Theoretical investigations have elucidated the mechanism of metal. Pyrazole is a simple aromatic ring an organic compound of the heterocyclic series that characterized fivemembered ring structure which comprises located adjacent two nitrogen atoms and three carbon atoms. Synthesis of n alkyne substituted methyl 1hpyrrole2carboxylate derivatives 7ad. There are two reasons for less reactivity of alkynes towards electrophillic addition reactions. Differences between nucleophilic, radical and electrophilic trajectories. Groups that are trans on the alkene will end up trans on the cyclopropane product. Formationofcsp boronate esters by borylativecyclization of. Synthesis of heterocycles via electrophilic cyclization of. Iodinemediated synthesis of heterocycles via electrophilic. Cyclization with palladium chloride in the presence of allyl bromide or electrophilic alkenes allowed for the intermediate vinylpalladium species to be trapped by the electrophile. Iodinevisible light photocatalysis for activation of.
Gold catalysed electrophilic cyclization reactions. Silver catalysed electrophilic cyclization reaction. Department of science, faculty of education, mus alparslan university, p. Electrophilic addition reactions the most common reactions of the alkenes are additions across the double bond to form saturated molecules. First, n alkyne substituted pyrrole ester derivatives were synthesized. Efficient routes towards the synthesis of pyrrolopyrazinone, pyrrolotriazinone and pyrrolooxazinone have been developed. Imidazoles from ketenimines and propargylic amines by silver. An unusual palladium migration has also been explored and applied to the synthesis of fluoren9ones.
Abstarct of the thesis entitled regioselective synthesis of polyheterocycles by the electrophilic iodocyclization of alkynes and metalcatalyzed diversification to be submitted by ms. Photocatalytic organic synthesis needs photocatalysts to initiate the reactions and to control the reaction paths. Synthesis of pyrazoles via electrophilic cyclization of alkynes containing thiophene volume. Synthesis of heterocycles and carbocycles by electrophilic. Competition studies in alkyne electrophilic cyclization reactions. Synthesis of 23hfuranones via electrophilic cyclization.
The cyclization of 35 to give 36 illustrates a rare example of a formal 6endodigendotrig process. Electrophilic cyclization of aryldiacetylenes in the synthesis of. Alkyne, electrophilic cyclization, hydrazine, hydrazone, pyrazole. Development of new c n and c p bond formations with alkenes. Copper and platinum catalysed electrophilic cyclization reactions. Nonenzymatic electrophilic addition of water to alkynes results in the formation of a ketone or an aldehyde, depending on the starting alkyne. Intramolecular nucleophilic and electrophilic cyclization of nalkynesubstituted pyrrole esters is described. Thus, enol ether 33 reacts in methanol to give heterocycle 34 as the only isolated product scheme 8. A variety of highly substituted 23hfuranones are readily prepared from 3alkynoate esters and the corresponding acids via electrophilic cyclization. The substitution pattern about the product arene is determined in two steps. Dec 01, 2005 a wide variety of substituted naphthalenes are readily prepared regioselectively under mild reaction conditions by the 6endodig electrophilic cyclization of appropriate arenecontaining propargylic alcohols by icl, i2, br2, nbs, and phsebr. First, nalkynesubstituted pyrrole ester derivatives were synthesized. Related cyclization of silyl enol ethers with alkynes catalyzed by wco. Competition studies in alkyne electrophilic cyclization.
Recent advances in the synthesis of thiophene derivatives. Feb 06, 2009 a wide range of carbocycles and heterocycles have been prepared by the electrophilic cyclization of functionallysubstituted alkynes 1 and by transition metalcatalyzed annulations. Pdf synthesis of pyrazoles via electrophilic cyclization of alkynes. Cbonds to generate new polycyclicframeworks such as borylated.
