Atom Transfer Radical Cyclization Research Articles

ChemInform Abstract: Copper‐Mediated Atom Transfer Radical Cyclizations with AIBN.

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.

P-MeOC 6H 4[formula omitted]/TiCl 3: a novel initiator for halogen atom-transfer radical reactions in aqueous media

With the combination of p-methoxybenzene-diazonium tetrafluoroborate with TiCl 3 as the initiator, a wide range of halogen atom-transfer radical addition or cyclization reactions could be efficiently implemented in aqueous solution at room temperature.

Enantiocontrolled Synthesis of (−)-9-epi-Pentazocine and (−)-Aphanorphine

We have developed novel asymmetric routes to (-)-9- epi-pentazocine and (-)-aphanorphine from a d-tyrosine derivative. The tricyclic frameworks of (-)-9- epi-pentazocine and (-)-aphanorphine were assembled stereoselectively via intramolecular Friedel-Crafts reaction of the corresponding bicyclic precursors, generated with titanium-promoted enyne cyclization and indium-initiated atom-transfer radical cyclization, respectively.

ChemInform Abstract: An Unusual Decarboxylative Benzannulation and Biaryl Formation During Copper(I)‐Promoted Halogen Atom Transfer Radical Cyclization of 2‐Allylaryl Trichloroacetates.

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.

Highly Selective Synthetic Reactions by the Combined Use of Organometallic Reagents and Radical Species

Abstract During these thirty years, we have pursued new methodologies in organic synthesis and developed many synthetically useful reactions. Among them, four topics are described in this article. (1) Regio- and stereoselective silylmetalation of acetylenes has been examined. Whereas platinum- or copper-catalyzed silylmagnesation of terminal acetylenes afforded (E)-1-silyl-1-alkene exclusively, palladium-catalyzed silylalumination with PhMe2Si-AlEt2 provided 2-silyl-1-alkenes with high regioselectivity. (2) Triethylborane induced radical addition of Ph3SnH to acetylenes gave 1-triphenylstannyl-1-alkenes in the presence of small amount of oxygen. The reaction has two distinguishing characteristics. One feature is that Et3B can initiate the radical reaction at low temperature, such as −78 °C. (3) The other distinctive feature of Et3B-induced radical reaction is that many solvents could be used for the reaction. Thus, water was chosen as a solvent, and Et3B-induced atom-transfer radical cyclization of iodo acetals and iodoacetates in water was examined. (4) Three types of organometallic ate complexes, R3MnMgBr, R3MgLi, and R3Co(L2)MgBr, were prepared and used for organic synthesis. Treatment of gem-dibromocyclopropane with trialkylmanganate provided alkylated cyclopropane after aqueous workup. Aryl and alkenyl halides could be converted into the corresponding magnesium reagents by the action of trialkylmagnesate via halogen–magnesium exchange. Finally, synthetic reactions catalyzed by cobalt complexes are described. Without suffering from β-elimination, cobalt complexes allow cross-coupling reactions of alkyl halides with Grignard reagents.

Synthesis, Structure, and Reactivity of the Methoxy-Bridged Dimer [Cp∧Ru(μ-OMe)]2 (Cp∧ = η5-1-Methoxy-2,4-di-tert-butyl-3-neopentylcyclopentadienyl)

The methoxy-bridged RuII complex [Cp∧Ru(μ-OMe)]2 (Cp∧ = η5-1-methoxy-2,4-di-tert-butyl-3-neopentylcyclopentadienyl) was obtained from the RuIII complex [Cp∧RuCl(μ-Cl)]2 by reaction with K2CO3 in methanol. In the presence of EtOH, the complex was converted into the ethoxy-bridged dimer [Cp∧Ru(μ-OEt)]2. Due to the steric demand of the Cp∧ π-ligand, complex [Cp∧Ru(μ-OMe)]2 behaves differently than the parent complex [Cp*Ru(μ-OMe)]2. Reaction with Me3SiCl in the presence of LiCl gave the electronically unsaturated complex [Cp∧Ru(μ-Cl)]2, whereas a tetrameric structure had been reported for the analogous Cp* complex. In contrast to the expected addition reaction, a monomeric complex [Cp∧Ru(CO)2(CO2Me)] was obtained by ligand insertion of CO in the Ru−OMe bond. Moreover, an unprecedented transformation of cyclooctadiene into ethylbenzene in the coordination sphere of Ru was observed. Complex [Cp∧Ru(μ-OMe)]2 was found to act as a highly active catalyst for atom transfer radical cyclization (ATRC) reactions on a diverse range of substrates such as N-substituted dichloro- and trichloroacetamides, enamides, ethers, and esters.

