Cyclization reactions of methylthioacetanilides

The cyclization reactions of methylthioacetanilides mediated by manganese(III) acetate and/or copper(II) acetate are described. Indolinones and indolinediones can be produced effectively via a 5-membered ring cyclization of methylthioacetanilides. The product distributions are highly dependent on the reaction conditions. In most cases, the electronic effect of the substituents on the aryl ring was found to significantly affect the yields of cyclization products. This cyclization reaction proceeded faster with manganese(III) acetate/copper(II) acetate.     

Theoretical studies on Myers-Saito and Schmittel cyclization mechanisms of hepta-1,2,4-triene-6-yne

The mechanisms of the Myers-Saito cyclization and the Schmittel cyclization of hepta-1,2,4-triene-6-yne are studied by ab initio multireference MO methods (CASSCF and MRMP2 methods). For the Myers-Saito cyclization, two transition states with C(s) and C? symmetries are located. The transition state with C1 symmetry is only 1.5 kcal/mol lower in energy than that with C(s) symmetry at the MRMP2 calculation level. The obtained activation energy at the transition state with C? symmetry and the reaction energy are 16.6 and 16.2 kcal/mol exothermic, respectively. For the Schmittel cyclization, two transition states with C(s) and C? symmetry are also obtained. The transition state with C? symmetry is 7.9 kcal/mol lower in energy than that with C(s) symmetry. The transition state with C? symmetry for Schmittel cyclization is 6.7 kcal/mol higher in energy than that for the Myers-Saito cyclization. The reaction mechanisms are analyzed by a CiLC-IRC method. The interactions of orbitals for the Myers-Saito and Schmittel cyclizations can be distinguished.     

Enantio- and diastereoselective stepwise cyclization of polyprenoids induced by chiral and achiral LBAs. A new entry to (-)-ambrox, (+)-podocarpa-8,11,13-triene diterpenoids, and (-)-tetracyclic polyprenoid of sedimentary origin

An enantio- and diastereoselective stepwise cyclization of polyprenoids induced by Lewis acid-assisted chiral Br?nsted acids (chiral LBAs) and achiral LBAs is described. In particular, the absolute stereocontrol in the initial cyclization of polyprenoids to form an A-ring induced by chiral LBAs and the importance of the nucleophilicity of the internal terminator in polyprenoids for the relative stereocontrol in subsequent cyclization are demonstrated. (-)-Ambrox was synthesized via the enantioselective cyclization of (E,E)-homofarnesyl triethylsilyl ether with tin(IV) chloride-coordinated (R)-2-(o-fluorobenzyloxy)-2'-hydroxy-1,1'-binaphthyl ((R)-BINOL-o-FBn) and subsequent diastereoselective cyclization with CF(3)CO(2)H.SnCl(4) as key steps. Protection of (E,E)-homofarnesol by a triethylsilyl group increased the enantioselectivity of chiral LBA-induced cyclization and both the chemical yield and diastereoselectivity in the subsequent cyclization. The enantioselective cyclization of homo(polyprenyl)arenes possessing an aryl group was also induced by (R)-BINOL-o-FBn.SnCl(4). Several optically active podocarpa-8,11,13-triene diterpenoids and (-)-tetracyclic polyprenoid of sedimentary origin were synthesized (75-80% ee) by the enantioselective cyclization of homo(polyprenyl)benzene derivatives induced by (R)-BINOL-o-FBn.SnCl(4) and subsequent diastereoselective cyclization induced by BF(3).Et(2)O/EtNO(2) or CF(3)CO(2)H .SnCl(4).     

Synthesis of sterically congested bicyclic tetrahydrofurans via Pd-catalyzed cyclization

Prins-type cyclization followed by palladium-catalyzed cyclization provided sterically congested bi- or tricyclic tetrahydrofurans, which are very stereoselective as well. cis-2,5-Disubstituted tetrahydrofurans obtained from Prins-type cyclization have an allenyl group and a functional group such as alcohol, carboxylic acid, and aryl halide. The tetrahydrofurans bearing an allene group underwent palladium-catalyzed cyclization to give sterically congested bi- or tricyclic tetrahydrofurans.     

聚异戊二烯在四氯化锡－对甲苯磺酸催化下的环化反应动力学研究

聚异戊二烯在四氯化锡－对甲苯磺酸催化下的环化反应动力学研究孙晓日（山东昌潍师范专科学校化学系，山东潍坊２６１０４３）顾江楠苏翠华余尚先李大珍（北京师范大学化学系，北京１００８７５）关键词聚异戊二烯，环化聚异戊二烯，环化反应，动力学环化聚异戊二烯是聚异...     

