Paired Electrosynthesis at Interdigitated Microband Electrodes: Exploring Diffusion and Reaction Zones in the Absence of a Supporting Electrolyte.

Electrosynthesis traditionally requires dedicated reactor systems and an added electrolyte, although some paired electrosynthesis processes are possible at interdigitated microband electrodes simply immersed in solution and without an intentionally added electrolyte. Here, 1,1'-ferrocenedimethanol oxidation and activated olefin electro-hydrogenation reactions are investigated as model processes at a Pt-Pt interdigitated microband array electrode with 5 µm width and with 5 µm interelectrode gap. Voltammetric responses for electro-hydrogenation are discussed, and product yields are determined in methanol (MeOH) in the presence/absence of an added electrolyte (LiClO4). An isotope effect is observed in CH3OD solvent, leading to olefin monodeuteration linked to a fast EC-type process close to the cathode surface (in the cathode reaction zone) rather than to charge annihilation in the interelectrode zone. A finite element simulation is employed to visualize/discuss reaction zones and to contrast the rate of charge annihilation processes with/without a supporting electrolyte.

Correction: Structural and Functional Analysis of the Symmetrical Type I Restriction Endonuclease R.EcoR124INT.

[This corrects the article DOI: 10.1371/journal.pone.0035263.].

Synthesis of mono-nitroxides and of bis-nitroxides with varying electronic through-bond communication.

Nitroxides are a unique class of persistent radicals finding a wide range of applications, from spin probes to polarizing agents, and recently bis-nitroxides have been used as proof-of-concept molecules for quantum information processing. Here we present the syntheses of pyrroline-based nitroxide (NO) radicals and give a comparision of two possible synthetic routes to form two key intermediates, namely 2,2,5,5-tetramethylpyrroline-1-oxyl-3-acetylene (TPA) and 1-oxyl-2,2,5,5-tetramethylpyrroline-3-carboxylic acid (TPC). TPC and TPA were then used as precursors for the synthesis of three model compounds featuring two distant NO groups with a variable degree of conjugation and thus electronic communication between them. Using relatively facile synthetic routes, we produced a number of mono- and bis-nitroxides with the structures of multiple compounds unambiguously characterized by X-ray crystallography, while Continuous Wave Electron Paramagnetic Resonance (CW-EPR) allowed us to quantify the electronic communication in the bis-nitroxides. Our study expands the repertoire of mono- and bis-nitroxides with possibilities of exploiting them for studying quantum coherence effects and as polarizing agents.

Brønsted acid-catalysed desilylative heterocyclisation to form substituted furans.

Heterocyclisation of tert-butyldimethylsilyl (TBS) protected γ-hydroxy-α,ß-unsaturated ketones catalysed by para-toluenesulfonic acid (p-TSA) to form substituted furans is reported. The reaction proceeds under mild conditions at room temperature in methanol to give a range of furan products (21 examples, up to 98% yield). Mechanistic experiments suggest the reaction proceeds via in situ deprotection followed by catalytic dehydrative heterocyclisation.

Arylboronic Acid-Catalyzed Racemization of Secondary and Tertiary Alcohols.

The use of 2-carboxyphenylboronic acid (5 mol %) and oxalic acid (10 mol %) with 2-butanone as a solvent for the racemization of a range of enantiomerically pure secondary and tertiary alcohols is demonstrated. The process is postulated to proceed via reversible Brønsted acid-catalyzed C-O bond cleavage through an achiral carbocation intermediate.

Brønsted Acid-Catalysed Dehydrative Substitution Reactions of Alcohols.

The direct, catalytic dehydrative substitution of alcohols is a challenging, yet highly desirable process in the development of more sustainable approaches to organic chemistry. This review outlines recent advances in Brønsted acid-catalysed dehydrative substitution reactions for C-C, C-O, C-N and C-S bond formation. The wide range of processes that are now accessible using simple alcohols as the formal electrophile are highlighted, while current limitations and therefore possible future directions for research are also discussed.