New reactivity patterns of copper(I) and other transition metal NHC complexes: application to ATRC and related reactions

Pre-formed transition metal–NHC complex is shown to be an effective catalyst for Atom Transfer Radical Cyclisation ( ATRC) reactions.

Synthesis of 2,4-disubstituted 3-chlorofurans and the effect of the chlorine substituent in furan Diels–Alder reactions

2,4-Disubstituted 3-chlorofurans were synthesized in 42–69% overall yields by CuCl/bpy-catalyzed halogen atom transfer radical cyclization of 1-substituted 2,2,2-trichloroethyl allyl ethers to 2-substituted 3,3-dichloro-4-(1-chloroalkyl)tetrahydrofurans followed by base promoted dehydrochlorination. Diels–Alder reactions of 4-substituted 2-(2-furyl)-, 2-styryl-, and 2-crotyl-3-chlorofurans with dimethyl acetylenedicarboxylate occurred exclusively on the chlorofurano diene moieties and not on the non-chlorinated furano diene or the chlorinated exocyclic diene alternatives, demonstrating the predominance of the halogen effect in the furan Diels–Alder reaction.

An unusual decarboxylative benzannulation and biaryl formation during copper(I)-promoted halogen atom transfer radical cyclization of 2-allylaryl trichloroacetates

CuCl/bpy-promoted halogen atom transfer radical cyclization of 2-allylaryl trichloroacetates in refluxing benzene gave benzannulated chloroarenes and benzannulated symmetrical biaryls along with reductive dehalogenation products. The unusual decarboxylative benzannulation and biaryl formation might be explained by a further intramolecular radical addition on the benzene ring of the eight-membered lactone intermediate, initially formed through 8- endo- trig halogen atom transfer radical cyclization, followed by decarboxylation, radical dimerization and dehydrochlorination reactions.

Atom‐Transfer Radical Addition (ATRA) and Cyclization (ATRC) Reactions Catalyzed by a Mixture of [RuCl2Cp*(PPh3)] and Magnesium

A new catalytic procedure for atom-transfer radical addition (ATRA) and cyclization (ATRC) reactions is described. The combination of the ruthenium(III) complex [RuCl(2)Cp*(PPh3)] (Cp*: pentamethylcyclopentadienyl) with magnesium allows these reactions to be performed under mild conditions with high efficiency. In most cases, the catalyst concentrations required are significantly lower than those used in previously reported procedures. It is suggested that magnesium acts as a reducing agent that generates and regenerates the catalytically active ruthenium(II) species. The precatalyst [RuCl(2)Cp*(PPh3)] has been analyzed by X-ray crystallography.

A copper-catalyzed domino radical cyclization route to benzospiro-indolizidinepyrrolidinones

In this Letter the synthesis of benzospiro-indolizidinepyrrolidinones is described by a domino atom transfer radical cyclization reaction using a copper catalyst. The structure of one of the products was established by single crystal X-ray diffraction. The investigated precursors, bearing a homo allyl substituent on the N-indole, result in a 5- exo- trig, followed by a 6- endo- trig cyclization. When the N-indole is substituted with an allyl group, only the spiro-cyclization occurs.

Copper(I)‐Catalyzed Chlorine Atom Transfer Radical Cyclization Reactions of Unsaturated α‐Chloro β‐Keto Esters.

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, please click on HTML or PDF.

Atom transfer radical cyclization (ATRC) applied to a chemoenzymatic synthesis of Quercus lactones

The natural fragrances (+)- trans whisky lactone 2 and (+)- trans cognac lactone 4, together with a minor amount of their (−)- cis stereoisomers, were prepared in 50% and 42% overall yield, respectively, starting from racemic 1-hepten-3-ol (±)- 5 and 1-octen-3-ol (±)- 6. The procedure involved first the enantioconvergent, lipase mediated transformation of the secondary allylic alcohols derived dichloroacetates (±)- 7 and (±)- 8 into the corresponding homochiral (+)- 7 and (+)- 8, combined with their cyclization under a transition metal catalyzed atom transfer process.

