Radical Cyclization Reactions Research Articles

Initiated chemical vapor deposition and light-responsive cross-linking of poly(vinyl cinnamate) thin films.

The first vapor-phase deposition of poly(vinyl cinnamate) (PVCin) is reported. Initiated chemical vapor deposition (iCVD) is used to synthesize PVCin thin films with an average thickness of 100 nm. Free radical polymerization and cyclization reactions compete during the deposition process, with approximately 45% of the repeat units undergoing cyclization. Exposure to UV light (λ = 254 nm) induces dimerization (cross-linking) of the PVCin, which is quantified using spectroscopic techniques. Approximately 90% of the free cinnamate moieties are dimerized at a UV dose of 300 mJ cm(-2) . PVCin is also incorporated into a copolymer with N-isopropylacrylamide, which exhibits a characteristic change in hydrophilicity with temperature. The copolymer is selectively cross-linked through a mask, and reversible swelling of patterns with 30 μm resolution is demonstrated by submerging the film in water.

An approach to the synthesis of naphtho[b]furans from allyl bromonaphthyl ethers employing sequential photoinduced radical cyclization and dehydrohalogenation reactions

A simple method has been developed for the efficient synthesis of naphtho[b]furans from allyl bromonaphthyl ethers. The approach utilizes a novel photochemical process involving sequential radical cyclization and dehydrohalogenation. Because light is a readily available, environmentally friendly reagent that produces no by-products, the new process serves as a green synthetic method.

Carbonylation Reactions of Alkyl Iodides through the Interplay of Carbon Radicals and Pd Catalysts

Numerous methods for transition metal catalyzed carbonylation reactions have been established. Examples that start from aryl, vinyl, allyl, and benzyl halides to give the corresponding carboxylic acid derivatives have all been well documented. In contrast, the corresponding alkyl halides often encounter difficulty. This is inherent to the relatively slow oxidative addition step onto the metal center and subsequent β-hydride elimination which causes isomerization of the alkyl metal species. Radical carbonylation reactions can override such problems of reactivity; however, carbonylation coupled to iodine atom transfer (atom transfer carbonylation), though useful, often suffers from a slow iodine atom transfer step that affects the outcome of the reaction. We found that atom transfer carbonylation of primary, secondary, and tertiary alkyl iodides was efficiently accelerated by the addition of a palladium catalyst under light irradiation. Stereochemical studies support a mechanistic pathway based on the synergic interplay of radical and Pd-catalyzed reaction steps which ultimately lead to an acylpalladium species. The radical/Pd-combined reaction system has a wide range of applications, including the synthesis of carboxylic acid esters, lactones, amides, lactams, and unsymmetrical ketones such as alkyl alkynyl and alkyl aryl ketones. The design of unique multicomponent carbonylation reactions involving vicinal C-functionalization of alkenes, double and triple carbonylation reactions, in tandem with radical cyclization reactions, has also been achieved. Thus, the radical/Pd-combined strategy provides a solution to a longstanding problem of reactivity involving the carbonylation of alkyl halides. This novel methodology expands the breadth and utility of carbonylation chemistry over either the original radical carbonylation reactions or metal-catalyzed carbonylation reactions.

Titanocene(III) Chloride Mediated Stereoselective Synthesis of Trisubstituted Tetrahydrofurans and a Spirolactone by Tandem Radical Reactions

AbstractThe titanocene(III) chloride (Cp2TiCl) mediated stereoselective synthesis of highly substituted tetrahydrofurans has been achieved by a reaction that proceeds through a tandem radical cyclization reaction between a Baylis–Hillman adduct and an activated bromo/iodo compound. The reaction of an epoxide with the Baylis–Hillman adduct furnished a spirolactone through a radical cyclization followed by an in situ lactonization. Cp2TiCl was prepared in situ from commercially available Cp2TiCl2and zinc dust in tetrahydrofuran.

Intermolecular Visible‐Light Photoredox Atom‐Transfer Radical [3+2]‐Cyclization of 2‐(Iodomethyl)cyclopropane‐1,1‐dicarboxylate with Alkenes and Alkynes

Radical chemistry! A visible-light-promoted, tin/boron-free intermolecular [3+2] atom-transfer radical cyclization reaction was developed by using iridium polyphenylpridinyl complex as the sensitizer. 2-(Iodomethyl)cyclopropane-1,1-dicarboxylate reacted with various alkenes and alkynes to form cyclopentane and cyclopentene derivatives.

ChemInform Abstract: Novel Synthesis and Functionalization of ortho—ortho Disubstituted Biphenyls and a Highly Condensed Novel Heterocycle Using Radical Cyclization Reaction.

AbstractLactam conjoined ortho, ortho′‐diaminated biphenyls, e.g. (IV), as well as complex heterocycles, e.g. (V), are obtained by radical cyclization of isatin derivatives.

