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International audience; Cycloisomerization of 1,6‐enynes to access azabicyclo[4.1.0]heptenes was achieved in the presence of commercially available [RuCl2(CO)3]2 after a comprehensive study on the electronic properties of ruthenium complexes. A series of 1,6‐enynes bearing an internal/terminal alkyne motif proved to be good candidates for substrates, giving their corresponding bicyclo[4.1.0]heptenes in good to excellent yields. Substitution patterns on either alkyne or alkene have no significant influence on the yields of bicyclic adducts.

International audience; The intramolecular [4+2] cycloadditions of dienynes was investigated using cobalt-based catalysts. Substrates without substitution on alkyne moiety were found to react under thermal activation. The use of a cobalt salt as catalyst made reactions cleaner by limiting the formation of byproducts. Cycloadditions with dienynes possessing a substituent on the alkyne pattern occurred only in presence of a cobalt catalyst which displayed a moderate to good activity depending on the substrate patterns.

International audience; Secondary phosphine oxides O = PHR 2 (SPOs) were identified as multitalented preligands for the chemoselective Pd-cata-lyzed oxidation of alcohols by a hydrogen-abstracting methodology. SPOs were found to promote the hydrogen-abstraction step as well as hydrogen transfer to a Michael acceptor by generating a putative active HÀPd species. The catalytic system operates under neutral conditions and was proven to be compatible with various electrophilic and nucleophilic func-tionalities within the substrates as well as water-and air-sensitive functional groups. The surge in transition-metal-based catalysis has unquestionably paved the way for the design of efficient catalytic systems in the field of the oxidation of alcohols, as evidenced by the numerous reports in this regard. [1] In particular, the recent ree-merging interest in using palladium(II)-based catalysts [2] in combination with oxygen [3] has conditioned the design of well-defined complexes for achieving highly selective transformations of primary or secondary alcohols into the corresponding aldehydes or ketones, respectively. [4] Such a Pd II-based approach typically involves a putative Pd–hydride species as the crossroads through alcoholate formation and subsequent b-H elimination. Completion of the catalytic cycle then requires either reoxidation of a Pd 0 species or direct reaction of HPdX with oxygen to regenerate the active catalyst (Scheme 1, pathway a). [5] Despite the clear environmental benefit of using oxygen and great advances achieved thereof, many serious issues such as intolerance of sensitive functional groups and the nature of the ligands may emerge in maintaining catalytic activity and/or regio-and chemoselectivity. [6] Alternatively, oxidizing alcohols in the absence of any formal reoxidant necessarily implies metal-mediated hydrogen transfers from the sub-strate to a hydrogen acceptor such as electron-poor alkenes. [7] This approach was recently termed " abstracting-hydrogen methodology " [8] (AHM) (Scheme 1, pathway b). Surprisingly, scarce literature precedent [9] in which this combination has convincingly been used proves that such a synergism remains to be harnessed. It should be noted that oxidation through hydrogen transfer is well documented within ruthenium chemistry. [7] However, most of the involved substrates are devoid of other functional groups, [10] probably owing to the high oxophi-licity of the metal and the basic conditions, which are usually required. The AHM-based approach is feasible if the HÀPd II species generated by alcohol oxidation reacts with the H-acceptor faster than it suffers from reductive elimination or a degradation process, and the quest for a multitalented preligand L is therefore of paramount importance. First, L should sufficiently provide electron density towards the metal but still maintain moderate steric hindrance. [11] Second, it should not promote intramolecular deprotonation of the PdÀH bond, which thus rules out a good number of bidentate nitrogen ligands. [12] Third, it should operate under neutral conditions to preserve the chemical integrity of both the PdÀH species and the sub-strate. Lastly, L would be synthetically useful only if it is both air and moisture stable and easy to handle. [13] In this context, finding an alternative to ligands that are able to stabilize HÀPd species such as pincer ligands is highly desirable. Our solution to tackle this vexing issue lies in secondary phosphine oxides [14] (SPOs, Scheme 2), which are air stable, [15] unaffected by water, [16] easy to handle, [14a] and good electron-donating preligands. [17] For instance, complex A, easily available from SPOs and Pd(OAc) 2 , [18] would be expected to generate a HÀPd species B through oxidation of an alcohol. Moreover, the six-membered hydrogen-bonded chelate structure of B would enable stabilization of a 14-electron cat-ionic Pd II complex, from which reductive elimination would be rather difficult. This peculiar structure would also allow strong minimization of the steric hindrance, as the edge between the P atom and the hydride could approach 1208. [19] In earlier studies, we noticed that treatment of Pd(dba) 2 (dba = dibenzylideneacetone) with rac-tert-butyl(phenyl)phos-phane oxide (L, 2 equiv.) and acetic acid (2 equiv.) in toluene resulted in the reduction of one C=C bond of the dba ligand (Scheme 3). [20] This result could be attributed to putative species C formed through ligand exchange. The loss of acetic acid would afford Pd II –hydride complex C, which upon loss of AcOH yields D. The latter then reacts with dba and AcOH to deliver E. This observation clearly highlights L as a Pd II ÀH generator preligand class, all the more so given that oxidative addition of AcOH to Pd 0 is known to proceed through an unfavorable equilibrium. [21] [a] Dr.