Copper(I)-Catalyzed Chlorine Atom Transfer Radical Cyclization Reactions of Unsaturated α-Chloro β-Keto Esters

Copper(I) chloride catalyzed chlorine atom transfer radical cyclization reactions of a series of olefinic alpha-chloro beta-keto esters were investigated. It was found that alpha-dichlorinated beta-keto esters were suitable substrates; the chlorine transfer mono or tandem radical cyclization reactions catalyzed by CuCl complex with bis(oxazoline) or bipyridine proceeded smoothly in dichloroethane at room temperature or 80 degrees C, providing cyclic and bicyclic compounds in moderate to high yield. [reaction: see text]

Asymmetric Synthesis of a Chiral Building Block for Cyclopentanoids: A Novel Enantioselective Synthesis of Preclavulone A

A new asymmetric approach to the hydroxylactone (+)-(3aR,4R,6aS)-4-(hydroxymethyl)-3a,4-dihydro-3H-cyclopenta[b]furan-2(6aH)-one (1), a key synthetic building block for cis-1,2-disubstituted five-membered ring derivatives (i.e., isoprostanes, jasmonates, and clavulones), has been described. A remarkable control of the absolute and relative configuration of the three stereocenters was achieved. Thus, the use of the Trost's asymmetric allylic alkylation strategy secured highly enantioenriched (R)-3-(nitromethyl)cyclopent-1-ene (13), which was smoothly converted to (R)-cyclopent-2-enecarboxylic acid (15) in excellent yield and high enantiomeric purity (>98% ee). 6-exo-trig atom-transfer radical cyclizations of ((R)-cyclopent-2-enyl)methyl 2-iodoacetate (12) produced exclusively the desired cis-fused delta-lactone (4aR,7aR)-hexahydro-5-iodocyclopenta[c]pyran-3(1H)-one (11), which was subsequently elaborated to hydroxylactone 1 through a stereocontrolled Pd(II)-mediated lactonization reaction. En route to preclavulone A, a putative elusive intermediate in the biosynthesis of clavulones, the synthetic utility of compound 1 was demonstrated. The key feature in this synthesis was the installation of the lower side chain via the Knochel organozinc sp3-sp C-C coupling protocol.

Solid-Supported Copper Catalysts for Atom-Transfer Radical Cyclizations

Solid-Supported Copper Catalysts for Atom-Transfer Radical Cyclizations

Atom transfer radical cyclization reactions (ATRC): synthetic applications

Atom transfer cyclization reactions (ATRC) provide rapid access to functionalized γ-butyrolactones.

A coordinatively unsaturated ruthenium methoxide as a highly effective catalyst for the halogen atom-transfer radical cyclization of N-allyl dichloroacetamides and related reactions

Atom-transfer radical cyclization (ATRC) catalyzed by coordinatively unsaturated ruthenium alkoxides 4 , [(η 5-C 5Me 5)Ru(OR)] 2, is investigated, and ruthenium methoxide 4a (R=Me) is found to exhibit excellent catalytic activity for the cyclization of N-allyl-α,α-dichloroacetamides at ambient temperature. Addition of some amounts of two-electron donor ligands such as pyridine and triphenylphosphine improves the catalyst efficiency to afford the corresponding γ-lactams in high yields. The high catalytic activity of this catalyst system enables to control the diastereoselectivity of this 5- exo cyclization kinetically. The present 4a /pyridine system is also effective for the 4- exo cyclization of N-vinylacetamides to afford the corresponding β-lactams in quantitative yields. The 4a /pyridine system is also active towards the ATRP of methyl methacrylate (MMA) at room temperature to afford the poly(MMA) with narrow molecular weight distributions ( M w/ M n=1.2) at the initial stage.

Synthesis of Highly Functionalized Spiro‐Indoles by a Halogen Atom Transfer Radical Cyclization.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access the actual ChemInform Abstract, please click on HTML or PDF.

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.