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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 ruthenium-catalyzed 1,6-enyne cyclization in the presence of bulky substituted terminal alkyne proceeds smoothly at room temperature to afford highly substituted five-membered cyclic compounds featuring a 1,5-erryne Motif. Deuterium-labeling experiments showed that the key ruthenacyclopentene intermediate undergoes cleavage of metal carbon bonds through the metal-assisted sigma-bond metathesis reaction, thus leading to the formation of C(sp(2))-H and C(sp(3))-C(sp) bonds.

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.

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.

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 bond and 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.

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.

The diastereoselectivity of the unprecedented coupling reaction depends on the presence of substituents on the bridgehead positions of the substrates.

Several phosphinous acid-coordinated platinum complexes were prepared and characterized. In the presence of secondary phosphine oxide (2 equiv), PtCl2(cod) was converted to a series of cis/trans platinum complexes PtCl2[R1R2POH]2 featuring phosphinous acids (PAs) as ligands (20−29). A balance between the steric and electronic effects of ligands governs their coordination mode. NMR experiments and density functional theory calculations show that the anti conformer for trans complexes is favored by intramolecular H···Cl bonding. PtCl2[R1R2POH]2 treated with NEt3 (1 equiv) gave bimetallic platinum complexes cis-[Pt2(μ-Cl)2{(R1R2PO)2H}2] characterized by 31P NMR and X-ray diffraction. An unusual monometallic platinum complex, cis-[PtCl2{(i-Bu)2PO}2H]−[HNEt3]+ (30), was isolated and characterized as a possible intermediate in the formation of dinuclear species. Silver acetate and triethylamine both reacted with PtCl2[(t-Bu)2POH]2 to yield new bulky Pt(κ2-acetato){[(t-Bu)2PO]2H} platinum complex 31. The structu...

The enantioselective cobalt-catalyzed [6+2] cycloadditions of cycloheptatriene 1 with alkynes 2 is reported. Chiral phosphoramidites based on 3,3′-disubstituted (R)-BINOL appeared to be efficient ligands, affording the corresponding cycloadducts with good yields and up to 92 % ee. A vibrational circular dichroism study afforded the absolute configuration of new chiral (+)-(1S,6R)-7-phenyl[4.2.1]bicyclo- nonatriene 3a and (−)-(1S,6R)-7-trimethylsilyl[4.2.1]bicyclononatriene 3c.

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.

2-(Pent-4-ynyl)norbornadienes undergo an intramolecular [2 + 2 + 2] cycloaddition in the presence of (nbd)RuCl2(PPh3)2 as a catalyst affording annelated deltacyclenes in good to excellent yields. The usefulness of the reaction is illustrated by the straighforward conversion of pentacyclene 2a into the angularly fused triquinane 19.

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.

A variety of diastereomerically pure azabicyclo[3.2.0]heptenes and oxazabicyclo[3.2.0]heptenes is readily prepared by Pt-catalyzed cycloisomerization reaction of corresponding enynes (I) and (III), respectively.

The homo-Diels–Alder (HDA) reaction of norbornadiene (NBD) and internal functionalized alkynes leading to 8,9-disubstituted deltacyclenes using readily available electron-rich phosphine–ruthenium(II) catalysts is described.

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).

A series of 1,6-dienes is cyclized to cyclopentene derivatives under neutral conditions with palladium chloride in ethanol or with in situ generated LPd2+ in acetonitrile.

CpRu(PPh 3 ) 2 I generated in situ by mixing Cp-Ru(PPh 3 ) 2 Cl and methyl iodide catalyzed the [2+2] cycloaddition ol norbornene (or norbornadiene) and disubtituted alkynes to afford functionalized cyclobutenes.

Asymmetric formation of quaternary centers by allylic alkylation of β-ketoesters using the chiral palladium QUIPHOS catalyst has been achieved. The results obtained not only depend on the reaction conditions but also on the structural features of both β-ketoesters and allylating agents. Enantiomeric excesses of up to 95% have been observed.