Total synthesis of zyzzyanones A–D

Zyzzyanones A–D is a group of biologically active marine alkaloids isolated from Australian marine sponge Zyzzya fuliginosa. They contain a unique bispyrroloquinone ring system as the core structure. The first total synthesis of all four zyzzyanones is described here. The synthesis of these alkaloids started from a previously known 6-benzylamino indole-4,7-quinone derivative and involves 6–7 steps. The key step in the synthesis involves the construction of a pyrrole ring in one step using a Mn(OAc)3 mediated oxidative free radical cyclization reaction of a 6-benzylamino indole-4,7-quinone derivative with 4-benzyloxyphenyl acetaldehyde diethyl acetal in CH3CN.

Electron transfer promoted photochemical reductive radical cyclization reactions of allyl 2-bromoaryl ethers

Tin-free, photoinduced electron transfer promoted reductive radical cyclization reactions of allyl 2-bromoaryl ethers in the presence of NaOH in 2-PrOH were found to take place efficiently to give 3-methyl-2,3-dihydrobenzofurans. In contrast to conventional radical cyclization reactions that employ AIBN/Bu3SnH in benzene, the new method utilizes NaOH and 2-PrOH that are both readily available and benign. Consequently, the newly developed photochemical process serves as a versatile and environmentally friendly method for carrying out aryl radical cyclization reactions.

Free radical cyclization reactions of allylsulfonyl substituted N-aryl amide derivatives

p-Toluenesulfonyl radical can be generated by the manganese(III) acetate oxidation of sodium p-toluenesulfinate. The corresponding alkyl radicals could be produced effectively by the p-toluenesulfonyl radical induced radical reaction of allylsulfonyl substituted N-aryl amides. These alkyl radicals undergo 5-exo-trig, 6-endo-trig, or 6-exo-trig cyclization onto the aromatic ring effectively. The product distribution is highly dependent on the substituent of aromatic ring and the stability of radical intermediate. This p-toluenesulfonyl radical induced reaction provides a synthetically useful method for the synthesis of dihydroquinolinones, azaspirocyclic cyclohexadienes, and spirodihydroquinolinones.

Photoinduced Electron Transfer Promoted Radical Ring Expansion and Cyclization Reactions of α-(ω-Carboxyalkyl) β-Keto Esters

Photoinduced electron transfer (PET) promoted decarboxylation of α-(ω-carboxyalkyl) β-keto esters undergoes radical ring expansion and cyclization reactions. This mild and environmentally friendly method can provide one-carbon expanded γ-keto esters and bicyclic alcohols, and the product distribution is strongly dependent on the length of the alkyl chain containing the terminal carboxylate group.

Radical Photocyclization Route for Macrocyclic Lactone Ring Expansion and Conversion to Macrocyclic Lactams and Ketones

A new method for the synthesis of macrocyclic lactones, lactams, and ketones, which utilizes photoinduced intramolecular radical cyclization reactions of substrates containing tethered carboxylic acids and α,β-unsaturated carbonyl moieties, has been uncovered. Photocyclization of the carboxylic acids tethered acrylate ester, which were prepared starting from the macrocyclic lactones, gave the two-carbon elongated macrocyclic lactones via decarboxylation. Similar photoreactions of carboxylic acid tethered acryl amide or α,β-unsaturated ketone moieties, which were also prepared starting from the macrocyclic lactones, produced macrocyclic lactams or ketones, respectively. The simple approach can be readily applied to the preparation of a variety of macrocyclic lactones, lactams, and ketones with tunable ring sizes.

Practical metal- and additive-free methods for radical-mediated reduction and cyclization reactions

Two facile, metal- and additive-free protocols for radical dehalogenation, deoxygenation and cyclization reactions are reported. Irradiation by household fluorescent light bulbs or the presence of an air atmosphere is shown to initiate the desired reactions, thus providing highly practical reaction setups for radical-mediated reductions and cyclizations.

Synthesis of Thienyl‐Substituted Dihydrofuran Compounds Promoted by Manganese(III) Acetate

AbstractRadical cyclization reactions of both aliphatic 1,3‐diones 1a and 1b and of cyclic 1,3‐diones 1c–1e with 2‐thienyl‐ and 3‐thienyl‐substituted alkenes 2a–2d in the presence of manganese(III) acetate were investigated. Thienyl‐substituted dihydrofurans 3 were obtained with moderate to high yields (Table 1–3). Also, the favorable effect of the thienyl substituent on the intermediate carbocation stability was evaluated by comparison with a phenyl substituent.

Synthesis of Pyrroloquinones via a CAN Mediated Oxidative Free Radical Reaction of 1,3-Dicarbonyl Compounds with Aminoquinones.

