Frank Rominger

Simple Gold‐Catalyzed Synthesis of Benzofulvenes—gem‐Diaurated Species as “Instant Dual‐Activation” Precatalysts

In the field of homogeneous transition-metal chemistry, gold plays a major role in the discovery of new reactions. Most of the transformations are based on the electrophilic activation of a multiple bond. The decrease of electron density upon p coordination of a carbophilic gold center allows nucleophilic attack. Now, in independent and parallel work the group of Zhang and our team have discovered a different reactivity which was so far unprecedented in the field of gold chemistry. Initial activation of an alkyne by s coordination to gold increases the nucleophilicity of the b-carbon atom of this alkyne. This first alkyne combines with a second alkyne, which is activated by p coordination, and highly reactive gold vinylidene intermediates are formed by this dual s/p activation. The Zhang group s publication on the synthesis of benzofulvenes now prompts us to publish our additional findings on that specific reaction. Since alkyl-substituted alkynes are readily available, a new fascinating reaction pathway was opened for the gold vinylidene intermediates. The first two elementary steps of this reaction are identical to the previous reactions, which seem to be general for this new sector of gold catalysis. Herein we report on the use of tertiary alkyl groups, the isolation of gem-diaurated species which prove to be ideal precatalysts for this type of transformation, the dynamics of the equilibrium involving these diaurated species, and the catalyst transfer in the context of a detailed mechanistic discussion. We investigated several diyne systems 1 with a terminal alkynyl group and a tert-alkyl-substituted alkynyl group as potential substrates for the gold(I)-catalyzed intermolecular arene addition. A new reaction was observed, the clean formation of a benzofulvene derivative, a class of compounds that usually is not easily available. No incorporation of the solvent benzene was observed. To optimize the reaction, we performed reactions of substrate 1 a (Table 1) with different gold catalysts and different counterions (see the Supporting Information); the well-established catalyst [(IPr)AuCl], in combination with AgNTf2 gave the best results. To evaluate the substrate scope, a small library of substrates was transformed to the corresponding products under the optimized conditions (Table 1). One advantage of substrates 1 is their easy two-step synthesis (Sonogashira reaction, Seyferth–Gilbert homologation) from commercially available 2-bromobenzaldehydes. With our test substrate 1a,

Cyclization of Propargylic Amides: Mild Access to Oxazole Derivatives

The substrate scope, the mechanistic aspects of the gold-catalyzed oxazole synthesis, and substrates with different aliphatic, aromatic, and functional groups in the side chain were investigated. Even molecules with several propargyl amide groups could easily be converted, delivering di- and trioxazoles with interesting optical properties. Furthermore, the scope of the gold(I)-catalyzed alkylidene synthesis was investigated. Further functionalizations of these isolable intermediates of the oxazole synthesis were developed and chelate ligands can be obtained. The use of Barluengas reagent offers a new and mild access to the synthetically valuable iodoalkylideneoxazoles from propargylic amides, this reagent being superior to other sources of halogens.

Mechanistic Switch in Dual Gold Catalysis of Diynes: C(sp3)–H Activation through Bifurcation—Vinylidene versus Carbene Pathways

The other side of the mountain: Changing the framework of diyne systems opens up new cyclization modes for dual gold catalysis. Instead of a 5-endo cyclization and gold vinylidenes a 6-endo cyclization gives rise to gold-stabilized carbenes as key intermediates for selective C-H insertions.

Gold Vinylidene Complexes: Intermolecular C(sp3)H Insertions and Cyclopropanations Pathways

Highly reactive gold vinylidene species are used for intermolecular C(sp(3))-H insertions into unactivated alkanes (see scheme). In addition, they can be regarded as synthons for alkylidene carbenes. Initiated by cyclopropanation of the vinylidene species/alkylidene carbenoide, cyclobutene derivatives are formed in a diastereoselective fashion by a ring-enlargement cascade in only one step.

