Olefin strain energy as a predictor of isolability

Data collection contains:Determination of the olefin stratin energy ranges corresponding to isolable, observable and unstable alkenes with contemporary forcefields - Bridgehead alkenes used to determine the olefin strain energy ranges corresponding to isolable, observable, and unstable  alkenes;Forcefield energies of alkenes S1-S25 and alkanes S1H2-S25H2;Olefin strain energies of alkenes S1-S25;Olefin strain energies of alkenes S1-S25 computed with different forcefields;Olefin strain energies of alkenes S1-S19 computed with different force fields, plotted against MM1 OS energy;Olefin strain energy calculations for natural products -Forcefield energies or bridgehead alkene natural products or putative bridgehead alkene natural products, and the  corresponding alkanes;Olefin strain energies of bridgehead alkene natural products or putative alkene natural products;OPLS_2005 Optimized geometries;Density Functional Theory (DFT) calculations -DFT calculations on NP's giving a measure of the amount of strain energy not captured by the forcefield;B3LYP-D3 optimized geometries and associated energies;A small set of alkenes for rapid estimation of OS cutoffs for other forcefield

The stereoselectivities of tributyltin hydride-mediated reductions of 5-bromo-D-glucuronides to L-iduronides are dependent on the anomeric substituent: syntheses and DFT calculations

One of the shortest synthetic routes to L-iduronic acid derivatives is via free radical reduction of the C-5 bromide of the corresponding protected D-glucuronic acid derivative. The epimerization of such C-5 bromides to the L-ido derivatives via reaction with tributyltin hydride was investigated. It was found that the stereoselectivity of the reaction was dependent on the anomeric substituent. If the substituent was fluoride the L-ido product was obtained exclusively in 65-72% yield whereas the O-methyl or O-acetyl derivatives led to isomeric mixtures of both the L-ido and D-gluco products in different ratios depending on the reaction conditions. DFT calculations were performed to determine the stereoelectronic factors that favour formation of the L-ido isomer from the fluoride and suggest the selectivity is due to a transition state gauche effect and an Sn-F interaction

Mediterranean-type diet and brain structural change from 73 to 76 years in a Scottish cohort

STUDY FUNDING The data were collected by a Research into Ageing programme grant; research continues as part of the Age UK–funded Disconnected Mind project. The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1), with funding from the BBSRC and Medical Research Council. Imaging and image analysis was performed at the Brain Research Imaging Centre (sbirc.ed.ac.uk/), Edinburgh, supported by the Scottish Funding Council SINAPSE Collaboration. Derivation of mean cortical thickness measures was funded by the Scottish Funding Council’s Postdoctoral and Early Career Researchers Exchange Fund awarded by SINAPSE to David Alexander Dickie. L.C.A.C. acknowledges funding from the Scottish Government's Rural and Environment Science and Analytical Services (RESAS) division.Peer reviewedPublisher PD

Aromatic interactions in asymmetric catalysis: control of enantioselectivity in Diels-Alder reactions catalysed by camphor-derived hydrazides

Density functional theory calculations (M06-2X//B3LYP) have been performed to determine the factors responsible for enantioselectivity in Diels-Alder reactions catalysed by two series of camphor-derived amines. Hydrazides 2 and sulfonylhydrazides 3 catalyze the reaction of cyclopentadiene with cinnamaldehyde to give the same enantiomer of cycloadduct. The calculations reveal that the two classes of catalysts control enantioselectivity by opposite mechanisms. Hydrazides 2 favour addition to the bottom face of a trans iminium cation, while sulfonylhydrazides 3 favour addition to the top face of a cis iminium ion. In the transition state for cycloadditions catalysed by 2, a stabilising CH-π interaction between the diene and a benzyl substituent α to the iminium nitrogen accelerates the reaction and enhances the enantioselectivity. The facial selectivity can be reinforced by appending onto the benzyl side-arm an α-methyl group that sterically hinders addition to the top face

Reductions of Phosphine Oxides and Sulfides by Perchlorosilanes: Evidence for the Involvement of Donor-Stabilized Dichlorosilylene

Hexachlorodisilane reduces phosphine oxides and sulfides to the corresponding phosphines with opposite stereoselectivities. Through quantum mechanical calculations, a new mechanistic picture is reported that explains these stereoselectivities. Phosphine oxides are shown to react via conventional phosphorane intermediates, but phosphine sulfides follow a dramatically different mechanism involving donor-stabilized SiCl₂

