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Herein, we report the utilization of Ni-Ni species as a manifold for enabling a "ring-walking" event by dynamic translocation of the metal center over the arene backbone. Experimental and computational studies support a translocation occurring via a 1,2-hydride shift. The synthetic applicability of the method is illustrated in a series of C-C bond formations that occur at distal C(sp 2 )-H sites of simple aryl pivalates.

The irradiation of ( Z )-4-arylidene-5(4 H )-oxazolones 1a-1u with blue light (465 nm) in the presence of the photosensitizer [Ru(bpy) 3 ](BF 4 ) 2 (2.5 mol%) and the Lewis acid BF 3 ·OEt 2 (2 equiv.) in deoxygenated methanol at room temperature affords the corresponding 1,2-diaminotruxinic cyclobutane bis-amino esters 2a-2u stereoselectively as the δ-isomer. Characterization of cyclobutanes 2 shows that the photocycloaddition takes place by the coupling of two Z -oxazolones in a head-to-head 1,2- anti way. This change in the orientation of the coupling is promoted by O- or/and N-bonding of the BF 3 additive. The δ-cyclobutanes 2 undergo a ring expansion when heated in methanol in the presence of NaOMe (1/1 molar ratio) to give densely substituted pyrrolidine-2,5-dicarboxylates 3 in a regio- and stereoselective way. The mechanism of the cyclobutane-to-pyrrolidine ring expansion has been elucidated using DFT methods.

From an (R)-(+)-pulegone-derived building block that incorporates the stereo-defined tertiary carbon bearing a methyl group, as found in the targeted sesquiterpenoid, a four-step synthesis of (-)-4-epi-presilphiperfolan-8-α-ol was achieved. The key processes involved are a ring-closing metathesis leading to a bridged alkene-tethered ketone and its subsequent Fe III -mediated metal-hydride atom transfer (MHAT) transannular cyclization. This synthetic method, implying an irreversible addition of a carbon-centered radical upon a ketone by means of a hydrogen atom transfer upon the alkoxy radical intermediate, was also applied in the synthesis of trans-fused hydrindanols structurally related to botrydial compounds., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Pd-catalyzed C-H functionalization reactions of non-directed substrates have recently emerged as an attractive alternative to the use of directing groups. Key to the success of these transformations has been the discovery of new ligands capable of increasing both the reactivity of the inert C-H bond and the selectivity of the process. Among them, a new type of S,O-ligand has been shown to be highly efficient in promoting a variety of Pd-catalyzed C-H olefination reactions of non-directed arenes. Despite the success of this type of S,O-ligand, its role in the C-H functionalization processes is unknown. Herein, we describe a detailed mechanistic study focused on elucidating the role of the S,O-ligand in the Pd-catalyzed C-H olefination of non-directed arenes. For this purpose, several mechanistic tools, including isolation and characterization of reactive intermediates, NMR and kinetic studies, isotope effects and DFT calculations have been employed. The data from these experiments suggest that the C-H activation is the rate-determining step in both cases with and without the S,O-ligand. Furthermore, the results indicate that the S,O-ligand triggers the formation of more reactive Pd cationic species, which explains the observed acceleration of the reaction. Together, these studies shed light on the role of the S,O-ligand in promoting Pd-catalyzed C-H functionalization reactions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A highly efficient enantioselective α-nitrogenation method of α,α-disubstituted aldehydes with azodicarboxylates promoted by a chiral carbamate-monoprotected cyclohexa-1,2-diamine as organocatalyst has been developed. The process was carried out without any solvent, and the corresponding α,α-disubstituted α-nitrogenated aldehydes were obtained with excellent yields and enantioselectivities up to 99% ee . The sustainability of the procedure was established through the calculation of green metrics, such as EcoScale and E-factor. In addition, theoretical calculations have been used to justify the obtained enantioselectivity sense.