The electrophilic cyclization of functionallysubstituted alkynes is a very promising route to an extraordinary range of medicinallyinteresting, functionallysubstituted heterocycles and carbocycles. Applications for novel 3arylisoquinoline syntheses john d. Available photocatalytic systems rely on electron transfer or energy transfer between the photoexcited catalysts and the substrates. Electrophilic phosphorus species generated in situ from secondary phosphine oxides and tf2o smoothly couple with alkynes possessing pendant nucleophiles to afford the corresponding phosphinated cyclization products in good yield. For example, phenylacetylene affords both 1,3,5 and 1,2,4c 6 r 3 h 3. Regioselective synthesis of polyheterocycles by the. The required diarylalkynes have been prepared by consecutive sonogashira reactions of appropriately substituted aryl halides and competitive cyclizations have been performed using i2, icl, nbs and phsecl as electrophiles. Palladium and electrophilic cyclization approaches to. In particular, electrophilic cyclization has been used for the synthesis of a variety of heterocycles, including benzobfurans, isochromenes, dihydroisoquinolines, isobenzofurans and coumestans. Many variations have been developed including cyclization of mixtures of alkynes and. In some reactions, alkynes are less reactive than alkenes. Synthesis of heterocycles via electrophilic cyclization of alkynes.
Nucleophilic and electrophilic cyclization of nalkyne. Metal cyclopropyl carbenes in the reactions of alkynes. Palladium and electrophilic cyclization approaches to carbo. The process is of historic interest as well as being applicable to organic synthesis. Recent advances in the synthesis of thiophene derivatives by cyclization of functionalized alkynes raffaella mancuso and bartolo gabriele, dipartimento di chimica e tecnologie chimiche, universita della calabria, via p. Terminal alkynes are essential to achieve bicyclic pyrrolofused pyridinones by a 6exodig process, while the presence of a phenyl group at the cc triple bond promotes the 7endodig cyclization giving pyrroloazepines. A vinylic carbocation is a key intermediate, and the reaction is accelerated with the use of a catalytic amount of strong acid. Neither product arises from a rearrangement of a carbocation. These heterocycle rings can be formed through endo or exocyclization modes, depending on. Recently, we and others have reported that the electrophilic cyclization of alkynes using. Such reactions are represented by the following general equation, where x and y represent elements in a compound that are capable of being added across the bond system of an alkene to form a. A wide range of carbocycles and heterocycles have been prepared by the electrophilic cyclization of functionallysubstituted alkynes 1 and by transition metalcatalyzed annulations. Net antimarkovnikov addition of water, tautomerization of enol to aldehydes for terminal alkynes.
This approach represents astepeconomical reaction which would simultaneously create new csp2. Recent advances in the synthesis of thiophene derivatives by. Groups that are cis on the alkene will end up cis on the cyclopropane product. The relative reactivity of various functional groups toward alkyne electrophilic cyclization reactions has been studied. Synthesis of heterocycles through electrophilic cyclization of alkynes containing heteroatom was reported. C n and c p bond formations via a traditional nucleophilic amination and phosphination and bd umpolung electrophilic amination and phosphination.
Antinucleophilic attack on the activated gold complex. Swager department of chemistry, massachusetts institute of technology, 77 massachusetts avenue, cambridge, massachusetts 029 received may 17, 1999 pyrylium salts have found uses in many areas of. Leading chemists from around the world provide authoritative firsthand information, including experimental procedures that offer readers. Due to greater electronegativity of sphybridized carbon atoms of a triple bond than sp2 hybridized carbon atoms of a double bond, pieelectrons o. Promoted electrophilic cyclization reaction of alkynes. Jan 19, 2007 synthesis of heterocycles and carbocycles by electrophilic cyclization of alkynes. Nucleophilic and electrophilic cyclization of nalkynesubstituted. Bucci, 12c, arcavacata di rende cs 87036, italy these authors contributed equally to this work. Synthesis of 3sulfenyl and 3selenylindoles by the pdcu. The same electrophilic reagents that add to alkenes also add to alkynes.
Synthesis of benzobthiophenes by electrophilic cyclization. As such, the geometry of the alkene is preserved in the product. The cyclopropanation reaction of an alkene with a carbene takes place in a single step. Final salt metathesis with mo t bu egenerr tes a a to complete the catalytic cycle. Several formal heteroborylative cyclization reactions have been recently reported, but little physicalorganic and mechanistic data are known.