Arylboronic Acid Catalyzed C-Alkylation and Allylation Reactions Using Benzylic Alcohols.

The arylboronic acid catalyzed dehydrative C-alkylation of 1,3-diketones and 1,3-ketoesters using secondary benzylic alcohols as the electrophile is reported, forming new C-C bonds (19 examples, up to 98% yield) with the release of water as the only byproduct. The process is also applicable to the allylation of benzylic alcohols using allyltrimethylsilane as the nucleophile (12 examples, up to 96% yield).

Correction: Structural and Functional Analysis of the Symmetrical Type I Restriction Endonuclease R.EcoR124I(NT).

[This corrects the article DOI: 10.1371/journal.pone.0035263.].

Unanticipated Silyl Transfer in Enantioselective α,ß-Unsaturated Acyl Ammonium Catalysis Using Silyl Nitronates.

The use of silyl nitronates is reported for the isothiourea-catalyzed synthesis of γ-nitro-substituted silyl esters containing up to two contiguous stereocenters in good yields with excellent enantioselectivities (up to 93% yield and 99:1 er). The serendipitously discovered formation of silyl ester products in this reaction demonstrates a novel platform for catalyst turnover in α,ß-unsaturated acyl ammonium catalysis.

Evaluating aryl esters as bench-stable C(1)-ammonium enolate precursors in catalytic, enantioselective Michael addition-lactonisations.

An evaluation of a range of aryl, alkyl and vinyl esters as prospective C(1)-ammonium enolate precursors in enantioselective Michael addition-lactonisation processes with (E)-trifluoromethylenones using isothiourea catalysis is reported. Electron deficient aryl esters are required for reactivity, with 2,4,6-trichlorophenyl esters providing optimal product yields. Catalyst screening showed that tetramisole was the most effective isothiourea catalyst, giving the desired dihydropyranone product in excellent yield and stereoselectivity (up to 90 : 10 dr and 98 : 2 er). The scope and limitations of this process have been evaluated, with a range of diester products being generated after ring-opening with MeOH to give stereodefined dihydropyranones with excellent stereocontrol (10 examples, typically ∼90 : 10 dr and >95 : 5 er).

Aryl Boronic Acid Catalysed Dehydrative Substitution of Benzylic Alcohols for C-O Bond Formation.

A combination of pentafluorophenylboronic acid and oxalic acid catalyses the dehydrative substitution of benzylic alcohols with a second alcohol to form new C-O bonds. This method has been applied to the intermolecular substitution of benzylic alcohols to form symmetrical ethers, intramolecular cyclisations of diols to form aryl-substituted tetrahydrofuran and tetrahydropyran derivatives, and intermolecular crossed-etherification reactions between two different alcohols. Mechanistic control experiments have identified a potential catalytic intermediate formed between the aryl boronic acid and oxalic acid.

A Selective Deprotection Strategy for the Construction of trans-2-Aminocyclopropanecarboxylic Acid Derived Peptides.

A procedure allowing access to unprecedented tripeptides containing a trans-2-aminocyclopropanecarboxylic acid residue in their central position has been established. The key features of the strategy are the use of a masked trans-2-aminocyclopropanecarboxylic acid monomer equivalent for C-terminal coupling and full N-Boc protection of all amide groups until the final step.

Isothiourea-Catalyzed Enantioselective Functionalization of 2-Pyrrolyl Acetic Acid: Two-Step Synthesis of Stereodefined Dihydroindolizinones.

Catalytic enantioselective functionalization of 2-pyrrolyl acetic acid with trichloromethyl enones using isothiourea catalysis is reported, leading to a range of stereodefined diesters and diamides after nucleophilic ring opening with either methanol or benzylamine (30 examples, up to >95:5 dr and >99:1 er). Subsequent intramolecular Friedel-Crafts reaction allows access to dihydroindolizinones in high yields and stereofidelity (6 examples, up to >95:5 dr and 99:1 er).

