Toward one‐pot olefin/thiophene block copolymers using an in situ ligand exchange

Block copolymers containing both conducting and insulating segments are of interest due to their enhanced electrical properties arising from their increased crystallization. Yet few methods exist for generating these copolymers, because the reaction conditions for synthesizing each block are often incompatible. Herein, efforts toward identifying a one‐pot, living polymerization method for synthesizing block copolymers of 1‐pentene and 3‐hexylthiophene is described. An in situ ligand exchange enables the optimal catalyst to be utilized for synthesizing each block. Even under these conditions, however, only homopolymers are observed. Computational studies modeling the ligand exchange reveal that the added stabilizing ligands likely inhibit propagation of the second block. These results suggest an ancillary ligand‐based “goldilocks” effect wherein catalysts that are stable yet still reactive are required. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1601–1605Combined experimental and computational studies revealed unexpected challenges in applying sequential catalysis for the streamlined synthesis of insulating/conducting block copolymers.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150553/1/pola29426_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150553/2/pola29426.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150553/3/pola29426-sup-0001-AppendixS1.pd

Automated Reaction Discovery Tools and their Application to Understanding Organometallic Reactions

Using computational simulations to model reaction mechanisms has been a common way to garner kinetic and thermodynamic information of a chemical system that can help to understand reaction rates and selectivities. The most widely used tools available for reaction path modeling, however, lend themselves to working best when chemical intuition or experimental data for a chemical reaction is available to help build the simulation. In order to model reaction mechanisms of chemical systems that have not been well studied, or even tested experimentally yet, new tools for simulation are needed that do not rely on chemical intuition or experimental data. Herein, new methods developed for reaction discovery are laid out and applied to understanding transition metal catalyzed reactions on a deeper level. The first tool, ZStruct, allows for the systematic exploration of chemical space for unimolecular and bimolecular reactions for both organic and organometallic reactions. This method requires minimal user guidance, with the only prior knowledge required being that of which atoms on each reactant may be participating in bond forming/breaking processes. This method has been applied to explore the following reaction: (1) methane activation by cisplatin, where 10 previously unexplored reaction pathways were identified. (2) Ni(II)-catalyzed beta-hydride elimination, where off cycle Ni-THF or Ni-pyridine intermediates were found to be thermodynamically favorable. (3) Palladium-catalyzed piperidine arylation, where the full catalytic cycle, including the rate limiting C-H activation step, as well as roles of important Ar-I and Cs-salt additives, were elucidated through ZStruct’s ability to explore chemical space. The second tool, CGen, allows for sampling conformational changes that reactants of interest can undergo, and use them to generate metal-reactant complexes. Using the conformers that are generated, reaction discovery using ZStruct can be done to understand how conformational changes impact the mechanism by which a reaction occurs. Additionally, CGen can also be used to create catalyst-reagent complexes (reagents could be counterions, solvent molecules, or any other molecular additives used experimentally) by aligning a catalyst and reagent of interest in different orientations, thus allowing for better sampling of molecular interactions during a reaction. CGen was used to explore the chemical space of ethylene polymerization with a Ti-constrained geometry catalyst (Ti-CGC). With this system the impact of the polymer chain conformation on the mechanism to ethylene insertion was investigated. The favorable pathways to insertion that were found involve polymer chain conformations that maximize the distance between Ti and the polymer chain. The barriers to insertion found with the naked cation system were lower than experimental results, implying that inclusion of the experimentally required borane counterion is important for generating a model that reflects experimental observations. Therefore, the same reaction was remodeled once with Me-B(C6F5)3- and again with B(C6F5)4-, and in both cases CGen was used to generate Counterion-catalyst complexes. The sampling of various counterion alignments and polymer chain conformations demonstrated that alignment/conformer combinations can actually impede monomer insertion from occurring. Additionally, the models showed that the difference in nucleophilic strength between the two counterions impact how energetically challenging monomer uptake prior to insertion is, as well as how each counterion positions itself with respect to the catalyst during monomer insertion. The insights gained using reaction discovery methods in this work gave way to a deeper understanding of how chemical interactions in-situ may be hindering or helping a chemical reaction to occur.PHDChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/151527/1/adewyer_1.pd

Computational study of an aza-Cope Mannich tandem reaction leading to pyrrolidine products under various conditions

Density functional methods are used to determine the energies of stationary points on the reaction pathways and activation barriers for an aza-Cope Mannich tandem reaction converting an oxazolidine into a pyrrolidine. Several steps in the reaction mechanism are examined to determine where stereoselectivity can be eroded. Specifically, we investigate the initial oxazolidine ring opening step, the aza-Cope rearrangement step and the C-C bond rotations that can occur prior to or following the aza-Cope rearrangement. The results of the calculations suggest that using a sterically-demanding chiral catalyst does not lead to selectivity toward one of two oxazolidine stereoisomers. In addition, this chiral catalyst does not prevent erosion of stereospecificity through C-C bond rotation in the iminium cation intermediates. Finally, in the presence of an achiral Lewis acid, when the oxazolidine substrate includes an isopropyl protecting group at the nitrogen center and a secondary carbinol carbon, activation barriers to C-C bond rotations that interconvert among stereoisomers are also sufficiently low to prevent stereoselectivity

Automated smartphone audiometry: Validation of a word recognition test app

Objectives/Hypothesis: Develop and validate an automated smartphone word recognition test. Study Design: Cross-sectional case-control diagnostic test comparison. Methods: An automated word recognition test was developed as an app for a smartphone with earphones. English-speaking adults with recent audiograms and various levels of hearing loss were recruited from an audiology clinic and were administered the smartphone word recognition test. Word recognition scores determined by the smartphone app and the gold standard speech audiometry test performed by an audiologist were compared. Results: Test scores for 37 ears were analyzed. Word recognition scores determined by the smartphone app and audiologist testing were in agreement, with 86% of the data points within a clinically acceptable margin of error and a linear correlation value between test scores of 0.89. Conclusions: The WordRec automated smartphone app accurately determines word recognition scores. Level of Evidence: 3b. Laryngoscope, 128:707–712, 2018

Automated Smartphone Audiometry: A Preliminary Validation of a Bone-Conduction Threshold Test App

Objective: To develop and validate an automated smartphone app that determines bone-conduction pure-tone thresholds. Methods: A novel app, called EarBone, was developed as an automated test to determine best-cochlea pure-tone bone-conduction thresholds using a smartphone driving a professional-grade bone oscillator. Adult, English-speaking patients who were undergoing audiometric assessment by audiologists at an academic health system as part of their prescribed care were invited to use the EarBone app. Best-ear bone-conduction thresholds determined by the app and the gold standard audiologist were compared. Results: Forty subjects with varied hearing thresholds were tested. Sixty-one percent of app-determined thresholds were within 5 dB of audiologist-determined thresholds, and 79% were within 10 dB. Nearly all subjects required assistance with placing the bone oscillator on their mastoid. Conclusion: Best-cochlea bone-conduction thresholds determined by the EarBone automated smartphone audiometry app approximate those determined by an audiologist. This serves as a proof of concept for automated smartphone-based bone-conduction threshold testing. Further improvements, such as the addition of contralateral ear masking, are needed to make the app clinically useful