The frontier orbitals of both cyclization pathways were analyzed in order to explain the large energetic barrier of the triplet cyclization. May 11, 2001 a new polymer, poly3,4bisphenylethynylstyrene, has been synthesized that undergoes a bergman reaction upon heating to yield a highly aromatic material. Sep 15, 2010 the bergman cyclization is an endothermic reaction and the formed 1,4. The true rate constant, k1, for the cyclization step and the ratio of constants for the retro bergman ring opening, k1, and the intermolecular hatom abstraction, k2, were determined from the dependence of cycloaromatization kinetics of ortho and parano2 substituted. Syntheses, structure, and reactivity of acyclic enetriyne. They do suggest that further cyclization to give the hoped for 2might be precluded by the long distances between radical center and neighboring alkynes in 4, but the radicals. An acyclic enediyne anticancer compound attributed to a. From a purely synthetic viewpoint, the radicals generated by the bergman cyclization have been used to initiate further. The journal of physical chemistry a 2006, 110 7, 25172526. The homopolymerization of enediynes through the bergman cyclization to. All these enediynes undergo thermaltriggered bergman cyclization at elevated temperature 160 c as revealed by dsc analysis. Frank pickard national institutes of health academia. Bergman cyclization of 4 10 equiv of 1,4chd, band at 3340 cm1 point toward additional or parallel chemical dmf.
Though the bergman cyclization is intuitively regarded as an aromatization reaction, the degree of. This route provides access to the aromatic target compounds in a two. Photochemical bergman cyclization and related photoreactions of enediynes download pdf. The highly reactive aromatic diradicals generated from bergman cyclization can undergo polymerization acting as either monomers or initiators of other vinyl monomers. Preparation of conjugated polyphenylenes from maleimide. Jan 25, 2016 the bergman cyclization is one of the most fascinating rearrangements in chemistry, with important implications in organic synthesis and pharmacology. Enediyne moieties were incorporated into linear polymers through copolymerization or postpolymerization modification. This image for the bergman cyclization needs to be corrected. The syntheses of enediynes 3 and 4 are depicted in scheme 1. Moreover, compounds 15 did not give any cycloaromatized products when left to stand at 90110 c in a solution of toluene for 24 hours in the presence of 1,4cyclohexadiene as.
Effect of extended benzannelation orientation on bergman and. The wording over the last arrow reads proton donor. From the kinetic data of enediynes 1ac it is concluded that electron withdrawing substituents are lowering the free activation energy in the bergman. The occurrence of bergman cyclization was confirmed with ir, nmr and dsc analysis. For example, the bergman cyclization 1 of z hexaljdiyn3ene 1 to 1pdidehydrobenzene 2 occurs at 200 oc with an estimated activation energy of about 32 kcal mol. With extended linear benzannelation, as in 6,7diethynylquinoxaline 1 figure 2, bergman cyclization becomes less thermodynamically favorable. Recent theoretical calcula 1 tions21 suggest c1c5 cyclization to fulvene 0 derivatives is competitive with c1c6 bergman cycliza 100 200 300 400 tion when bulky groups are present at the alkyne ter temperature oc mini, which may partly explain the formation of multiple photolysis products from 4a compared to the figure 2.
Bergman cyclization in polymer chemistry and material. Heating this monomer to 150c for 2 d did indeed form a polymer, however, ftir analysis verified that it was not a polyphenylenederived material in that the two bands at 935810 cm1 and 880795 cm. Abstraction of hydrogen atoms from the dna backbone by the diradical leads to single and doublestranded dna cleavage and. Bergman cyclization in polymer chemistry and material science.
The bergman cyclization is an endothermic reaction and the formed 1,4. Pdf bergman cyclization of acyclic amino acid derived. Pdf photochemical generation of enediyne for bergman. Reversible bergman cyclization by atomic manipulation nature. These natural substrates have a means to trigger this cycloaromatization process. Recent advances of the bergman cyclization in polymer. The bergman cyclization or bergman reaction or bergman cycloaromatization is an organic. Crc handbook of organic photochemistry and photobiology.
