Utilization of 13C NMR Carbon Shifts for the Attribution of Diastereomers in Methyl-Substituted Cyclohexanes.

In this report, we address the challenge of assigning diastereomers for methyl cyclohexanes, particularly those with quaternary centers, which remains nontrivial despite modern NMR techniques. By utilizing a HSQC NMR experiment to identify methyl-carbons coupled with a simple conformational analysis, we identified an effective and quite general method for assigning stereochemistry, even in cases where diastereomeric mixtures are inseparable.

An N-Heterocyclic Quinodimethane: A Strong Organic Lewis Base Exhibiting Diradical Reactivity.

We report the preparation of a new organic σ-donor with a C6H4-linker between an N-heterocyclic carbene (NHC) and an exocyclic methylidene group, which we term N-heterocyclic quinodimethane (NHQ). The aromatization of the C6H4-linker provides a decisive driving force for the reaction of the NHQ with an electrophile and renders the NHQ significantly more basic than analogous NHCs or N-heterocyclic olefins (NHOs), as shown by DFT computations and competition experiments. In solution, the NHQ undergoes an unprecedented dehydrogenative head-to-head dimerization by C-C coupling of the methylidene groups. DFT computations indicate that this reaction proceeds via an open-shell singlet pathway revealing the diradical character of the NHQ. The product of this dimerization can be described as conjugated N-heterocyclic bis-quinodimethane, which according to cyclic voltammetry is a strong organic reducing agent (E1/2=-1.71 V vs. Fc/Fc+) and exhibits a remarkable small singlet-triplet gap of ΔES→T=4.4 kcal mol-1.

Synthesis and characterization of a formal 21-electron cobaltocene derivative.

Metallocenes are highly versatile organometallic compounds. The versatility of the metallocenes stems from their ability to stabilize a wide range of formal electron counts. To date, d-block metallocenes with an electron count of up to 20 have been synthesized and utilized in catalysis, sensing, and other fields. However, d-block metallocenes with more than formal 20-electron counts have remained elusive. The synthesis and isolation of such complexes are challenging because the metal-carbon bonds in d-block metallocenes become weaker with increasing deviation from the stable 18-electron configuration. Here, we report the synthesis, isolation, and characterization of a 21-electron cobaltocene derivative. This discovery is based on the ligand design that allows the coordination of an electron pair donor to a 19-electron cobaltocene derivative while maintaining the cobalt-carbon bonds, a previously unexplored synthetic approach. Furthermore, we elucidate the origin of the stability, redox chemistry, and spin state of the 21-electron complex. This study reveals a synthetic method, structure, chemical bonding, and properties of the 21-electron metallocene derivative that expands our conceptual understanding of d-block metallocene chemistry. We expect that this report will open up previously unexplored synthetic possibilities in d-block transition metal chemistry, including the fields of catalysis and materials chemistry.

The entropic penalty for associative reactions and their physical treatment during routine computations.

A systematic study of the entropic penalty for associative reactions is presented. It is shown that computed solution-phase Gibbs free energies typically overestimate entropic contributions. This entropic penalty for associative reactions in solution, i.e., if the number of particles decreases along the reaction coordinate (sum of stoichiometric numbers ), originates from the insufficient treatment of entropic effects by implicit solvent models. We propose an additive correction scheme to Gibbs free energies that is suitable for routine applications by non-expert users. This correction is based on Garza's formalism for the solution-phase entropy [A. J. Garza, J. Chem. Theory Comput., 2019, 15, 3204.] that is physically sound and embedded into an efficient black-box type algorithm. To critically evaluate the entropic penalty and its proposed treatment, we compiled an experimental benchmark set of 31 ΔrG and 22 in 15 different solvents. Using a representative best-practice computational protocol (at wave function theory (WFT) based DLPNO-CCSD(T) and density functional theory (DFT) based revDSD-PBEP86-D4 level with an implicit solvent model), we determined a sizeable entropic penalty ranging from 2-11 kcal mol-1. Using the correction scheme presented herein, the entropic penalty is corrected to the chemical accuracy of ≤1 kcal mol-1 (WFT and DFT). The same applies to at the WFT level. Barriers at the DFT level are overestimated by 2 kcal mol-1 (classic) and underestimated by 2 kcal mol-1 (corrected). This effect is attributed to the finding that barriers computed at the DFT level are systematically 2-3 kcal mol-1 lower than barriers obtained with WFT.

