ABT

An efficient, metal-free, silicon–hydrogen bond functionalization based on the microwave-assisted reaction of readily available enynones and silanes is reported. This process seemingly proceeds through a 2-furyl carbene species, a particularly elusive intermediate. Preliminary studies on the metal-free oxygen–hydrogen and nitrogen–hydrogen bond functionalization of representative alcohols, azoles and sulfonamides are also provided.

José Barluenga, emeritus professor at the University of Oviedo, passed away on September 7, 2016. Barluenga was one of the leading Spanish chemists of his generation, with research interests including metal-mediated activation of alkenes and alkynes, β-functionalized organolithium compounds, iodination reactions, asymmetric Diels–Alder reactions, carbene complexes, and cross-coupling reactions.

The alkylative carboxylation of allenamide catalyzed by an N-heterocyclic carbene (NHC)–copper(I) complex [(IPr)CuCl] with CO₂ and dialkylzinc reagents was investigated. The reaction of allenamides with dialkylzinc reagents (1.5 equiv) and CO₂ (1 atm.) proceeded smoothly in the presence of a catalytic quantity of [(IPr)CuCl] to afford (Z)-α,β-dehydro-β-amino acid esters in good yields. The reaction is regioselective, with the alkyl group introduced onto the less hindered γ-carbon, and the carboxyl group introduced onto the β-carbon atom of the allenamides. The first step of the reaction was alkylative zincation of the allenamides to give an alkenylzinc intermediate followed by nucleophilic addition to CO₂. A variety of cyclic and acyclic allenamides were found to be applicable to this transformation. Dialkylzinc reagents bearing β-hydrogen atoms, such as Et₂Zn or Bu₂Zn, also gave the corresponding alkylative carboxylation products without β-hydride elimination. The present methodology provides an easy route to alkyl-substituted α,β-dehydro-β-amino acid ester derivatives under mild reaction conditions with high regio- and stereoselectivtiy.

Alkylation and CO₂ Incorporation: The alkylative carboxylation of allenamides with dialkylzinc reagents and carbon dioxide in the presence of a catalytic amount of an N-Heterocyclic Carbene (NHC)–copper complex was achieved. The reactions proceed through Cu-catalyzed carbozincation of allenamides with dialkylzinc reagents and the subsequent nucleophilic addition of the resulting alkenyl zinc species to CO₂ (see scheme).

A three-component gold(I)-catalyzed synthesis of 2-imidazoyl-1-pyrazolylbenzenes from 1-propargyl-1H-benzotriazoles is described here. Initially the benzotriazole derivative suffers an intramolecular 5-endo-dig cyclization to form a triazapentalene. This dipolar compound is able to perform an intermolecular and regioselective attack to a gold-activated alkyne. After triazole breakage, the pyrazole ring and an α-imino gold carbene complex are formed. Finally, the iminocarbene is captured by a nitrile to form an imidazole ring.

The reactions between alkenylboronic acids and tosylhydrazones derived from substituted cyclohexanones lead to the construction of disubstituted cyclohexanes with total regio- and stereoselectivity. In these transition-metal-free processes, a Csp³−Csp² and Csp³−H bond are formed on the same carbon atom. The stereoselective reaction is general for 2-, 3-, and 4-substituted cyclohexanone tosylhydrazones, as well as for 2-substituted cyclopentanones. However, no stereoselectivity is observed for acyclic derivatives. DFT computational modeling suggests that the stereoselectivity of the reaction is determined by the approach of the boronic acid to the diazocyclohexane on its most stable chair conformation through an equatorial trajectory.

An orphan transformation: Two bonds on the same carbon atom Csp³−Csp² and Csp³−H bonds are formed in a diastereoselective manner by reaction of tosylhydrazones of substituted cyclic ketones with alkenyl boronic acids. This transition-metal-free reductive coupling represents a solution for a previously unavailable stereoselective transformation of carbonyl compounds (see scheme).

A protocol involving a gold(I)-catalyzed reaction to elaborate cyclic frames by selective trimerization reactions of N-allenylsulfonamides is reported. Efficiency in the formation of the target [2+2+2] products depends on the concentration of the reagents, the nature of the ancillary ligand on the gold catalyst, and, to a significant extent, on the selection of a low reaction temperature. This singular catalytic allene cycloaddition gives adducts in high isolated yields. In addition to representing a new gold-catalyzed reaction, the reported allenamide cyclotrimerization offers a significant extension to the scant number of allenes that have effectively entered this cyclization mode by use of other metal-catalyzed reactions. Upon aromatization of the assembled adducts, the overall reaction matches the outcome of related and widely investigated alkyne trimerization reactions.

Granting gilding access to triskelium-like molecules: The first examples of a gold-catalyzed [2+2+2]-cycloaddition reaction of tosylallenamides are presented. Upon ligand screening, conditions have been devised to favor the direct assembly of molecules with this particular shape.