A synthetic approach to a functionalized ABC-tricyclic framework of calyciphilline A-type alkaloids, a building block toward this class of alkaloids, is reported. The key synthetic steps involve a radical cyclization to form the hydroindole system and piperidine ring closure through a stereocontrolled aldol cyclization. The resulting alcohol allows the methyl group to be installed in the bowl-shaped azatricyclic structure; this crucial reaction takes place with configuration retention. The synthesis of azatricyclic compound I constitutes a formal synthesis of himalensine A.

In this paper, we present an unprecedented and general umpolung protocol that allows the functionalization of silyl enol ethers and of 1,3-dicarbonyl compounds with a large range of heteroatom nucleophiles, including carboxylic acids, alcohols, primary and secondary amines, azide, thiols, and also anionic carbamates derived from CO 2 . The scope of the reaction also extends to carbon-based nucleophiles. The reaction relies on the use of 1-bromo-3,3-dimethyl-1,3-dihydro-1λ 3 [d][1,2]iodaoxole, which provides a key α-brominated carbonyl intermediate. The reaction mechanism has been studied experimentally and by DFT, and we propose formation of an unusual enolonium intermediate with a halogen-bonded bromide., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

A dual catalytic manifold that enables site-selective functionalization of unactivated sp 3 C-O bonds in cyclic acetals with aryl and alkyl halides is reported. The reaction is triggered by an appropriate σ*-p orbital overlap prior to sp 3 C-O cleavage, thus highlighting the importance of conformational flexibility in both reactivity and site selectivity. The protocol is characterized by its excellent chemoselectivity profile, thus offering new vistas for activating strong σ sp 3 C-O linkages.

A catalytic method to synthesize a broad array of cyclometalated (C^N)gold(III) complexes is reported here. An unprecedented Rh-to-Au III transmetalation allows the facile transfer of (C^N) ligands between these two metals in a redox-neutral process. The reaction employs commercially available precursors and proceeds under mild and environmentally benign conditions. Both experimental and computational studies support a multistep transmetalation from rhodium to gold as the underlying mechanism for these transformations. This process involves first, a rate-determining transfer of the C ligand followed by the subsequent incorporation of the N donor to form the monocyclometalated (C^N)gold(III) species., (© 2022 Wiley-VCH GmbH.)

Six- and seven-membered ring-fused, functionalized cyclopentadienes can be obtained in moderate to excellent yields by a cascade process entailing the Au(I)-catalyzed propargyl Claisen rearrangement/Nazarov cyclization of propargyl vinyl ethers, the hetero-Diels-Alder reaction with dialkylazodicarboxylates, and the spontaneous conversion of cycloaddition products into cyclopentadienes by a highly regioselective cleavage of a C-N bond. Depending on the treatment of the crude reaction mixtures, two types of products can be obtained: cyclopentadienes with pendant hydrazine and aldehyde moieties that intramolecularly react to form hemiaminals are obtained in 43-52% overall yields when the crude reaction mixtures are left over K 2 CO 3 in a DCM solution. Instead, by reducing in situ the aldehyde group just after addition of the heterodienophile, the regioselective C-N bond cleavage generates the corresponding cyclopentadienes bearing a hydrazine and an alcohol appendage in excellent yields (66-82%) over four steps, all in one pot. Two examples from the latter class of compounds were also converted into ring-fused, functionalized cyclopentadienes, bearing a protected amino group, by the selective N-N cleavage of the hydrazine moiety.

