Radical-polar Crossover Reaction Research Articles

ChemInform Abstract: Radical-Polar Crossover Reactions with a Water-Soluble Tetrathiafulvalene Derivative.

Abstract The water-soluble TTF reagent 7 undergoes the radical-polar crossover reaction in 1:1 acetone:water with a range of arenediazonium tetrafluoroborates and in water with diazonium chlorides. Purification of the reaction products is greatly facilitated by using 7 compared with TTF.

ChemInform Abstract: Synthesis of the Acutumine Spirocycle via a Radical—Polar Crossover Reaction.

AbstractChemInform 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.

Carbometalation of unactivated alkenes by zinc enolate derivatives

The carbometalation reaction of zinc enolates and related stabilised organometallics on unactivated double bonds has emerged over the past decade as a mechanistically interesting and synthetically useful reaction. This Perspective is devoted to these challenging and apparently contra-thermodynamic transformations, with a special focus on recent mechanistic considerations involving radical–polar crossover reaction pathways.

Synthesis of the Acutumine Spirocycle via a Radical−Polar Crossover Reaction

A new radical-polar crossover reaction was developed that consists of intramolecular conjugate addition of an aryl radical followed by enolate formation and hydroxylation. A C-C bond, a C-O bond, and two congested stereocenters are created in the process. The product is obtained as a single isomer. The method was used to synthesize the spirocyclic subunit of the alkaloid acutumine.

Solid-Supported Copper Catalysts for Atom-Transfer Radical Cyclizations: Assessment of Support Type and Ligand Structure on Catalyst Performance in the Synthesis of Nitrogen Heterocycles

A range of solid supported pyridinemethanimine 9-11 and polyamine 12-15 ligands have been prepared on silica, polystyrene, and JandaJel supports. The CuCl and CuBr complexes of these supported ligands have been used to assess both the effect of the ligand type and the nature of the support upon a representative range of copper-mediated atom transfer 5-exo-trig 6, 24-25, 5-exo-dig 26, 4-exo-trig 28, and 5-endo-trig 27, 38 radical cyclizations to give nitrogen heterocycles. In addition, the effect of the nature of the support on the stereochemical outcome of the 5-exo cyclization of 25 has been probed. Generally, it was found that the type of support (e.g., polystyrene, silica, or JandaJel) had very little effect upon the efficiency and selectivity of the processes but that the nature of the ligand type immobilized was the important factor. Thus, the 5-exo cyclization of 6 and 24-26 proceeded more rapidly with the PMI ligands 9-11, whereas 4-exo cyclizations 28 and 5-endo radical polar crossover reactions 27 and 38 proceeded more efficiently with the JJ-TEDETA ligand 15. The efficiency of the supported ligands was also compared to their solution counterparts 4 and 5. The reusability of P-PMDETA ligand system 13 was assessed in the cyclization of 6.

Domino 1,4‐Addition/Carbocyclization Reaction through a Radical–Polar Crossover Reaction

Die Annahme eines Radikalprozesses erklärt die Reaktivität und Selektivität einer Eintopf-Zwei- oder -Dreikomponenten-Dominoreaktion, die aus 1,4-Addition, Carbocyclisierung und Reaktion mit einem Elektrophil besteht. Diese Mischung aus Radikalreaktion und polarer Reaktion führt stereoselektiv zu 3,4-disubstituierten 3-Methoxycarbonylpyrrolidinen (siehe Schema).

Domino 1,4-addition/carbocyclization reaction through a radical-polar crossover reaction.

Radical processes explain the reactivity and selectivity observed in a one-pot, two- or three-component domino reaction, which consists of 1,4-addition, carbocyclization, and quenching with electrophiles. This radical–polar crossover reaction leads stereoselectively to 3,4-disubstituted 3-methoxycarbonylpyrrolidines (see scheme).

Oxidative 5-Endo Cyclization of Enamides Mediated by Ceric Ammonium Nitrate

[reaction: see text] Ceric ammonium nitrate mediates the oxidative 5-endo radical-polar crossover reactions of beta-enamide esters to give 5,5-C,O-disubstituted-gamma-lactams. Trapping of the intermediate cations leads to 5-hydroxy- or 5-alkoxy-gamma-lactams depending upon the reaction conditions. The methodology was used to synthesize the basic heterocyclic ring fragments of the natural products L-755,807, Quinolacticin C, and PI-091.

Tandem Radical Addition—Aldol Condensations: Evidence for the Formation of Zinc Enolates in Diethylzinc Mediated Radical Additions to N‐Enoyloxazolidinones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Tandem radical addition–aldol condensations: evidence for the formation of zinc enolates in diethylzinc mediated radical additions to N-enoyloxazolidinones

Diethylzinc mediated addition of alkyl radicals to chiral N-enoyloxazolidinones is immediately followed by homolytic substitution at zinc leading to a zinc enolate; the trapping of the latter in a subsequent aldol condensation serves as a useful mechanistic probe; overall this reaction sequence constitutes a novel example of a one pot, three-component, radical-polar crossover reaction.

Atom transfer radical cyclisation reactions mediated by copper complexes.

This article describes recent advances in the use of copper complexes in mediating atom transfer radical cyclisation reactions (ATRC). Recent developments have included the design of activated complexes which mediate the cyclisation of tri-, di-, and mono-halo derived substrates at ambient temperatures. Using this methodology, cyclisation to give a variety of ring sizes (4-18 membered rings) has been demonstrated. In addition tandem and radical-polar crossover reactions have also been developed. The design of solid supported and perfluorous complexes that mediate cyclisations may make this approach to the synthesis of rings more attractive towards industrial applications.