International audience; Palladium(II) acetate in association with secondary phosphine oxides provides an efficient catalytic system for [2+1] cycloadditions starting from oxanorbornene derivatives and tertiary propargyl esters giving rise to vinylidenecyclopropanes. This reaction is specific to bidentate phosphinito-phosphinous acid ligands generated from secondary phosphine oxides. The [2+1] cycloaddition was found broad in scope with a high tolerance to various functional groups. Moreover, vinylidenecyclopropanes were straightforwardly converted into oxabicyclo[3.2.1]oct-2-ene derivatives through a palladium-catalyzed ring-expansion. Finally, the oxa bridge cleavage of oxatricyclic compounds allows the obtention of functionalized 7-membered carbocycles.

Electron-rich half-sandwich ruthenium complex CpRuI(PPh3)2, generated in situ, catalyzed the coupling reaction of 7-azabenzonorbornadienes with alkynes to form 3a,9b-dihydrobenzo[g]indoles. This transformation involves the cleavage of one C-N bond of the bicyclic alkene and formation of two (C-C and C-N) bonds at the acetylenic carbons. The scope and limitations of the reaction are addressed according to the substitution patterns of the alkyne and of the substituent at the nitrogen atom of the azabenzonorbornadiene.

International audience; We disclosed therein a new reaction of reductive isomerization of methylenecyclopropanes (MCPs) to vinylcyclopropanes (VCPs).On treatment with sodium metal in liquid ammonia, MCPs bearing a C−O bond at allylic position undergo both a reductive cleavage of the C−O bondand an isomerization of the C−C double bond giving rise to VCPs. The scope of the reductive isomerization was investigated and showed a broad applicability since various functional groups are tolerated. MCP substrates were straightforwardly prepared by a palladium-promoted [2 + 1] cycloaddition between norbornene derivatives with alkynes.

Depending on the variation of the temperature and on the nature of the substituent of alk-1-ynes 2, the enantioselectivity of the deltacyclene formation in the cobalt catalysed [2+2+2] cycloaddition of norbornadiene 1 and acetylenes 2, can be achieved with up to 98%. The best enantioselectivities observed around 14 °C are in agreement with the Isoinversion principle (IIP).

International audience; An efficient palladium-catalyzed [2 + 1]cycloaddition between ynamides and norbornenes or norbornadienes is reported. Both phosphapalla- dacycles and palladium/secondary phosphine oxide catalytic systems were found to be competent for the transformation allowing the preparation of ami- nomethylenecyclopropanes. The reaction showed general applicability to various functionalized bicyclo[2.2.1]hept-2-enes and ynamides. A chiral phosphapalladacycle was tested to carry out this transformation in an enantioselective fashion.

International audience; Cycles everywhere: The selectivity in the transformations of 1,3-diones to carbo- cycles by palladium-catalyzed bisallylic alkylations is strongly dependent of the phosphine that is employed (see scheme). Moreover, synthesized vinylcy- clopentenes can be easily transformed into cyclohexadiene derivatives through a carbon carbon allylic bond cleavage.

International audience; Platinum complexes bearing phosphinous acids have efficiently promoted a tandem intermolecular sequence of [2+1]/[3+2] cycloaddition reactions. This process gave access to novel tricyclic systems and the cascade reactions were regio- and diastereoselective (see scheme; Cy=cyclohexyl). The [3+2] cycloaddition reaction was investigated further and two different alkyne partners were used.

The electrophilic activations of bicyclo[4.2.1]nonatrienes by 4-isopropyl-1,2,4-triazolinedione, N-iodosuccinimide, or an epoxidation/acidic ring-opening sequence is reported. The subsequent in situ trappings by water, alcohols, or benzoic acids led to original tricyclo[4.2.1.0(2,8)]non-3-enes with high regio- and stereoselectivities. The synthetic potentiality of these synthons is illustrated by the straightforward access to a fused cyclopropane featuring six consecutive controlled stereocenters.