1,2-Carboboration of Arylallenes by In Situ Generated Alkenylboranes for the Synthesis of 1,4-Dienes.

We herein report a novel method for the coupling of unactivated alkynes and arylallenes, which relies on an unprecedented and regioselective 1,2-carboboration of the allene by an alkenylborane. The alkenylborane is conveniently prepared in situ by hydroboration of an alkyne with Piers' borane, i. e., HB(C6 F5 )2 . The boryl-substituted 1,4-dienes that are formed by this carboboration are well-suited for a subsequent Suzuki-Miyaura coupling with aryl iodides. This allowed us to develop a three-step, one-pot protocol for the synthesis of aryl-substituted 1,4-dienes. The generality of the reaction was demonstrated by the synthesis of twenty dienes with modular variations of all three reaction partners. The mechanism of the new 1,2-carboboration was investigated using dispersion corrected double-hybrid DFT computations that allowed us to rationalize the chemo- and regioselectivity of this key step.

Piers' Borane-Induced Tetramerization of Arylacetylenes.

We herein report that the reaction of Piers' borane, i. e. HB(C6 F5 )2 , with an excess of arylacetylenes at room temperature leads to tetramerization of the acetylene and the diastereoselective formation of boryl-substituted tetra-aryl-tetrahydropentalenes. The reaction mechanism was investigated by isotope labeling experiments and DFT computations. These investigations indicate that a series of 1,2-carboboration reactions form an octatetraene that undergoes an electrocyclization. Two skeletal rearrangements then presumably lead to the formation of the tetrahydropentalene core. Overall, this intricate and unprecedented transformation comprises five carbon-carbon bond formations in a single reaction.

Indene formation upon borane-induced cyclization of arylallenes, 1,1-carboboration, and retro-hydroboration.

We herein report the reaction of arylallenes with tris(pentafluorophenyl)borane that yields pentafluorophenyl substituted indenes. The tris(pentafluorophenyl)borane induces the cyclization of the allene and transfers a pentafluorophenyl ring in the course of this reaction. A Hammett plot analysis and DFT computations indicate a 1,1-carboboration to be the C-C bond-forming step.

Boron-Ligand Cooperation: The Concept and Applications.

The term boron-ligand cooperation was introduced to describe a specific mode of action by which certain metal-free systems activate chemical bonds. The main characteristic of this mode of action is that one covalently bound substituent at the boron is actively involved in the bond activation process and changes to a datively bound ligand in the course of the bond activation. Within this review, how the term boron-ligand cooperation evolved is reflected on and examples of bond activation by boron-ligand cooperation are discussed. It is furthermore shown that systems that operate via boron-ligand cooperation can complement the reactivity of classic intramolecular frustrated Lewis pairs and applications of this new concept for metal-free catalysis are summarized.

Formation of Nucleophilic Allylboranes from Molecular Hydrogen and Allenes Catalyzed by a Pyridonate Borane that Displays Frustrated Lewis Pair Reactivity.

Here we report the in situ generation of nucleophilic allylboranes from H2 and allenes mediated by a pyridonate borane that displays frustrated-Lewis-pair reactivity. Experimental and computational mechanistic investigations reveal that upon H2 activation, the covalently bound pyridonate substituent becomes a datively bound pyridone ligand. Dissociation of the formed pyridone borane complex liberates Piers borane and enables a hydroboration of the allene. The allylboranes generated in this way are reactive towards nitriles. A catalytic protocol for the formation of allylboranes from H2 and allenes and the allylation of nitriles has been devised. This catalytic reaction is a conceptually new way to use molecular H2 in organic synthesis.

Semihydrogenation of Alkynes Catalyzed by a Pyridone Borane Complex: Frustrated Lewis Pair Reactivity and Boron-Ligand Cooperation in Concert.

The metal-free cis selective hydrogenation of alkynes catalyzed by a boroxypyridine is reported. A variety of internal alkynes are hydrogenated at 80 °C under 5 bar H2 with good yields and stereoselectivity. Furthermore, the catalyst described herein enables the first metal-free semihydrogenation of terminal alkynes. Mechanistic investigations, substantiated by DFT computations, reveal that the mode of action by which the boroxypyridine activates H2 is reminiscent of the reactivity of an intramolecular frustrated Lewis pair. However, it is the change in the coordination mode of the boroxypyridine upon H2 activation that allows the dissociation of the formed pyridone borane complex and subsequent hydroboration of an alkyne. This change in the coordination mode upon bond activation is described by the term boron-ligand cooperation.