The irradiation of ( Z )-2-phenyl-4-aryliden-5(4 H )-oxazolones 1 in deoxygenated CH 2 Cl 2 at 25 °C with blue light (465 nm) in the presence of [Ru(bpy) 3 ](BF 4 ) 2 (5% mole ratio) as a triplet photocatalyst promotes the [2+2] photocycloaddition of the C═C bonds of the 4-arylidene moiety, thus allowing the completely regio- and stereoselective formation of cyclobutane-bis(oxazolone)s 2 as single stereoisomers. Cyclobutanes 2 have been unambiguously characterized as the μ-isomers and contain two E -oxazolones coupled in an anti -head-to-head form. The use of continuous-flow techniques in microreactors allows the synthesis of cyclobutanes 2 in only 60 min, compared with the 24-48 h required in batch mode. Ring opening of the oxazolone heterocycle in 2 with a base affords the corresponding 1,2-diaminotruxinic bis-amino esters 3 , which are also obtained selectively as μ-isomers. The ruthenium complex behaves as a triplet photocatalyst, generating the reactive excited state of the oxazolone via an energy-transfer process. This reactive excited state has been characterized as a triplet diradical 3 ( E / Z )- 1* by laser flash photolysis (transient absorption spectroscopy). This technique also shows that this excited state is the same when starting from either ( Z )- or ( E )-oxazolones. Density functional theory calculations show that the first step of the [2+2] cycloaddition between 3 ( E/Z )- 1* and ( Z )- 1 is formation of the C(H)-C(H) bond and that ( Z ) to ( E ) isomerization takes place at the 1,4-diradical thus formed.

Here, we present a new stereoselective alkylation of titanium(IV) enolates of chiral N -acyl oxazolidinones with tert -butyl peresters from Cα-branched aliphatic carboxylic acids, which proceeds through the decarboxylation of the peresters and the subsequent formation of alkyl radicals to produce the alkylated adducts with an excellent diastereoselectivity. Theoretical calculations account for the observed reactivity and the outstanding stereocontrol. Importantly, the resultant compounds can be easily converted into ligands for asymmetric and catalytic transformations.

A straightforward, user-friendly, efficient protocol for the one pot, ZnI 2 -catalyzed allenylation of terminal alkynes with pyrrolidine and ketones, toward trisubstituted allenes, is described. Trisubstituted allenes can be obtained under either conventional heating or microwave irradiation conditions, which significantly reduces the reaction time. A sustainable, widely available, and low-cost metal salt catalyst is employed, and the reactions are carried out under solvent-free conditions. Among others, synthetically valuable allenes bearing functionalities such as amide, hydroxyl, or phthalimide can be efficiently prepared. Mechanistic experiments, including kinetic isotope effect measurements and density functional theory (DFT) calculations, suggest a rate-determining [1,5]-hydride transfer during the transformation of the intermediate propargylamine to the final allene., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

A novel strategy for the synthesis of policyclic trifluoromethyl arenes has been devised. It involves a DBU-promoted tandem cycloaromatization reaction of dicyanoalkenes and fluorinated conjugated sulfinyl imines. This unprecedented transformation is a metal-free and air-tolerant process that takes place from readily available starting materials under mild reaction conditions.

The indium(III)-catalyzed cascade cycloisomerization reaction of 1,5-enynes with pendant aryl nucleophiles is reported. The reaction proceeds in cascade under mild reaction conditions, using InI 3 (5 mol %) as a catalyst with a range of 1,5-enynes furnished with aryl groups (phenyl and phenol) at alkene ( E and Z isomers) and with terminal and internal alkynes. Using 1-bromo-1,5-enynes, a one-pot sequential indium-catalyzed cycloisomerization and palladium-catalyzed cross-coupling with triorganoindium reagents were developed. The double cyclization is stereospecific and operates via a biomimetic cascade cation-olefin through 1,5-enyne cyclization ( 6-endo - dig ) and subsequent C-C hydroarylation or C-O phenoxycyclization. Density functional theory (DFT) computational studies on 1,5-enynyl aryl ethers support a two-step mechanism where the first stereoselective 1,5-enyne cyclization produces a nonclassical carbocation intermediate that evolves to the tricyclic reaction product through a S E Ar mechanism. Using this approach, a variety of tricyclic heterocycles such as benzo[ b ]chromenes, phenanthridines, xanthenes, and spiroheterocyclic compounds are efficiently synthesized with high atom economy.

