Eduardo Rubio

Intermolecular [2+2] Reaction of N‐Allenylsulfonamides with Vinylarenes: Enantioselective Gold(I)‐Catalyzed Synthesis of Cyclobutane Derivatives

Allenes are useful reagents for the [2+2] cycloaddition reaction, which is a powerful process for the synthesis of cyclobutanes. This carbocyclic motif is present in bioactive compounds and has unique reactivity. Gold catalysis triggers the functionalization of allenes and assists several intramolecular allenene reactions which allow the preparation of bicyclic frames that contain cyclobutane motifs. The gold-catalyzed enantioselective intramolecular [2+2] reaction of allenenes has been recently accomplished. 8] Moreover, racemic versions of related intermolecular processes have been disclosed. An enantioselective version is highly desirable as it would provide a yet unknown and straightforward entry into optically active cyclobutanes from readily available allenamides and alkenes, in a sole synthetic operation. We are pleased to report herein the first asymmetric gold-catalyzed intermolecular allenene[2+2] cycloaddition. At the start of this study, previous work on the goldcatalyzed cyclization of allenamides and alkenes supported a stepwise reaction (Scheme 1). The activation of the allene by the gold(I) catalyst facilitates a subsequent attack of the olefin. Further evolution of the cationic vinyl gold intermediate gives rise to the cyclobutane. Thus, it should be feasible to control the stereochemistry of the newly formed stereocenter from the remaining ligand on the gold catalyst. An exploratory survey to identify appropriate experimental conditions was conducted with sulfonylallenamide (1 a) and 4-methoxystyrene (2a), which were chosen as model compounds on the basis of the high reactivity previously observed (Scheme 2). Gold(I)-complexes derived from enantiopure phosphoramidite ligands were tested and gave satisfactory control of the enantioselectivity. Selected representative reaction conditions are summarized in Scheme 2. Interestingly, the depicted ligands, which are either commercially available or easy to prepare, produce excellent results at 70 8C after just one hour. Gold(I) catalysts obtained from (R,R)-bis(1-phenylethylamine) and either (R)-VANOL or the corresponding (S)-1,1’-spirobiindane7,7’-diol leading to (S)-SIPHOS-PE (L1 and L3, respectively) gave chiral cyclobutane 3a in good yield and enantioselectivity at an unusually low reaction temperature for a goldcatalyzed process, the low temperature can be used because of the high reactivity of the allene. In contrast, related gold(I)

Intramolecular iodoarylation reaction of alkynes : easy access to derivatives of benzofused heterocycles

The iodoarylation reaction of heteroatom-tethered omega-arylalkynes offers an efficient and straightforward entry to heterocycles. As a result, both C-C ring-closing from readily available precursors, and concomitant selective iodination take place. The first related study conducted in water is presented.

Intermolecular Reaction of Internal Alkynes and Imines: Propargyl Tosylates as Key Partners in a Gold-Catalyzed [4 + 1] Unusual Cyclization Leading to Cyclopent-2-enimines

Propargyl tosylates react with N-tosylaldimines to afford cyclopent-2-enimines in a gold-catalyzed process that involves a deep reorganization of both substrates. The formal [4 + 1] cyclization is initiated by a 1,2-migration of the tosylate that eventually generates a substituted 1,3-diene. Subsequent interaction with the imine launches a series of reaction steps prior to a Nazarov-like cyclization to yield the final product.

Discrimination of Diazo Compounds Toward Carbenoids: Copper(I)‐Catalyzed Synthesis of Substituted Cyclobutenes

In the last few years the role of diazo compounds in organic synthesis, particularly in cyclization reactions via metal carbenoids (metal: ruthenium, copper, rhodium, etc.) has been prominent. By taking advantage of the ease with which these metal carbenes collapse into the corresponding symmetrical alkenes (homocoupling), we and others have been able to access nonsymmetrical alkenes by the selective heterocoupling of diazoacetate esters with copper(I) and ruthenium(II) carbene complexes [Eq. (1)]. Interestingly, the metal-catalyzed selective cross-coupling reaction between two different diazo substrates has been reported recently [Eq. (2)].

First [4+2] cycloaddition of alkynyl Fischer carbene complexes with heterodienes. Facile synthesis of 1,4-dihydropyridines from 1-azadienes

Neutral 1-azadienes react in a [4 + 2] fashion with alkynyl Fischer carbene complexes to afford regioselectively substituted 1,4-dihydropyridines.

