Visible-Light-Promoted Tandem Skeletal Rearrangement/Dearomatization of Heteroaryl Enallenes.

Access to complex three-dimensional molecular architectures via dearomatization of ubiquitous aryl rings is a powerful synthetic tool, which faces, however, an inherent challenge to overcome energetic costs due to the loss of aromatic stabilization energy. Photochemical methods that allow one to populate high-energy states can thus be an ideal strategy to accomplish otherwise prohibitive reaction pathways. We present an original dearomative rearrangement of heteroaryl acryloylallenamides that leads to complex fused tricycles. The visible-light-promoted method occurs under mild conditions and tolerates a variety of functional groups. According to DFT modeling used to rationalize the outcome of the cascade, the reaction involves a sequential [2+2] allene-alkene photocycloaddition, which is followed by a selective retro- [2+2] step that paves the way for the dearomatization of the heteroaryl partner. This scenario is original with respect to the reported photochemical reactivity of similar substrates and thus holds promise for ample future developments.

Boosting Energy-Transfer Processes via Dispersion Interactions.

The generation of open-shell intermediates under mild conditions has opened broad synthetic opportunities during this century. However, these reactive species often require a case specific and tailored tuning of experimental parameters in order to efficiently convert substrates into products. We report a general approach that can overcome these ubiquitous limitations for several visible-light promoted energy-transfer processes. The use of either naphthalene (5-20 equiv.) or simple binaphthyl derivatives (10-30 mol %) greatly increases their efficiency, giving rise to a new strategy for catalysis. The trend is consistent among different media, photocatalysts, light sources and substrates, allowing one to improve existing methods, to more easily optimize conditions for new ones, and, moreover, to disclose otherwise inaccessible reaction pathways.

Base-promoted Conia-ene cyclization of propargyl amides.

We report a tBuOK-promoted synthesis of 1,3-dihydro-2H-pyrrol-2-one and 4-methylenepyrrolidin-2-one systems via Conia-ene like intramolecular cyclization. The method features extremely short reaction times (5 min) and mild reaction conditions (rt), enabling the trapping of a propargyl unit by an amide enolate. An intriguing anionic chain mechanism is at work, which can trigger the isomerization of an exo-alkene giving access to the otherwise elusive endo-product.

Closing the Cycle as It Begins: Synthesis of ortho-Iodobiaryls via Catellani Reaction.

Despite the advances in the field of carbon-halogen bond formation, the straightforward catalytic access to selectively functionalized iodoaryls remains a challenge. Here, we report a one-pot synthesis of ortho-iodobiaryls from aryl iodides and bromides by palladium/norbornene catalysis. This new example of Catellani reaction features the initial cleavage of a C(sp2 )-I bond, followed by the key formation of a palladacycle through ortho C-H activation, the oxidative addition of an aryl bromide and the ultimate restoration of the C(sp2 )-I bond. A large variety of valuable o-iodobiaryls has been synthesized in satisfactory to good yields and their derivatization have been described too. Beyond the synthetic utility of this transformation, a DFT study provides insights on the mechanism of the key reductive elimination step, which is driven by an original transmetallation between palladium(II)-halides complexes.

Sequential Strategies to Trigger Mild Dearomative Diels-Alder Cyclizations.

Dihydronaphthalenes are present in several functional molecules, but their assembly is challenging. However, a sequential strategy can induce the key annullation of an alkyne with a vinylarene under mild conditions. Products form in good yields, with ample functional tolerance via domino nucleophilic substitution and dearomative Diels-Alder and ene reactions. DFT modeling data show that alkali cations are crucial to ensure a smooth dearomative cyclization on the in situ generated intermediates.

Visible-Light Promoted Intramolecular para-Cycloadditions on Simple Aromatics.

Dearomative cycloadditions are a powerful tool to access a large chemical space exploiting simple and ubiquitous building blocks. The energetic burden due to the loss of aromaticity has however greatly limited their synthetic potential. We devised a general intramolecular method that overcomes these limitations thanks to the photosensitization of allenamides. The visible-light-promoted process gives complex [2.2.2]-(hetero)-bicyclooctadienes at room temperature, likely through the stabilization of transient (bi)radicals by naphthalene. The reaction tolerates several valuable functionalities, offering a convenient handle for a myriad of applications, including original isoindoles and metal complexes.

Diastereoselective synthesis of tetrahydropyranes via Ag(I)-initiated dimerization of cinnamyl ethers.

We present herein the first synthesis of tetrahydropyranes promoted by a silver salt. Cinnamyl ethers undergo a formal dimerization affording the target heterocycle via sequential C-O bond cleavage/C-H bond functionalization. The cascade allows one to assemble three new bonds and to establish up to four stereocenters. The reaction likely proceeds through a cationic manifold that forms the target in a diastereoselective fashion.

