Potassium Thiocyanate as Source of Cyanide for the Oxidative α‑Cyanation of Tertiary Amines

Oxidation at the sulfur of the safe-to-handle potassium thiocyanate releases cyanide units that are trapped in the presence of co-oxidized tertiary amines to form α-amino nitriles. These cyanations work in aqueous solutions and do not require a catalyst, nor do they form toxic byproducts

Nucleophilic Reactivities of Bleach Reagents

The nucleophilicities of the oxidants hydroperoxide, hypochlorite, hypobromite, bromite, and peroxymonosulfate were determined by following the kinetics of their reactions with a series of benzhydrylium ions of known electrophilicity (<i>E</i>) in alkaline, aqueous solutions at 20 °C. The reactivities of the oxidants correlate only weakly with their basicities. Analyzing the rate constants by using the relationship log <i>k</i>₂ = <i>s</i>_N(<i>N</i> + <i>E</i>) gave the parameters <i>N</i> (and <i>s</i>_N), which were applied to predict the rates of Weitz–Scheffer epoxidations

Reactions of Carbocations with Unsaturated Hydrocarbons: Electrophilic Alkylation or Hydride Abstraction?

Benzhydryl cations were used as reference electrophiles to determine the hydride donor reactivities of unsaturated hydrocarbons. The kinetics of the reactions were followed by UV−vis spectroscopy and conductivity measurements, and it was found that the second-order rate constants for the hydride transfer processes were almost independent of the solvents or counterions employed. The rate constants correlate linearly with the previously published empirical electrophilicity parameters E of the benzhydrylium ions. Therefore, the linear free energy relationship log k(20 °C) = s(E + N) could be employed to characterize the hydride reactivities of the hydrocarbons by the nucleophilicity parameters N and s. The similarity of the slopes s for hydride donors and π-nucleophiles allows a direct comparison of the reactivities of these different functional groups based on their nucleophilicity parameters N. Since nucleophilicity parameters of −5 N < 0 have been found for a large variety of allylic and bisallylic hydride donors, a rule of thumb is derived that hydride transfer processes may compete with carbon−carbon bond-forming reactions when carbocations are combined with olefins of π-nucleophilicity N < 0

Inverse Solvent Effects in Carbocation Carbanion Combination Reactions: The Unique Behavior of Trifluoromethylsulfonyl Stabilized Carbanions

Second-order rate constants for the reactions of the trifluoromethylsulfonyl substituted benzyl anions 1a−e (CF3SO2CH-−C6H4−X) with the benzhydrylium ions 2f−j and structurally related quinone methides 2a−e have been determined by UV−vis spectroscopy. The reactions proceed approximately 10−40 times faster in methanol than in DMSO leading to the unique situation that these carbocation carbanion combinations are faster in protic than in dipolar aprotic media. The pKa values of some benzyl trifluoromethylsulfones were determined in methanol (1c-H, 17.1; 1d-H, 16.0; 1e-H, 15.0) and found to be 5 units larger than the corresponding values in DMSO. Rate and equilibrium measurements thus agree that the trifluoromethylsulfonyl substituted benzyl anions 1a−e are more effectively solvated by ion−dipole interactions in DMSO than by hydrogen bonding in methanol. Brønsted correlations show that in DMSO the trifluoromethylsulfonyl substituted carbanions 1 are less nucleophilic than most other types of carbanions of similar basicity, indicating that in DMSO the intrinsic barriers for the reactions of the localized carbanions 1 are higher than those of delocalized carbanions, including nitroalkyl anions. The situation is reversed in methanol, where the reactions of the localized carbanions 1 possess lower intrinsic barriers than those of delocalized carbanions as commonly found for proton-transfer processes. As a consequence, the relative magnitudes of intrinsic barriers are strongly dependent on the solvent

Comparison of the Electrophilicities of the Free and the (Tricarbonyl)iron-Coordinated Tropylium Ion

The kinetics of the reactions of the tropylium ion (1) and the (tricarbonyl)iron-coordinated tropylium ion (6) with allylsilanes, allylstannanes, and other uncharged nucleophiles were studied photometrically and conductometrically. The second-order rate constants were independent of the counterions, indicating rate-determining carbon−carbon bond formation. The electrophilicity parameters of the (tricarbonyl)iron complexes of the tropylium ion E(6) = −3.81 ± 0.24 and of the dihydrotropylium ion E(22) = −9.88 indicate that the former is 105−106 times more reactive toward nucleophiles. Comparison with the electrophilicity parameter of the free tropylium ion E(1) = −4.62 ± 0.57 shows that coordination by Fe(CO)3 affects its electrophilic reactivity only slightly. Density-functional calculations are used to rationalize the relative reactivities in terms of thermodynamic effects and frontier orbital interactions. On the basis of the linear free enthalpy relationship log k = s(E + N) one can predict that the free and the Fe(CO)3-coordinated tropylium ion react with nucleophiles (N > −1) at room temperature

Sequential Oxidative α‑Cyanation/Anti-Markovnikov Hydroalkoxylation of Allylamines

