Atom transfer radical polymerization through N‐chlorosulfonamides

Controlled polymerizations of vinyl monomers such as methyl methacrylate and styrene are achieved using N‐chloro,N‐propyl‐p‐toluenesulfonamide (NCPT) together with a cuprous bromide/hexahexyl triethylenetetramine (CuBr/H‐TETA) complex. Although N‐halosulfonamides are known to decompose radically to give free chlorine, NCPT alone (without a cuprous complex) does not initiate any polymerization even in prolonged reaction times. Instead these add to the double bonds to give 2‐chloroethylsulfonamides. In the present polymerization system a good chlorine donator (NCPT) is combined with an organic soluble complex (CuBr/H‐TETA) to perform atom transfer radical polymerizations (ATRPs) in homogenous conditions. The linear proportionality of the molecular weights to the conversions and straight lines observed in ln(M₀/M) (where M₀ and M are the monomer contents at the beginning and at any time, respectively) versus time plots indicate typical controlled polymerization characteristics. The use of freshly prepared NCPT is advisable due to its slow and spontaneous decomposition when standing at room temperatures. Because of their easy preparation, N‐chlorosulfonamides can be used and are preferred instead of special halogen compounds commonly used in copper mediated ATRP. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 2691–2695, 2001     

2,2,2‐Trifluoroacetophenone as an Organocatalyst for the Oxidation of Tertiary Amines and Azines to N‐Oxides

A cheap, mild and environmentally friendly oxidation of tertiary amines and azines to the corresponding N‐oxides is reported by using polyfluoroalkyl ketones as efficient organocatalysts. 2,2,2‐Trifluoroacetophenone was identified as the optimum catalyst for the oxidation of aliphatic tertiary amines and azines. This oxidation is chemoselective and proceeds in high‐to‐quantitative yields utilizing 10 mol % of the catalyst and H₂O₂ as the oxidant.     

Atom Transfer Radical Polymerization of N‐Isopropylacrylamide

Summary: Controlled polymerization of N‐isopropylacrylamide (NIPAAM) was achieved by atom transfer radical polymerization (ATRP) using ethyl 2‐chloropropionate (ECP) as initiator and CuCl/tris(2‐dimethylaminoethyl)amine (Me₆TREN) as a catalytic system. The polymerization was carried out in DMF:water 50:50 (v/v) mixed solvent at 20 °C. The first order kinetic plot was linear up to 92% conversion. Controlled molecular weights up to 2.2 × 10⁴ and low polydispersities (1.19) were obtained. The living character of the polymerization was also demonstrated by self‐blocking experiments. Block copolymers with N,N‐dimethylacrylamide (DMAAM) and 3‐sulfopropyl methacrylate (SPMA) were successfully prepared.

Molecular weights and polydispersities of polyNIPAAM versus NIPAAM conversion for two different degrees of polymerization.     

Hydrogen‐transfer reduction of α,β‐unsaturated carbonyl compounds catalyzed by naphthyridine‐functionalized N‐heterocyclic carbene complexes

Substitution of silver complex of 2‐chloro‐7‐(mesitylimidazolylidenylmethyl)naphthyridine (NpNHC) with palladium(II), rhodium(I) and iridium(I) metal precursors provided [Pd(C ,N ‐NpNHC)(η³‐allyl)](BF₄) ( 5 ), RhCl(COD)(C ‐NpNHC) ( 6a ) and IrCl(COD)(C ‐NpNHC) ( 6b ), respectively. Abstraction of chloride from 6a and 6b with AgBF₄ provided the chelation complexes [Rh(COD)(C ,N ‐NpNHC)](BF₄) ( 7a ) and Ir(COD)(C ,N ‐NpNHC)(BF₄) ( 7b ), respectively. All complexes were characterized using NMR and elemental analyses and the structural details of 5 and 6a were further confirmed using X‐ray crystallography. In catalytic activity studies, complex 5 was found to be an effective catalyst in the hydrogen‐transfer reduction of α,β‐unsaturated carbonyl compounds into the corresponding saturated carbonyl compounds.     