New Concepts in Tetrathiafulvalene Chemistry.

Tetrathiafulvalene (TTF) and its derivatives were originally prepared as strong electron-donor molecules for the development of electrically conducting materials. This Review emphasizes how TTF and its derivatives offer new and in some cases little-exploited possibilities at the molecular to the supramolecular levels, as well as in macromolecular aspects. TTF is a well-established molecule whose interest goes beyond the field of materials chemistry to be considered an important building block in supramolecular chemistry, crystal engineering, and in systems able to operate as machines. At the molecular level, TTF is a readily available molecule which displays a strong electron-donor ability. However, its use as a catalyst for radical-polar crossover reactions, thus mimicking samarium iodide chemistry, has only recently been addressed. Important goals have been achieved in the use of TTF at the macromolecular level where TTF-containing oligomers, polymers, and dendrimers have allowed the preparation of new materials that integrate the unique properties of TTF with the processability and stability that macromolecules display. The TTF molecule has also been successfully used in the construction of redox-active supramolecular systems. Thus, chemical sensors and redox-switchable ligands have been prepared from TTF while molecular shuttles and molecular switches have been prepared from TTF-containing rotaxanes and catenanes. A large synthetic effort has been devoted to the preparation of the so-called organic ferromagnets, many of which are derived from TTF. The main task in these systems is the introduction of ferromagnetic coupling between the conduction electrons and localized electrons. TTF has also played a prominent role in molecular electronics where TTF-containing D-sigma-A molecules have allowed the preparation of the first confirmed unimolecular rectifier. Recently, it has been confirmed that TTF can display efficient nonlinear optic (NLO) responses in the second and third harmonic generation as well as a good thermal stability. These findings can be combined with the redox ability of TTF as an external stimuli to provide a promising strategy for the molecular engineering of switchable NLO materials. Fullerenes endowed with TTF exhibit outstanding photophysical properties leading to charge-separated (CS) states that show remarkable lifetimes.

Radical-polar crossover reactions with a water-soluble tetrathiafulvalene derivative

The water-soluble TTF reagent 7 undergoes the radical-polar crossover reaction in 1:1 acetone:water with a range of arenediazonium tetrafluoroborates and in water with diazonium chlorides. Purification of the reaction products is greatly facilitated by using 7 compared with TTF.

Free radicals in synthesis. Clean reagents affording oxidative or reductive termination

Abstract Neurotoxic organotin reagents currently play a key role in radical chemistry. As a result, this is an important area for development of new clean replacement reactions. The pharmaceutical industry in particular has had to avoid use of radical methodology for the formation of carbon_carbon bonds for this reason. With the current dawn in green chemistry, a host of new clean radical methods is beginning to flourish. Our aim has been to develop new nontoxic methodology for carbon_carbon bond formation by radical chemistry, which would provide either reductive termination (giving a hydrogen atom to the ultimate radical, as happens with tributyltin hydride), or oxidative functionalization, installing a useful polar group at the site of the ultimate radical. Two methods for effecting radical reactions in an environmentally friendly way are presented: (i) The tetrathiafulvalene (TTF)-mediated radical-polar crossover reaction converts arenediazonium salts to aryl radicals, which have sufficient lifetime to cyclize onto alkenes—the resulting alkyl radicals couple with TTF+• to afford sulfonium salts which, in turn, undergo solvolysis to alcohols, ethers or amides. The method provides the key step in a synthesis of (±)-aspidospermidine. (ii) Hypophosphite salts and hypophosphorous acid, on the other hand, form C_C bonds with reductive termination. These economical reagents afford radicals efficiently, starting from aryl iodides, alkyl bromides, and alkyl iodides, and give very easy separation of products from by-products.

Radical-polar crossover reactions with polymer-supported tetrathiafulvalene

Polymer-supported tetrathiafulvalene reagents have been prepared and their reactivity in redical-polar crossover reactions compared to tetrathiafulvalene itself. The reagents give easy separation of products. A regeneration step permits re-use of the polymer-supported reagent.

Intramolecular termination of radical-polar crossover reactions

Cyclic ethers result from intramolecular trapping of cations formed through the radical-polar crossover process.

Tetrathiafulvalene-mediated stereoselective synthesis of the tetracyclic core of Aspidosperma alkaloids

A novel route to advanced synthetic precursors of Aspidosperma alkaloids is described, utilising radical-polar crossover reactions.

On The Mechanism of the Tetrathiafulvalene-Mediated Radical-Polar Crossover Reactions

Strong evidence supports the previously proposed mechanism of the radical-polar crossover reactions, and discounts a totally ionic mechanism. © 1997 Elsevier Science Ltd.

Synthesis of functionalised indolines by radical-polar crossover reactions

Functionalised indolines have been prepared by treating tetrathiafulvalene (TTF) with 2-(N-acyl-N -allylamino)benzenediazonium tetrafluoroborates. N-Benzoyl-protected substrates afford complex reaction mixtures due to competing radical cyclisation onto the benzoyl group. Acetamides react more efficiently affording good yields of product alcohols when the reactions are carried out in moist acetone

Studies of the tetrathiafulvalene mediated radical-polar crossover reaction directed toward the total synthesis of alkaloid natural products

The carbon skeleton of octahydro-1 H-pyrrolo[2,3- d]carbazole ( 4), a tetracylic sub-unit which is common to a wide range of alkaloid natural products has been prepared by two approaches which exploit the one-pot radical-polar crossover chemistry mediated by tetrathiafulvalene. Both approaches proceed with complete stereoselectivity.