For a while, the reactivity of gold complexes was largely dominated by their Lewis acid behavior. In contrast to the other transition metals, the elementary steps of organometallic chemistry—oxidative addition, reductive elimination, transmetallation, migratory insertion—have scarcely been studied in the case of gold or even remained unprecedented until recently. However, within the last few years, the ability of gold complexes to undergo these fundamental reactions has been unambiguously demonstrated, and the reactivity of gold complexes was shown to extend well beyond π-activation. In this Review, the main achievements described in this area are presented in a historical context. Particular emphasis is set on mechanistic studies and structure determination of key intermediates. The electronic and structural parameters delineating the reactivity of gold complexes are discussed, as well as the remaining challenges.

Sitting on a gold mine? In the past few years, the reactivity of gold complexes has been extended well beyond Lewis acid behavior and electrophilic activation of π-substrates. Elementary steps considered highly unlikely, if not impossible, for gold complexes have been unambiguously demonstrated, offering new perspectives in gold catalysis.

A gold(I)-catalyzed intermolecular annulation of N-allenamides at the proximal CC bond has been achieved. In their Communication on page 14849 ff., J. Zhang et al. show that both enantiomers of the products are obtained with high regio-, diastereo-, and enantioselectivity by using either diastereomer of a chiral phosphoramidite as ligand. In the picture, the enantiomers of the products are easily controlled by the magician’s hands with the aid of the gold rings on the fingers.

A gold(I)-catalyzed synthesis of indanones from trimethylsilylacetylenes and acylsilanes is presented. The reaction is initiated through a synergistic acylsilane activation–gold acetylide formation and involves consecutive alkyne σ-gold(I) addition, π-activation, and 1,2-migration of a silyl group. Studies performed on the reaction mechanism allowed to establish the nature of the silyl migrating group and invoke the participation of a gold(I) carbenoid intermediate. The reaction is completed by a gold(I) CH functionalization step.

The elegant way: A gold(I)-catalyzed synthesis of indanones from trimethylsilylacetylenes and acylsilanes was developed. The reaction involves a synergistic acylsilane activation–gold acetylide formation and consecutive alkyne σ-gold(I) addition, π-activation, and 1,2-silyl migration. Mechanistic studies suggest the participation of a gold(I) carbenoid intermediate.

The zinc-catalyzed reaction of cyclopropenes with alkenes leading to vinylcyclopropane derivatives is reported. A broad range of alkenes (including highly substituted or functionalized alkenes) is compatible with this protocol. On the basis of trapping experiments and computational studies, this cyclopropanation reaction is proposed to proceed through initial formation of an electrophilic zinc vinyl carbenoid intermediate, which may be involved in a concerted cyclopropanation reaction. The reported protocol represents an unprecedented and simple strategy for the catalytic generation of zinc vinyl carbenoids, which are promising intermediates in organic synthesis.

Open and close! The title reaction provides a convenient and general route to relevant vinylcyclopropane derivatives. Mechanistic studies support the participation of a zinc vinylcarbene intermediate, which may be subsequently involved in a concerted cyclopropanation reaction. This method represents a step towards identifying suitable precursors for the catalytic generation of zinc carbenoids.

A catalytic asymmetric aldol addition/cyclization reaction of unactivated ketones with isocyanoacetate pronucleophiles has been developed. A quinine-derived aminophosphine precatalyst and silver oxide were found to be an effective binary catalyst system and promoted the reaction to afford chiral oxazolines possessing a fully substituted stereocenter with good diastereoselectivities and excellent enantioselectivities.

A stereoselective aldol reaction of unactivated ketones and isocyanoacetate pronucleophiles is catalyzed by a binary catalyst system consisting of an aminophosphine precatalyst and silver(I) oxide and affords oxazoline products with a fully substituted β-carbon atom. The reaction is efficient and broad in scope and proceeds with high diastereo- and enantioselectivity.

Gold-catalyzed cycloadditions of ethyl diazoacetate, nitrosoarenes, and vinyldiazo carbonyl species to yield isoxazolidine derivatives stereoselectively are described. Treatment of these isoxazolidine products with the same catalyst results in a novel 1,2-H shift/[3,3] rearrangement to give benzo[b]azepine compounds. The mechanism of this skeletal rearrangement is elucidated with deuterium-labeling experiments.

A little shifty: The title reaction yields isoxazolidine derivatives stereoselectively. Treatment of these isoxazolidine products with the same catalyst results in a novel 1,2-H shift/[3,3] rearrangement to give benzo[b]azepine compounds. The mechanism of this skeletal rearrangement is elucidated with deuterium-labeling experiments. FG=functional group.

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 CH bond into gold vinylidene as the step responsible for the formation of the new carbon–carbon bond.

Golden dance: The cycloisomerization reaction of 1-(iodoethynyl)-2-(1-methoxyalkyl)arenes gives the corresponding 3-iodo-1-substituted-1H-indene. Gold(I) catalysis triggers a selective intramolecular carbon–carbon bond-forming event, which involves the insertion of benzylic CH bonds in the catalytically assembled gold(I) iodovinylidene intermediate.