A C=O⋠⋠⋠Isothiouronium Interaction Dictates Enantiodiscrimination in Acylative Kinetic Resolutions of Tertiary Heterocyclic Alcohols.

A combination of experimental and computational studies have identified a C=O⋅⋅⋅isothiouronium interaction as key to efficient enantiodiscrimination in the kinetic resolution of tertiary heterocyclic alcohols bearing up to three potential recognition motifs at the stereogenic tertiary carbinol center. This discrimination was exploited in the isothiourea-catalyzed acylative kinetic resolution of tertiary heterocyclic alcohols (38 examples, s factors up to >200). The reaction proceeds at low catalyst loadings (generally 1 mol %) with either isobutyric or acetic anhydride as the acylating agent under mild conditions.

Synthesis of the natural product descurainolide and cyclic peptides from lignin-derived aromatics.

Alternative sources of potential feedstock chemicals are of increasing importance as the availability of oil decreases. The biopolymer lignin is viewed as a source of useful mono-aromatic compounds as exemplified by the industrial scale production of vanillin from this biomass. Alternative lignin-derived aromatics are available in pure form but to date examples of the use of these types of compounds are rare. Here we address this issue by reporting the conversion of an aromatic keto-alcohol to the anti- and syn-isomers of Descurainolide A. The key step involves a rhodium-catalyzed allylic substitution reaction. Enantio-enriched allylic alcohols were generated via an isothiourea-catalyzed kinetic resolution enabling access to both the (2R,3R) and (2S,3S) enantiomers of anti-Descurainolide A. In addition we show that the lignin-derived keto-alcohols can be converted into unnatural amino acid derivatives of tyrosine. Finally, these amino acids were incorporated into cyclic peptide scaffolds through the use of both chemical and an enzyme-mediated macrocylisation.

N- to C-sulfonyl photoisomerisation of dihydropyridinones: a synthetic and mechanistic study.

The scope and limitations of a photoinitiated N- to C-sulfonyl migration process within a range of dihydropyridinones is assessed. This sulfonyl transfer proceeds without erosion of either diastereo- or enantiocontrol, and is general across a range of N-sulfonyl substituents (SO2R; R = Ph, 4-MeC6H4, 4-MeOC6H4, 4-NO2C6H4, Me, Et) as well as C(3)-(aryl, heteroaryl, alkyl and alkenyl) and C(4)-(aryl and ester) substitution. Crossover reactions indicate an intermolecular step is operative within the formal migration process, although no crossover from C-sulfonyl products was observed. EPR studies indicate the intermediacy of a sulfonyl radical and a mechanism is proposed based upon these observations.

Tandem Palladium and Isothiourea Relay Catalysis: Enantioselective Synthesis of α-Amino Acid Derivatives via Allylic Amination and [2,3]-Sigmatropic Rearrangement.

A tandem relay catalytic protocol using both Pd and isothiourea catalysis has been developed for the enantioselective synthesis of α-amino acid derivatives containing two stereogenic centers from readily accessible N,N-disubstituted glycine aryl esters and allylic phosphates. The optimized process uses a bench-stable succinimide-based Pd precatalyst (FurCat) to promote Pd-catalyzed allylic ammonium salt generation from the allylic phosphate and the glycine aryl ester. Subsequent in situ enantioselective [2,3]-sigmatropic rearrangement catalyzed by the isothiourea benzotetramisole forms syn-α-amino acid derivatives with high diastereo- and enantioselectivity. This methodology is most effective using 4-nitrophenylglycine esters and tolerates a variety of substituted cinnamic and styrenyl allylic ethyl phosphates. The use of challenging unsymmetrical N-allyl-N-methylglycine esters is also tolerated under the catalytic relay conditions without compromising stereoselectivity.