The stereoselective formation of 8-substituted deltacyclanes by homo Diels–Alder (HDA) reaction using a phosphine modified nickel catalyst generated by reduction of Ni(acac) 2 with alkylaluminums is discussed. Depending on the nature of the alkene and on the nickel catalytic system, fair to excellent exo selectivity are observed. A switch in selectivity favoring the endo -cycloadduct is observed when the polar methoxycarbonyl group substituted alkene is activated with aluminum species.

Many palladium-catalyzed organic reactions with tailored ligands, besides the princess of asymmetric catalysis, allylic alkylation, are suitable for enantioselective organic synthesis. This is clearly illustrated by the large number of promising examples such as the Heck reaction, and Wacker-type oxidations, cycloadditions, cycloisomerizations, carbonylations, and copolymerization of alkenes with carbon monoxide.

Angular triquinanes such as (+)-silphinan-3,5-dione, silphin-3-en-3,5-dione or 2-bromosilphin-3-en-3,5-dione have been obtained from (+)-β-cedrene in seven steps and an overall yield of 8%.

The title reaction shows general applicability to various functionalized bicyclo[2.2.1]hept-2-enes, such as (I), (IV), (VII), (IX), and (XI) and ynamides.

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.

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.

Ultrasonics efficiently promotes the Ullmann-Goldberg condensation of 2-halogenobenzoic acids and primary aromatic amines to obtain various N-arylanthranilic acids.

Stereoselective dehydrative alkylation/annulation of hydroxy β-diketones, β-ketoesters or β-diesters using Mitsunobu conditions (Bu3P/DEAD) proceeds under mild and essentially neutral conditions affording cis fused bicyclic dihydrofurans in good yields.

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.

The diastereoselectivity of the unprecedented coupling reaction depends on the presence of substituents on the bridgehead positions of the substrates.

A one-step synthesis of disubstituted brendane derivatives is described starting from (commercially) available vinyl norbornene by the Wacker-type oxidation with PdCl2/CuCl2 or PdCl2/CuCln/O2 (n=1,2). In addition to the formation of a new carbon carbon bond two different nucleophilic groups are incorporated with complete chemio-, regio- and high (>90%) stereoselectivity. The NMR and X-Ray structure analysis of a σ-π-palladium-bipyridine complex clearly establishes the stereochemistry of the prerogative intermediate and the position of the coordinated vinyl group in an ‘extracyclic’ position before the insertion-cyclisation step. This stereochemistry establishes the oxidative cleavage of the cyclised (cis-insertion) organopalladium intermediate to proceed with predominant (90%) inversion of configuration. A further ring opening reaction via Baeyer-Villiger oxidation has been developed showing the usefullness of the brendane derivatives for an easy access to functionalized quinane system(s) with complete stereocontrol of 5 stereogenic centers.

Platinum complex PPT catalyzes the unprecedented intermolecular sequence performed with norbornadiene and alkynes.

The Herrmann—Beller phosphapalladacycle catalyzes the reaction at room temperature without addition of any base.

[6 + 2] Cycloadditions between cycloheptatrienes with allenes have been investigated. Cobalt salts were found to promote this transformation efficiently. Moreover, this reaction was found to be highly selective since only one regioisomer was obtained with an excellent E/Z-selectivity.

The Herrmann-Beller (H-B) phosphapalladacycle catalyzed the addition of terminal alkynes to unsymmetrical gem-disubstituted cyclopropenes to give alkynylcyclopropanes as single diastereomers in good to excellent yields. The stereofacial discrimination at the approach of the bulky alkynylpalladium species is believed responsible for the diastereoselectivity control of the addition reaction.

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.

International audience; [6 + 2] Cycloadditions between cycloheptatrienes with allenes have been investigated. Cobalt salts were found to promote this transformation efficiently. Moreover, this reaction was found to be highly selective since only one regioisomer was obtained with an excellent E/Z-selectivity.

An efficient intramolecular [2+2] photocycloaddition of alkyl hex-2-enopyranosid-4-uloses allows the construction of two new cyclic systems annelated to the pyranoside moiety with stereocontrol of 3 or 4 carbogenic centers. The regioselective ring cleavage of the cycloadducts affording new bicyclic pyranoid compounds is described.

Ultrasonics efficiently promotes the Ullmann-Goldberg condensation of 2-halogenobenzoic acids and primary aromatic amines to obtain various N-arylanthranilic acids.