Metal-free decarboxylative allylation of oxime esters under light irradiation.

Allylation reactions, often used as a key step for constructing complex molecules and drug candidates, typically rely on transition-metal (TM) catalysts. Even though TM-free radical allylations have been developed using allyl-stannanes, -sulfides, -silanes or -sulfones, much less procedures have been reported using simple and commercially available allyl halides, that are used for the preparation of the before-mentioned allyl derivatives. Here, we present a straightforward photocatalytic protocol for the decarboxylative allylation of oxime esters using allyl bromide derivatives under metal-free and mild conditions. This methodology yields a diverse variety of functionalized molecules including several pharmaceutically relevant molecules.

N2 Functionalization via Molybdenum-Nitride Complex: Stepwise BH Bond Additions.

Reactivity of (triphosphine)MoIV-nitrido complex generated by N2 splitting, toward boranes is reported. The simple adduct Mo≡N→BH3 is observed with BH3.SMe2 while 1,2 addition is evidenced with 9-BBN leading to H-Mo=NBR2. A second addition of BH3.SMe2 is facile and forms an unprecedented complex featuring two bridging H between two B and the Mo centers. Addition of PMe3 or BH3.SMe2 promotes reductive elimination and N-H bond formation. The full sequence of functionalization at Mo≡N obtained after N2 splitting is therefore evidenced in this work.

Assessing Combinations of B(C6 F5 )3 and N2 -Derived Molybdenum Nitrido Complexes for Heterolytic Bond Activation.

Two different dinitrogen-derived molybdenum nitrido complexes varying by their geometry, ligand spheres and oxidations states were shown to engage their N ligand in dative bonding with the strong Lewis acid B(C6 F5 )3 . The stable adducts were assessed for frustrated Lewis pair-type heterolytic E-H bond splitting of hydrosilanes (E=Si) and HB(C6 F5 )2 . Whereas Si-H bond activation was achieved, HB(C6 F5 )2 was shown to substitute B(C6 F5 )3 in a quantitative or equilibrated fashion, depending on the nature of the nitrido complex. No B-H bond splitting was observed. Thermodynamics of these reactions, computed by DFT, are in agreement with the experimental outcomes.

Ammonia Synthesis at Room Temperature and Atmospheric Pressure from N2 : A Boron-Radical Approach.

Ammonia, NH3 , is an essential molecule, being part of fertilizers. It is currently synthesized via the Haber-Bosch process, from the very stable dinitrogen molecule, N2 and dihydrogen, H2 . This process requires high temperatures and pressures, thereby generating ca 1.6 % of the global CO2 emissions. Alternative strategies are needed to realize the functionalization of N2 to NH3 under mild conditions. Here, we show that boron-centered radicals provide a means of activating N2 at room temperature and atmospheric pressure whilst allowing a radical process to occur, leading to the production of borylamines. Subsequent hydrolysis released NH4 + , the acidic form of NH3 . EPR spectroscopy supported the intermediacy of radicals in the process, corroborated by DFT calculations, which rationalized the mechanism of the N2 functionalization by R2 B radicals.

Molecular Electrochemical Reductive Splitting of Dinitrogen with a Molybdenum Complex.

Nitrogen reduction under mild conditions (room T and atmospheric P), using a non-fossil source of hydrogen remains a challenge. Molecular metal complexes, notably Mo based, have recently been shown to be active for such nitrogen fixation. We report electrochemical N2 splitting with a MoIII triphosphino complex [(PPP)MoI3 ], at room temperature and a moderately negative potential. A MoIV nitride species was generated, which is confirmed by electrochemistry and NMR studies. The reaction goes through two successive one electron reductions of the starting Mo species, coordination of a N2 molecule, and further splitting to a MoIV nitride complex. Preliminary DFT studies support the formation of a bridging MoI N2 MoI dinitrogen dimer evolving to the Mo nitride via a low energy transition state. This example joins a short list of molecular complexes for N2 electrochemical reductive cleavage. It opens a door to electrochemical proton-coupled electron transfer (PCET) conversion studies of N2 to NH3 .

Chirogenesis in Zinc Porphyrins: Theoretical Evaluation of Electronic Transitions, Controlling Structural Factors and Axial Ligation.