Dependence of the cyclization behavior of multifunctional network molecules on molecular size

The tendency for cyclization of nonlinear network molecules is quantitatively expressed by the cyclization probability, defined as the ratio of cyclization to total reaction rate. In contrast to branching, the rate of cyclization depends on the configurational statistical mechanics of segments joining functional groups. Direct integration of the joint configurational probability density in the subspace of encounters yields the distribution of the number of configurationally formed intramolecular functional group encounters (nearest neighbors). Statistically independent network segments are assumed to obey the Gaussian statistics. A recursive relationship for the distribution of chain lengths is developed, and it is shown that for large molecular sizes this relationship tends to a limiting distribution. Corresponding average and standard deviation follow power law dependence on degree of polymerization (DP). With these results, cyclization probabilities are explicitly expressed as functions of DP. When segmental diffusion is the rate controlling factor, cyclization is similar to short range (or primary) cyclization. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 861–870, 2005     

炔烃分子内环化反应合成含氮杂环化合物研究进展

分子内氮原子参与的炔烃环化反应是构成含氮杂环化合物(例如吲哚类化合物等)的最重要途径之一. 从两个方面对分子内氮杂原子与炔的环化反应研究新进展进行了综述: 过渡金属催化分子内环化反应和分子内亲电环化反应. 此外, 对环化反应的机理也做了较详细的描述.     

6-Endo-dig versus 5-exo-dig: Exploring Radical Cyclization Preference with First-, Second-, and Third-row Linkers using High-level Quantum Chemical Methods

As an expansion upon Baldwin rules, the cyclization reactions of hex-5-yn-1-yl radical systems with different first-, second-, and third-row linkers are explored at the CCSD(T) level via means of the SMD(benzene)-G4(MP2) thermochemical protocol. Unlike C, O, and N linkers, systems with B, Si, P, S, Ge, As, and Se linkers are shown to favor 6-endo-dig cyclization. This offers fundamental insights into the rational synthetic design of cyclic compounds. A thorough analysis of stereoelectronic effects, cyclization barriers, and intrinsic barriers illustrates that structural changes alter the cyclization preference by mainly impacting 5-exo-dig reaction barriers. Based on the high-level computational modeling, we proceed to develop a new tool for cyclization preference prediction from the correlation between cyclization barriers and radical structural parameters (e. g., linker bond length and bond angle). A strong correlation is found between the radical attack trajectory angle and the reaction barrier heights, i. e., cyclization preference. Finally, the influence of stereoelectronic effects on the two radical cyclization pathways is further investigated in stereoisomers of hypervalent silicon system, which provides novel insight into cyclization control.     

Formation of polyimide from benzophenonetetracarboxylic acid diester complexes with different diamines. 4. Gas-chromatographic study of thermal cyclization of complexes

Thermal cyclization of H complexes is characterized by one rate constant which significantly distinguishes it from thermal cyclization of polyamido acids. The degree of completion of thermal cyclization of the H complex and its rate are determined by diffusion processes related to the structure of the H complex and mobility (softening) of the system during thermal cyclization.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1006–1011, May, 1991.We would like to thank V. V. Shamanin for discussing the results.     

On the regioselectivity of the cyclization of enyne-ketenes: a computational investigation and comparison with the Myers-Saito and Schmittel reaction

The Moore (C(2)-C(7)) cyclization and the alternative C(2)-C(6) cyclization of enyne-ketenes belong to the family of biradical cyclization reactions such as the Bergman reaction of ene-diynes, both the cyclizations of enyne-allenes and enyne-cumulenes. The latter garnered substantial interest due to their antitumor efficacy. The mechanisms of both cyclization modes of enyne-ketenes are still unclear, but as the enyne-ketenes can formally be regarded as heteroanalogues of enyne-allenes, both cyclizations are expected to react via biradical routes. Nevertheless, as shown recently for cyclic allenes, the substitution of a methylene group by oxygen can lead to different energetic ordering of the electronic states of the key intermediates. To elucidate the mechanism, the present work investigates the course of both cyclization modes for various model compounds. To reveal general motifs for the large family of biradical cyclizations, a comparison with enyne-allenes is performed.     

Round trip radical reactions from acyclic precursors to tricyclo [5.3.1.0]undecanes. A new cascade radical cyclization approach to (+/-)-isogymnomitrene and (+/-)-gymnomitrene

The synthesis and "round trip radical cyclization" of 11-iodo-2,7,11-trimethyldodec-6-en-5-one are described. The round trip cyclization is a sequence of 5-exo, 6-endo, and 5-exo cyclizations in which the last radical cyclization occurs at the same carbon atom as the initial radical generation. The key second (6-endo) cyclization produces two stereoisomers, one of which cyclizes efficiently to isogymnomitrene ketone, while the other cyclizes inefficiently to gymnomitrene ketone. Efforts to influence the kinetic or thermodynamic outcome of the second cyclization were not successful, and the results are contrasted with a related cyclization of Jung and Rayle where thermodynamic control was readily established.     