The electron-rich cyclopentadienylruthenium complex CpRuCl(PPh3)2 turns out to be an efficient catalyst for the regio- and stereoselective cyclopropanation of bicyclic alkenes with tertiary propargylic carboxylates. The reaction provides 1,2,3-trisubstituted cyclopropanes in high yields as a single stereoisomer instead of the expected cyclobutenes via [2 + 2] cycloaddition. Functional groups such as ethers, esters, alcohols, phenols, ketones, esters, carboxylic anhydrides, nitriles, halides, sulfones, imides, carbamates, and azines are tolerated with the catalyzed reaction. An efficient cyclopropanation of cyclobutenes was also demonstrated, providing the strained bicyclo[2.1.0(1,3)]pentane framework.

Herrmann−Beller (H−B) phosphapalladacycle selectively catalyzed the addition of terminal alkynes across one double bond of norbornadiene to afford exo-5-alkynyl-bicyclo[2.2.1]hept-2-enes. The reaction shows general applicability to various functionalized alkynes and bicyclo[2.2.1]hepta-2,5-dienes. Insights into the mechanism of this reaction are discussed.

The cobalt-catalyzed [6+2] cycloaddition of cyclooctatetraene 1 with alkynes 3 affords monosubstituted bicyclo[4.2.2]deca-2,4,7,9-tetraenes 4 in fair to good yields. Due to the valence tautomerism, 1,3,5-cyclooctatriene 2, in equilibrium with bicyclo[4.2.0]octa-2,4-diene A, and alkynes 3 are converted to 10 and 11 according to [6+2] and [4+2] cycloadditions, respectively.

[reaction: see text] The CoI2(dppe)/Zn/ZnI2 system effectively catalyzes the [6 + 2] cycloaddition of cycloheptatriene with terminal alkynes to afford 7-alkyl-bicyclo[4.2.1]nona-2,4,7-trienes in fair to excellent yields. The catalyst proved to be tolerant toward functional groups such as ketone, sulfone, ester, ketal, ether, alcohol, imide, and nitrile. The enantioselective cycloaddition of CHT and phenylacetylene with BINOL phosphoramidite ligand 4 afforded the cycloadduct 3a (R = Ph) in 91% yield and 74% ee.

When copper salts are added to a mixture of 3,5-dimethylpyrazole and ethyl-acrylate, a substitution reaction between dimethylpyrazole and ethylacrylate is observed.

The cyclodimerization of several functionalized dienes with nickel(0) catalysts has been studied. When a functional group, such as a methoxycarbonyl or a trimethylsiloxy group, is bonded directly to the terminal carbon of the diene grouping, a completely regio- and stereo-selective dimerization is observed and trans -1,2-disubstituted cycloocta-3,7-dienes are formed in good yields (80–90%). When one carbon atom separates the functional group from the diene group, the yield drops significantly (to 30%), and the stereoselectivity and the clean nature of the reaction are completely lost. The effect of the nature of the nickel catalyst and the influence of the reductive organoaluminum species are discussed. The particular structure and the stereochemical features of the cyclooctadiene derivatives allow a better understanding of the various steps involved in the catalytic process. A reaction mechanism is proposed.

