Nickel-Catalyzed Intramolecular Hydrosilylation of Alkynes: Embracing Conventional and Electrochemical Routes.

Nickel-catalyzed intramolecular hydrosilylation can be efficiently achieved with high regio- and stereoselectivities through two distinct methodologies. The first approach utilizes a conventional method, involving the reduction of nickel salt (NiBr2-2,2'-bipyridine) using manganese metal. The second method employs a one-step electrochemical reaction, utilizing the sacrificial anode process and NiBr2bipy catalysis. Both methods yield silylated heterocycles in good to high yields through a syn-exo-dig cyclization process. Control experiments and molecular electrochemistry (cyclic voltammetry) provided further insights into the reaction mechanism.

High pressure promoted dearomatization of nitroarenes by [4+2] cycloadditions with silyloxydienes.

Simple nitroarenes such as nitronaphthalenes and nitroquinolines smoothly undergo dearomatizing [4+2] cycloadditions with silyloxydienes under 16 kbar. Highly functionalized 3-dimensional polycyclic adducts bearing a tetrasubstituted carbon centre at the ring junction are obtained in one step from simple raw materials. This unprecedented dearomative Diels-Alder process is performed at room temperature without any chemical promoter, illustrating the exceptional role of high pressure as a physical promoter.

Modular access to substituted germoles by intramolecular germylzincation.

Intramolecular alkyne germylzincation giving access to a wide range of germoles is achieved from triarylhydrogermanes in the presence of diethylzinc and AIBN as radical initiator. The reaction proceeds through activation of the Ge-H bond, leading to a heteroarylzinc intermediate after cyclisation, which can then be involved in a post-functionalisation reaction. Our results show that only 5-endo-dig cyclizations occur, with benzogermoles being exclusively obtained.

How electrophilic are 3-nitroindoles? Mechanistic investigations and application to a reagentless (4+2) cycloaddition.

The electrophilicity of 4 different 3-nitroindole derivatives has been evaluated by Mayr's linear free energy relationship (log k(20 °C) = sN(E + N)) and reveals unexpected values for aromatic compounds, in the nitrostyrene range. 3-Nitroindoles are sufficiently electrophilic to interact with a common diene namely the Danishefsky's diene at room temperature, in the absence of any activator, to furnish smoothly the dearomatized (4+2) cycloadducts in good yields.

Nickel-Catalyzed Electrochemical Cyclization of Alkynyl Aryl Iodide and the Domino Reaction with Aldehydes.

An intramolecular carbometallation of a triple bond promoted by electrochemistry and mediated by nickel catalysis is described. This domino process transforms various aryl halides bearing a propargyl chain into substituted heterocycles in one single operation, with high stereoselectivities and in good to high yields. This reaction, characterized by a cyclic voltammetry set of experiments, proceeds following a syn-exo-dig cyclization process. When run at 80 °C, vinylbenzofuranes that are suitable substrates for cycloaddition reactions are obtained.

Synthetic Applications of Nickel-Catalyzed Cross-Coupling and Cyclisation Reactions.

Since the first studies about fifty years ago, the direct formation of C-C bonds, catalyzed by nickel complexes, has appeared as an important research topic, and has re-emerged recently as a renewal of nickel chemistry. This account provides a summary of the use of nickel complexes in catalysis, and highlights the evolution of our own research.

Intertwined Analytical, Experimental and Theoretical Studies on the Formation and Structure of a Copper Dienolate.

The reaction of a silyl dienolate, a Cu(II) salt and TBAT yielding the corresponding copper dienolate is addressed. A combined NMR and cyclic voltammetry analysis first highlight the role of TBAT in the Cu(II) to Cu(I) reduction and the structure of the precatalytic species. From these first results a second set of NMR and theoretical studies enable the determination of the structure and the mechanism of formation of the copper dienolate catalytic species. Finally, we showed that that the copper catalyst promote the E/Z s-cis/s-trans equilibration of the silyl dienolate precursor through a copper dienolate intermediate. All of these results unveil some peculiarities of the catalytic and asymmetric vinylogous Mukaiyama reaction.