Regiochemistry in aryl radical cyclization onto methylenecycloalkanes

Bu(3)SnH-mediated aryl radical cyclization onto methylenecycloalkanes having a phenylthio, an ester, or a nitrile group at the terminus of the alkenic bond provides exclusively exo cyclization products. The results are in sharp contrast to those reported for nonsubstituted methylenecycloalkanes, which give exclusively endo cyclization products. Formation of endo cyclization products has been suggested to be a result of a consecutive 5-exo cyclization of an aryl radical and neophyl rearrangement. The exo-selective aryl radical cyclization offers a new method for synthesizing fused aromatic compounds containing a benzylic quaternary carbon atom.     

Preparation of alpha-(2,2-diphenylhydrazino)lactones and related compounds by radical cyclization: use of glyoxylic acid hydrazone derivatives

Glyoxylic acid diphenylhydrazone (2a) and the corresponding O-benzyloxime (2b) are easily esterified in high yield by beta-bromo alcohols. The resulting esters undergo radical cyclization to alpha-(2,2-diphenylhydrazino)- or alpha-[(phenylmethoxy)amino]lactones on treatment with tributyltin hydride. Esters for radical cyclization were also made using a beta-(phenylseleno) alcohol and an enol ether. Several derivatives of glyoxylic acid were evaluated, but none was as effective as 2a or 2b. The imine 28 was prepared by an indirect route; it undergoes radical cyclization with displacement of the nitrogen substituent (28 --> 30) so that an alpha-amino lactone can be generated by acid hydrolysis of the cyclization product.     

Thermo-chemical reactions and structural evolution of acrylamide-modified polyacrylonitrile

<正>Thermal properties of acrylonitrile(AN)-acrylamide(AM) copolymers for carbon fibers were studied by DSC and in situ FTIR techniques in nitrogen(N_2) and air flows.The cyclization mechanism and stabilization behavior of polyacrylonitrile(PAN) were discussed.In N_2 flow,it was found that AM had the ability to initiate and accelerate cyclization process,which was confirmed by the fact that the initiation of nitriles shifted to a lower temperature.Compared to AN homopolymer,the initiation temperature of cyclization was ahead 32 K by introducing 3.59 mol%AM into the copolymer.The exothermic reaction was relaxed due to the presence of two separated exothermic peaks.Accompanied by DSC,in situ FTIR and calculation of activation energy,the two peaks were proved to be caused by ionic cyclization and free radical cyclization,respectively,and the corresponding cyclization mechanism was proposed.With increasing in AM content,the ionic cyclization tends to be dominant and the total heat liberated first increases and then decreases.For AN homopolymer,the activation energy of cyclization is 179 kJ/mol.For AN-AM copolymer(containing 3.59 mol%AM),the activation energy of ionic cyclization is 96 kJ/mol and that of free radical cyclization is 338 kJ/mol.In air flow,similar cyclization routes occur and the difference is the contribution of oxidation.The oxygen in environment has no remarkable effect on cyclization of AN homopolymer but retards the cyclization of AN-AM copolymers.For AN-AM copolymer with 3.59 mol%AM,the cyclization temperature is postponed 10℃in air.     

Indium-mediated atom-transfer and reductive radical cyclizations of iodoalkynes: synthesis and biological evaluation of HIV-protease inhibitors

Novel indium-mediated radical cyclization reactions of aliphatic iodoalkynes have been studied. Treatment of iodoalkynes with a catalytic amount of In (0.1 equiv) and I(2) (0.05 equiv) promotes atom-transfer 5-exo cyclization to give five-membered alkenyl iodides. In contrast, reaction with In (2 equiv) and I(2) (1 equiv) yields reductive 5-exo cyclization products via the same 5-exo cyclization. Both processes are most likely initiated by low-valent indium species. To demonstrate versatility of these reactions, optically active HIV protease inhibitors were synthesized by this reductive cyclization method. Among them, several products, which contain a hydroxyethylamine dipeptide isostere as a transition state-mimicking substructure, proved to possess potent activity (IC(50) = 5-39 nM) against a wide spectrum of HIV strains, including multidrug-resistant variants.     