Dimerizing cascades of enallenamides reveal the visible-light-promoted activation of cumulated C-C double bonds.

The visible-light-promoted activation of conjugated C-C double bonds is well developed, while that of cumulated systems is underexplored. We present the feasibility of this challenging approach. The localization of a triplet on an allenamide arm can be favored over that on a conjugated alkene. Allenamides with an arylacryloyl arm dimerize at room temperature in the presence of visible light and an iridium(iii) photocatalyst. Two orthogonal polycyclizations took place and their outcome is entirely dictated by the substitution of the alkene partner. Both cascades afford complex molecular architectures with high selectivity. Products form through the ordered rearrangement of twelve π electrons, providing a [3.2.0] bicyclic unit tethered to a fused tricycle, whose formation included an aryl C-H functionalization step, using disubstituted alkenes. The outcome was reverted with trisubstituted ones, which gave rise to taxane-like bridged tricycles that had two six-membered lactams flanking a cyclooctane ring, which was established through the creation of four alternate C-C bonds.

Evolution of Triangular All-Metal Aromatic Complexes from Bonding Quandaries to Powerful Catalytic Platforms.

This manuscript describes an overview on the literature detailing the observation of trinuclear complexes that present delocalized metal-metal bonds similar to those of regular aromatics, which are formed combining main group elements. A particular emphasis is given to the structural and electronic features of aromatic clusters that are sufficiently stable to allow their isolation. In parallel to the description of their key bonding properties, the work presents reported catalytic applications of these complexes, which already span from elaborated C-C-forming cascades to highly efficient cross-coupling methods. These examples present peculiar aspects of the unique reactivity exerted by all-metal aromatic complexes, which can often be superior to their established, popular mononuclear peers in terms of chemoselectivity and chemical robustness.

Pd-Catalysed oxidative carbonylation of α-amino amides to hydantoins under mild conditions.

The first example of palladium-catalysed oxidative carbonylation of unprotected α-amino amides to hydantoins is described here. The selective synthesis of the target compounds was achieved under mild conditions (1 atm of CO), without ligands and bases. The catalytic system overrode the common reaction pathway that usually leads instead to the formation of symmetrical ureas.

Is Aromaticity a Driving Force in Catalytic Cycles? A Case from the Cycloisomerization of Enynes Catalyzed by All-Metal Aromatic Pd3+ Clusters and Carboxylic Acids.

The work details a mechanistic study based on density functional theory modeling on the cycloisomerization of polyunsaturated substrates catalyzed by all-metal aromatic tripalladium complexes and carboxylic acids. These clusters are an emerging class of catalysts for a variety of relevant transformations, including C-C forming processes that occur under mild conditions and display synthetic features complementary to those of established mononuclear complexes. This study is the first computational one devoted to the comprehension of the series of elementary steps involved in a synthetic transformation catalyzed by an all-metal aromatic complex. Present results confirm previous experimental hints on the striking mechanistic differences exerted by these clusters with respect to the usual cyclization pathways of related substrates. Moreover, the catalytic cycle involving present all-metal aromatic clusters closely parallels the mechanism of the aromatic substitution of regular arenes.

Inter/Intramolecular Cascade of 1,6-Enynes Catalyzed by All-Metal Aromatic Tripalladium Complexes and Carboxylic Acids.

Trinuclear all-metal aromatic clusters are an original class of molecules with a cyclic and planar metal core. Characterized by peculiar metal-metal delocalized bonds, they represent a new frontier in transition-metal catalysis. We report a study on C-C-forming reactions of polyunsaturated substrates catalyzed by trinuclear all-metal aromatic palladium clusters. The synthesis of two new families of tricyclic compounds was obtained with a broad functional group tolerance under mild reaction conditions. A peculiar regio- and diastereoselectivity characterized the method, demonstrating that trinuclear palladium complexes are complementary to their popular mononuclear peers. Furthermore, preliminary studies on the mechanism of these polycyclization reactions revealed unique features of the homogeneous catalytic system.

Ambient Synthesis of Tricyclic Naphthalenes via Stepwise Styryl-yne Dearomative Diels-Alder Cyclization.

A cascade of styrylynols promoted by MnO2 allows the synthesis of fused tricycles with a naphthalene core. The reaction occurs under ambient conditions, offering a practical synthetic tool because of the inexpensive and abundant manganese species. The method affords products through the sequential oxidation of a propargyl alcohol, stepwise Diels-Alder cyclization, and finally rearomatization. According to density functional theory, the usually unfavorable stepwise Diels-Alder mechanism is instead a general tool for eliciting otherwise challenging dearomative annulation.

Photoelectric properties of aromatic triangular tri-palladium complexes and their catalytic applications in the Suzuki-Miyaura coupling reaction.