Enantioselective Oxidative Aerobic Dealkylation of N‐Ethyl Benzylisoquinolines by Employing the Berberine Bridge Enzyme

N‐Dealkylation methods are well described for organic chemistry and the reaction is known in nature and drug metabolism; however, to our knowledge, enantioselective N‐dealkylation has not been yet reported. In this study, exclusively the (S)‐enantiomers of racemic N‐ethyl tertiary amines (1‐benzyl‐N‐ethyl‐1,2,3,4‐tetrahydroisoquinolines) were dealkylated to give the corresponding secondary (S)‐amines in an enantioselective fashion at the expense of molecular oxygen. The reaction is catalyzed by the berberine bridge enzyme, which is known for C? C bond formation. The dealkylation was demonstrated on a 100 mg scale and gave optically pure dealkylated products (ee>99 %).     

Cofactor‐Free Light‐Driven Whole‐Cell Cytochrome P450 Catalysis

Cytochromes P450 can catalyze various regioselective and stereospecific oxidation reactions of non‐functionalized hydrocarbons. Here, we have designed a novel light‐driven platform for cofactor‐free, whole‐cell P450 photo‐biocatalysis using eosin Y (EY) as a photosensitizer. EY can easily enter into the cytoplasm of Escherichia coli and bind specifically to the heme domain of P450. The catalytic turnover of P450 was mediated through the direct transfer of photoinduced electrons from the photosensitized EY to the P450 heme domain under visible light illumination. The photoactivation of the P450 catalytic cycle in the absence of cofactors and redox partners is successfully conducted using many bacterial P450s (variants of P450 BM3) and human P450s (CYPs 1A1, 1A2, 1B1, 2A6, 2E1, and 3A4) for the bioconversion of different substrates, including marketed drugs (simvastatin, lovastatin, and omeprazole) and a steroid (17β‐estradiol), to demonstrate the general applicability of the light‐driven, cofactor‐free system.     

Mechanistic Insight into Formation of Oxo‐Iron(IV) Porphyrin π‐Cation Radicals from Enzyme Mimics of Cytochrome P450 in Organic Solvents

Two new models for cytochrome P450 in which the thiolate axial ligand is replaced by an RSO₃^? group, form oxo‐iron(IV) porphyrin π‐cation radicals as sole oxidation products in “peroxo shunt” reactions (see scheme) independent of the nature of the employed solvent (polar or non‐polar) and electronic nature of the porphyrin rings.

     

A Bistable Molecular Switch Driven by Photoinduced Hydrogen‐Atom Transfer

The occurrence of photoinduced hydrogen atom transfer between two remote spots of a molecule is experimentally demonstrated. This photoprocess involves the intermediacy of an intramolecular “crane”. In an experimental case study, 7‐hydroxy‐4‐methylquinoline‐8‐carbaldehyde monomers isolated in low‐temperature Ar matrices are investigated. On UV (λ>295 nm) irradiation, a hydrogen atom is transferred from the O⁷H group to the N¹ atom of the quinoline ring. Subsequent irradiation with UV (λ>360 nm) light reveals that the phototransformation is partially photoreversible. In the studied hydrogen‐atom‐transfer process, the exocyclic carbaldehyde group plays the role of an intramolecular crane. The possible application of systems analogous to 7‐hydroxy‐4‐methylquinoline‐8‐carbaldehyde as optically driven molecular switches is discussed.     

Pd‐Catalyzed Decarboxylative Cross‐Coupling of 2‐Carboxyazine N‐Oxides with Various (Hetero)aryl Halides

Decarboxylative cross‐coupling reactions of substituted 2‐carboxyazine N‐oxides, with a variety of (hetero)aryl halides, by bimetallic Pd⁰/Cu^I and Pd⁰/Ag^I catalysis are reported. Two possible pathways, a conventional bimetallic‐catalyzed decarboxylative arylation, as well as a protodecarboxylative/direct C?H arylation sequence have been considered. These methods provide the first general decarboxylative arylation methodology for the 2‐carboxyazine series.     

Metal‐Free Hydrogen Atom Transfer from Water: Expeditious Hydrogenation of N‐Heterocycles Mediated by Diboronic Acid

A hydrogenation of N‐heterocycles mediated by diboronic acid with water as the hydrogen atom source is reported. A variety of N‐heterocycles can be hydrogenated with medium to excellent yields within 10 min. Complete deuterium incorporation from stoichiometric D₂O onto substrates further exemplifies the H/D atom sources. Mechanism studies reveal that the reduction proceeds with initial 1,2‐addition, in which diboronic acid synergistically activates substrates and water via a six‐membered ring transition state.     

