Most cyclizations have a high activation energy barrier and therefore temperatures around 200 c are needed for the cycloaromatization. They explain the phases of formation of unidirectional polyphenylene chains via the bergman reaction as follows. The bergman cyclization reaction generates a diradical, which then becomes benzene after the addition of two hydrogen atoms or h dot. An acyclic enediyne anticancer compound attributed to a. Triggering of the bergman cyclization by photochemical ring. Generating an epub file may take a long time, please be patient. Synthesis of angularly fused aromatic compounds from. Onsurface formation of onedimensional polyphenylene. This complex is stable to both air oxidation and metalmediated bergman cyclization under ambient conditions due to the nearly idealized tetrahedral geometry. C1c5 cyclization in 2001 schreiner calculated that the barrier for c1c5 cyclization was 41 kcalmol while c1c6 was only 25 kcalmol in 2008 pascal calculated that the c1c5 pathway was possible and then accomplished it schreiner, p.
Rapid bergman cyclization of 1,2diethynylheteroarenes changsik kim and k. The triplet enediyne and transition state were found to have c 2 symmetry, which. Not being an md, biochemist or molecular biologist, i have no idea how long said enediyne drugs would take to. Pdf efficient and accurate characterization of the. It is the most famous and wellstudied member of the general class of cycloaromatization reactions. Reaction of 2 equiv of 1,2bisdiphenylphosphinoethynylbenzene dppeb, 1 with ptcodcl2 followed by treatment with n2h4 yields the reduced pt0 metalloenediyne, ptdppeb2, 2. Efficient and accurate characterization of the bergman cyclization. We computed the singlet and triplet potential energy surfaces for the bergman cyclization of zhex3ene1,5diyne using the ccsd and eomsfccsd methods. Efficient and accurate characterization of the bergman. This file is made available under the creative commons cc0 1. Enediyne 1 is a csymmetrical planar molecule with a conjugated ssystem. The homopolymerization of enediynes through the bergman cyclization. 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. The conjugated polyphenylenes are further characterized by uvvis and malditof mass spectroscopy ms.
Photoisomerization as a trigger for bergman cyclization. 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. The role of orbital symmetry in bergman cyclization. Enediyne moieties were incorporated into linear polymers through copolymerization or postpolymerization modification. An external file that holds a picture, illustration, etc. Bergman cyclization synthetic application of the bergman cyclization is rare. The design and activation of enediyne prodrugs that cleave dna upon bergman cyclization 1 remains a formidable synthetic challenge. Rapid bergman cyclization of 1,2diethynylheteroarenes. His discovery of the bergman cyclization was completed far in advance of the discovery of enediynes anticancer properties. The bergman cyclization or bergman reaction or bergman cycloaromatization is an organic. Request pdf an acyclic enediyne anticancer compound attributed to a bergman cyclization at physiological temperature enediyne cytotoxic drugs have attracted much attention because of their. The bergman cyclization is one of the most fascinating rearrangements in chemistry, with important implications in organic synthesis and pharmacology.
The person who associated a work with this deed has dedicated the work to the public domain by waiving all of their rights to the work worldwide under law, including all related and neighboring rights, to the extent allowed by law. Pdf dft calculations provide a reliable description of the bergman. Electronic control of the bergman cyclization acs publications. Preparation of conjugated polyphenylenes from maleimide. Ellman eugene higgins professor of chemistry, yale university 2010present professor of pharmacology, yale university 2010present professor of cellular and molecular pharmacology, uc san francisco 19992010 professor of chemistry, uc berkeley 19992010 associate professor of chemistry, uc berkeley 19971998 assistant professor of chemistry, uc berkeley 19921997. Bergman cyclization 1,8 napthalimide derivatives by. Electrophilic cyclization of aryldiacetylenes in the. Design and synthesis of heterocycle fused enediyne prodrugs activable at will pdf. Onsurface formation of onedimensional polyphenylene through bergman cyclization qiang sun, chi zhang, zhiwen li, huihui kong, qinggang tan, aiguo hu, and wei xu, college of materials science and engineering, key laboratory for advanced civil engineering materials ministry of education, tongji university, caoan road 4800, shanghai 201804, p. Bergman cyclization d d d d h h d d 200 oc gas phase. The enediyne antitumor antibiotics utilize complex molecular architectures to control delivery and activation of enediyne warheads, leading to their potent cytotoxicity. An ab initio exploration of the bergman cyclization. Cyclization onto carbonyl group by sp 3 or sp 2 carboncentered radicals and other related cyclizations. Incorporation of oxygen11a and nitrogen atoms11b,c into enediyne macrocyclic system promotes the cyclization, whereas thiaenediynes are.
More than 2,600 structures illustrate key concepts throughout the book. 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. Login after studying the bergman cyclization bc and related cyclizations, now when i look at compounds that im interested in, i think about how or if the bc might be employed in their synthesis or application. Chapters are organized according to the different cyclization intermediatescationic, radical, anionic, and metal complex intermediates. Activation energies for bergman cyclization see the solid line in the inset that connects the reactive carbon sites, c1 and c6, for species 3 and for the c1. Utilizing redoxmediated bergman cyclization toward the.