Reversible bergman cyclization by atomic manipulation. Bergman cyclization synthetic application of the bergman cyclization is rare. The bergman cyclization is one of the most fascinating rearrangements in chemistry, with important implications in organic synthesis and. Such high endothermicity is not surprising because, unlike in the bergman cyclization, the product is not stabilized by aromaticity. Design and synthesis of heterocycle fused enediyne prodrugs activable at will pdf. Article views are the countercompliant sum of full text article downloads since november 2008 both pdf and html across all. Triggered calicheamicin can undergo the bergman cyclization at body temperature only if present in its e chair form activation enthalpy 16. The role of orbital symmetry in bergman cyclization. The latter undergo spontaneous facile bergman cyclization at or below room temperature. Depending on its stability, intermediate 6 may undergo dearomatization to form either starting material 5 or a rearranged enediyne 7. The resulted enediyne containing copolymers were then subjected to intramolecular chain collapse under ultradilute condition or applying a continuous addition technique. Enediyne dimerization vs bergman cyclization request pdf.
Finally, it has been shown that eenediynes do not undergo the bergman cyclization we therefore prepared e1phenylhexa3ene1,5diyne. Polar effects in the transition state of the bergman cyclization. Efficient and accurate characterization of the bergman. Rapid bergman cyclization of 1,2diethynylheteroarenes changsik kim and k. Bergman cyclization major reference works wiley online. Bergman cyclization is a chemical process during which highly reactive aryl diradicals. Preparation of conjugated polyphenylenes from maleimidebased.
Polymeric nanoparticles were synthesized through bergman cyclization mediated intramolecular chain collapse. Taking into account the estimated cyclization barrier of 42 kcalmol, the fulvene diradical. A bergman cyclization approach to polymers for thinfilm. This cyclization reaction is an electronic rearrangement where the 1,5diyne3ene moiety rearranges to form a 1,4didehydrobenzene diradical. Funk, 1996 turro, 1994 another example of unsaturated molecule undergoes rearrangement with thermal and photochemical mechanism would allow controlled activation of drug dilgam ahmadli. Tuning rate of the bergman cyclization of benzannelated. The bergman cyclization of benzannelated enediynes is highly sensitive to ortho substitution.
Turkmen group meeting bergman cyclization zaleski, 2001 j. The occurrence of bergman cyclization is evidenced by ir and nmr spectroscopy. Bergman cyclization of enediynes, regarded as a promising strategy for anticancer drugs, now finds its own niche in the area of polymer chemistry and material science. Reactant destabilization in the bergman cyclization. All structured data from the file and property namespaces is available under the creative commons cc0 license. In bergman cycli zation the anli symmetric combination nl n2 of th hybrid orbitals at the radical sites in 1,4dehydrobenzene is preferentially stabilized via throughbond interactions. The bergman cyclization or bergman reaction or bergman cycloaromatization is an organic reaction and more specifically a rearrangement reaction taking place when an enediyne is heated in presence of a suitable hydrogen donor scheme 1. Effect of extended benzannelation orientation on bergman. Creating a reactive enediyne by using visible light. Rapid bergman cyclization of 1,2diethynylheteroarenes. A strong exothermal peak was found starting at 49 c, which, to the best of our knowledge, is among the lowest onset temperature for thermal bergman cyclization of an acyclic enediyne, and is very close to physiological temperature, implying a. The bergman cyclization influence of ring strain the most widely studied, and arguably most influential way to alter the reactivity of the bergman cyclization is through generation of a strained conformation. Facile approach for preparing porous organic polymers through. Bergman cyclization has shown great promise in constructing conjugated polymers.
