On-Surface Synthesis and Determination of the Open-Shell Singlet Ground State of Tridecacene.

The character of the electronic structure of acenes has been the subject of longstanding discussion. However, convincing experimental evidence of their open-shell character has so far been missing. Here, we present the on-surface synthesis of tridecacene molecules by thermal annealing of octahydrotridecacene on a Au(111) surface. We characterized the electronic structure of the tridecacene by scanning probe microscopy, which reveals the presence of an inelastic signal at 126 meV. We attribute the inelastic signal to spin excitation from the singlet diradical ground state to the triplet excited state. To rationalize the experimental findings, we carried out many-body ab initio calculations as well as model Hamiltonians to take into account the effect of the metallic substrate. Moreover, we provide a detailed analysis of how the dynamic electron correlation and virtual charge fluctuation between the molecule and metallic surface reduces the singlet-triplet band gap. Thus, this work provides the first experimental confirmation of the magnetic character of tridecacene.

Gold-Catalyzed Synthesis of Small Rings.

Three- and four-membered rings, widespread motifs in nature and medicinal chemistry, have fascinated chemists ever since their discovery. However, due to energetic considerations, small rings are often difficult to assemble. In this regard, homogeneous gold catalysis has emerged as a powerful tool to construct these highly strained carbocycles. This review aims to provide a comprehensive summary of all the major advances and discoveries made in the gold-catalyzed synthesis of cyclopropanes, cyclopropenes, cyclobutanes, cyclobutenes, and their corresponding heterocyclic or heterosubstituted analogs.

Chiral Auxiliary Approach for Gold(I)-Catalyzed Cyclizations.

Two different classes of stereoselective cyclizations have been developed using a chiral auxiliary approach with commercially available [JohnPhosAu(MeCN)SbF6 ] as catalyst. First, a stereoselective cascade cyclization of 1,5-enynes was achieved using the Oppolzer camphorsultam as chiral auxiliary. In this case, a one-pot cyclization-hydrolysis sequence was developed to directly afford enantioenriched spirocyclic ketones. Then, the stereoselective alkoxycyclization of 1,6-enynes was mediated by an Evans-type oxazolidinone. A reduction-hydrolysis sequence was selected to remove the auxiliary to give enantioenriched ß-tetralones. DFT studies confirmed that the steric clash between the chiral auxiliary and alkene accounts for the experimentally observed diastereoselective cyclization through the Si face.

H-Bonded Counterion-Directed Enantioselective Au(I) Catalysis.

A new strategy for enantioselective transition-metal catalysis is presented, wherein a H-bond donor placed on the ligand of a cationic complex allows precise positioning of the chiral counteranion responsible for asymmetric induction. The successful implementation of this paradigm is demonstrated in 5-exo-dig and 6-endo-dig cyclizations of 1,6-enynes, combining an achiral phosphinourea Au(I) chloride complex with a BINOL-derived phosphoramidate Ag(I) salt and thus allowing the first general use of chiral anions in Au(I)-catalyzed reactions of challenging alkyne substrates. Experiments with modified complexes and anions, 1H NMR titrations, kinetic data, and studies of solvent and nonlinear effects substantiate the key H-bonding interaction at the heart of the catalytic system. This conceptually novel approach, which lies at the intersection of metal catalysis, H-bond organocatalysis, and asymmetric counterion-directed catalysis, provides a blueprint for the development of supramolecularly assembled chiral ligands for metal complexes.

H-Bonded Counterion-Directed Catalysis: Enantioselective Gold(I)-Catalyzed Addition to 2-Alkynyl Enones as a Case Study.

H-bonded counterion-directed catalysis (HCDC) is a strategy wherein a chiral anion that is hydrogen-bonded to the achiral ligand of a metal complex is responsible for enantioinduction. In this article we present the application of H-bonded counterion-directed catalysis to the Au(I)-catalyzed enantioselective tandem cycloisomerization-addition reaction of 2-alkynyl enones. Following the addition of C-, N- or O-centered nucleophiles, bicyclic furans were obtained in moderate to excellent yield and enantioselectivity (28 examples, 59-96 % yield, 62 : 38 to 95 : 5 er). The optimal catalytic system, comprising a phosphinosquaramide Au(I) chloride complex and a BINOL-derived phosphoramidate Ag(I) salt, was selected in a combinatorial fashion from a larger library with the help of high-throughput screening. An enantioselectivity switch of ca. 120 Δee% was observed upon addition of the achiral Au(I) component to the Ag(I) salt.

