K. N. Houk

Transition states and energetics of nucleophilic additions of thiols to substituted α,β-unsaturated ketones: Substituent effects involve enone stabilization, product branching, and solvation

CBS-QB3 enthalpies of reaction have been computed for the conjugate additions of MeSH to six α,β-unsaturated ketones. Compared with addition to methyl vinyl ketone, the reaction becomes 1-3 kcal mol(-1) less exothermic when an α-Me, β-Me, or β-Ph substituent is present on the C=C bond. The lower exothermicity for the substituted enones occurs because the substituted reactant is stabilized more by hyperconjugation or conjugation than the product is stabilized by branching. Substituent effects on the activation energies for the rate-determining step of the thiol addition (reaction of the enone with MeS(-)) were also computed. Loss of reactant stabilization, and not steric hindrance, is the main factor responsible for controlling the relative activation energies in the gas phase. The substituent effects are further magnified in solution; in water (simulated by CPCM calculations), the addition of MeS(-) to an enone is disfavored by 2-6 kcal mol(-1) when one or two methyl groups are present on the C=C bond (ΔΔG(‡)). The use of CBS-QB3 gas-phase energies in conjunction with CPCM solvation corrections provides kinetic data in good agreement with experimental substituent effects. When the energetics of the thiol additions were calculated with several popular density functional theory and ab initio methods (B3LYP, MPW1PW91, B1B95, PBE0, B2PLYP, and MP2), some substantial inaccuracies were noted. However, M06-2X (with a large basis set), B2PLYP-D, and SCS-MP2 gave results within 1 kcal mol(-1) of the CBS-QB3 benchmark values.

Modular mesoionics: understanding and controlling regioselectivity in 1,3-dipolar cycloadditions of Münchnone derivatives.

1,3-Dipolar cycloadditions of mesoionic 1,3-dipoles (Münchnones, imino-Münchnones, and phospha-Münchnones) with alkynes offer versatile, modular synthetic routes to pyrroles. Reactivity and regioselectivity differ markedly for different members of this series, and we report here the first general rationale for differences in reactivity by means of a systematic investigation of 1,3-dipolar cycloadditions involving electron-poor and electron-rich alkynes. Competition kinetic measurements indicate that Münchnones and phospha-Münchnones are nucleophilic 1,3-dipoles that react most rapidly with electron-poor alkynes. However, the regioselectivities of cycloadditions are found to undergo an inversion as a function of alkyne ionization potential. The exact point at which this occurs is different for the two dipoles, allowing rational control of the pyrrole formed. The origins of these reactivities and regioselectivities are examined computationally. Frontier molecular orbital predictions are found not to be accurate for these reactions, but transition state calculations give correct predictions of reactivity and selectivity, the origins of which can be analyzed using the distortion/interaction model of reactivity. Cycloadditions with electron-poor alkynes are shown to favor the regioisomer that has either the most favorable TS interaction energy (Münchnones or imino-Münchnones) or the smallest TS distortion energy (phospha-Münchnones). Cycloadditions with more electron-rich aryl-substituted alkynes, on the other hand, generally favor the regioisomer that has the smaller TS distortion energy. These insights delineate the synthetically important distinctions between Münchnones and phospha-Münchnones: phospha-Münchnones undergo highly regioselective cycloadditions with electron-poor alkynes that do not react selectively with Münchnones, and the reverse is true for cycloadditions of Münchnones with electron-rich alkynes.

Different transition structures for [2,3]-wittig rearrangements of stabilized and unstabilized allyloxy methyl anions : rationale for the dichotomous sense of stereoselection

Abstract Transition structures of [2,3]-Wittig rearrangements of allyloxymethyl anion, allyloxypropargyl anion, allyloxyacetaldehyde anion, and their 1-methyl (crotyl) and 3-methyl analogs have been located. The transition structure of the rearrangement of allyloxymethyl anion is extremely early, with the CC bond nearly unformed, and largely reflects inversion of the carbanion center and breaking of C 3 O 4 bond. The transition structure becomes much different when the anion is stabilized by an ethynyl substituent; now the CC forming bond is 2.3 A, and the CO bond is only slightly broken. The ethynyl group is calculated to strongly prefer exo orientation. In agreement with experimental observations, formation of Z-alkene is calculated to be slightly favored for the rearrangment of 3-methyl-allyloxymethyl anion, while E-alkene is formed exclusively when the anion is stabilized by an ethynyl group. The ethynyl group also shows the exo preference in E− and Z-crotyl ether cases, while the formyl group prefers the endo position in the E-crotyl system. Thus, not only the general trend of E to anti and Z to syn diastereoselection but also the anomalous sense of E to syn selectivity for carbonyl substituents can be rationalized.

A Solid‐State Effect Responsible for an Organic Quintet State at Room Temperature and Ambient Pressure

A stable organic diradicaloid with an intermolecular quintet at room temperature as a polycrystalline solid is studied. The conclusion is supported by the observation of the ΔMs = ±2 forbidden transition, electron spin resonance (ESR) simulations, and density functional theory (DFT) calculations. In addition, the molecule, as the active component of a device, is an outstanding near-infrared photodetector with detectivity over 10(11) cm Hz(1/2) W(-1) at 1200 nm.

Structures of α-lithiomethanol and α-lithiomethylamine; and an ab initio study

LiCH2OH and LiCH2NH2 are suggested by ab initio molecular-orbital theory to posses a number of isomeric forms; in the lowest energy structures the hydroxy- or amino-group bridges the C–Li bond and extra stabilisation results.

Retro-cycloadditions and sigmatropic shifts: the C 7 H 8 and C 7 H 10 potential energy surfaces

Retro-cycloadditions and thermal rearrangements of hydrocarbons have been investigated with density functional theory (B3LYP) and complete active space multiconfiguration self consistent field theory (CASSCF and CASPT2). We review recent results from our laboratories. Subjects are the laser-induced retro-Diels- Alder reactions of norbornene, thermal retro-Diels-Alder reactions of norbornenes and isopropylidenorbornene, 1,3-sigmatropic shifts of vinylcyclopropane and bicyclo(3.2.0)heptenes, and the 1,5-sigmatropic shifts of norcaradienes. The competition between concerted and stepwise processes and the nature of diradicals formed in these processes are described.

Formation of Aminocyclopentadienes from Silyldihydropyridines: Ring Contractions Driven by Anion Stabilization

Highly functionalized aminocyclopentadienes can be formed through the rearrangement of anions generated from readily prepared 6-silyl-1,2-dihydropyridines by desilylation with fluoride. The scope and generality of the reaction was defined, and diverse transformations were performed on the highly functionalized products. A mechanism and driving force for the rearrangement were identified from experiments and DFT calculations.