Bernd F. Straub

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

Summary The copper-catalyzed azide–alkyne cycloaddition (CuAAC) is one of the most broadly applicable and easy-to-handle reactions in the arsenal of organic chemistry. However, the mechanistic understanding of this reaction has lagged behind the plethora of its applications for a long time. As reagent mixtures of copper salts and additives are commonly used in CuAAC reactions, the structure of the catalytically active species itself has remained subject to speculation, which can be attributed to the multifaceted aggregation chemistry of copper(I) alkyne and acetylide complexes. Following an introductory section on common catalyst systems in CuAAC reactions, this review will highlight experimental and computational studies from early proposals to very recent and more sophisticated investigations, which deliver more detailed insights into the CuAAC’s catalytic cycle and the species involved. As diverging mechanistic views are presented in articles, books and online resources, we intend to present the research efforts in this field during the past decade and finally give an up-to-date picture of the currently accepted dinuclear mechanism of CuAAC. Additionally, we hope to inspire research efforts on the development of molecularly defined copper(I) catalysts with defined structural characteristics, whose main advantage in contrast to the regularly used precatalyst reagent mixtures is twofold: on the one hand, the characteristics of molecularly defined, well soluble catalysts can be tuned according to the particular requirements of the experiment; on the other hand, the understanding of the CuAAC reaction mechanism can be further advanced by kinetic studies and the isolation and characterization of key intermediates.

The Mechanism of Hydroamination of Allenes, Alkynes, and Alkenes Catalyzed by Cyclopentadienyltitanium–Imido Complexes: A Density Functional Study

Considerable effort has been directed towards the development of procedures for hydroamination across carbon – carbon multiple bonds, and several catalytic systems for allene, alkyne, and alkene hydroamination have been investigated.[1] However, a general catalyst for the hydroamination of nonactivated unsaturated hydrocarbons remains elusive. A catalyst for the selective anti-Markovnikov addition of amines to terminal alkenes would be of particular interest [Eq. (1)].

Highly Diastereoselective Arylations of Substituted Piperidines

A highly diastereoselective methodology for the preparation of various substituted piperidines via Negishi cross-couplings with (hetero)aryl iodides was developed. Depending on the position of the C-Zn bond relative to the nitrogen (position 2 vs position 4), the stereoselectivity of the coupling can be directed toward either the trans- or cis-2,4-disubstituted products. Density functional theory calculations on the relative stabilities of the Zn and Pd intermediates were performed to explain the high diastereoselectivities obtained. A novel 1,2-migration of Pd further expands this method to the stereoselective preparation of 5-aryl-2,5-disubstituted piperidines.

Predicting the Cis−Trans Dichloro Configuration of Group 15−16 Chelated Ruthenium Olefin Metathesis Complexes: A DFT and Experimental Study

Gradient-corrected (BP86) and hybrid (M06-L) density functional calculations were used to study the relative stability of cis and trans-dichloro X-chelated benzylidene ruthenium complexes (X = O, S, Se, N, P). Calculations in the gas phase differed from experimental results, predicting the trans-dichloro configuration as being more stable in every case. The addition of Poisson-Boltzmann (PBF) continuum approximation (dichloromethane) corrected the disagreement and afforded energies consistent with experimental results. Novel N, Se, and P chelated ruthenium olefin metathesis complexes were synthesized to evaluate calculation predictions. These findings reinforce the importance of including solvent corrections in DFT calculations of ruthenium metathesis catalysts and predict that stronger sigma donors as chelating atoms tend to electronically promote the unusual and less active cis-dichloro configuration.

Mechanism of copper(I)-catalyzed cyclopropanation: a DFT study calibrated with copper(I) alkene complexes

Abstract The complete catalytic cycle of copper-catalyzed cyclopropanation is investigated by density functional model calculations. The study focuses on obtaining accurate relative stabilities of the ligand–metal cores of all catalytic intermediates and transition states. The copper iminophosphanamide [H2P(NH2)2κ2N]Cu serves as model fragment, since three copper catalyst key intermediates with an iminophosphanamide ligand have been isolated or detected. The electronic structure of the active intermediates, copper(I) carbenes of the d10-ML3 type, and their reactivity towards ethene and vinyl alcohol is investigated. The reliability of the computed data is confirmed by their comparison with experimental data of [t-Bu2P(NSiMe3)2κ2N]Cu alkene and alkyne complexes, using relative ligand binding strengths and alkene ligand rotation barriers. The uncharged nature of the model complexes minimizes solvation artifacts and thus renders the evaluation of associative and dissociative ligand exchange pathways possible. The associative alkene ligand exchange with diazoalkane to a κN,κO-diazoalkane complex, subsequent intramolecular rearrangement to a κC-complex and N2 extrusion are identified on the most probable pathway to the electrophilic copper(I) carbene complexes of the Fischer type. They are predicted to react with alkenes to labile cupracyclobutanes with a planar N2CuIIIC2 core, which undergo facile reductive elimination of a cyclopropane derivative.