Gold and Palladium Combined for Cross-Coupling†

The use of gold catalysts as highly active tools for efficient and atom-economic transformations continues to grow exponentially. In contrast to other transition metals, the most significant limitation of homogeneous gold catalysts seems to be the inferior ability of gold to change oxidation states during catalytic cycles. Of the few reported homogeneous gold-catalyzed coupling reactions in which changes in oxidation states in catalytic cycles are presumed, they are all accomplished at elevated temperatures wherein heterogeneous catalysis should at least be considered. One approach to broadening the scope of gold-catalyzed coupling reactions was accomplished by the use of external stoichiometric oxidants instead of oxidation by the substrate. 4] Whereas recently only symmetric molecules could be synthesized by the oxidative dimerization of gold(III) intermediates, Zhang and co-workers reported an impressive oxidative crosscoupling reaction using Selectfluor as reoxidizing reagent. In our opinion, there is another option to extend the scope of homogeneous gold chemistry: the transmetalation of the in situ generated organogold species A to other transition metals such as palladium species B (Scheme 1). In these reactions strong stoichiometric oxidizing reagents could be avoided, and the reluctance of the gold species to undergo an oxidation state change could become an advantage as the orthogonal reactivity of the two metals could guarantee highly selective reactions. Our initial experiments to achieve a double catalytic conversion gave only low yields, potentially caused by the ligand exchange processes between the two different metal centers. Therefore we decided to turn to transmetalation experiments using stoichiometric amounts organogold compounds to simplify the reaction conditions. To the best of our knowledge, a general study of the transmetalation abilities of organogold compounds with catalytic amounts of palladium is lacking. So far there are only few examples for transmetalation and gold. Herein we present a study of the gold/palladium system by using stoichiometric amounts of organogold compounds and catalytic amounts of palladium complexes in cross-coupling reactions. Our initial foray into the cross-coupling of organogold intermediates began with an assessment of palladium catalysts 1–7 (Figure 1) for the model reaction of iodobenzene and triphenylphosphine vinyl gold 8a. Of the different

Gold-Catalyzed Highly Selective Photoredox C(sp2)−H Difluoroalkylation and Perfluoroalkylation of Hydrazones

The first gold-catalyzed photoredox C(sp(2) )-H difluoroalkylation and perfluoroalkylation of hydrazones with readily available RF -Br reagents is reported. The resulting gem-difluoromethylated and perfluoroalkylated hydrazones are highly functionalized, versatile molecules. A mild reduction of the coupling products can efficiently produce gem-difluoromethylated β-amino phosphonic acids and β-amino acid derivatives. In mechanistic studies, a difluoroalkyl radical intermediate was detected by an EPR spin-trapping experiment, indicating that a gold-catalyzed radical pathway is operating.

