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To investigate the dynamic stereochemical inversion behavior of pillar[5]arenes (P[5]s) in more detail, we synthesized a series of novel rim-differentiated P[5]s with various substituents and examined their rapid rotations by variable-temperature NMR (203–298 K). These studies revealed for the first time the barrier of “methyl-through-the-annulus” rotation (ΔG‡ = 47.4 kJ·mol–1 in acetone) and indicated that for rim-differentiated P[5]s with two types of alkyl substituents, the smaller rim typically determines the rate of rotation. However, substituents with terminal C=C or C≡C bonds give rise to lower inversion barriers, presumably as a result of attractive π–π interactions in the transition state. Finally, data on a rim-differentiated penta-methyl-penta-propargyl P[5] exhibited the complexity of the overall inversion dynamics.

The increased use of both pillar[5]arenes and pillar[6]arenes, stimulated by increasingly efficient syntheses of both, has brought forward the question as to what drives the intermediates in this Friedel–Crafts ring formation to form a pillar[5]arene, a pillar[6]arene, or any other sized macrocycle. This study sets out to answer this question by studying both the thermodynamics and kinetics involved in the absence and presence of templating solvents using high-end wB97XD/6-311G(2p,2d) DFT calculations.

A highly substituent-dependent rearrangement allows for the novel and SOCl2-induced divergent synthesis of 3-methylthioquinolin-2-ones and 3-methylthiospiro[4.5]trienones through intramolecular electrophilic cyclization of N-aryl propyamides. DMSO acts as both solvent and sulfur source, and use of DMSO-h6/d6 enables the incorporation of SCH3 or SCD3 moieties to the 3-position of the heterocyclic framework. Different para-substituents trigger divergent reaction pathways leading to the formation of quinolin-2-ones for mild substituents and spiro[4,5]trienones for both electron-withdrawing and -donating substituents, respectively. On the basis of both computational and experimental results, a new mechanism has been put forward that accounts for the exclusive spirolization/defluorination process and the surprising substituent effects.

Stimulated by its success in both bioconjugation and surface modification, we studied the strain-promoted oxidation-controlled cycloalkyne–1,2-quinone cycloaddition (SPOCQ) in three ways. First, the second-order rate constants and activation parameters (ΔH⧧) were determined of various cyclooctynes reacting with 4-tert-butyl-1,2-quinone in a SPOCQ reaction, yielding values for ΔH⧧ of 4.5, 7.3, and 12.1 kcal/mol, for bicyclo[6.1.0]non-4-yne (BCN), cyclooctyne (OCT), and dibenzoazacyclooctyne (DIBAC), respectively. Second, their reaction paths were investigated in detail by a range of quantum mechanical calculations. Single-configuration theoretical methods, like various DFT and a range of MP2-based methods, typically overestimate this barrier by 3–8 kcal/mol (after inclusion of zero-point energy, thermal, and solvation corrections), whereas MP2 itself underestimates the barrier significantly. Only dispersion-corrected DFT methods like B97D (yielding 4.9, 6.4, and 12.1 kcal/mol for these three reactions) and high-level CCSD(T) and multireference multiconfiguration AQCC ab initio approaches (both yielding 8.2 kcal/mol for BCN) give good approximations of experimental data. Finally, the multireference methods show that the radical character in the TS is rather small, thus rationalizing the use of single-reference methods like B97D and SCS-MP2 as intrinsically valid approaches.

The solvolysis pattern of polyenol ethers in protic solvents was investigated using semiempirical molecular orbital methods with the recently developed PM3 parametrization. The complex mechanisms recently proposed for these solvolyses are substantiated and refined by our calculations. Most polyenol ethers react preferably via electron transfer with dioxygen. The radicals formed in this way combine regioselectively to form a hydroperoxide zwitterion. Two imitations to this electron-transfer pathway can be formulated: (1) if the polyene chain is short (mono- and dienol compounds), the oxidation potential is too high for electron transfer to occur and enol ether hydrolysis via protonation of the conjugated chain is observed; (2) if the alkoxy chain is protonated at the C β' -hydroxyl group, products resulting from a different ionic route are observed

A study of the charge distribution in the 1-hydropyrenyl anion (2 - ), and of its regioselectivity toward electrophilic attack was undertaken. In order to obtain reliable information on the reactive positions in 2 - , a model with the same conjugated system was prepared, which has its 1-position fixed with a spirocyclopentane ring. Highly resolved 1 H and 13 C NMR spectra of this spiro[cyclopentane-1,1'-[1H]pyrenyl] anion (1 - ) and of 2 - were obtained. These spectra could be completely assigned by means of COSY, NOESY, and 2D 1 H- 13 C COSY techniques. According to the 13 C NMR measurements, 5-Cof 1 - and 2 - bears the highest negative charge. The results of PM3 semiempirical calculations support this finding, and furthermore, a large HOMO coefficient was calculated at the quaternary 3a-C of 2 - , suggesting that this position is susceptible toward attack by soft electrophiles. In full agreement with the 13 C NMR and PM3 results, 5-C of 1 - and 2 - show the highest reactivity toward electrophilic attack, while the quaternary 3a-C of 1 - and 2 - is attacked by soft electrophiles

The dehydrohalogenation reactions of PhCH(2)-CH(2)Cl and PhCHCl-CX(2)LG (X = H, F; LG = F, Cl) with methoxide have been studied using PM3 quantum chemical calculations in vacuo and within a dielectric medium. For PhCH(2)-CH(2)Cl and PhCHCl-CH(2)Cl the loss of HCl is predicted to occur via an E2 mechanism, while for the other three compounds loss of hydrogen halide occurs via a two-step mechanism, with a hydrogen-bonded carbanion as an intermediate. The mechanistic implications of these calculations are discussed in comparison with experimental data.