In the present work, sixteen different zinc porphyrins (possessing different meso substituents) with and without a chiral guest were modelled using DFT and TD-DFT approaches in order to understand the influence of various controlling factors on electronic circular dichroism (ECD) spectra. Two major aspects are influenced by these factors: excitation energy of the electronic transitions and their intensity. In the case of excitation energy, the influence increases in the following order: orientation of the peripheral substituents

Benchmarking computational methods and influence of guest conformation on chirogenesis in zinc porphyrin complexes.

Circular dichroism (CD) is a convenient and widely used tool for investigating structures of chiral molecules. However, the unambiguous simulation of CD spectra is not a trivial task, because the accuracy of theoretical calculations depends on the nature of the system. In the present work, the induced CD spectra of six zinc porphyrin complexes with chiral guests were simulated by using different DFT methods. The best agreement between theoretical and experimental results for the Soret (B) band absorption region was achieved with the ωB97X-D, CAM-B3LYP, and M06-2X functionals with implicit inclusion of solvent effects (SMD model). Also, a good correlation between the simulated and experimental spectra was obtained with the DZVP basis sets, however a more accurate simulation of the length- and velocity rotational strengths needed larger TZVP basis sets. Additionally, the conformation of the chiral guest influences the chirogenic mechanism.

Efficient alkene hydrosilation with bis(8-quinolyl)phosphine (NPN) nickel catalysts. The dominant role of silyl-over hydrido-nickel catalytic intermediates.

A cationic nickel complex of the bis(8-quinolyl)(3,5-di-tert-butylphenoxy)phosphine (NPN) ligand, [(NPN)NiCl]+, is a precursor to efficient catalysts for the hydrosilation of alkenes with a variety of hydrosilanes under mild conditions and low catalyst loadings. DFT studies reveal the presence of two coupled catalytic cycles based on [(NPN)NiH]+ and [(NPN)NiSiR3]+ active species, with the latter being more efficient for producing the product. The preferred silyl-based catalysis is not due to a more facile insertion of alkene into the Ni-Si (vs. Ni-H) bond, but by consistent and efficient conversions of the hydride to the silyl complex.

Aerobic and Ligand-Free Manganese-Catalyzed Homocoupling of Arenes or Aryl Halides via in Situ Formation of Aryllithiums.

Ligand-free manganese-catalyzed homocoupling of arenes or aryl halides can be carried out under aerobic conditions via the in situ formation of the corresponding aryllithiums. A wide range of biaryls and derivatives has been obtained, and a mechanism involving monomeric manganese-oxo complexes has been proposed on the basis of DFT calculations.

Room-Temperature Functionalization of N2 to Borylamine at a Molybdenum Complex.

Intermolecular, stepwise functionalization by BH bonds of a (triphosphine)MoIV -nitrido complex generated by N2 splitting is reported. The imido-hydride and di-hydride-amido MoIV complexes have been isolated and characterized. Addition of PinBH to the [Mo(H)2 (N(BPin)2 )]+ complex at room temperature results in the liberation of borylamines from the metal center.

Domino Pd0 -Catalyzed C(sp3 )-H Arylation/Electrocyclic Reactions via Benzazetidine Intermediates.

The Pd0 -catalyzed C(sp3 )-H arylation of 2-bromo-N-methylanilides leads to unstable benzazetidine intermediates that rearrange to benzoxazines through 4π electrocyclic ring-opening and 6π electrocyclization. The introduction of a bulky, non-activatable amide group on the nitrogen atom was key to favor the challenging reductive elimination step and disfavor undesired reaction pathways.

Dehydrogenative coupling of 4-substituted pyridines mediated by a zirconium(ii) synthon: reaction pathways and dead ends.

The mechanism of the reductive homocoupling of pyridine derivatives mediated by the ZrII synthon [(PNP)Zr(η6-toluene)Cl] (1) has been investigated. Selective transformation into three different types of product complexes has been observed, depending on the N-heterocyclic substrate employed: the bipyridyl complexes 3-R (R = Me, Et, t Bu, Bn, Ph, CHCHPh), which are the homocoupling products, the η2-((4-dimethylamino)pyridyl) complex 4 as well as the bis(isoquinolinyl) complex 5. By deuterium labelling experiments the participation of the ligand backbone in the pyridine coupling reaction via potential cyclometallation steps was ruled out. Based on DFT modelling of the possible reaction sequences a reaction mechanism for the coupling sequence could be identified. The latter is initiated by a reductive syn C-C coupling rather than based on an initial C-H activation of the pyridine substrate.