This dissertation focuses on cyclization reactions of 1,6-enynes involving ruthenium catalysts. Three different types of cyclization were developed from readily available precursors, such as 1,6-enynes and alkynes. In one application, a novel ruthenium-catalyzed hydroalkynylative cyclization of 1,6-enynes using terminal alkynes as co-reactants was explored. This reaction provides and entry to five-membered rings featuring an exocyclic 1,5-enyne motif. A neutral electron-rich ruthenium complex Cp*Ru(cod)Cl proved to be the catalyst of choice for these transformations. In another application, using the same complex, the ruthenium-catalyzed [2+2+2] cycloaddition of 1,6-enynes and alkynes was developed. Both internal and terminal alkynes were suitable substrates to access bicyclohexadienes with high yields in a single step. An intriguing ruthenium-catalyzed bicycloannulation of nitrogen-tethered 1,6-enynes has also been developed. For these cyclizations, only the electrophilic and alkynophilic ruthenium complex [RuCl2(CO)3]2 was able to perform the reaction. The exclusive formation of 3-azabicylo[4.1.0]hept-1-enes was observed with 1,6-enynes featuring an internal alkyne unit. These cyclization reactions fulfil the atom-economical reactions principle and are discussed on the basis of their mechanisms of formation., Cette thèse porte sur les réactions de cyclisation des 1,6-enynes impliquant des catalyseurs de ruthénium. Trois types différents de cyclisation ont été élaborés à partir de précurseurs facilement disponibles, tels que les 1,6-enynes et alcynes. Dans un premier temps, une nouvelle cyclisation hydroalcynylante des 1,6-enynes, à l'aide d'alcynes terminaux comme co-réactifs, catalysée par le ruthenium a été explorée. Cette réaction fournit une méthode de synthèse de cycles à cinq chaînons doté d'un motif 1,5-enyne exocyclique. Un complexe du ruthenium neutre et riche en électrons, Cp*Ru(cod)Cl, s'est avéré être le catalyseur de choix de ces transformations. Dans un deuxième temps, en utilisant le même complexe, la cycloaddition [2+2+2] des 1,6-enynes et alcynes catalysée par le ruthénium a été développée. Les alcynes internes et terminaux sont appropriés pour accéder en une seule étape aux bicyclohexadienes avec de hauts rendements. Une bicycloannulation inhabitelle des 1,6-enynes, intégrant un atome d’azote, catalysée par le ruthénium a également été élaborée. Pour ces cyclisations, seul un complexe du ruthénium électrophile et alkynophile tel que [RuCl2(CO)3]2 a été en mesure d'effectuer la réaction. La formation exclusive des 3-azabicylo[4.1.0]hept-1-enes a été observée avec les 1,6-enynes dotés d'une unité alcyne interne. Ces réactions de cyclisation, respectant le principe des réactions à économie d’atome, sont discutées et sur la base de leur mécanisme de formation.

In this manuscript, we have described an access to bicyclo[2.1.0]pentanes via two metal-Catalyzed reactions, namely a platinum-Catalyzed cycloisomerization of heteroatom-Tethered 1,6-Enynes and the subsequent ruthenium-Catalyzed cyclopropanation of cyclobutenes with tertiary propargyl carboxylates.First, we have developed the Pt(II)-Catalyzed formation of cyclobutenes from nitrogen and oxygen-Tethered 1,6-Enynes to form aza- and oxabicyclo[3.2.0]hept-6-Enes respectively. It is shown that the presence of alkyl substituent(s) at propargyl position and the use of weakly coordinating solvents such as DMA are the key elements favoring the formation of cyclobutenes.Second, the availability of cyclobutenes from the cycloisomerization of 1,6-Enynes has allowed their utilization for the construction of strained bicyclo[2.1.0]pentane structures as single diastereomers in good to excellent yield through a ruthenium-Catalyzed cyclopropanation. It provides a safe method which avoid the use of the hazardous diazo compounds precursors of carbenes to generate functionalized bicyclo[2.1.0]pentane frameworks in high yields under mild conditions., Dans ce manuscrit, nous avons décrit l'accès aux dérivés bicyclo[2.1.0]pentanes via deux réactions métalo-Catalysées, à savoir une cycloisomérisation d’énynes-1,6 catalysée par le platine et la cyclopropanation de cyclobutènes catalysée par le ruthénium à l’aide carboxylates propargyliques tertiaires. Tout d'abord, nous avons développé la formation, catalysée par Pt(II), de cyclobutènes à partir d’énynes-1,6 reliés par un hétéroatome (azote ou oxygène) pour former les aza- et oxa-Bicyclo[3.2.0]hept-6-Ènes respectivement. Il est montré que la présence de substituant(s) alkyle(s) en position propargylique et l'utilisation de solvants faiblement coordonnés, tels que le DMA sont les caractéristiques principales favorisant la formation de cyclobutènes. Ensuite, la disponibilité de cyclobutènes issus de la cycloisomérisation des 1,6-Énynes a permis leur utilisation pour la construction de systèmes bicyclo[2.1.0]pentanes par la mise en œuvre d’une cyclopropanation catalysée par le ruthénium utilisant les carboxylates propargyliques tertiaires. Ces composés sont obtenus sous la forme d’un diastéréomère unique avec des rendements bons à excellents. Cette réaction fournit une alternative sûre aux méthodes utilisant les dangereux composés diazo précurseurs de carbène pour générer les bicyclo[2.1.0]pentanes fonctionnalisés dans des conditions douces et avec des rendements élevés.