The facile dearomatization of nitroaromatic compounds using lithium enolates of unsaturated ketones in conjugate additions and (4+2) formal cycloadditions.

The dearomatization of conventional nitroarenes by lithiated enolates derived from methyl vinyl ketones easily takes place, following a formal (4+2) cycloaddition process. While nitroindoles react readily with in situ generated conjugated enolates, the deaggregation of these latter species using HMPA extends the reaction scope to the more aromatic nitronaphthalenes and pyridines.

Direct Syn Addition of Two Silicon Atoms to a C≡C Triple Bond by Si-Si Bond Activation: Access to Reactive Disilylated Olefins.

A catalytic intramolecular silapalladation of alkynes affords, in good yields and stereoselectively, syn-disilylated heterocycles of different chemical structure and size. When applied to silylethers, this reaction leads to vinylic silanols that undergo a rhodium-catalyzed addition to activated olefins, providing the oxa-Heck or oxa-Michael products, depending on the reaction conditions.

Cobalt-Catalyzed Carbozincation of Ynamides.

An original cobalt-catalyzed ynamide carbozincation leading mainly to diverse 3-aryl enamides with mild reaction conditions and good functional-group tolerance has been developed. This reaction displays an excellent regio- and total stereoselectivity and opens the way to appealing synthetic applications. Moreover, this approach allows the selective synthesis of biologically relevant 3,5-disubstituted oxazolone frameworks.

Access to Silylated Pyrazole Derivatives by Palladium-Catalyzed C-H Activation of a TMS group.

A simple and efficient approach to new silylated heterocycles of potential interest in medicinal chemistry is presented. A set of bromophenyl trimethylsilyl pyrazole intermediates can be transformed by direct organometallic routes into two families of regioisomeric iodoaryl substrates; using either arylzinc or aryllithium chemistry, the TMS group remains on the pyrazole ring or translocates to the aryl moiety. These two families can then be efficiently transformed into benzo silino pyrazoles thanks to a single-step cyclization relying on the Pd-catalyzed activation of a non-activated C(sp(3) )-H bond alpha to a silicon atom. The experimental conditions used, which are fully compatible with the pyrazole ring, suggest that this reaction evolves through a concerted metalation-deprotonation (CMD) mechanism.

Direct Carboxylation of Aryl Tosylates by CO2 Catalyzed by In situ-Generated Ni(0).

A novel Ni(0) -catalyzed carboxylation of aryl tosylates with carbon dioxide has been achieved under moderate temperatures and atmospheric pressure. In this procedure, the active Ni(0) species is generated in situ by simply mixing the Ni(0) precatalyst [NiBr2 (bipy)] with an excess of manganese metal. This approach requires neither a glove-box nor the tedious preparation of sophisticated intermediate organometallic derivatives. This mild, convenient, and user-friendly process is successfully applied to the valorization of carbon dioxide and the synthesis of versatile reactants with broad tolerance of substituents.

Intramolecular carbolithiation of heterosubstituted alkynes: an experimental and theoretical study.

A series of heterosubstitued alkynes was successfully submitted to the intramolecular carbolithiation of their triple bond. We show that the addition is stereoselective because of the control exerted by the terminal substituent X on the geometry of the transition state. A complementary DFT study suggests that the addition is anti when a strong Li-X interaction occurs.

Carbolithiation of chloro-substituted alkynes: a new access to vinyl carbenoids.

The intramolecular carbolithiation of a series of chloro-substituted alkynes leads to exocyclic alkylidene carbenoids of which both nucleophilic and electrophilic characters can be drove. A sole stereoselective 5-exo-dig addition takes place, probably because of a strong and persisting Li-Cl interaction arising before the transition state.

Anionic access to silylated and germylated binuclear heterocycles.