Theoretical Investigation of the Mechanisms and Stereoselectivities of Reductions of Acyclic Phosphine Oxides and Sulfides by Chlorosilanes

Computational studies were performed to explain the highly varied stereoselectivities obtained in the reductions of acyclic phosphine oxides and sulfides by different chlorosilanes. The reductions of phosphine oxides by HSiCl₃, HSiCl₃/Et₃N, and Si₂Cl₆ and the reductions of phosphine sulfides by Si₂Cl₆ (all in benzene) were explored by means of B3LYP, B3LYP-D, and SCS-MP2 calculations. For the reductions of phosphine oxides by HSiCl₃, the calculations support the mechanism proposed by Horner in which a hydride is transferred from silicon to phosphorus through a four-centered, frontside transition state. This mechanism leads to retention of stereochemistry at phosphorus. For the other three reductions, two classes of mechanisms were explored. Phosphorane-based mechanisms that were previously proposed by Mislow and involve SiCl₃^– were compared with novel alternative mechanisms that involve nonionic rearrangement processes. In one of these, donor-stabilized SiCl₂ is formed as an intermediate. The calculations support a phosphorane-based mechanism for the reductions of phosphine oxides by HSiCl₃/Et₃N and Si₂Cl₆ (which proceed with inversion) but favor the rearrangement pathways for the reductions of phosphine sulfides by Si₂Cl₆ (which proceed with retention)

Origins of stereoselectivity in uncatalyzed and ZnBr2-catalyzed Diels–Alder reactions of a chiral sulfinylquinone

Density functional theory calculations are reported which explore how a chiral sulfinyl substituent controls the stereoselectivities of the Diels-Alder reactions of a 2-p-tolylsulfinylbenzoquinone. The π-facial stereoselectivities vary depending on the diene (cyclopentadiene or trans-piperylene) and on the presence or absence of a ZnBr2 catalyst. The stereoselectivities are shown to be controlled by steric effects and non-covalent (CH-π) interactions. The calculations reveal that the active dienophile in the ZnBr2-catalyzed reactions is likely to be a 1 : 2 complex of the dienophile and catalyst, not a 1 : 1 complex as commonly assumed

Do anti-Bredt natural products exist? Olefin strain energy as a predictor of isolability

Bredts rule holds a special place in the realm of physical organic chemistry, but its application to natural products chemistry - the field in which the rule was originally formulated - is not well defined. Herein, the use of olefin strain (OS) energy as a readily calculated predictor of the stability of natural products containing a bridgehead alkene is introduced. Schleyer first used OS energies to classify parent bridgehead alkenes into "isolable", "observable", and "unstable" classes. OS calculations on natural products, using contemporary forcefield methods, unequivocally predict all structurally verified bridgehead alkene natural products to be "isolable". Thus, when one assigns the structure of a putative bridgehead alkene natural product, an OS in the "observable" or "unstable" ranges is a red flag for error

Effects of substituents on the stabilities of phosphonyl radicals and their hydroxyphosphinyl tautomers

High-level ab initio quantum chemical methods have been used to calculate the radical stabilization energies (RSEs) of phosphonyl radicals XYP(=O)· bearing a range of substituents X and Y. The main influences on these radicals' stabilities are σ-effects. Due to the high positive charge on phosphorus, σ-withdrawal is destabilizing, and σ-donation is stabilizing. The pyramidal geometry at phosphorus minimizes the effect of stabilization by π-delocalization, while the potentially stabilizing effect of lone-pair donation is outweighed by concomitant σ-withdrawal. Thus, the calculated RSEs of phosphonyl radicals XHP(=O)· increase in the order X = F < MeN < MeO < CF < Bu < MeN < NC < H < Ph < MeS < MeSi. The tautomeric hydroxyphosphinyl radicals X(OH)P· exhibit a different set of substituent effects, with RSEs increasing in the order X = CF < MeN < MeN < MeO < Bu < H < MeS < MeSi < F < NC < Ph. In these radicals, both the σ- and π-properties of the X substituent influence stability, in tandem with those of the OH group. A comparison of the absolute enthalpies of isomeric phosphonyl and hydroxyphosphinyl radicals indicates that the hydroxyphosphinyl radicals X(OH)P· are more stable than the phosphonyl radicals XYP(=O)·. This is not a common situation in phosphorus chemistry. It is primarily attributed to the greater phosphorus p character of the singly occupied molecular orbital (SOMO) in the hydroxyphosphinyl radicals compared with the phosphonyl tautomers. As in closed-shell phosphorus species, the magnitude of the effect is modulated by the electronegativity of the substituent X