Mar 30, 2012 this page was last edited on 23 november 2016, at 07. An enediyne monomer is employed to prepare a microporous organic polymer through bergman cyclization. Bergman cyclization of enediynes, regarded as a promising strategy for anticancer drugs, now finds its own. In early investigations, nicolaou proposed that the overriding determinant of enediyne reactivity is the interatomic distance between. Bergman cycloaromatization an overview sciencedirect. An intermediate biradical is formed docking energy. In the third year of this grant we have explored substituent effects on the photo bergman cyclization of our quinoxalenediyne model system scheme 1. Onsurface formation of onedimensional polyphenylene through. Pdf accelerated bergman cyclization of porphyrinicenediynes. Reaction mixture was checked by tlc and after 8 h shows consumption of starting compound. Conjugated polyphenylenes 7 are obtained by simply heating these enediynes 6 under vacuum. They explain the phases of formation of unidirectional polyphenylene chains via the bergman reaction as follows. Bergman cyclization to the corresponding diradical intermediate can increase or decrease relative to 1,2diethynylbenzene.
Pdf cosensitization of n719 with polyphenylenes from. Visible light is used to create an active enediyne for bergman cyclization by taking advantage of a well. The occurrence of the cycloaromatization reaction is characterized through thermal analysis and absorption spectroscopy. Unfortunately, they did not compute the activation barrier for this process. Syntheses, thermal reactivities, and computational studies of. Nov 01, 2011 bergman cyclization in polymer chemistry and material science bergman cyclization in polymer chemistry and material science xiao, yuli. Metal charge transfer sibaprasad bhattacharyya department of chemistry, indiana university, 800 e.
Pdf reductive bergmantype cyclizations of crossconjugated. An ab initio exploration of the electronic structure of the. B i nucleophiletriggered bergman cyclization used by callike enediynes. This conversion of an enediyne to a benzene derivative is called the bergman cyclization.
In addition, the dna cleavage abilities of these new enediynes under thermal and photochemical conditions are reported. Palladiumcatalyzed cycloaromatization polymerization of. Organic letters photochemical and thermal bergman cyclization. Such files may be downloaded by article for research use if there is a public use license linked to. Moreover, the conjugated polymers generated through bergman cyclization. The triplet enediyne was found to distort out of c 2v symmetry into c 2 symmetry. Bergman cyclization of acyclic amino acid derived enediynes leads to the formation of 2,3dihydrobenzo f isoindoles. Reductive bergman type cyclizations of crossconjugated enediynes to fulvene and fulvalene anions. Surface and solution mediated studies of small molecule enediyne. Results from nmr, raman scattering, photoluminescence and uv. Reactant destabilization in the bergman cyclization and. Pdf substituent effects on the bergman cyclization of z. Here, from the interplay of scanning tunneling microscopy imaging and density functional theory calculations, we report for the first time onsurface formation of onedimensional polyphenylene chains through bergman cyclization followed by radical polymerization on cu110. Apr 19, 2011 fluorinated naphthalene derivatives were prepared by bergman cyclization of fluorinated benzo.
Bergman cyclization is the orbitalsymmetryallowed rearrangement of a z3ene1,5diyne to a 1,4didehydrobenzene diradical 5, scheme 1. Control of this reaction by substrate modification would allow aromatic diradicals to be generated selectively. The bergman cyclization leads to the biradical 3, which adds to the. Controlled acceleration and inhibition of bergman cyclization. It is the most famous and wellstudied member of the general class of cycloaromatization reactions. The resultant splitting between the frontier orbi tals is crucial in making bergman cyclization a thermally symmetry allowed process. Nov 01, 2018 the attributed thermal bergman cyclization of enediyne 3 is characterized with differential scanning calorimetry dsc experiment esi fig. Bergman cyclization vs c1c5 cyclization showing diradical orbitals. Enediynes leads to the formation of 2,3dihydrobenzo f isoindoles.