Doublet-Singlet-Doublet Transition in a Single Organic Molecule Magnet On-Surface Constructed with up to 3 Aluminum Atoms.

Starting from a long aza-starphene neutral and nonmagnetic organic molecule, a single-molecule magnet is on-surface constructed using up to 3 light nonmagnetic aluminum (Al) atoms. Seldom observed in solution with transition-metal atoms and going from 1 to 3 Al coordinated atoms, the doublet-singlet-doublet transition is easily on-surface accessible using the scanning tunneling microscope single-atom and single-molecule manipulations on a gold(111) surface. With 3 coordinated Al atoms, the lateral vibration modes of the Al3-aza-starphene molecule magnet are largely frozen. Using the Kondo states, this opens the observation of the in-phase Al vertical atom vibrations and out-of-phase central phenyl vibrations.

Shape-Shifting Molecules: Unveiling the Valence Tautomerism Phenomena in Bare Barbaralones.

We report a state-of-the-art spectroscopic study of an archetypical barbaralone, conclusively revealing the valence tautomerism phenomena for this bistable molecular system. The two distinct 1- and 5-substituted valence tautomers have been isolated in a supersonic expansion for the first time and successfully characterized by high-resolution rotational spectroscopy. This work provides irrefutable experimental evidence of the [3,3]-rearrangement in barbaralones and highlights the use of rotational spectroscopy to analyze shape-shifting mixtures. Moreover, this observation opens the window toward the characterization of new fluxional systems in the isolation conditions of the gas phase and should serve as a reference point in the general understanding of valence tautomerism.

Rh(II)-Catalyzed Alkynylcyclopropanation of Alkenes by Decarbenation of Alkynylcycloheptatrienes.

Alkynylcyclopropanes have found promising applications in both organic synthesis and medicinal chemistry but remain rather underexplored due to the challenges associated with their preparation. We describe a convenient two-step methodology for the alkynylcyclopropanation of alkenes, based on the rhodium(II)-catalyzed decarbenation of 7-alkynyl cycloheptatrienes. The catalytic system employed circumvents a fundamental problem associated with these substrates, which usually evolve via 6-endo-dig cyclization or ring-contraction pathways under metal catalysis. This unique performance unlocks a rapid access to a diverse library of alkynylcyclopropanes (including derivatives of complex drug-like molecules), versatile intermediates that previously required much lengthier synthetic approaches. Combining experiments and DFT calculations, the complete mechanistic picture for the divergent reactivity of alkynylcycloheptatrienes under metal catalysis has been unveiled, rationalizing the unique selectivity displayed by rhodium(II) complexes.

Silver-Free Au(I) Catalysis Enabled by Bifunctional Urea- and Squaramide-Phosphine Ligands via H-Bonding.

A library of gold(I) chloride complexes with phosphine ligands incorporating pendant (thio)urea and squaramide H-bond donors was prepared with the aim of promoting chloride abstraction from Au(I) via H-bonding. In the absence of silver additives, complexes bearing squaramides and trifluoromethylated aromatic ureas displayed good catalytic activity in the cyclization of N-propargyl benzamides, as well as in a 1,6-enyne cycloisomerization, a tandem cyclization-indole addition reaction and the hydrohydrazination of phenylacetylene. Kinetic studies and DFT calculations indicate that the energetic span of the reaction is accounted by both the chloride abstraction step, facilitated by the bidentate H-bond donor via an associative mechanism, and the subsequent cyclization step.

Assembly of Complex 1,4-Cycloheptadienes by (4+3) Cycloaddition of Rhodium(II) and Gold(I) Non-Acceptor Carbenes.

