Synthesis of Symmetrical and Unsymmetrical 1,3-Diheteroarylbenzenes Through Palladium-Catalyzed Direct Arylation of Benzene-1,3-disulfonyl Dichloride and 3-Bromobenzenesulfonyl Chlorides

International audienceThe palladium-catalyzed synthesis of unsymmetrical 1,3-diheteroarylbenzenes was investigated. The first synthetic pathway relies on the desymmetrization of benzene-1,3-disulfonyl dichloride through two successive palladium-catalyzed direct desulfitative arylations with two different heteroarenes. The second strategy employs the orthogonal functionalization of 3-bromobenzenesulfonylchloride using an iterative C–H bond arylation sequence, namely, palladium-catalyzed direct desulfitative arylation followed by a palladium-catalyzed direct arylation step using aryl bromide as the coupling partner. The synthesis of symmetrical 1,3-diheteroarylbenzenes was also investigate

Synthesis of heterocycles via palladium-catalyzed coupling of vinylic halides and functionally-substituted alkenes

Palladium-catalyzed coupling is a very convenient and useful method for the synthesis of heterocycles in organic synthesis. We have successfully developed the palladium-catalyzed coupling of vinylic halides and functionally-substituted alkenes for the synthesis of oxygen and nitrogen heterocycles. The palladium-catalyzed coupling of vinylic halides and o-vinylic benzoic acids affords good yields of 3,4-dihydroisocoumarins under very mild reaction conditions. The palladium-catalyzed coupling of vinylic halides with o-vinylic and allylic phenols provides mixtures of 2,3-dihydrobenzofurans and 3,4-dihydrobenzopyrans in most cases with high isomeric ratios;This process has been applied successfully to the synthesis of nitrogen heterocycles. The palladium-catalyzed coupling of vinylic halides and olefinic sulfonamides provides pyrrolidines and piperidines in good yields. Like the analogous reactions of phenols, the palladium-catalyzed coupling of vinylic halides with o-vinylic and allylic anilines produces a mixture of 2,3-dihydroindoles and 1,2,3,4-tetrahydroquinolines with high isomeric ratios in most cases. Interestingly, the reactions of N-tosyl-o-isopropenylaniline provides 2,3-dihydrobenzazepines exclusively in moderate to good yields;The synthesis of carbocycles via palladium-catalyzed coupling hasn\u27t been accomplished successfully and further investigation is needed

Preparation of an Epoxide Precursor for Palladium-Catalyzed Trimethylenemethane Cycloaddition

In order to produce a highly functionalized five-membered ring useful for further synthetic processes via palladium catalysis, a series of precursors need to be synthesized in order to form the epoxide used in cyclic formation. First, a trimethylsilane alcohol is synthesized from beta-methallyl alcohol. The alcohol will then be subjected to Swern oxidation conditions, forming a TMS aldehyde. The aldehyde prepared will then undergo epoxidation, forming the desired precursor for Palladium catalyzed cycloaddition. These reactions occur in good conversion, and a good amount of epoxide is being amassed for use in the palladium-catalyzed cycloaddition research

Regioselective zincation of indazoles using TMP2Zn and Negishi cross-coupling with aryl and heteroaryl iodides.

The metalation of various SEM-protected functionalized indazoles with TMP2Zn provides 3-zincated indazoles which undergo palladium-catalyzed Negishi cross-couplings in good yields

Palladium-Catalyzed Cross-Coupling and Related Reactions of Non-Classical Electrophiles Focusing on Esters

This thesis summarizes work related to the development of mild palladium-catalyzed cross- coupling reactions of phenyl- and benzyl- esters, which undergo different C-O bond cleavage selectivity, the scope of the reactions and applications, and mechanistic understanding of precatalyst activation and the oxidative addition steps. The first chapter of this thesis is an introduction summarizing palladium-catalyzed cross-coupling reactions of non-classical electrophiles. The second chapter focus on the development of mild palladium-catalyzed non- decarbonylative Suzuk-Miyuara and Buchwald Hartwig cross-coupling reactions of phenyl aryl- and alkyl-esters to generate ketenes and amides, respectively. The third chapter is the extension of the Suzuki-Miyuara reactions to phenyl ester derivatives of aspartic acid to synthesize aryl amino ketones. Chapter four describes the development of mild palladium-catalyzed Suzuki-Miyuara reactions of diaryl methyl 2,3,4,5,6-pentafluorobenzoates to synthesize triarylmethanes.The first appendix describes preliminary work on palladium-catalyzed benzylic decarboxylation reactions as a more atom economical method for the synthesis of diarylmethanes. The second appendix describes preliminary work on palladium-catalyzed Suzuki-Miyaura reactions of activated aziridines and stoichiometric reactions of phosphine ligated nickel complexes with activated aziridines

Synthesis of carbo- and heterocycles via palladium-catalyzed annulation of alkenes and alkynes

