Electrochemical generation of silver acetylides from terminal alkynes with a Ag anode and integration into sequential Pd-catalysed coupling with arylboronic acids

An electro-oxidative method for generating silver acetylides from acetylenes with a Ag anode was developed. The reaction could be integrated into a Pd-catalysed electrochemical Sonogashira-type reaction. In the presence of the catalytic amount of Pd(OAc)(2) and 4-BzO-TEMPO, electro-generated silver acetylides reacted immediately with arylboronic acids to afford the corresponding coupling adducts in high yields

Oxidative Carbonylation of Dipropargylarylamines

The catalytic oxidative methoxycarbonylation reaction of N,N-dipropargylarylamines has been investigated. PdCl2-CuCl2 has been studied as a catalytic system. Consecutive reactions of substitutive and additive methoxycarbonylation have been going in this process, which has been complicated by dimerisation, polymerization and cyclization processes. Apparently the results of process are determined by stability of intermediate reactionary complexes with participation of catalytic system PdCl2-CuCl2. The structures of synthesized cyclic amino triesters are established by analysis of experimental spectra NMR 1H and 13C, comparison with calculated spectra of possible hypothetic structures and estimation of thermodynamics properties by Joback fragmentation and MOPAC Semi-empirical PM3 methods

Part I: Studies toward the total synthesis of Trocheliophorolide A. part II: Studies on the development of a palladium-catalyzed carbonylative cross-coupling towards the synthesis of alkenyl alkynyl ketones

In Part I, efforts toward the total synthesis of a novel antibacterial γ-lactone, Trocheliophorolide A, are described. The natural product was isolated from Red Sea soft corals S. trocheliophorum and L. arboreum. Biological assays show that this compound exhibits significant growth inhibition of bacterial cell lines S. aureus and B. subtilis. The structure consists of an (S)-β-angelica lactone ring connected to an ynediene side chain. Our strategy employs synthesis of the lactone ring as a stannylfuranone, which will be Stille coupled with vinylidene dibromide to form an alkenyl bromide. This alkenyl bromide will be cross-coupled with an enynyl metal species to install the remainder of the sidechain, affording the target natural product. The stannylfuranone ring was constructed using a tandem palladium-catalyzed hydrostannation-lactonization protocol. In Part II, a study towards the synthesis of alkenyl alkynyl ketones via a novel palladiumcatalyzed carbonylative cross-coupling reaction of alkynyl halides and alkenylstannanes is discussed. Initial efforts have focused on optimization of the direct cross-coupling of the two components in the absence of carbon monoxide pressure antecedent to development of the carbonylative coupling reaction

Development of a Parallel Strategy for the Synthesis of a Library of 2-(3-Formyl-5-arylfuran-2-yl)ethylcarbamates from Dihydropyridinones

2,3-Dihydropyridin-4(1H)-ones were utilized as scaffolds for the syntheses of libraries of 5-arylethynyl-2,3-dihydropyridin-4(1H)-ones and 2-(3-formyl-5-arylfuran-2-yl)ethylcarbamates. 2,3-Dihydropyridin-4(1H)-ones were prepared from piperidones, ynones, and pyridones and used for the synthesis of a library of 5-arylethynyl-2,3-dihydropyridin-4(1H)-ones employing a Sonogashira reaction. Further reaction of these compounds using an Au(III)-catalyzed cyclization method yielded formylfurans. N-Boc and N-benzyl protected 2,3-dihydropyridin-4(1H)-ones were prepared for the Sonogashira reaction. N-Boc-protected 5-iodo-2,3-dihydropyridin-4(1H)-ones provided tert-butyl 5-arylethynyl-4-oxo-3,4-dihydropyridine-1(2H)-carboxylates in moderate to excellent yields while the N-Bn-protected enaminones provided low yields of 5-arylethynyl-1-benzyl-2,3-dihydropyridin-4(1H)-ones. Furan formation was achieved by Au(III)-catalyzed and Cu-mediated cyclizations. (±)tert-Butyl 1-(3-formyl-5-phenylfuran-2-yl)propan-2-ylcarbamates were obtained during the Sonogashira reactions catalyzed by Cu(I), while (±)tert-Butyl 1-(3-formyl-5-phenylfuran-2-yl)-3-phenylpropan-2-ylcarbamates were formed by the Au(III)-catalyzed cyclization. A library of 16 compounds of highly substituted furans was synthesized in moderate to excellent yields