The formal (4+3) cycloaddition of 1,3-dienes with Rh(II) and Au(I) non-acceptor vinyl carbenes, generated from vinylcycloheptatrienes or alkoxyenynes, respectively, leads to 1,4-cycloheptadienes featuring complex and diverse substitution patterns, including natural dyctiopterene C' and a hydroxylated derivative of carota-1,4-diene. A complete mechanistic picture is presented, in which Au(I) and Rh(II) non-acceptor vinyl carbenes were shown to undergo a vinylcyclopropanation/Cope rearrangement or a direct (4+3) cycloaddition that takes place in a non-concerted manner.

Rhodium(III)-Catalyzed Synthesis of Skipped Enynes via C(sp3 )-H Alkynylation of Terminal Alkenes.

The RhIII -catalyzed allylic C-H alkynylation of non-activated terminal alkenes leads selectively to linear 1,4-enynes at room-temperature. The catalytic system tolerates a wide range of functional groups without competing functionalization at other positions. Similarly, the vinylic C-H alkynylation of α,ß- and ß,γ- unsaturated amides gives conjugated Z-1,3-enynes and E-enediynes.

Enantioselective Alkoxycyclization of 1,6-Enynes with Gold(I)-Cavitands: Total Synthesis of Mafaicheenamine C.

Chiral gold(I)-cavitand complexes have been developed for the enantioselective alkoxycyclization of 1,6-enynes. This enantioselective cyclization has been applied for the first total synthesis of carbazole alkaloid (+)-mafaicheenamine C and its enantiomer, establishing its configuration as R. The cavity effect was also evaluated in the cycloisomerization of dienynes. A combination of experiments and theoretical studies demonstrates that the cavity of the gold(I) complexes forces the enynes to adopt constrained conformations, which results in the high observed regio- and stereoselectivities.

From Palladium to Gold Catalysis for the Synthesis of Crushed Fullerenes and Acenes.

The quest for organic materials with improved optoelectronic properties has stimulated the development of new strategies for the preparation of polycyclic aromatic hydrocarbons. Within this context, transition metal catalysis offers unparalleled opportunities for the assembly of complex molecular architectures. The palladium-catalyzed direct C-H arylation provides straight access to biaryls without the need of prefunctionalization at the nucleophilic site, which is attractive from the perspective of the synthesis of polyarenes. Mechanistically, this reaction was found to be different from an electrophilic aromatic substitution, involving the abstraction of a proton by an external base in the key metalation step. Using readily available C27 truxene as the starting material, a concise synthetic route consisting of a threefold benzylation and subsequent palladium-catalyzed arylation led to C60 polyarenes, also referred to as "crushed fullerenes", which could be converted into C60 fullerene by laser-induced cyclodehydrogenation in the gas phase or by thermal cyclodehydrogenation on a platinum surface. A conceptually related strategy based on the use of a highly electrophilic gold(I) complex as the catalyst for the threefold intramolecular hydroarylation of truxene derivatives was applied for the synthesis of decacyclenes. Using gold(I) catalysis, we have also developed a variety of synthetically useful protocols for the cycloisomerization of readily available 1,n-enynes as well as for the addition for nucleophiles to these unsaturated substrates. In one of these transformations, 1,7-enynes bearing aryl-substituted alkynes undergo formal [4 + 2] cycloaddition reactions via gold(I)-catalyzed 6-exo-dig cyclization and intramolecular Friedel-Crafts-type reaction to form tricyclic compounds bearing a dihydronaphthalene core. A related transformation led to a general synthesis of hydroacenes, which are known to be stabilized precursors of the corresponding conjugated acenes with enhanced solubility. A wide variety of dihydrotetracenes featuring electron-donating and electron-withdrawing groups, as well as dihydropentacene and dihydrohexacene could be easily obtained. A simple variation of our synthetic route led to tetrahydro-derivatives of higher acenes with up to 11 linearly fused six-membered rings. The dehydrogenation of tetrahydroacenes on a metallic substrate using the tip of a scanning tunneling microscopy instrument or by thermal annealing enabled the preparation of the whole series of higher acenes from heptacene up to previously unknown undecacene, whose structure was confirmed by noncontact atomic force microscopy. This work provided a unique opportunity for the analysis of the evolution of the transport gap in the acene series on Au(111). Furthermore, heptacene was also generated by on-surface dehydrogenation on Ag(001) from tetrahydroheptacene and a dibrominated derivative.