Isolation and structural characterization of a titanacyclopropane as key intermediate in the double aryl Grignard addition to 2-(arylethynyl)pyridine derivatives.

A titanacyclopropane species, which is a key reaction intermediate in the Ti(OiPr)4-mediated double aryl Grignard addition to 1,2-di(pyridin-2-yl)ethyne and related alkynes, was isolated and fully characterized. Based on this observation a one-pot synthesis of diarylated 1,2-di(pyridin-2-yl)ethanes and 2-(1,2,2-triarylvinyl)-pyridines was developed, including the tetraarylation of V-shaped 2,6-bis(arylethynyl)pyridines.

A mechanochemical approach to access the proline-proline diketopiperazine framework.

Ball milling was exploited to prepare a substituted proline building block by mechanochemical nucleophilic substitution. Subsequently, the mechanocoupling of hindered proline amino acid derivatives was developed to provide proline-proline dipeptides under solvent-free conditions. A deprotection-cyclization sequence yielded the corresponding diketopiperazines that were obtained with a high stereoselectivity which could be explained by DFT calculations. Using this method, an enantiopure disubstituted Pro-Pro diketopiperazine was synthesized in 4 steps, making 5 new bonds using a ball mill.

Mild Decarboxylative C-H Alkylation: Computational Insights for Solvent-Robust Ruthenium(II) Domino Manifold.

Computational studies on decarboxylative C-H alkenylations provided key insights into the solvent-robust nature of C-H activation/decarboxylation domino reactions. These properties were exploited for ruthenium(II)-catalyzed C-H alkylations by a decarboxylative process with ample scope under copper-free and silver-free reaction conditions.

New Titanium Borylimido Compounds: Synthesis, Structure, and Bonding.

We report a combined experimental and computational study of the synthesis and electronic structure of titanium borylimido compounds. Three new synthetic routes to this hitherto almost unknown class of Group 4 imide are presented. The double-deprotonation reaction of the borylamine H2NB(NAr'CH)2 (Ar' = 2,6-C6H3iPr2) with Ti(NMe2)2Cl2 gave Ti{NB(NAr'CH)2}Cl2(NHMe2)2, which was easily converted to Ti{NB(NAr'CH)2}Cl2(py)3. This compound is an entry point to other borylimides, for example, reacting with Li2N2pyrNMe to form Ti(N2pyrNMe){NB(NAr'CH)2}(py)2 and with 2 equiv of NaCp to give Cp2Ti{NB(NAr'CH)2}(py) (23). Borylamine-tert-butylimide exchange between H2NB(NAr'CH)2 and Cp*Ti(NtBu)Cl(py) under forcing conditions afforded Cp*Ti{NB(NAr'CH)2}Cl(py), which could be further substituted with guanidinate or pyrrolide-amine ligands to give Cp*Ti(hpp){NB(NAr'CH)2} (16) and Cp*Ti(NpyrNMe2){NB(NAr'CH)2} (17). The Ti-Nim distances in compounds with the NB(NAr'CH)2 ligand were comparable to those of the corresponding arylimides. Dialkyl- or diaryl-substituted borylamines do not undergo the analogous double-deprotonation or imide-amine exchange reactions. Reaction of (Cp″2Ti)2(µ2:η1,η1-N2) with N3BMes2 gave the base-free, diarylborylimide Cp″2Ti(NBMes2) (26) by an oxidative route; this compound has a relatively long Ti-Nim bond and large Cp″-Ti-Cp″ angle. Reaction of 16 with H2NtBu formed equilibrium mixtures with H2NB(NAr'CH)2 and Cp*Ti(hpp)(NtBu) (ΔrG = -1.0 kcal mol-1). In contrast, the dialkylborylimide Cp*Ti{MeC(NiPr)2}(NBC8H14) (2) reacted quantitatively with H2NtBu to give the corresponding tert-butylimide and borylamine. The electronic structures and imide-amine exchange reactions of half-sandwich and sandwich titanium borylimides have been evaluated using density functional theory (DFT), supported by quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analysis, and placed more generally in context with the well-established alkyl- and arylimides and hydrazides. The calculations find that Ti-Nim bonds for borylimides are stronger and more covalent than in their organoimido or hydrazido analogues, and are strongest for alkyl- and arylborylimides. Borylamine-tert-butylimide exchange reactions fail for H2NBR2 (R = hydrocarbyl) but not for H2NB(NAr'CH)2 because the increased strength of the new Ti-Nim bond for the former is outweighed by the increased net H-N bond strengths in the borylamine. Variation of the Ti-Nim bond length over short distances is dominated by π-interactions with any appropriate orbital on the Nim atom organic substituent. However, over the full range of imides and hydrazides studied, overall bond energies do not correlate with bond length but with the Ti-Nim σ-bond character and the orthogonal π-interaction.