Pyrroloquinone ring systems are important structural units present in many biologically active molecules including a number of marine alkaloids. For example, they are found in a series of marine metabolites, such as tsitsikammamines, zyzzyanones, wakayin, and terreusinone. Several of these alkaloids have exhibited antimicrobial, antimalarial, antifungal, antitumor, and photoprotecting activities. Synthesis of pyrroloquinone unit is the key step in the synthesis of many of these important organic molecules. Here, we present a ceric (IV) ammonium nitrate (CAN) mediated oxidative free radical cyclization reaction of 1,3-dicarbonyl compounds with aminoquinones as a facile methodology for making various substituted pyrroloquinones. 1,3-dicarbonyl compounds used in this study are ethyl acetoacetate, acetylacetone, benzoyl acetone, and N,N-dimethyl acetoacetamide. The aminoquinones used in this study are 2-(benzylamino)naphthalene-1,4-dione and 6-(benzylamino)-1-tosyl-1H-indole-4,7-dione. The yields of the synthesized pyrroloquinones ranged from 23–91%.

Total synthesis of (±)-sacidumlignans D and A through Ueno–Stork radical cyclization reaction

Efficient synthesis of (±)-sacidumlignan D (4) has been successfully achieved employing Ueno-Stork radical cyclization of α-bromo acetal 21 as a key step. Two synthetic approaches for the symmetrical diaryl ketone 19 have been discussed in detail. Notably, sacidumlignan A (1) can be also efficiently synthesized in only 7 steps with 25% overall yield, where acid triggered tandem reaction starting from analogous Ueno-Stork cyclization product 27 played an important role. Moreover, potentially biomimetic conversion from (±)-sacidumlignan D (4) to sacidumlignan A (1) could be realized.

Copper(ii) chloride mediated (aza)oxindole synthesis by oxidative coupling of Csp2–H and Csp3–H centers: substrate scope and DFT study

A CuCl2 mediated direct intramolecular oxidative coupling of Csp(2)-H and Csp(3)-H centers gives access to 3,3-disubstituted oxindoles containing aromatic, heteroaromatic and alkyl substituents as well as a heteroatom at the quaternary center in good to excellent yields. The reaction is carried out in the presence of NaOtBu and CuCl2 in DMF at 110 °C. The key step of this reaction is the formation of an amidyl radical by one electron oxidation of amide enolate followed by an intramolecular radical cyclization reaction (homolytic aromatic substitution reaction). A detailed DFT study shows that the cyclization of the amidyl radical is the rate-limiting step in the oxindole synthesis, whereas the second single electron transfer (SET) becomes the rate-determining step in the aza-oxindole formation. Computational data are in agreement with the experimentally observed relative reactivity and regioselectivity.

Intramolecular cyclization reaction mechanism and regioselectivities of unsubstituted and benzene-substituted 4-penteniminyl radicals: A DFT investigation

The cyclization mechanisms and regioselectivities of 4-penteniminyl and benzene-substituted 4-penteniminyl radicals were investigated systematically by density functional theory method and Marcus theory. For the 4-penteniminyl radical, the 5-exo-trig cyclization via a boat-like transition state was found to be the dominant pathway, whereas for the benzene-substituted 4-penteniminyl ring closure processes the 6-endo-trig is the favorable reaction mode. The preferred 5-exo-trig over 6-endo-trig in 4-penteniminyl radical cyclization is believed to come from a stereoelectronic effect and can be elucidated by orbital interactions between HOMO of iminyl radical and FMO of unsaturated CC double bond in the transition state models. The Marcus theory analysis demonstrated that the surprising regiochemistry of benzene-substituted 4-penteniminyl radical cyclization can be attributed to a thermodynamic effect. The extremely high thermodynamic stability of 6-endo-trig product radical resulting from strong p–π delocalization of unpaired electron in benzene ring leads to a significant decrease in reaction activation energy, and further makes the reaction regioselectivity reverse dramatically relative to the unsubstituted system. Therefore, the kinetic and thermodynamic effects dominate the regioselectivities of 4-penteniminyl and benzene-substituted 4-penteniminyl radical cyclization reactions, respectively.

ChemInform Abstract: Ruthenium‐Catalyzed Atom Transfer Radical Addition Reactions

AbstractReview: 53 refs.

ChemInform Abstract: Unexpected Formation of Stannolanes and Trigonal Bipyramidal Tin Complexes by Radical Cyclization Reaction.

AbstractThe radical cyclization of chiral aza‐Morita—Baylis—Hillman adducts (I) with Bu3SnH yields bicyclic stannolanes (III) with high diastereoselectivity.

Novel synthesis and functionalization of ortho–ortho disubstituted biphenyls and a highly condensed novel heterocycle using radical cyclization reaction

This paper describes a novel synthetic route for the preparation of ortho–ortho disubstituted biphenyls and compounds possessing highly condensed ring system represented by structures X and Y, respectively. Several approaches, such as intermolecular Grubb's olefin metathesis, Heck and, Suzuki reactions were incorporated to functionalize the core structures of X and Y making it suitable for the preparation of a library of compounds.