On the Structure of Intermediates in Enyne Gold(I)-Catalyzed Cyclizations: Formation of trans-Fused Bicyclo[5.1.0]octanes as a Case Study.

The nature of cyclopropyl gold(I) carbene-type intermediates has been reexamined as part of a mechanistic study on the formation of cis- or trans-fused bicyclo[5.1.0]octanes in a gold(I)-catalyzed cascade reaction. Benchmark of DFT methods together with QTAIM theory and NBO analysis confirms the formation of distinct intermediates with carbenic or carbocationic structures in the cycloisomerizations of enynes.

Small Gold(I) and Gold(I)-Silver(I) Clusters by C-Si Auration.

Auration of o-trimethylsilyl arylphosphines leads to the formation of gold and gold-silver clusters with ortho-metalated phosphines displaying 3c-2e Au-C-M bonds (M=Au/Ag). Hexagold clusters [Au6 L4 ](X)2 are obtained by reaction of (L-TMS)AuCl with AgX, whereas reaction with AgX and Ag2 O leads to gold-silver clusters [Au4 Ag2 L4 ](X)2 . Oxo-trigold(I) species [Au3 O]+ were identified as the intermediates in the formation of the silver-doped clusters. Other [Au5 ], [Au4 Ag], and [Au12 Ag4 ] clusters were also obtained. Clusters containing PAu-Au-AuP structural motif display good catalytic activity in the activation of alkynes under homogeneous conditions.

Iridium-Catalyzed ß-Alkynylation of Aliphatic Oximes as Masked Carbonyl Compounds and Alcohols.

An Ir-catalyzed C(sp3 )-H alkynylation of aliphatic ketones, aldehydes, and alcohols was achieved by using the corresponding oxime derivatives and a IrIII catalyst. This general reaction is selective towards primary C(sp3 )-H bonds and can be used for the late-stage C-H alkynylation of complex molecules.

Kilian Muñiz (1970-2020).

Kilian Muñiz passed away unexpectedly on March 16th, 2020, at the age of only 49. Kilian was a leading figure in the field of catalytic (di-)amination reactions. He will be remembered as one of the finest, most passionate chemists, a dear colleague, and, most of all, as a close friend.

Acetylene as a Dicarbene Equivalent for Gold(I) Catalysis: Total Synthesis of Waitziacuminone in One Step.

The gold(I)-catalyzed reaction of acetylene gas with alkenes leads to (Z,Z)-1,4-disubstituted 1,3-butadienes and biscyclopropanes depending on the donor ligand on gold(I). Acetylene was generated in situ from calcium carbide and water in a user-friendly procedure. Reaction of acetylene with 1,5-dienes gives rise stereoselectively to tricyclo[5.1.0.02,4 ]octanes. This novel double cyclopropanation has been applied to the one step total synthesis of the natural product waitziacuminone from acetylene and geranyl acetone.

Enantioselective Folding of Enynes by Gold(I) Catalysts with a Remote C2-Chiral Element.

Chiral gold(I) catalysts have been designed based on a modified JohnPhos ligand with a distal C2-2,5-diarylpyrrolidine that creates a tight binding cavity. The C2-chiral element is close to where the C-C bond formation takes place in cyclizations of 1,6-enynes. These chiral mononuclear catalysts have been applied for the enantioselective 5-exo-dig and 6-endo-dig cyclization of different 1,6-enynes as well as in the first enantioselective total synthesis of three members of the carexane family of natural products. Opposite enantioselectivities have been achieved in seemingly analogous reactions of 1,6-enynes, which result from different chiral folding of the substrates based on attractive aryl-aryl interactions.

Gold(I)-Catalyzed Intramolecular C(sp3 )-H Insertion by Decarbenation of Cycloheptatrienes.

A novel synthesis of indanes and dihydronaphtalenes based on the intramolecular insertion into C(sp3 )-H bonds of gold(I) carbenes generated by retro-Buchner reaction (decarbenation) has been developed. Deuterium-labeling and kinetic isotope effect experiments, DFT calculations, and generation of the proposed carbene intermediate from a well-characterized gold(I) carbenoid support the involvement of a three-center concerted mechanism for the C(sp3 )-H functionalization process.