Jan Paradies

Metal‐Free Hydrogenation of Unsaturated Hydrocarbons Employing Molecular Hydrogen

The metal-free activation of hydrogen by frustrated Lewis pairs (FLPs) is a valuable method for the hydrogenation of polarized unsaturated molecules ranging from imines, enamines, and silyl enol ethers to heterocycles. However, one of the most important applications of hydrogenation technology is the conversion of unsaturated hydrocarbons into alkanes or alkenes. Despite the fast development of the FLP chemistry, such reactions proved as highly challenging. This Minireview provides an overview of the basic concepts of FLP chemistry, the challenge in the hydrogenation of unsaturated hydrocarbons, and first solutions to this central transformation.

Palladium-catalyzed C-S coupling: access to thioethers, benzo[b]thiophenes, and thieno[3,2-b]thiophenes.

The first C-S bond formation/cross-coupling/cyclization domino reaction using thiourea as a cheap and easy to handle dihydrosulfide surrogate has been developed. Structurally important biarylthioether, benzo[b]thiophenes, and thieno[3,2-b]thiophene scaffolds are provided in high yield.

Functional‐Group Tolerance in Frustrated Lewis Pairs: Hydrogenation of Nitroolefins and Acrylates

Apart from molecular hydrogen (H2), [1] other small molecules, such as CO2, [2] N2O, [3] NO, and SO2, [5] were targeted by frustrated Lewis pairs (FLPs) and resulted in the fixation or activation of these small molecules by Lewis acid interaction. Consequently, functionalized molecules, such as a,b-unsaturated esters, sulfoxides, or nitro compounds, are challenging substrates for FLP-catalyzed hydrogenations, and strategies toward higher functional-group tolerance are topic of current research. So s et al. demonstrated that bulky mesityl-substituted boranes could attain a level of functional-group tolerance according to the size exclusion principle. Other modifications of boranes to achieve stronger and weaker Lewis acidity in conjunction with FLP chemistry were reported. In particular, weaker Lewis acids appear to be favorable for the reduction of electron-deficient double bonds, such as a,b-unsaturated ketones, owing to the pronounced nucleophilicity of the corresponding hydridoborate anion. However, reduced Lewis acidity might also suppress the H2 activation, and a careful balance must be met. To date, there has been no report on the FLP-catalyzed hydrogenation of nitroolefins and acrylates. Only recently, B(C6F5)3 (1) was applied for the reduction of strongly electrophilic malonates at elevated temperatures and pressure (80 8C, 60 bar H2). [10a] Herein we report the reactivity of B(2,6-F2-C6F3)3 (2) as Lewis acid in FLP-catalyzed hydrogenations and its unique structural features in solid state and solution. The unprecedented FLP-mediated hydrogenation of nitroolefins and a,b-unsaturated esters under mild conditions (RT or 40 8C; 4 bar H2) was established. In contrast to the size-exclusion concept, in this case functional-group tolerance was solely achieved by modification of the electronic nature of the Lewis acid and the Lewis base. We initiated our studies with the synthesis of the borane B(2,6-F2-C6H3)3–THF adduct (2·THF) according to Naumann. Surprisingly, 2 has not been studied in FLP chemistry to date, even though it resembles an electronically modified B(C6F5)3 with identical steric shielding. The solidstate structure of 2 was established and displays similar structural features to BPh3 (Figure 1a). [14]

Electronic effects of triarylphosphines in metal-free hydrogen activation: a kinetic and computational study

The frustrated Lewis pair-mediated reversible hydrogen activation is studied as a function of the electron-donor quality of a series of phosphines. The increasing acidity of the generated phosphonium species leads to a stepwise lowering of the temperature for the highly reversible H2-activation and permits concrete classification for the first time. The influence of the acid strength on the metal-free hydrogenation of selected olefins is investigated by kinetic experiments and quantum chemical calculations. Detailed information for the rate-determining steps fully support our mechanistic model of a protonation step prior to hydride transfer. The rate of hydrogenation is strongly dependent on the electronic nature of the phosphine and of the acidity of the corresponding phosphonium cation. A careful balance of these two factors provides highly efficient metal-free hydrogenation catalysts. The provided findings are used to revise the reactivity of Lewis bases in the hydrogenation of imines, one of the most recognized applications of FLPs.