The tandem gold(I)-catalyzed rearrangement/Nazarov reaction of enynyl acetates in which the double bond is embedded in a piperidine ring was computationally and experimentally studied. The theoretical calculations predict that the position of the propargylic acetate substituent has a great impact on the reactivity. In contrast to our previous successful cyclization of the 2-substituted substrates, where the nitrogen favors the formation of the cyclized final product, the substitution at position 3 was computed to have a deleterious effect on the electronic properties of the molecules, increasing the activation barriers of the Nazarov reaction. The sluggish reactivity of 3-substituted piperidines predicted by the calculations was further confirmed by the results obtained with some designed substrates., (Copyright © 2020, Zanella et al.; licensee Beilstein-Institut.)

The Au I -catalyzed reaction between terminal alkynes and aromatic haloalkynes proceeds through divergent pathways depending on the nature of the catalyst counteranion. Thus, cationic complexes containing strongly basic NHC ligands and noncoordinating anions such as BAr F 4 catalyze the cis haloalkynylation of the terminal alkyne, whereas introduction of a weakly basic triflate counteranion results in the stereoselective hydroalkynylation of the haloalkyne, yielding haloenyne products in good yields and complete trans selectivity. Experimental and computational studies suggest that the hydroalkynylation reaction takes place via nucleophilic attack of the terminal alkyne to the C2 carbon of the activated haloalkyne, assisted by a concerted proton abstraction by the triflate, and that the protodeauration is the turnover-limiting step, in agreement with an observed primary kinetic isotope effect.

A protocol for the Pd(II)-catalyzed C-H alkenylation reaction of substituted N -allylanilines via an unusual 6- endo process has been developed. A density functional theory (DFT) study of the mechanistic pathway has shown that the coordination of the remote protecting group to the palladium center is determinant for the control of the regioselectivity in favor of the 6- endo process. The reaction would proceed via prior activation of the alkene. This procedure constitutes a mild and efficient method for the synthesis of 1,4-dihydroquinoline derivatives from simple and readily accessible substrates.

Simple treatment of chiral titanium(IV) enolates with diacyl peroxides produces highly diastereoselective decarboxylative alkylations to efficiently deliver the corresponding adducts, most of which are not accessible through any of the current alkylating procedures. Such an unprecedented alkylation proceeds through an SET process that triggers the decomposition of the peroxide into a carbon-centered radical that finally combines with the resulting Cα radical. The procedure has been applied to the enantioselective synthesis of arundic acid.

The selective synthesis of α-functionalized ketones with two similar enolizable positions can be accomplished using allylic alcohols and iridium(III) catalysts. A formal 1,3-hydrogen shift on allylic alcohols generates catalytic iridium-enolates in a stereospecific manner, which are able to react with electrophiles to yield α-functionalized ketones as single constitutional isomers. However, the employment of nucleophiles to react with the nucleophilic catalytic enolates in this chemistry is still unknown. Herein, we report an umpolung strategy for the selective synthesis of α-alkoxy carbonyl compounds by the reaction of iridium enolates and alcohols promoted by an iodine(III) reagent. Moreover, the protocol also works in an intramolecular fashion to synthesize 3(2H)-furanones from γ-keto allylic alcohols. Experimental and computational investigations have been carried out, and mechanisms are proposed for both the inter- and intramolecular reactions, explaining the key role of the iodine(III) reagent in this umpolung approach.

A catalyst-driven one-pot reaction sequence is developed for the enantio- and diastereoselective synthesis of tetrasubstituted cyclohexenes from simple unsaturated ketones or thioesters. The method involves a tertiary amine/squaramide-catalyzed α-selective addition of transiently generated trienolates to nitroolefins, subsequent base-catalyzed double bond isomerization, and an intramolecular (vinylogous) 1,6-addition reaction, a rare key carbocyclization step that proceeded with essentially perfect stereocontrol., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)