Sterically crowded diphosphinomethane ligands: molecular structures, UV-photoelectron spectroscopy and a convenient general synthesis of tBu2PCH2PtBu2 and related species

A series of highly crowded symmetric and unsymmetric diphosphinomethanes R2PCH2PR′2, important ligands in transition metal chemistry and catalysis, namely tBu2PCH2PtBu2 (dtbpm, 1), Cy2PCH2PCy2 (dcpm, 2), tBu2PCH2PCy2 (ctbpm, 3), tBu2PCH2PiPr2 (iptbpm, 4) and tBu2PCH2PPh2 (ptbpm, 5), has been prepared in high yields, using a general and convenient route, which is described in detail for 1. Other than 4, which is a colourless liquid, these compounds are crystalline solids at room temperature. Their molecular structures have been determined by single crystal X-ray diffraction, along with that of the higher homologue of 1, tBu2CH2CH2tBu2 (dtbpe, 6). The solid-state structures of the dioxide of 1, tBu2P(O)CH2P(O)tBu2 (7), and of two phosphonium cations derived from 1, protonated [tBu2P(H)CH2PtBu2]+ (8+) and the chlorophosphonium ion [tBu2P(Cl)CH2PtBu2]+ (9+), are also described and show a distinct structural influence of the tetracoordinate P centres. The gas phase UV-photoelectron spectra of the diphosphines 1–6 have been measured. Their first two ionisation potentials are found to be nearly degenerate and all are in the low energy range from 7.5 to 7.8 eV. Comparison with related mono- and bidentate phosphines demonstrates that 1–6 are excellent σ-donors towards metals, in accord with their known coordination chemistry. Molecular geometries and electronic structures of the diphosphine systems have been studied by quantum chemical calculations and are compared to experiment. Unlike standard semiempirical methods (AM1, PM3, MNDO), which give rather poor minimum structures and seem inadequate for such sterically crowded systems, ab initio calculations (RHF/6-31G**) predict molecular geometries with reasonable accuracy and reflect the observed trends in experimental ionisation potentials.

Iodocyclization of o-alkynylbenzamides revisited: formation of isobenzofuran-1(3H)-imines and 1H-isochromen-1-imines instead of lactams.

The iodocyclization of o-alkynylbenzamides with various electrophiles has been reported to yield five- or six-membered lactams by nucleophilic attack of the amide nitrogen onto the triple bond. While the formation of an isobenzofuran-1(3H)-imine with two bulky substituents under Larock conditions was initially attributed to steric hindrance, we found out that cyclization via the amide oxygen is the rule rather than the exception. Thus, the structures of the products reported in the literature need to be revised.

Mechanistic Investigations of a Stable, Highly Active, Extremely Sterically Shielded Molecular Gold Catalyst

An N‐heterocyclic carbene gold complex IPr**AuNTf2 has been synthesized, spectroscopically investigated, structurally characterized, and used as a highly active and stable catalyst in the Hashmi phenol synthesis (IPr**=1,3‐di‐p‐tolylimidazol‐2‐ylidene with four di‐tert‐butylbenzhydryl ortho substituents, Tf=trifluoromethansulfonyl). A side reaction comprises an irreversible arene oxide ring opening with subsequent 1,2 methyl shift. The advantage of the steric demand of the ancillary ligand was explained by higher equilibrium concentrations of the cationic gold species, the circumvention of inactive dinuclear intermediates, and the inhibition of catalyst decomposition pathways. The methanol addition–hydration of alkynes featured a turnover‐limiting proton transfer step of an alkenylgold catalyst resting state, indicated by a large primary kinetic isotope effect and an alkyne competition experiment.

A Synthesis of Pseudoconhydrine and Its Epimer via Hydroformylation and Dihydroxylation

A synthesis of the alkaloid pseudoconhydrine and its epimer has been achieved using tandem hydroformylation-condensation to form the six-membered ring and stereoselective dihydroxylation to introduce oxygenation. The stereoselectivity of dihydroxylation can be explained by lipophilic and electrostatic effects, supported by DFT calculations. The alkaloids can be obtained either by regioselective dehydroxylation or by rearrangement, followed by reduction.

Copper and Silver Carbene Complexes without Heteroatom-Stabilization: Structure, Spectroscopy, and Relativistic Effects.

Salts of a copper and a silver carbene complex were prepared from dimesityl diazomethane, made possible by the steric shielding of the N-heterocyclic carbene (NHC) ancillary ligand IPr**. The mint-green complex [IPr**Ag=CMes2 ](+) [NTf2 ](-) is the first isolated silver carbene complex without heteroatom donor substituents. Single-crystal X-ray diffraction provides evidence for a predominant carbenoid character, and supports the postulation of such reactive species as intermediates in silver-catalyzed C-H activation reactions. The greenish yellow copper carbene complex [IPr**Cu=CMes2 ](+) [NTf2 ](-) has spectroscopic properties in between the isostructural silver complex and the already reported emerald green gold carbene complex. A comparison in the Group 11 series indicates that relativistic effects are responsible for the strong σ bond and the significant π back-bonding in the gold carbene moiety.