[2.2]Paracyclophane derived bisphosphines for the activation of hydrogen by FLPs: application in domino hydrosilylation/hydrogenation of enones

The heterolytic splitting of hydrogen by two types of [2.2]paracyclophane derived bisphosphines (1, 2a and 2b) in combination with tris(pentafluorophenyl)borane (3) at room temperature is described. The corresponding frustrated Lewis pairs (FLPs) exhibit different behavior in the activation of hydrogen. This results from diverse steric and electronic properties of the bisphosphines. The reactivity of the frustrated Lewis pairs was exploited in the first diastereoselective domino hydrosilylation/hydrogenation reaction catalyzed by FLPs.

Frustrated Lewis Pair-Catalyzed Cycloisomerization of 1,5-Enynes via a 5-endo-dig Cyclization/Protodeborylation Sequence.

The first frustrated Lewis pair-catalyzed cycloisomerization of a series of 1,5-enynes was developed. The reaction proceeds via the π-activation of the alkyne and subsequent 5-endo-dig cyclization with the adjacent alkene. The presence of PPh3 was of utmost importance on the one hand to prevent side reactions (for example, 1,1-carboboration) and on the other hand for the efficient protodeborylation to achieve the catalytic turnover. The mechanism is explained on the basis of quantum-chemical calculations, which are in full agreement with the experimental observations.

Frustrated Lewis Pair Catalyzed Dehydrogenative Oxidation of Indolines and Other Heterocycles

An acceptorless dehydrogenation of heterocycles catalyzed by frustrated Lewis pairs (FLPs) was developed. Oxidation with concomitant liberation of molecular hydrogen proceeded in high to excellent yields for N-protected indolines as well as four other substrate classes. The mechanism of this unprecedented FLP-catalyzed reaction was investigated by mechanistic studies, characterization of reaction intermediates by NMR spectroscopy and X-ray crystal analysis, and by quantum-mechanical calculations. Hydrogen liberation from the ammonium hydridoborate intermediate is the rate-determining step of the oxidation. The addition of a weaker Lewis acid as a hydride shuttle increased the reaction rate by a factor of 2.28 through a second catalytic cycle.

Autoinduced Catalysis and Inverse Equilibrium Isotope Effect in the Frustrated Lewis Pair Catalyzed Hydrogenation of Imines

The frustrated Lewis pair (FLP)-catalyzed hydrogenation and deuteration of N-benzylidene-tert-butylamine (2) was kinetically investigated by using the three boranes B(C6F5)3 (1), B(2,4,6-F3-C6H2)3 (4), and B(2,6-F2-C6H3)3 (5) and the free activation energies for the H2 activation by FLP were determined. Reactions catalyzed by the weaker Lewis acids 4 and 5 displayed autoinductive catalysis arising from a higher free activation energy (2 kcal mol(-1)) for the H2 activation by the imine compared to the amine. Surprisingly, the imine reduction using D2 proceeded with higher rates. This phenomenon is unprecedented for FLP and resulted from a primary inverse equilibrium isotope effect.

Structure-Reactivity Relationship in the Frustrated Lewis Pair (FLP)-Catalyzed Hydrogenation of Imines.

The autoinduced, frustrated Lewis pair (FLP)-catalyzed hydrogenation of 16-benzene-ring substituted N-benzylidene-tert-butylamines with B(2,6-F2 C6 H3 )3 and molecular hydrogen was investigated by kinetic analysis. The pKa values for imines and for the corresponding amines were determined by quantum-mechanical methods and provided a direct proportional relationship. The correlation of the two rate constants k1 (simple catalytic cycle) and k2 (autoinduced catalytic cycle) with pKa difference between imine and amine pairs (ΔpKa ) or Hammetts σ parameter served as useful parameters to establish a structure-reactivity relationship for the FLP-catalyzed hydrogenation of imines.

Ansa-metallocene polymerization catalysts derived from [2+2]cycloaddition reactions of bis(1-methylethenyl-cyclopentadienyl)zirconium systems

Bis(1-methylethenyl-cyclopentadienyl)zirconium dichloride (7a) was prepared by a fulvene route. Photolysis at 0°C with Pyrex-filtered UV light resulted in a rapid and complete intramolecular [2+2]cycloaddition reaction to yield the corresponding cyclobutylene-bridged ansa-zirconocene dichloride isomer (8a). This is one of the rare examples of an organic functional group chemistry that leads to carbon–carbon coupling at the framework of an intact sensitive group 4 bent metallocene complex. More sterically hindered open metallocenes that bear bulky isopropyl or tert-butyl substituents at their Cp rings in addition to the active 1-methylethenyl functional group undergo the photochemical ansa-metallocene ring closure reaction equally facile. The metallocene systems used and obtained in this study have served as transition metal components for the generation of active metallocene propene polymerization catalysts.