The photoelectric properties and catalytic activities of substituted triphenylphosphine and sulfur/selenium ligand supported aromatic triangular tri-palladium complexes 1-4, abbreviated as [Pd3]+, were investigated. The cyclic voltammogram of [Pd3]+ in CH3CN-nBu4NPF6 showed a single quasi-reversible wave which was consistent with their robust property and provided preliminary proof for their electron transfer processes in catalysis. With excitation at 267 nm, [Pd3]+ exhibited strong ratiometric fluorescence at 550 and 780 nm at a temperature gradient from 77 K to 287 K. These peculiar triangular tri-palladium complexes showed excellent catalytic activities and exclusive reactivity with aryl iodides over the other halogenated aromatics in the Suzuki-Miyaura coupling reaction. The electronic and steric hindrance effects of substituents on the aryl iodides and aryl boronic acids including heteroaromatics like pyridine, pyrazine and thiophenes were explored and most substrates achieved up to 99% of yields. (2-[1,1'-Biphenyl]-2-ylbenzothiazole) which was analogous to the selective cyclooxygenase-2 (COX-2) inhibitors was also synthesized with our tri-palladium catalyst and gave good isolated yield (94%). The study of the catalytic process revealed that the mechanism of the reaction may involve the replacement of the sulphur ligand on [Pd3]+ by iodine from aryl iodides, which was beneficial for the matching of C-I bond energy.

Orthogonal Syntheses of 3.2.0 Bicycles from Enallenes Promoted by Visible Light.

Enallenes can be readily converted into two families of 3.2.0 (hetero)bicycles with high diastereoselectivities through the combination of visible light with a suitable Ir(III) complex (1 mol %). Two complementary pathways, namely, a photocycloaddition versus a radical chain, can then take place. Both manifolds grant complete regiocontrol of the allene difunctionalization. This is accompanied by an original 1,3-group shift using sulfonyl allenamides that deliver a congested tetrasubstituted headbridging carbon in the corresponding product.

"Bottled" spiro-doubly aromatic trinuclear [Pd2Ru]+ complexes.

Following an ongoing interest in the study of transition metal complexes with exotic bonding networks, we report herein the synthesis of a family of heterobimetallic triangular clusters involving Ru and Pd atoms. These are the first examples of trinuclear complexes combining these nuclei. Structural and bonding analyses revealed both analogies and unexpected differences for these [Pd2Ru]+ complexes compared to their parent [Pd3]+ peers. Noticeably, participation of the Ru atom in the π-aromaticity of the coordinated benzene ring makes the synthesized compound the second reported example of 'bottled' double aromaticity. This can also be referred to as spiroaromaticity due to the participation of Ru in two aromatic systems at a time. Moreover, the [Pd2Ru]+ kernel exhibits unprecedented orbital overlap of Ru d z 2 AO and two Pd d xy or d x 2-y 2 AOs. The present findings reveal the possibility of synthesizing stable clusters with delocalized metal-metal bonding from the combination of non-adjacent elements of the periodic table which has not been reported previously.

Visible-Light-Promoted Polycyclizations of Dienynes.

A variety of linear dienynes can deliver complex tetracyclic frameworks in the presence of an IrIII complex and visible light. Product formation involves the generation of four new C-C bonds and six contiguous stereocenters, which decorate two [3.1.0] bicyclic units tethered through their bridging quaternary carbon atoms. The internal alkyne acts as a formal dicarbenoid for the generation of two cyclopropanes in these radical cation cascades. This behavior has not been previously observed for organic reactive intermediates and can be extended to intermolecular reactions and diendiynes.

Synthesis of Imidazolidin-2-ones and Imidazol-2-ones via Base-Catalyzed Intramolecular Hydroamidation of Propargylic Ureas under Ambient Conditions.

The first organo-catalyzed synthesis of imidazolidin-2-ones and imidazol-2-ones via intramolecular hydroamidation of propargylic ureas is reported. The phosphazene base BEMP turned out to be the most active organo-catalyst compared with guanidine and amidine bases. Excellent chemo- and regioselectivities to five-membered cyclic ureas have been achieved under ambient conditions, with a wide substrate scope and exceptionally short reaction times (down to 1 min). A base-mediated isomerization step to an allenamide intermediate is the most feasible reaction pathway to give imidazol-2-ones, as suggested by DFT studies.

Palladium(0)/benzoic acid catalysis merges sequences with D2O-promoted labelling of C-H bonds.

The combination of a Pd(0) complex with benzoic acid in the presence of D2O enables the synthesis of valuable families of highly deuterated organics through elaborate sequential reactions. The catalytic system can convert 2-butyne fragments into the corresponding d-dienamides, which can then readily deliver labeled polycyclic quinone motifs. Propargylated tryptamines lead to formation of highly enriched tetrahydrocarbolines through the C-H activation of their unprotected indole ring. Mechanistic studies reveal the ordered series of events that regulate the outcome of these complex reactions, which include multiple, sequential and selective H/D scrambling from the cheapest and safest deuterium source.