Efficient Organocatalytic Dehydrogenation of Ammonia Borane.

Dehydrogenation of ammonia borane by sterically encumbered pyridones as organocatalysts is reported. With 6-tert-butyl-2-thiopyridone as the catalyst, a turnover frequency (TOF) of 88 h-1 was achieved. Experimental mechanistic investigations, substantiated by DLPNO-CCSD(T) computations, indicate a mechanistic scenario that commences with the protonation of a B-H bond by the mercaptopyridine form of the catalyst. The reactive intermediate formed by this initial protonation was observed by NMR spectroscopy and the molecular structure of a surrogate determined by SCXRD. An intramolecular proton transfer in this intermediate from the NH3 group to the pyridine ring with concomitant breaking of the S-B bond regenerates the thiopyridone and closes the catalytic cycle. This step can be described as an inorganic retro-ene reaction.

Reversible Hydrogen Activation by a Pyridonate Borane Complex: Combining Frustrated Lewis Pair Reactivity with Boron-Ligand Cooperation.

A pyridone borane complex that liberates dihydrogen under mild conditions is described. The reverse reaction, dihydrogen activation by the formed pyridonate borane complex, is achieved under moderate H2 pressure (2 bar) at room temperature. DFT and DLPNO-CCSD(T) computations reveal that the active form of the pyridonate borane complex is a boroxypyridine that can be described as a single component frustrated Lewis pair (FLP). Significantly, the boroxypyridine undergoes a chemical transformation to a neutral pyridone donor ligand in the course of the hydrogen activation. This unprecedented mode of action may thus, in analogy to metal-ligand cooperation, be regarded as an example of boron-ligand cooperation.

Manganese-Catalyzed N-Formylation of Amines by Methanol Liberating H2 : A Catalytic and Mechanistic Study.

The first example of a base metal (manganese) catalyzed acceptorless dehydrogenative coupling of methanol and amines to form formamides is reported herein. The novel pincer complex (iPr-PNH P)Mn(H)(CO)2 catalyzes the reaction under mild conditions in the absence of any additives, bases, or hydrogen acceptors. Mechanistic insight based on the observation of an intermediate and DFT calculations is also provided.

The Ferraquinone-Ferrahydroquinone Couple: Combining Quinonic and Metal-Based Reactivity.

A ferraquinone-ferrahydroquinone organometallic redox couple was prepared and characterized. Intricate cooperativity of the metal was observed with different positions on the ligand. This allowed cooperative activation of small molecules like molecular hydrogen, oxygen, and bromine. Likewise, dehydrogenation of alcohols was achieved through 1,6 metal-ligand cooperation.

Reversible Aromaticity Transfer in a Bora-Cycle: Boron-Ligand Cooperation.

Aromaticity is a central concept in chemistry. Reaction pathways involving reversible ligand dearomatization sequences emerged as a powerful tool for bond activation by metal complexes. Exploring this concept with a metal-free system, we have synthesized a pyridine-coordinated aminoborane which undergoes a temperature-induced formal dearomatization of the pyridine ring. NMR studies and DFT calculations revealed that this formal dearomatization sequence led to an aromaticity switch and the formation of a six-π-electron boron-containing heteroaromatic system. Disrupting this aromatic system by coordination of an amine or a carboxylic acid to the boron center enabled N-H activation and O-H cleavage, leading to an unprecedented reversal aromaticity switch.

Template Catalysis by Metal-Ligand Cooperation. C-C Bond Formation via Conjugate Addition of Non-activated Nitriles under Mild, Base-free Conditions Catalyzed by a Manganese Pincer Complex.

The first example of a catalytic Michael addition reaction of non-activated aliphatic nitriles to α,ß-unsaturated carbonyl compounds under mild, neutral conditions is reported. A new de-aromatized pyridine-based PNP pincer complex of the Earth-abundant, first-row transition metal manganese serves as the catalyst. The reaction tolerates a variety of nitriles and Michael acceptors with different steric features and acceptor strengths. Mechanistic investigations including temperature-dependent NMR spectroscopy and DFT calculations reveal that the cooperative activation of alkyl nitriles, which leads to the generation of metalated nitrile nucleophile species (α-cyano carbanion analogues), is a key step of the mechanism. The metal center is not directly involved in the catalytic bond formation but rather serves, cooperatively with the ligand, as a template for the substrate activation. This approach of "template catalysis" expands the scope of potential donors for conjugate addition reactions.