Development of Methods for the Heteroatom Functionalization of Cyclopropenes

The main focus of this thesis is the stereoselective funtionalization of cyclopropenes mainly via the addition of H-X (hetroatom-hydrogen) moieties across the strained double bond. It is broken up into three chapters, each one devoted to different methods allowing for direct funtionalization of these uniquely interesting and highly reactive carbocycles. The first chapter is devoted to the palladium catalyzed hydrophosphorylation and hydrophosphinylation of cyclopropenes. This methodology allows for the direct ring retentive funtionalization of cyclopropenes with a pronucleophilic entity, which up until now has been extremely scarce. Aside from the synthetic value, the methodology also provides access to highly funtionalized stereodefined cyclopropylphosphonates which have a proven track record as medicinaly relevant substrates. The second chapter focuses on intermolecular formal nucleophilic substitutions of bromocyclopropanes. This method aims for the construction of highly functionalized cyclopropyl ethers via direct nucleophilic attack of O-based pronucleophiles to in situ generated, highly reactive cyclopropene intermediates. The diastereoselectivity of the reaction is controlled either by sterics or through directing effects providing highly streo-defined donor-acceptor cyclopropanes. Chapter three describes highly efficient and diastereoselective medium ring closures occurring upon intramolecular attack of a tethered alkoxide nucleophile at bromocyclopropane. The reaction proceeds via initial 1,2-dehydrobromination to produce a cyclopropene intermediate, followed by nucleophilic addition across the strained C=C bond, to produce cyclopropane-fused medium heterocycles

Palladium catalyzed reactions of 2-EN-4-YNE carbonates with organoboronic acids

Thesis (Master)--İzmir Institute of Technology, Chemistry, İzmir, 2011Includes bibliographical references (leaves: 60-64)Text in English; Abstract: Turkish and Englishxii, 248 leavesRecently, transition metal catalyzed carbon-carbon bond formation reactions gain numerous importance in organic chemistry. Especially, palladium catalyzed carbon-carbon bond formation reactions provide lots of advantages in organic synthesis. For instance, palladium catalyst is extensively used in many allene formation reactions of various substrates such as propargyl and enyne compounds. This thesis describes the preparation of E-configured aryl or alkenyl functionalized vinylallene structures via the reaction of a 2-en-4-yne carbonates with organoboronic acids in the presence of Pd (0) precursor. This method, which proceeds through formation of s-vinylallenylpalladium intermediate, is applicable for both (E)- and (Z)- configured enyne carbonates and appeared to have wider scope for both organoboronic acids and enyne substrates. The reaction of the carbonate of an enantiomerically enriched enynol reagent with phenylboronic acid under the optimal conditions was proceeded and center-to-axis chirality transfer selectivity was investigated. Complete racemization was observed

Synthesis and Photophysical Studies of Pyrrolocytosine Derivatives

Pyrrolocytosine (pC) derivatives are used in the study of nucleic acid structure, function and in the design of the hybridization probes. They have unique properties including small size and Watson-Crick base pairing capability and impressive fluorescent properties. However, they exhibit variation in the fluorescence properties upon incorporation into single-stranded DNA and double-stranded DNA. This study analyzes the effect of the nearest neighbours on the fluorescence properties of phenylpyrrolocytosine (PhpC) and provides a guide to the proper design of the PhpC containing fluorescent probes. Moreover, the possibility of photoinduced electron transfer (PET) as the underlying mechanism of the unusual photophysical behavior of PhpC in response to different nearest neighbours is investigated by measurement of the redox potentials of the PhpC. Furthermore, the possibility of the fluorescence resonance energy transfer (FRET) between PhpC and p-NO2-PhpC for potential utilization in the design of molecular beacons is investigated by fluorescence studies

Synthesis of heterocycles via palladium-catalyzed carbonylative annulation of internal and terminal alkynes