A simple access to silylated and germylated binuclear heterocycles, based on an original anionic rearrangement, is described. A set of electron-rich and electron-poor silylated aromatic and heteroaromatic substrates were tested to understand the mechanism and the factors controlling this rearrangement, in particular its regioselectivity. This parameter was shown to follow the rules proposed before from a few examples. Then, the effect of the substituents borne by the silicon itself, in particular the selectivity of the ligand transfer, was studied. Additionally, this chemistry was extended to germylated substrates. A hypervalent germanium species, comparable to the putative intermediate proposed with silicon, seems to be involved. However, a pathway implicating the elimination of LiCH2Cl was observed for the first time with this element, leading to unexpected products of the benzo-oxa (or benzo-aza) germol-type.

Influence of the acetylenic substituent on the intramolecular carbolithiation of alkynes: a DFT theoretical study.

A theoretical study of the intramolecular 5-exo-dig carbolithiation of substituted propargyl o-lithioaryl ethers, leading to dihydrobenzofurans, has been performed. The results show that a DFT description of the reaction (B3P86, 6-31G**) matches the experimental data provided that an explicit solvation by two molecules of THF is considered. To take place, the cyclization also implies that the acetylenic chain adopts a conformation in which a significant interaction arises between the lithium and the C≡C triple bond. Reaching the cyclization TS requires the passage of an activation barrier that should not be higher than 12-13 kcal mol(-1). From a thermodynamic point of view, the reaction is exothermic whatever the substituent R (from approximately -40 to -62 kcal mol(-1)). In the starting substrate, a supplementary interaction between the Li and a substituent at the propargylic position can develop, influencing the future double-bond configuration. Thus, derivatives exhibiting an R-Li interaction tend to provide E olefins. In contrast, when no coordination between the lithium cation and the terminal R occurs, syn carbolithiation takes place, and the configuration of the exocyclic olefin is likely to be Z. This hypothesis accounts for most of the experimental results published before.

Intramolecular carbonickelation of alkenes.

The efficiency of the intramolecular carbonickelation of substituted allylic ethers and amines has been studied to evaluate the influence of the groups borne by the double bond on this cyclization. The results show that when this reaction takes place, it affords only the 5-exo-trig cyclization products, viz. dihydrobenzofurans or indoles. Depending on the tethered heteroatom (O or N), the outcome of the cyclization differs. While allylic ethers are relatively poor substrates that undergo a side elimination and need an intracyclic double bond to proceed, allylic amines react well and afford indoline and indole derivatives. Finally, the synthesis of the trinuclear ACE core of a morphine-like skeleton was achieved by using NiBr2bipy catalysis.

Intramolecular sila-Matteson rearrangement: a general access to silylated heterocycles.

A series of new silylated heterocycles has been efficiently prepared using an intramolecular silicon version of the Matteson rearrangement, providing two isomers of binuclear heterocycles. This method applies to a large variety of substrates, a direct relationship between the Hammett constants of the aromatic substituents and the isomer ratio being observed. Complementary experiments suggest that a common pentaorganosilicate species is involved.

Synthetic applications of the nickel-catalyzed cyclization of alkynes combined with addition reactions in a domino process.

Carbonickelations of alkynes and functionalization of the resulting vinylnickel moiety have been performed efficiently in a nickel-catalyzed domino cyclization-condensation process. This reaction, which does not require the preparation of any other organometallic reagent, proceeds only by exo-dig cyclization. This convenient and mild method constitutes a one-pot synthesis of substituted dihydrobenzofurans, chromans, isochromans, indoles, or indanes. Theses valuable products are generally obtained in good yields and high stereoselectivity. They are shown to be useful synthons for rapid access to functionalized polycyclic skeletons.

Heterocyclization by catalytic carbonickelation of alkynes: a domino sequence involving vinylnickels.

Reaction of Ni(0) in the presence of iodoarylethers leads, after syn intramolecular carbonickelation of the triple bond, to nucleophilic vinylnickels which can be trapped, in a tandem process, by various electrophiles introduced at the onset of the reaction.