Intramolecular CH Activation through Gold(I)‐Catalyzed Reaction of Iodoalkynes

The cycloisomerization reaction of 1-(iodoethynyl)-2-(1-methoxyalkyl)arenes and related 2-alkyl-substituted derivatives gives the corresponding 3-iodo-1-substituted-1H-indene under the catalytic influence of IPrAuNTf2 [IPr=1,3-bis(2,6-diisopropyl)phenylimidazol-2-ylidene; NTf2=bis(trifluoromethanesulfonyl)imidate]. The reaction takes place in 1,2-dichloroethane at 80 °C, and the addition of ttbp (2,4,6-tri-tert-butylpyrimidine) is beneficial to accomplish this new transformation in high yield. The overall reaction implies initial assembly of an intermediate gold vinylidene upon alkyne activation by gold(I) and a 1,2-iodine-shift. Deuterium labeling and crossover experiments, the magnitude of the recorded kinetic primary isotopic effect, and the results obtained from the reaction of selected stereochemical probes strongly provide support for concerted insertion of the benzylic C-H bond into gold vinylidene as the step responsible for the formation of the new carbon-carbon bond.

Gold(I)-catalyzed hydroarylation reaction of aryl (3-iodoprop-2-yn-1-yl) ethers: synthesis of 3-iodo-2H-chromene derivatives

Summary An efficient entry to the preparation of elusive 4-unsubstituted-3-iodo-2H-chromenes has been accomplished as result of a catalytic cyclization. Thus, upon exposition of [(3-iodoprop-2-yn-1-yl)oxy]arenes to IPrAuNTf2 (3 mol %), in 1,4-dioxane at 100 °C, the desired heterocyclic motif is readily assembled. This process nicely tolerates a variety of functional groups and, interestingly, it is compatible with the presence of strong electron-withdrawing groups attached to the arene. The overall transformation can be termed as a new example of a migratory cycloisomerization and, formally, it involves well-blended 1,2-iodine shift and hydroarylation steps.

Synthesis and structure of ruthenium(IV) complexes featuring N-heterocyclic ligands with an N-H group as the hydrogen-bond donor: hydrogen interactions in solution and in the solid state.

The synthesis and characterization of novel ruthenium(IV) complexes [Ru(η(3):η(3)-C(10)H(16))Cl(2)L] [L = 3-methylpyrazole (2b), 3,5-dimethylpyrazole (2c), 3-methyl-5-phenylpyrazole (2d), 2-(1H-pyrazol-5-yl)phenol (2e), 6-azauracile (3), and 1H-indazol-3-ol (4)] are reported. Complex 2e is converted to the chelated complex [Ru(η(3):η(3)-C(10)H(16))Cl(κ(2)-N,O-2-(1H-pyrazol-3-yl)phenoxy)] (5) by treatment with an excess of NaOH. All of the ligands feature N-H, O-H, or C═O as the potential hydrogen-bonding group. The structures of complexes 2a-2c, 2e, 3, and 5 in the solid state have been determined by X-ray diffraction. Complexes 2a-2c and 3, which contain the pyrazole N-H group, exhibit intra- and intermolecular hydrogen bonds with chloride ligands [N-H···Cl distances (Å): intramolecular, 2.30-2.78; intermolecular, 2.59-2.77]. Complexes 2e and 3 bearing respectively O-H and C═O groups also feature N-H···O interactions [intramolecular (2e), 2.27 Å; intermolecular (3), 2.00 Å]. Chelated complex 5, lacking the O-H group, only shows an intramolecular N-H···Cl hydrogen bonding of 2.42 Å. The structure of complex 3, which turns out to be a dimer in the solid state through a double intermolecular N-H···O hydrogen bonding, has also been investigated in solution (CD(2)Cl(2)) by NMR diffusion studies. Diffusion-ordered spectroscopy experiments reveal an equilibrium between monomer and dimer species in solution whose extension depends on the temperature, concentration, and coordinating properties of the solvent. Preliminary catalytic studies show that complex 3 is highly active in the redox isomerization of the allylic alcohols in an aqueous medium under very mild reaction conditions (35 °C) and in the absence of a base.

Stereoselective cyclopropanation of 1-azadienes with Fischer carbene complexes

1-Aza-1,3-dienes, including a 1-aza-1,3,5-triene, are cyclopropanated by pentacarbonyl(methoxy)phenylchromium to give trans-cyclopropaneimines stereoselectively; their transformation into cyclopropane aldehydes and five-membered heterocycles is also described.

C-C Bond Formation between Fischer Carbene Complexes and Allylic Alcohols by a [3,4] Sigmatropic Rearrangement Promoted by a [1,2] M(CO)5 Shift.

A [1,2] M(CO)5 shift promotes a [3,4] sigmatropic rearrangement after the addition of allylic alcohols to Fischer alkenylcarbene complexes of tungsten or chromium in the presence of alkoxide ions. This opens a new synthetic route to the adducts 1. The reaction is also applicable to propargylic alcohols. [M]=Mo(CO)5 , W(CO)5 .