Pdf synthesis of substituted isoquinolines by electrophilic. A metalfree electrophilic phosphination reaction has been developed. We show the general twostep mechanism for electrophilic addition of. Depending on catalysts and conditions, alkynes add one or two equivalents of hydrogen. Intramolecular nucleophilic and electrophilic cyclization of n alkyne substituted pyrrole esters is described. Two competitive mechanisms i and ii were explored without or with 2,6. This electrophilic cyclization methodology has been applied to a variety of unsymmetrical. Free nis promoted electrophilic cyclization of alkynes. Preliminary nmr studies show that phosphirenium species may be involved as intermediates of the. Formationofcsp boronate esters by borylativecyclization. Mechanistic studies of formal thioboration reactions of. Nucleophilic and electrophilic cyclization of nalkynesubstituted pyrrole.
Nucleophilic cyclization reaction of compounds 7ad and acetylation of 12c. In this dissertation the scope and limitations of several electrophilic cyclization processes have been presented. Trimerization of unsymmetrical alkynes gives two isomeric benzenes. An efficient synthesis of iodo substituted pyrano4,3. The ultimate and only reference source in this field, this handbook discusses the latest advances on the reactions leading to the formation of cyclic structures and includes chapters presenting the most synthetically attractive cyclization reactions. Regioselective 5aendoadig electrophilic iodocyclization of. Synthesis of heterocycles via electrophilic cyclization of alkynes containing heteroatom. Jan 06, 2006 recently, we and others have developed efficient methods for the synthesis of various carbo and heterocyclic compounds through electrophilic cyclization of appropriate orthofunctionalized aromatic acetylenes. Alkynes characteristically undergo reactions that show that they are doubly unsaturated, meaning that each alkyne unit is capable of adding two equivalents of h 2, halogens or related hx reagents x halide, pseudohalide, etc. The electrophilic cyclization reactions of alkynes are a powerful approach for the preparation of functionalized isochromenes, which are key. Synthesisof2,3disubstitutedbenzofuransbythe palladium.
Jan 2017, accepted 07 apr 2017, published 04 may 2017. Cacchi and coworkers have previously reported the synthesis of 3iodobenzobfurans by the iodocyclization of alkynylphenols. For example, in a molecule with an ene and an yne group, addition occurs preferentially at the ene. The results indicate that the nucleophilicity of the. Pyrylium salts via electrophilic ortho cyclization. Being a cycloaddition reaction, it has high atom economy. Pyrazole is a simple aromatic ring an organic compound of the heterocyclic series that characterized fivemembered ring structure which. We show the general twostep mechanism for electrophilic addition of br2 to an alkene in figure 10. Jul 31, 2015 previous work on electrophilic cyclization using iodonium salts only succeeded when the alkyne substituent was capable of electronically stabilizing the vinyl cation intermediate e. Synthesis of nalkyne substituted methyl 1hpyrrole2carboxylate derivatives 7ad. Additions are the most common reactions using alkenes and alkynes addition to. Thus alkynes, like alkenes, undergo electrophilic addition reactions because of their weak pi bonds.
Pdf competition studies in alkyne electrophilic cyclization. Synthesis of pyrazoles via electrophilic cyclization of alkynes. Cyclization reaction an overview sciencedirect topics. Despite being less stable than an alkene, an alkyne is less reactive than an alkene, since reactivity depends on. Chapter 1 describes the synthesis of 2,3disubstituted benzobfurans by the palladiumcatalyzed coupling and electrophilic cyclization of terminal alkynes. Alkynes are characteristically more unsaturated than alkenes. Reaction in which the elements of water h and oh are. Development of new c n and c p bond formations with. Trapti aggarwal, department of chemistry, university of delhi for the award of doctor of philosophy. Pph3auntf2 was found to be an excellent catalyst to catalyze both of the friedelcrafts and furan alkyne cyclization reactions in the same vessel. Electrophilic reactions exercises chemistry libretexts. An unusual palladium migration has also been explored and applied to the synthesis of.
We now investigate the catalystfree formal thioboration reaction of alkynes to gain mechanistic insight into bchlorocatecholborane clbcat in its new role as an alkynophilic lewis acid in. Synthesis of heterocycles via electrophilic cyclization of alkynes containing heteroatom benhur godoi, ricardo f. Mechanistic studies of formal thioboration reactions of alkynes. Reaction in which halogen is introduced into a molecule 3 hydration.
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