Biosynthesis of Biscognienyne B Involving a Cytochrome P450‐Dependent Alkynylation

The alkyne is a biologically significant moiety found in many natural products and a versatile functional group widely used in modern chemistry. Recent studies have revealed the biosynthesis of acetylenic bonds in fatty acids and amino acids. However, the molecular basis for the alkynyl moiety in acetylenic prenyl chains occurring in a number of meroterpenoids remains obscure. Here, we identify the biosynthetic gene cluster and characterize the biosynthetic pathway of an acetylenic meroterpenoid biscognienyne B based on heterologous expression, feeding experiments, and in vitro assay. This work shows that the alkyne moiety is constructed by an unprecedented cytochrome P450 enzyme BisI, which shows promiscuous activity towards C5 and C15 prenyl chains. This finding provides an opportunity for discovery of new compounds, featuring acetylenic prenyl chains, through genome mining, and it also expands the enzyme inventory for de novo biosynthesis of alkynes.     

Alkynylation of C (O)–H Bonds Enabled by Photoredox‐Mediated Hydrogen‐Atom Transfer

The development of new hydrogen‐atom transfer (HAT) strategies within the framework of photoredox catalysis is highly appealing for its power to activate a desired C−H bond in the substrate leading to its selective functionalization. Reported here is the first photoredox‐mediated hydrogen‐atom transfer method for the efficient synthesis of ynones, ynamides, and ynoates with high regio‐ and chemoselectivity by direct functionalization of C (O)−H bonds. The broad synthetic application of this method has been demonstrated by the selective functionalization of C(O)−H bonds within complex molecular scaffolds.     

Rhodium(III)‐Catalyzed CC and CO Coupling of Quinoline N‐Oxides with Alkynes: Combination of CH Activation with O‐Atom Transfer

[Cp*Rh^III]‐catalyzed C? H activation of arenes assisted by an oxidizing N? O or N? N directing group has allowed the construction of a number of hetercycles. In contrast, a polar N? O bond is well‐known to undergo O‐atom transfer (OAT) to alkynes. Despite the liability of N? O bonds in both C? H activation and OAT, these two important areas evolved separately. In this report, [Cp*Rh^III] catalysts integrate both areas in an efficient redox‐neutral coupling of quinoline N‐oxides with alkynes to afford α‐(8‐quinolyl)acetophenones. In this process the N? O bond acts as both a directing group for C? H activation and as an O‐atom donor.     

Amide‐Substituted Titanocenes in Hydrogen‐Atom Transfer Catalysis

Two new catalytic systems for hydrogen‐atom transfer (HAT) catalysis involving the N?H bonds of titanocene(III) complexes with pendant amide ligands are reported. In a monometallic system, a bifunctional catalyst for radical generation and reduction through HAT catalysis depending on the coordination of the amide ligand is employed. The pendant amide ligand is used to activate Crabtree's catalyst to yield an efficient bimetallic system for radical generation and HAT catalysis.     

Stoichiometric vs Catalytic MeLi Reaction with the Mixture of (ẽ5‐C5H5)Fe(CO)2l and P(OR)3: Nucleophilic Methylation vs Arbuzov‐Like Dealkylation

The reaction of stoichiometric MeLi with the 1:1 mixture of (?⁵‐C₅H₅)Fe(CO)₂I/P(OR)₃ (R = Me, Et, and Ph) at ?78°C changes the bonding mode between metal and ring from (?⁵‐C₅H₅) to (?⁴‐exo‐MeC₅H₅) and the oxidation state of metal from Fe(II) to Fe(O), the novel complexes (?⁴‐exo‐MeC₅H₅)Fe(CO)₂P(C)R)₃ being obtained in 45‐57% yields. The reaction of trace MeLi with the 1:1 mixture of (?⁵‐C₅H₅)Fe(CO)₂I/P(OMe)₃ at ?78°C results in 70% yield of the phosphonate complex (?⁵‐C₅H₅)Fe(CO)₂P(O)(OMe)₂ which is an Arbuzov‐like dealkylation product from the cationic intermediate [(?⁵‐C₅H₅)Fe(CO)₂P(OMe)₃⁺] and the iodide. The amines could assist the Arbuzov‐like dealkylation of [(?⁵‐C₅H₅)Fe(CO)₂P(OMe)₃⁺] [PF₆^?] where iron‐carbamoyl intermediates are likely involved in the case of primary amines.