Iron-catalyzed oxidative α-cyanations at tertiary allylamines in the allylic position are followed by anti-Markovnikov additions of alcohols across the vinylic CC double bonds of the initially generated α-amino nitriles. These consecutive reactions generate 2-amino-4-alkoxybutanenitriles from three reactants (allylamines, trimethylsilyl cyanide, and alcohols) in one reaction vessel at ambient temperature

Lewis Acidity Scale of Diaryliodonium Ions toward Oxygen, Nitrogen, and Halogen Lewis Bases

Equilibrium constants for the associations of 17 diaryliodonium salts Ar2I+X– with 11 different Lewis bases (halide ions, carboxylates, p-nitrophenolate, amines, and tris­(p-anisyl)­phosphine) have been investigated by titrations followed by photometric or conductometric methods as well as by isothermal titration calorimetry (ITC) in acetonitrile at 20 °C. The resulting set of equilibrium constants KI covers 6 orders of magnitude and can be expressed by the linear free-energy relationship lg KI = sI LAI + LBI, which characterizes iodonium ions by the Lewis acidity parameter LAI, as well as the iodonium-specific affinities of Lewis bases by the Lewis basicity parameter LBI and the susceptibility sI. Least squares minimization with the definition LAI = 0 for Ph2I+ and sI = 1.00 for the benzoate ion provides Lewis acidities LAI for 17 iodonium ions and Lewis basicities LBI and sI for 10 Lewis bases. The lack of a general correlation between the Lewis basicities LBI (with respect to Ar2I+) and LB (with respect to Ar2CH+) indicates that different factors control the thermodynamics of Lewis adduct formation for iodonium ions and carbenium ions. Analysis of temperature-dependent equilibrium measurements as well as ITC experiments reveal a large entropic contribution to the observed Gibbs reaction energies for the Lewis adduct formations from iodonium ions and Lewis bases originating from solvation effects. The kinetics of the benzoate transfer from the bis­(4-dimethylamino)-substituted benzhydryl benzoate Ar2CH–OBz to the phenyl­(perfluorophenyl)­iodonium ion was found to follow a first-order rate law. The first-order rate constant kobs was not affected by the concentration of Ph­(C6F5)­I+ indicating that the benzoate release from Ar2CH–OBz proceeds via an unassisted SN1-type mechanism followed by interception of the released benzoate ions by Ph­(C6F5)­I+ ions

Resolving the Mechanistic Complexity in Triarylborane-Induced Conjugate Additions

Previous studies have shown that the catalytically active species in the Lewis acid-catalyzed addition reactions of allyl silanes or silyl enol ethers to carbonyl compounds or Michael acceptors are often silylium-carbonyl adducts rather than the adducts of the carbonyl group with the Lewis acid used for the induction of the reaction. Indirect evidence for such catalyst variations has so far been derived from double-label crossover experiments and comparisons of absolute reaction rates. We have now performed a detailed investigation on the kinetics and mechanism of the triarylborane-initiated conjugate addition reactions of allylsilanes and silyl enol ethers to α,β-unsaturated carbonyl compounds. NMR spectroscopic monitoring of such reactions gave rise to sigmoidal kinetic profiles, allowing us to directly follow the change of the catalytically active Lewis acid from triarylboranes in the induction period to silylium ions during the main part of the reaction. Crossover experiments and the isolation of four- and five-membered cyclic intramolecular trapping products provided further insight into the mechanism. DFT calculations of various mechanistic variants and kinetic modeling elucidated the operation of a complex reaction network, which rationalizes the experimental observations

One-Bond-Nucleophilicity and -Electrophilicity Parameters: An Efficient Ordering System for 1,3-Dipolar Cycloadditions

Diazoalkanes are ambiphilic 1,3-dipoles that undergo fast Huisgen cycloadditions with both electron-rich and electron-poor dipolarophiles but react slowly with alkenes of low polarity. Frontier molecular orbital (FMO) theory considering the 3-center-4-electron π-system of the propargyl fragment of diazoalkanes is commonly applied to rationalize these reactivity trends. However, we recently found that a change in the mechanism from cycloadditions to azo couplings takes place due to the existence of a previously overlooked lower-lying unoccupied molecular orbital. We now propose an alternative approach to analyze 1,3-dipolar cycloaddition reactions, which relies on the linear free energy relationship lg k2(20 °C) = sN(N + E) (eq 1) with two solvent-dependent parameters (N, sN) to characterize nucleophiles and one parameter (E) for electrophiles. Rate constants for the cycloadditions of diazoalkanes with dipolarophiles were measured and compared with those calculated for the formation of zwitterions by eq 1. The difference between experimental and predicted Gibbs energies of activation is interpreted as the energy of concert, i.e., the stabilization of the transition states by the concerted formation of two new bonds. By linking the plot of lg k2 vs N for nucleophilic dipolarophiles with that of lg k2 vs E for electrophilic dipolarophiles, one obtains V-shaped plots which provide absolute rate constants for the stepwise reactions on the borderlines. These plots furthermore predict relative reactivities of dipolarophiles in concerted, highly asynchronous cycloadditions more precisely than the classical correlations of rate constants with FMO energies or ionization potentials. DFT calculations using the SMD solvent model confirm these interpretations