New Scandium Borylimido Chemistry: Synthesis, Bonding, and Reactivity.

We report a combined synthetic, mechanistic, and theoretical study of the first borylimido complex of a rare earth metal, (NacNacNMe2)Sc{NB(NAr'CH)2} (25, Ar' = 2,6-C6H3iPr2, NacNacNMe2 = Ar'NC(Me)CHC(Me)NCH2CH2NMe2). Thermolysis of the methyl-borylamide (NacNacNMe2)Sc(Me){NHB(NAr'CH)2} (18) generated transient imide 25 via rate-determining, first-order methane elimination (KIE ≈ 8.7). In the absence of external substrate, 25 underwent a reversible cyclometalation reaction (sp3 C-H bond addition to Sc═Nimide) with a methyl group of the NacNacNMe2 ligand forming {MeC(NC6H3iPrCH(Me)CH2)CHC(Me)NCH2CH2NMe2}Sc{NHB(NAr'CH)2} (21). In the presence of pyridine or DMAP, reversible sp2 C-H bond activation occurred, forming orthometalated complexes (NacNacNMe2)Sc{NHB(NAr'CH)2}(η2-4-NC5H3R) (R = H or NMe2). In situ reaction of 25 with HCCTol gives irreversible sp C-H bond activation under kinetic control, and with MeCCPh [2+2] cycloaddition to Sc═Nimide takes place. These reactions represent the first substrate activation processes for any metal-bound borylimide. The bonding in 25 and the mechanism and thermodynamics of the reactions have been studied using density functional theory (DFT), supported by quantum theory of atoms in molecules and natural bond orbital analysis. Although the borylimido and arylimido dianions studied here are formally isoelectronic and possess comparable frontier molecular orbitals, the borylimido ligand is both a better π-donor and σ-donor, forming stronger and shorter metal-nitrogen bonds with somewhat reduced ionicity. Despite this, reactions of these types of borylimides with C-H or C≡C bonds are all more exothermic and more strongly activating than for the corresponding arylimides. DFT calculations on model systems of differing steric bulk unpicked the underlying thermodynamic factors controlling the reactions of 25 and its reaction partners, and a detailed comparison was made with the previously described arylimido homologues.

η(6) -Arene-Zirconium-PNP-Pincer Complexes: Mechanism of Their Hydrogenolytic Formation and Their Reactivity as Zirconium(II) Synthons.