Reductive Cleavage of CO2 by Metal-Ligand-Cooperation Mediated by an Iridium Pincer Complex.

A unique mode of stoichiometric CO2 activation and reductive splitting based on metal-ligand-cooperation is described. The novel Ir hydride complexes [((t)Bu-PNP*)Ir(H)2] (2) ((t)Bu-PNP*, deprotonated (t)Bu-PNP ligand) and [((t)Bu-PNP)Ir(H)] (3) react with CO2 to give the dearomatized complex [((t)Bu-PNP*)Ir(CO)] (4) and water. Mechanistic studies have identified an adduct in which CO2 is bound to the ligand and metal, [((t)Bu-PNP-COO)Ir(H)2] (5), and a di-CO2 iridacycle [((t)Bu-PNP)Ir(H)(C2O4-κC,O)] (6). DFT calculations confirm the formation of 5 and 6 as reversibly formed side products, and suggest an η(1)-CO2 intermediate leading to the thermodynamic product 4. The calculations support a metal-ligand-cooperation pathway in which an internal deprotonation of the benzylic position by the η(1)-CO2 ligand leads to a carboxylate intermediate, which further reacts with the hydride ligand to give complex 4 and water.

Mechanistic investigations of the catalytic formation of lactams from amines and water with liberation of H2.

The mechanism of the unique lactam formation from amines and water with concomitant H2 liberation with no added oxidant, catalyzed by a well-defined acridine-based ruthenium pincer complex was investigated in detail by both experiment and DFT calculations. The results show that a dearomatized form of the initial complex is the active catalyst. Furthermore, reversible imine formation was shown to be part of the catalytic cycle. Water is not only the oxygen atom source but also acts as a cocatalyst for the H2 liberation, enabled by conformational flexibility of the acridine-based pincer ligand.

Mechanistic insight into the ruthenium-catalysed anti-Markovnikov hydration of alkynes using a self-assembled complex: a crucial role for ligand-assisted proton shuttle processes.

A combined computational and experimental study is presented that investigates the mechanism of the anti-Markovnikov hydration of phenylacetylene by [Ru(η(5)-C5H5)(6-DPPAP)(3-DPICon)](+) (where 6-DPPAP = 6-(diphenylphosphino)-N-pivaloyl-2-aminopyridine) and 3-DPICon = 3-diphenylphosphinoisoquinolone). The proposed mechanism, modelled using density functional calculations, involves an initial alkyne-vinylidene tautomerism, which occurs via a ligand-assisted proton shuttle (LAPS) mechanism. Intramolecular ligand assistance from the 6-DPPAP and 3-DPICon ligands, particularly the basic nitrogen of 6-DPPAP, is also involved in subsequent stages of the mechanism and three LAPS processes in total are observed. The self-assembled ligand backbone helps to create a water-binding pocket close to the metal centre, which facilitates nucleophilic attack of water at the vinylidene α-carbon and mediates protonation and deprotonation of subsequent acyl and vinyl intermediates. Experimental evidence is also presented for a novel non-productive catalyst deactivation pathway, which appears to arise from an initial lactam-lactim tautomerism of the 3-DPICon ligand followed by coupling with a vinylidene.

Mechanistic investigations of the rhodium catalyzed propargylic CH activation.

Previously we reported the redox-neutral atom economic rhodium catalyzed coupling of terminal alkynes with carboxylic acids using the DPEphos ligand. We herein present a thorough mechanistic investigation applying various spectroscopic and spectrometric methods (NMR, in situ-IR, ESI-MS) in combination with DFT calculations. Our findings show that in contrast to the originally proposed mechanism, the catalytic cycle involves an intramolecular protonation and not an oxidative insertion of rhodium in the OH bond of the carboxylic acid. A σ-allyl complex was identified as the resting state of the catalytic transformation and characterized by X-ray crystallographic analysis. By means of ESI-MS investigations we were able to detect a reactive intermediate of the catalytic cycle.