Computational Study of the Cyclization of 5-Hexenyl, 3-Oxa-5-hexenyl and 4-Oxa-5-hexenyl Radicals

The intramolecular cyclization of 5-hexenyl radicals continues to be an important synthetic method for the construction of five-membered rings. The synthetic utility arises from the high degree of regioselectivity to give predominantly cyclopentyl products in high yield under mild conditions. Recently we reported product cyclization studies on 4-oxa perturbed 5-hexenyl radical. In this paper we report our results from a computational study (UB3LYP and UCCSD(T)) of the cyclization of a series of 5-hexenyl and 3- and 4-oxa-5-hexenyl radicals. Three highly conserved cyclization transitions states (exo-chair, exo-boat and endo-chair) were located for 10 acyclic radicals. Activation en-ergies were calculated for the three modes of cyclization for each radical. Calculated values for the exo/endo cycliza-tion ratios had a high level of agreement with experiment and predictions were offered for two cases that have not been experimentally tested. The increased percentage of exo-cyclization with 3- and 4-oxa substitution is the result of an increase in the energy difference between the exo- and endo-chair transition states compared to the hydrocarbon sys-tems. The decreased rate of cyclization of the 4-oxa compounds is primarily due to the stabilization of the initial acy-clic radical by the vinyl ether linkage. The increase in the rate of cyclization with 3-methyl substitution is due to the increased conformational energy of the starting acyclic radical

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

Weak Acidity of Vinyl CH Bonds Enhanced by Halogen Substitution

As shown by the rates of proton–deuteron exchange in ethylenes with halogen substituents, the weak acidity of vinyl CH bonds is enhanced by halogen substitution. Relative rates of exchange in basic deuterium oxide reflect the relative acidities. Substitution in the α position has the strongest effect. Less electronegative halogens such as bromine increase the acidity more than does fluorine. The vinyl CH acid strengths correlate closely with the energies of deprotonation of isolated molecules into isolated anions, as computed with the MP2/cc-pVQZ model. The smaller deprotonation energies are associated with the stronger acids. Atomic charges from a natural bond order analysis done with the MP2/aug-cc-pVQZ model show that the negative charge becomes more dispersed in the anions of the stronger acids. Results are given for 13 haloethylenes and for 6 halogen-substituted butadienes, cyclopropenes, and a cyclobutene

Computational Study of the Cyclization of 5-Hexenyl, 3-Oxa-5-Hexenyl and 4-Oxa-5-Hexenyl Radicals

The intramolecular cyclization of 5-hexenyl radicals continues to be an important synthetic method for the construction of five-membered rings. The synthetic utility arises from the high degree of regioselectivity to give predominantly cyclopentyl products in high yield under mild conditions. Recently we reported product cyclization studies on 4-oxa perturbed 5-hexenyl radical. In this paper we report our results from a computational study (UB3LYP and UCCSD(T)) of the cyclization of a series of 5-hexenyl and 3- and 4-oxa-5-hexenyl radicals. Three highly conserved cyclization transitions states (exo-chair, exo-boat and endo-chair) were located for 10 acyclic radicals. Activation en-ergies were calculated for the three modes of cyclization for each radical. Calculated values for the exo/endo cycliza-tion ratios had a high level of agreement with experiment and predictions were offered for two cases that have not been experimentally tested. The increased percentage of exo-cyclization with 3- and 4-oxa substitution is the result of an increase in the energy difference between the exo- and endo-chair transition states compared to the hydrocarbon sys-tems. The decreased rate of cyclization of the 4-oxa compounds is primarily due to the stabilization of the initial acy-clic radical by the vinyl ether linkage. The increase in the rate of cyclization with 3-methyl substitution is due to the increased conformational energy of the starting acyclic radical

Rule of Five Cyclizations in and 5-Hexenyl Radicals and Photocyclizations of 1,5-Hexadienes: Effect of 4-Oxa Substitution

The effect of 4-oxa substitution on the regiochemistry and rate of 5-hexenyl radical cyclizations was investigated, as a potential model for [2 + 2] photocycloadditions of 2-acyl-4-oxa-1,5-hexadienes. Increasing the electron density in the alkene decreases the rate of cyclization in the 4-oxa-hexenyl radicals, relative to the all carbon analogs, but has little effect on the regioselectivity of the cyclization. The radical model does not reproduce the high degree of 1,6 closure, observed in the [2 + 2] photocycloadditions for 4-oxa-1,5-hexadiene 1a. However, the radical model does reinforce the interpretation that ground state conformational effects, engendered by substitution remote from the reacting centers have important rate consequences for cyclization reactions. Copyright © 2007 John Wiley & Sons, Ltd

AB INITIO STRUCTURES FOR 90irc^{irc}-TWISTED {\em s-trans}-1,3-BUTADIENE AND FOR CYCLOOCTATETRENE; THE NAKED sp2^{2}-sp2^{2} BOND AND OTHER DISCLOSURES ABOUT EQUILBRIUM STRUCTURES OF BUTADIENE

R. Engeln, D. Consalvo, J. Reuss, Chem. Phys. 160, 427 (1992).Author Institution: Department of Chemistry, Washington State University, Pullman, WA 99164-4630; Department of Chemistry and Biochemistry, Oberlin College, Oberlin, OH 44074The bond length of a carbon-carbon sp$^{2}$-sp$^{2}$ $\sigma$-bond without the perturbing effects of $\pi$-electron interactions has been estimated by high-level ab initio calculations [CCSD(T)/cc-pVNQ with CBS extrapolation] on two prototypical systems: a 90$^{irc}$-twisted form of butadiene and the tub conformer of cyclooctatetraene. The butadiene system yields a value of 1.4818 \AA, considerably longer than previous estimates. The corresponding bond length in cyclooctatetraene is slightly shorter due to some $\pi$-electron delocalization. Ab initio results for related equilibrium structures of other rotamers/transition states of butadiene along the internal rotation coordinate (C-C bond) will be reported and compared with an experimental potential function.

Hydroxylamine catalyzed Nazarov cyclizations of divinyl ketones

The first examples of iminium catalyzed Nazarov cyclizations of divinyl ketones are presented. Experiments describing hydroxylamine catalysis of the cyclization of eight alpha-alkoxy divinyl ketones (60-79% yield) and one unactivated divinyl ketone (38% yield) are reported. Phenyl substitution at the beta-position of the divinyl ketone inhibits cyclization, whereas beta-alkyl substituted beta-alkoxy divinyl ketones readily cyclize. (C) 2015 Elsevier Ltd. All rights reserved