The cyclometalated monobenzyl complexes [(Cbzdiphos(R) -CH)ZrBnX] 1 (iPr) Cl and 1 (Ph) I reacted with dihydrogen (10 bar) to yield the η(6) -toluene complexes [(Cbzdiphos(R) )Zr(η(6) -tol)X] 2 (iPr) Cl and 2 (Ph) I (cbzdiphos=1,8-bis(phosphino)-3,6-di-tert-butyl-9H-carbazole). The arene complexes were also found to be directly accessible from the triiodide [(Cbzdiphos(Ph) )ZrI3 ] through an in situ reaction with a dibenzylmagnesium reagent and subsequent hydrogenolysis, as exemplified for the η(6) -mesitylene complex [(Cbzdiphos(Ph) )Zr(η(6) -mes)I] (3 (Ph) I). The tolyl-ring in 2 (iPr) Cl adopts a puckered arrangement (fold angle 23.3°) indicating significant arene-1,4-diido character. Deuterium labeling experiments were consistent with an intramolecular reaction sequence after the initial hydrogenolysis of a Zr-C bond by a σ-bond metathesis. A DFT study of the reaction sequence indicates that hydrogenolysis by σ-bond metathesis first occurs at the cyclometalated ancillary ligand giving a hydrido-benzyl intermediate, which subsequently reductively eliminates toluene that then coordinates to the Zr atom as the reduced arene ligand. Complex 2 (Ph) I was reacted with 2,6-diisopropylphenyl isocyanide giving the deep blue, diamagnetic Zr(II) -diisocyanide complex [(Cbzdiphos(Ph) )Zr(CNDipp)2 I] (4 (Ph) I). DFT modeling of 4 (Ph) I demonstrated that the HOMO of the complex is primarily located as a "lone pair on zirconium", with some degree of back-bonding into the C≡N π* bond, and the complex is thus most appropriately described as a zirconium(II) species. Reaction of 2 (Ph) I with trimethylsilylazide (N3 TMS) and 2 (iPr) Cl with 1-azidoadamantane (N3 Ad) resulted in the formation of the imido complexes [(Cbzdiphos(R) )Zr=NR'(X)] 5 (iPr) Cl-NAd and 5 (Ph) I-NTMS, respectively. Reaction of 2 (iPr) Cl with azobenzene led to N-N bond scission giving 6 (iPr) Cl, in which one of the NPh-fragments is coupled with the carbazole nitrogen to form a central η(2) -bonded hydrazide(-1), whereas the other NPh-fragment binds to zirconium acting as an imido-ligand. Finally, addition of pyridine to 2 (iPr) Cl yielded the dark purple complex [(Cbzdiphos(iPr) )Zr(bpy)Cl] (7 (iPr) Cl) through a combination of CH-activation and C-C-coupling. The structural data and UV/Vis spectroscopic properties of 7 (iPr) Cl indicate that the bpy (bipyridine) may be regarded as a (dianionic) diamido-type ligand.

Deciphering Selectivity in Organic Reactions: A Multifaceted Problem.

Computational chemistry has made a sustained contribution to the understanding of chemical reactions. In earlier times, half a century ago, the goal was to distinguish allowed from forbidden reactions (e.g., Woodward-Hoffmann rules), that is, reactions with low or high to very high activation barriers. A great achievement of computational chemistry was also to contribute to the determination of structures with the bonus of proposing a rationalization (e.g., anomeric effect, isolobal analogy, Gillespie valence shell pair electron repulsion rules and counter examples, Wade-Mingos rules for molecular clusters). With the development of new methods and the constant increase in computing power, computational chemists move to more challenging problems, close to the daily concerns of the experimental chemists, in determining the factors that make a reaction both efficient and selective: a key issue in organic synthesis. For this purpose, experimental chemists use advanced synthetic and analytical techniques to which computational chemists added other ways of determining reaction pathways. The transition states and intermediates contributing to the transformation of reactants into the desired and undesired products can now be determined, including their geometries, energies, charges, spin densities, spectroscopy properties, etc. Such studies remain challenging due to the large number of chemical species commonly present in the reactive media whose role may have to be determined. Calculating chemical systems as they are in the experiment is not always possible, bringing its own share of complexity through the large number of atoms and the associated large number of conformers to consider. Modeling the chemical species with smaller systems is an alternative that historically led to artifacts. Another important topic is the choice of the computational method. While DFT is widely used, the vast diversity of functionals available is both an opportunity and a challenge. Though chemical knowledge helps, the relevant computational method is best chosen in conjunction with the nature of the experimental systems and many studies have been concerned with this topic. We will not address this aspect but give references in the text. Usually, a computational study starts with the validation of the method by means of benchmark calculations vs accurate experimental data or state-of-the-art calculations. Finally, computational chemists can bring more than the sole determination of the reaction pathways through the analysis of the electronic structure. In our case, we have privileged the NBO analysis, which has the advantage of describing interactions on the basis of terms and concepts that are shared within the chemical community. In this Account, we have chosen to select representative reactions from our own work to highlight the diversity of situations than can be addressed nowadays. These include selective activation of C(sp(3))-H bonds, selective reactions with low energy barriers, involving closed shell or radical species, the role of noncovalent interactions, and the importance of considering side reactions.