In this dissertation, the synthesis of a wide variety of carbo- and heterocycles has been achieved via palladium-catalyzed annulation of vinylic cyclopropanes, vinylic cyclobutanes, 1,4-dienes and internal alkynes;The first part of the thesis discusses the palladium-catalyzed intermolecular arylation of functionally-substituted cyclic alkenes. The regioselectivity of the products significantly depends on the base employed in the reaction and the functional groups present on the cyclic olefin;The second part discusses the synthesis of benzofuran, indole, and tetrahydroquinoline derivatives via palladium-catalyzed annulation of vinylic cyclopropanes, vinylic cyclobutanes and 1,4-dienes. Ortho-functionalized aryl iodides react with these alkenes in the presence of palladium acetate and an appropriate base to afford carbo- and heterocycles with good regioselectivity;The third part of this thesis discusses the synthesis of 2,3-disubstituted indoles via palladium-catalyzed annulation of internal alkynes. The annulation process provides a convenient entry into variously substituted indoles;The fourth part discusses other examples of the palladium-catalyzed annulation of internal alkynes. The annulation provides disubstituted indene, benzopyran, isoquinoline, and isocoumarin derivatives regioselectively;In conclusion, the palladium-catalyzed annulation of alkenes and alkynes provides a convenient, new route to the synthesis of a wide variety of carbo- and heterocycles. The process also exhibits high regioselectivity, proceeds under mild reaction conditions in high yields, and accommodates a wide variety of functionality

Palladium-Catalyzed Oxidation of β-C(sp3)-H Bonds of Primary Alkylamines through a Rare Four-Membered Palladacycle Intermediate.

Site-selective functionalizations of C-H bonds are often achieved with a directing group that leads to five- or six-membered metallacyclic intermediates. Analogous reactions that occur through four-membered metallacycles are rare. We report a challenging palladium-catalyzed oxidation of primary C-H bonds β to nitrogen in an imine of an aliphatic amine, a process that occurs through a four-membered palladacyclc intermediate. The success of the reaction relies on the identification, by H/D exchange, of a simple directing group (salicylaldehyde) capable of inducing the formation of this small ring. To gain insight into the steps of the catalytic cycle of this unusual oxidation reaction, a series of mechanistic experiments and density functional theory (DFT) calculations were conducted. The experimental studies showed that cleavage of the C-H bond is rate-limiting and formation of the strained four-membered palladacycle is thermodynamically uphill. DFT calculations corroborated these conclusions and suggested that the presence of an intramolecular hydrogen bond between the oxygen of the directing group and hydroxyl group of the ligating acetic acid is crucial for stabilization of the palladacyclic intermediate

Palladium-Catalyzed Synthesis of N-Vinyl Pyrroles and Indoles

A stereospecific palladium-catalyzed N-vinylation of azaheterocycles with vinyl triflates is described. Cyclic and acyclic vinyl triflates along with nonnucleophilic azaheterocycles were found to be substrates for this palladium-catalyzed synthesis of N-vinyl pyrrole and indole derivatives

Syntheses of indoles and natural indole alkaloids from 2-nitrostyrene derivatives

A short and flexible synthesis of 2,3-disubstituted indoles employing a Barluenga-type palladium-catalyzed cross-coupling of p-tosylhydrazones with 2-nitroarylhalides followed by a palladium-catalyzed, carbon monoxide-mediated reductive cyclization was developed. Significantly better overall yields were obtained performing the two-step reaction sequence in a one-pot reaction. Secondly, in order to facilitate biological studies of ergotryptamine, a recently isolated ergot alkaloid, it was selected as a target for synthesis. In an attempt to synthesize ergotryptamine, a palladium catalyzed Kosugi-Migita-Stille cross coupling, a Mizoroki-Heck reaction, and a carbon monoxide-mediated palladium-catalyzed reductive cyclization were utilized as the key steps. Using a similar synthetic approach, synthesis of another indole norpsilocin, a component of magic mushroom, was accomplished in two additional steps. Additionally, a selection of β-acyl-β-alkyl substituted 2-nitrostyrenes were subjected to a palladium-catalyzed, carbon monoxide-mediated reductive cyclization. 2-Substituted 3-acylindoles with rearranged carbon skeleton were observed in all cases. In addition to indoles, small amounts of the corresponding quinolone-N-oxide and/or quinoline were isolated as side products in a number of cases. The cyclization precursors, β-acyl-β-alkyl substituted 2-nitrostyrenes, were synthesized via either a Wittig reaction or an aldol condensation. Finally, a short synthetic sequence leading to two marine diastereomeric azepino indole alkaloids hyrtioreticulins C and D was completed. A reductive amination via a trans-imination, a regioselective intramolecular Mizoroki-Heck reaction, and a palladium-catalyzed reductive cyclization were the major steps in the synthetic sequence

THIOUREA COMPOSITIONS AND USES THEREOF

The invention provides N,N'-disubstituted monothiourea or bis-thiourea-Pd(0) complexes that are useful as catalysts for palladium-catalyzed Heck reaction of aryl iodides and bromides with olefins, and as catalysts for palladium catalyzed Suzuki reactions of organoboric compounds and aryl halides.published_or_final_versio