Bergman cyclization of 3hexene1,5diyne 1 and the reactivity is especially critical for biochemical applications in ub3lyp631g activation barriers for the cyclization of enediynes which enediynes need to produce diradical species at body. Pdf isolation of electronic from geometric contributions. Therefore, the monosubstituted enediynes 7a7t a substituent, b hydrogen and the disubstituted enediynes 7aa7tt a b. An ab initio exploration of the bergman cyclization acs publications. Cycloaromatization an overview sciencedirect topics. Synthesis of new small molecule enediynes is discussed, the thermodynamics of bergman cyclization is considered and evaluated, and. Basak reports a real interesting use of this reaction to create polycyclic aromatics. Jul 30, 2015 the bergman cyclization has strongly impacted on a number of fields including pharmaceutics, synthetic chemistry, and material science. Photochemical bergman cyclization tetrahedron lett. Cycloaromatization of 4a was performed with 10 equiv of 1,4cyclohexadiene 1,4chd in dmf at 175 c scheme 2. Dilgam ahmadli turkmen group meeting bergman cyclization 21. Bergman cyclization along the internal reaction coordinate irc path.
Formation of polymeric nanoparticles via bergman cyclization. The bergman cyclization is one of the most fascinating rearrangements in chemistry, with important implications in organic synthesis and pharmacology. The plasma etch resistance of the polymer has been measured by reactive ion etching rie in sulfur hexafluoride and. Recent advances of the bergman cyclization in polymer science. The bergman cyclization allows the construction of substituted arenes through the thermal or photochemical cycloaromatization of enediynes in the presence of. The bergman cyclization reaction generates a diradical, which then becomes benzene after the addition of two hydrogen atoms or h dot. Triggering of the bergman cyclization by photochemical ring. Iii bergman cyclization used by c1027, mdp, and the putative precursors to fijiolides, sporolides, acms, and cyanosporasides. Bergman cycloaromatization an overview sciencedirect topics. We previously reported the successful photo bergman cyclization of 2,3diethyl5,6bisphenylethynylquinoxaline to 2,3diethyl8,9diphenylbenzofquinoxaline in 17% yield. The intramolecular chain collapse was characterized with gpc, dsc, and afm. Request pdf enediyne dimerization vs bergman cyclization highlevel quantum chemical calculations reveal that the dimerization of enediynes to 1,3butadiene1,4diyl diradicals is. Only isomer 2 has the enediyne structure required to produce a diradical that can be trapped as compound 3. The next step was performing bergman cyclization in solution and isolation of products.
H h cl cl rh ccl 4 heat heat radical 1,4 dehydrobenzene. However, the application of this reaction in polymer science is still limited due to the harsh reaction condition and illdefined structure of the achieved polymers. Russell department of chemistry, university of miami, 1 memorial drive, coral gables, florida 33124 received may 8, 1998 the synthesis and cyclization of acyclic quinoxaline, pyridine, and pyrimidine enediynes are described. To provide further insight into bergman cyclization energetics, computational studies were performed to compare changes in the cyclization enthalpy barrier, reaction enthalpy, and barrier of retro bergman ringopening. Aromaticity criteria magnetic susceptibility exaltations, nucleus independent chemical shifts nics, and aromatic stabilization energy ase evaluations for enediyne and enyneallene cyclizations evaluated at ubsblyp631g all agree that the degrees of cyclic electron delocalization of the benzenoid systems formed by the bergman 3 and myers. This finding opens possibilities for the rational design of conformerspecific and phdependent dnacleaving agents.
Conformational and electronic consequences in crafting. The bergman cyclization or bergman reaction or bergman cycloaromatization is an organic reaction and more specifically a rearrangement reaction taking place. Pdf reactant destabilization in the bergman cyclization. The diradical intermediates stemmed from enediynes can not only cause dna cleavage under physiological conditions but also function as monomer or initiator participants in polymer science. The chemistry of ninemembered enediyne natural products. Pdf accelerated bergman cyclization of porphyrinic.
Ring opening reverse bergman cyclization was then followed by atomic manipulation to form two phenyl rings. Files are available under licenses specified on their description page. The bergman cyclization has strongly impacted on a number of fields including pharmaceutics, synthetic. To elaborate the concept of weak interactions and their effect on bergman cyclization bc, several 1,2. Bergman cyclization d d d d h h d d 200 oc gas phase. Ccsd t investigation of the bergman cyclization enediyne.
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