An accurate description of the bergman reaction using. The last chapter covers macrolactonization, vicinal tricarbonal, and bergman enediyne reactions, which are of particular interest today. The bergman cyclization is a challenging reaction to model because of the multiconfigurational nature of the diradical species. The bergman cyclization is a challenging reaction to model because of the multi configurational nature of the diradical species. The bergman cyclization forms a 1,4benzenediyl diradical a highly reactive species, that reacts with a h donor to give the corresponding arenes. Controlling the reactivity of bergman and myerssaito cyclizations. Best example of nazarov cyclization for csir net chemical science gate chemistry duration. The process involved a bergman cyclization bc as the key step of an unprecedented tandem radical reaction. Bergman cyclization, schreinerpascal cyclization, myerssaito cyclization, schmittel cyclization, garratt. Indeed, name reactions are not only the fruit of pioneering organic chemists, but also our contemporaries whose combined dis. The latter undergo spontaneous facile bergman cyclization at or below room. C5 photochemical cyclization of enediynes journal of. Media in category bergman cyclization the following 21 files are in this category, out of 21 total.
Isotope pattern analysis on the ms spectra of the conjugated polyphenylenes shows that the chain ends of the polymers consist of a considerable amount of unmasked. Assembly of fused indenesvia au i catalyzed c1c5 cyclization of enediynes bearing an internal nucleophile. Cheminform is a weekly abstracting service, delivering concise information at a glance that was extracted from about 200 leading journals. Bergman cycloaromatization an overview sciencedirect. Files available from the acs website may be downloaded for personal use only. Dft analysis shows that the barrier to the second cyclization is 5. The bergman cyclization allows the construction of substituted arenes through the thermal or photochemical cycloaromatization of enediynes in the presence of. Scheme 5 sunlightinduced bergman cyclization of strained orthodialkynylarenes. Russell photochemical and thermal bergman cyclization of a pyrimidineenediynol and enediynone. Intramolecular bergman cyclization results in diradical intermediates, and subsequently the formation of polyphenylene chains occurs due to radical. Reliable description of the diradical state requires incorporation of both dynamic and static electron correlation effects. Reviewing old knowledge while learning new old knowledge, is that not, after all, a pleasure.
What links here related changes upload file special pages permanent link page information wikidata item cite this page. Experiment and computational study on the regioselectivity of. To access a cheminform abstract, please click on html or pdf. Photochemical bergman cyclization and related photoreactions of enediynes. Investigating the cyclization of enediyne analogs using. Density functional theory was used to locate reactants, products, and transition states along the bergman. Reversible bergman cyclization by atomic manipulation. The bergman cyclization has strongly impacted on a number of fields including pharmaceutics, synthetic chemistry, and material science. Pdf an accurate description of the bergman reaction using. Note that the word spontaneous doesnt mean instantaneous but could be hours or days depending on structure. Ccsd t investigation of the bergman cyclization enediyne. Pdf reversible bergman cyclization by atomic manipulation.
Polymeric nanoparticles were synthesized through bergman cyclization mediated intramolecular chain collapse. Recent advances of the bergman cyclization in polymer science. Its multiple bonds are slightly longer than those in i or 9 figures 1 and 2, while the formal single bond. Cyclization onto olefinic group and aromatic group by sp 2 carboncentered radicals. Bergman cyclization i as well as for some reference reactions are summarized in tables 1 and 2. Intramolecular pericyclic reactions of acetylene derivatives leading to dehydroaromatic and related species volume. Thermal bergman cyclization of tetraalkynylporphyrins affords the dialkynylpicenoporphyrins in trace to 30 % yields, but no fully cyclized bispicenoporphyrin. View the article pdf and any associated supplements and figures for a period of 48 hours. This image for the bergman cyclization needs to be corrected. Pdf the bergman cyclization is one of the most fascinating rearrangements in chemistry, with important implications in organic synthesis and. 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. Unfortunately, they did not compute the activation barrier for this process.
Kc russell publications northern kentucky university. Department of chemistry, university of wisconsineau claire, p. The wording over the last arrow reads proton donor. The cyclization is induced thermally or photochemically. The occurrence of bergman cyclization is evidenced by ir and nmr spectroscopy. The bergman cyclization is an endothermic reaction and the formed 1,4.
H h cl cl rh ccl 4 heat heat radical 1,4 dehydrobenzene. This cyclization reaction is an electronic rearrangement where the 1,5diyne3ene. The bergman cyclization leads to the biradical 3, which adds to the. The electronic configurational mixing from a closed. Investigating the cyclization of enediyne analogs using density functional theory presented by dylan jay estep1 in partial fulfillment of the requirements for graduation with the deans scholars honors degree in biochemistry supervised by sean m. Incorporation of enediynes into anticancer drugs remains an intriguing yet elusive strategy for the design of therapeutically active agents. Bergman 1942 is a professor at the university of california, berkeley.
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