Stable Hexacenes through Nitrogen Substitution

The stabilization of larger acenes is a demanding task both synthetically as well as conceptually to be solved in different ways. Neither unsubstituted hexacene nor its higher homologues are stable, but their existence can be demonstrated in suitable matrixes. In the case of pentacene, two strategically attached TIPS-ethynyl groups suffice to fully stabilize and solubilize this material (TIPS = triisopropylsilyl). In larger acenes, however, two TIPS-ethynyl groups do not provide enough stabilization to furnish long-term persistent representatives. Anthony et al. demonstrated that even sterically encumbered hexacenes (with two tris(trimethylsilyl)silylethynyl substituents) react in solution under butterfly dimerization with a half-life of around 20 minutes. Only the introduction of four more aryl groups in lateral positions increases the stability of higher acenes so far that the Wudl and Chi groups could obtain persistent heptacene derivatives with a half-life of up to one week in solution. But even here, formation of endoperoxides is observed after some time. The laterally attached phenyl groups lead to isolation of the p systems with respect to their next neighbors, as evidenced by single-crystal structure analysis. We demonstrate herein that nitrogen atoms introduced into the acene skeleton give persistent disubstituted heterohexacenes, which are stable even when stored for longer periods of time. The palladium-catalyzed coupling of 1 with 2 in the presence of the ligand L gave the tetrazaacene 3 after oxidation with MnO2 in good yields (Scheme 1). [8, 9] The dichlorobenzoquinoxaline 4 also couples in good yields to give 5 (Scheme 2) However, attempts to oxidize 5 by MnO2, IBX = 2-iodoxybenzoic acid, N-bromosuccinimide (NBS), potassium chromate, pyridinium chlorochromate (PCC), or Cu(OAc)2 were fruitless. Difficult-to-separate product mixtures formed, but not the desired acene. This behavior was not entirely unexpected, as Kummer and Zimmermann had already unsuccessfully attempted to oxidize 6, readily obtained by co-melting of diaminonaphthalene and dihydroxyanthracene at 220 8C, using chloroanil or PbO2. Azahexacenes remained unknown. To maximize the shielding effect of the TIPS groups, it might be better to attach them in the center of the molecule. Consequently, 7a,b were coupled to 2 (Scheme 3). The Pdcatalyzed coupling works very well in the presence of L and furnishes 8a,b in good to excellent yields (92 %, 56%). Both are dehydrogenated by MnO2 into the azaacens 9 a,b in 56% and 74% yield, but it is not clear why this reaction does not work for 5. The heteroacenes 9a and 9b are greenish black crystalline powders, stable under laboratory conditions both as solids and in solutions, which display a green-yellow color. By NMR spectroscopy we could not detect endoperoxide formation or dimerization of 9 to butterfly cycloadducts. In our case, triisopropylsilyl and even the triethylsilyl groups are sufficient to stabilize and solubilize the hexacene skeleton, but 9b is considerably less soluble than 9a. To extend this chemistry, we prepared 7c in a multistep synthesis starting from diaminoScheme 1. Palladium-catalyzed synthesis of 3. dba = dibenzylideneacetone.

The First Catalytic Synthesis of an Acrylate from CO2 and an Alkene—A Rational Approach

For more than three decades the catalytic synthesis of acrylates from the cheap and abundantly available C(1) building block carbon dioxide and alkenes has been an unsolved problem in catalysis research, both in academia and industry. Herein, we describe a homogeneous catalyst based on nickel that permits the catalytic synthesis of the industrially highly relevant acrylate sodium acrylate from CO(2), ethylene, and a base, as demonstrated, at this stage, by a turnover number of greater than 10 with respect to the metal.

Gold-catalyzed synthesis of chroman, dihydrobenzofuran, dihydroindole, and tetrahydroquinoline derivatives.

Different furans containing an ynamide or alkynyl ether moiety in the side chain were prepared. The gold-catalyzed transformation of these compounds delivered dihydroindole, dihydrobenzofuran, chroman, and tetrahydroquinoline derivatives at room temperature through very fast reactions. Furthermore, the stabilizing effect of the heteroatom directly attached to the intermediate arene oxides led to highly selective reactions, even in the case of only mono-substituted furans, which is quite different from previous results obtained with non-heteroatom-substituted alkynes.

Dual Gold Catalysis: σ,π‐Propyne Acetylide and Hydroxyl‐Bridged Digold Complexes as Easy‐To‐Prepare and Easy‐To‐Handle Precatalysts

A series of dinuclear gold σ,π-propyne acetylide complexes were prepared and tested for their catalytic ability in dual gold catalysis that was based on the reaction of an electrophilic π-complex of gold with a gold acetylide. The air-stable and storable catalysts can be isolated as silver-free catalysts in their activated form. These dual catalysts allow a fast initiation phase for the dual catalytic cycles without the need for additional additives for acetylide formation. Because propyne serves as a throw-away ligand, no traces of the precatalyst are generated. Based on the fast initiation process, side products are minimized and reaction rates are higher for these catalysts. A series of test reactions were used to demonstrate the general applicability of these catalysts. Lower catalyst loadings, faster reaction rates, and better selectivity, combined with the practicability of these catalysts, make them ideal catalysts for dual gold catalysis.