. The enzyme-catalysis involves an acyl-enzyme intermediate formation as a key-step. From the copolymerization results a new mechanism is proposed, that involves the formation of the acyl-enzyme intermediate (acylation step) and/or the nucleophilic attack of the propagationg alcohol end to the carbonyl carbon of the intermediate to open the monomer ring (deacylation step) as the rate-determining step. The structure of the propagating alcohol end (primary or secondary) affects much on which step is more operative.