The subject of this dissertation is the study of palladium-catalyzed reactions of internal and terminal alkynes with ortho-substituted aryl iodides such as, o-iodophenols and N-substituted o-iodoanilines, in the presence of carbon monoxide (carbonylative annulation). The exploration of these reactions have led to the development of efficient syntheses of the important heterocycles coumarins and 2-quinolones.;3,4-Disubstituted coumarins are efficiently synthesized by the palladium-catalyzed annulation of internal alkynes by o-iodophenols in the presence of just one atmosphere of carbon monoxide. The use of a sterically unhindered pyridine base is essential to achieve high yields. The reaction accommodates a number of organic functional groups both on the alkyne and the o-iodophenol, thus affording a wide variety of coumarins in moderate to good yields. The main disadvantage of the process is formation of mixtures of regioisomers in reactions employing unsymmetrical alkynes.;The use of N-substituted o-iodoanilines as annulating agents provides an efficient synthesis of 3,4-disubstituted 2-quinolones. In this process, the selection of the nitrogen protecting group is crucial for the success of the reaction. The best results are obtained utilizing alkyl carbamates, tosylamides and trifluoroacetamides. The major features of this process are similar to those of the coumarin synthesis.;These annulation processes are the first examples of the insertion of an alkyne into the arylpalladium bond occurring in preference to the insertion of CO. We have shown that the unusual order of insertion arises from the low reactivity of the initially formed acylpalladium complex towards internal alkynes.;Utilizing the reaction conditions developed for the carbonylative annulation of internal alkynes we have been able to affect the carbonylative annulation of terminal alkynes by o-iodophenols or o-iodoaniline derivatives to afford coumarins or 2-quinolones, respectively, in modest yields. The formation of coumarins and 2-quinolones in this process is in stark contrast with all previously described palladium-catalyzed carbonylative annulations of terminal alkynes, which have afforded chromones and 4-quinolones. Moreover, under our reaction conditions terminal alkynes insert into the carbon-palladium bond instead of undergoing a Sonogashira-type coupling. This reaction pathway is confirmed by an isotope labeling experiment

Sonogashira Coupling Routes to Ortho-Alkynl-and- Fused-Ring Sydnones

In the present work, suitably functionalized arylsydnones were used to synthesize a variety of ortho-alkynyl sydnones both as potential precursors to novel sydnoquinolines and to provide non-linear optical (NLO) species of interest to Wright-Patterson Air Force Base (WPAFB). The versatile intermediate, 3-(2-(trimethylsilylethynyl)phenyl)sydnone, was prepared in good yield by the coupling of 3-(2-iodophenyl)sydnone with trimethylsilyl acetylene under Sonogashira conditions. From this intermediate, several ortho-alkynyl sydnones were prepared via a one-pot desilylation with tetrabutylammonium fluoride and Sonogashira coupling with para-substituted aryl iodides. In addition, a three-reaction-in-one-pot procedure was developed to access some of these species directly from 3-(2- iodophenyl)-sydnone. Subsequent reaction of these species with electrophiles has been examined as an avenue to novel sydnoquinolines. For example, there is evidence that the electrophile phenylselenyl chloride has induced cyclization of 3-(2- (phenylethynyl)phenyl)sydnone and 3-(2-(4-methoxyphenylethynyl)phenyl)sydnone in moderate yield. Similarly, concentrated sulfuric acid has effected cyclization of 3-(2- (phenylethynyl)phenyl)sydnone and 3-(2-(4-bromophenylethynyl)phenyl)sydnone, also in low yield. In contrast, trifluoroacetic acid and trifluoromethanesulfonic acid transform these species into novel cinnolines, presumably via sydnone ring cleavage followed by acid-induced cyclization. Sonogashira coupling routes were used to add additional para-alkynylphenyl moieties to the above-mentioned ortho-alkynyl sydnones and generate oligomeric alkynyl sydnones. The aim of this endeavor was to fulfill an interest of the United States Air Force in these species as ligands for the preparation of platinum-centered NLO materials. 3-(2-Ethynylphenyl)sydnone was synthesized from 3-phenylsydnone in a three-step process with an overall yield of 27% to analytically pure material. Similarly, 3-(2-(4- ethynylphenyl-ethynyl)phenyl)sydnone, was synthesized in seven steps at an overall yield of 21%, and 3-(2-(4-(4-ethynyl)phenylethynyl)phenylethynyl)phenyl)sydnone was synthesized in ten steps at an overall 11% yield. A great aid to obtaining these relatively high overall yields was the ability to perform multiple steps of the syntheses in one pot (e.g. three reactions in one pot) at certain points en route. Finally, the above oligomeric alkynyl sydnones were converted into the corresponding 3,4-dicarbomethoxypyrazoles (potential NLO monomers) in moderate to good yield by 1,3-dipolar cycloaddition with dimethylacetylene dicarboxylate