Gold-catalyzed reactions of 2-alkynyl-phenylamines with alpha,beta-enones

[reaction: see text] The gold-catalyzed reaction of 2-alkynyl-phenylamines with alpha,beta-enones represents a new general one-pot entry into C-3-alkyl-indoles by sequential reactions. Gold-catalyzed sequential cyclization/alkylation, N-alkylation/cyclization, or N-alkylation/cyclization/alkylation reactions leading to different indoles can be directed by changing the 2-alkynyl-phenylamine 1/alpha,beta-enone 3 ratio and the reaction temperature. Unusual gold-catalyzed rearrangement reaction of indoles are observed at 140 degrees C. New gold-catalyzed formation of propargyl-alkyl ether under mild conditions and the hydration reaction of N-acetyl-2-ethynyl-phenylamine are reported.     

An extremely facile aza-Bergman rearrangement of sterically unencumbered acyclic 3-aza-3-ene-1,5-diynes

The factors that affect the kinetics of the aza-Bergman cyclization of aza-enediynes (C,N-dialkynyl imines) have not previously been elucidated. Here we report our kinetic studies of the aza-Bergman reactions of a series of 6-triisopropylsilyl and 6-unsubstituted 1-phenyl-4-aryl-3-aza-3-ene-1,4-diynes in which the aryl group is phenyl, o-(methoxy)phenyl, or p-(methoxy)phenyl. These aza-enediynes are prepared as single isomers in modest yield from the corresponding 1-aryl-3-(triisopropylsilyl)propynone oximes. These aza-enediynes undergo aza-Bergman reaction followed by a rapid retro-aza-Bergman cyclization to afford beta-alkynyl acrylonitrile products. In no case are products corresponding to trapping the intermediate 2,5-didehydropyridine diradical isolated. While the rate of aza-Bergman cyclization is not greatly affected by the nature of the 4-aryl substituent, the rate is very dependent on the nature of the 6-substituent. 1-Phenyl-4-aryl-3-aza-3-ene-1,5-diynes that lack a 6-substituent undergo aza-Bergman cyclization spontaneously at 20 degrees C with first-order half-lives of 36-78 min. The effect of solvent on the kinetics of aza-Bergman cyclization of 1,4-diphenyl-3-aza-3-ene-1,5-diyne was investigated. The rate of this cyclization is solvent dependent, proceeding more rapidly in less polar solvents.     

Myers–Saito and Schmittel cyclizations of enyne-(hetero)-1,2,3-trienes: A DFT study on the structure–reactivity relationship

The Myers–Saito (C²–C⁷) cyclization and the alternative Schmittel (C²–C⁶) cyclization of enyne-1,2,3-triene 1R and its hetero analogues 2R–5R were investigated by using pure density functional theory method (BPW91) in connection with the 6-311G(d, p) basis set. It has been shown that heteroatom-containing reactants lower significantly reaction barriers for both cyclization modes and reduce the difference between the barrier of the C²–C⁷ cyclization mode and that of the C²–C⁶ one. The Myers–Saito cyclization of 4R is associated with the smallest reaction barrier and the highest exothermicity. Whereas the Schmittel cyclization of 4R is exothermic, all the others are predicted to be endothermic.     

Can Flory-Stockmayer theory be applied to predict conventional free radical polymerization of multivinyl monomers? A study via Monte Carlo simulations

The conventional free radical polymerization (FRP) of multivinyl monomers (MVMs) inevitably leads to gelation even at low monomer conversion resulting in difficulties to control and monitor the reaction process. Flory and Stockmayer (F-S theory) studied it based on two fundamental assumptions: (1) independent and equivalent vinyl groups; (2) no intramolecular cyclization. However, until now its applicability to FRP of MVMs (especially regarding the extent of intramolecular cyclization) is still controversial. In this paper, Monte Carlo simulations are used to study FRP of divinyl monomers by two kinetic models: with/without cyclization models. The results of the simulations are compared with the calculated gel points based on F-S theory and the experimental data. It is found that the intramolecular cyclization has a negligible impact on the polymerization process and the gel point before gelation, which are in agreement with the prediction by F-S theory, but the effect becomes significant above the gel points.     

Palladium‐Catalyzed Cascade Cyclization/Alkynylation Reactions

Palladium‐catalyzed cascade cyclization reactions have witnessed significant improvements in recent years. Among them, palladium‐catalyzed cascade cyclization/alkynylation are especially attractive, which can assemble structurally diverse monocyclic, bicyclic, fused polycyclic, and spirocyclic skeletons with excellent chemoselectivities. In this Minireview, palladium‐catalyzed cascade cyclization/alkynylation have been summarized and discussed in detail with focus on oxypalladation and aminopalladation‐initiated cascade cyclization, intramolecular Heck‐type cascade cyclization, carbocyclizations, cascade cyclizations, and other types of cascade cyclization reactions. Some significant and representative synthetic methodologies and their synthetic applications and reaction mechanisms have also been described.