Synthesis of Pyrrolidine-2-ylidenes from Isoxazolines and Allenes.

A diastereoselective addition and rearrangement reaction has been developed for the synthesis of pyrrolidine-2-ylidenes from N-isoxazolines and electron-deficient allenes. This method proceeds via the rearrangement of a proposed -alkenylisoxazoline intermediate to generate densely functionalized pyrrolidine-2-ylidenes under simple catalyst-free conditions that tolerate ketone substituents and install relative stereochemistry at positions 3 and 4 of the heterocycle. Reaction optimization and the substrate scope are described in addition to studies evaluating the reactivity of the -dione and enaminone groups of the products.

Students' Experiences with the Science and Engineering Practices in a Workshop-Based Undergraduate Research Experience.

This paper presents a phenomenographic investigation on students' experiences about research and poster presentations in a workshop-based undergraduate research experience with a focus on how the experience connects to the Science and Engineering Practices (SEPs) of the NRC and the principles of CUREs. This provides insight into how these structured research experiences reflect particular SEPs and also elements of scientific practice that are not captured in the SEPs as they have been formulated previously. This work showcases the importance of future applications, failure, and creativity as additional science practices necessary for students to engage in authentic science.

Cyclization Reactions of In Situ-Generated Acyl Ketene with Ynones to Form Oxacycles.

Acyl ketenes react with polar unsaturated functional groups to give unique heterocyclic rings, yet reactions with unpolarized unsaturated functional groups have not been reported. Herein, we describe two effective ring-forming reactions between acetyl ketene and electron-deficient alkynes. The first reaction involves in situ tethering between acetyl ketene and nucleophile-containing 1,3-diynones, which promotes sequential intramolecular 1,6/1,4-additions to generate 2-methylene-2-pyrans in various yields (24-91%).

Intramolecular Carboxyamidation of Alkyne-Tethered O-Acylhydroxamates through Formation of Fe(III)-Nitrenoids.

We developed intramolecular carboxyamidations of alkyne-tethered O-acylhydroxamates followed by either thermally induced spontaneous or 4-(dimethylamino)pyridine-catalyzed O→O or O→N acyl group migration. Under iron-catalyzed conditions, the carboxyamidation products were generated in high yield from both Z-alkene and arene-tethered substrates. DFT calculations indicate that the iron-catalyzed carboxyamidation proceeds via a stepwise mechanism involving iron-imidyl radical cyclization followed by intramolecular acyloxy transfer from the iron center to the alkenyl radical center to furnish the cis-carboxyamidation product.

Categorizing Student Learning about Research, Nature of Science, and Poster Presentation in a Workshop-Based Undergraduate Research Experience.

This article examines student experiences in a workshop-based undergraduate research experience studying the activity and inhibition of salivary amylase that provides students with the chance to participate in authentic scientific research prior to the start of their undergraduate studies, following the structure of a course-based undergraduate research experience (CURE). Understanding student experiences at this point in their studies is important because research experiences at the beginning of university studies have been shown to increase retention in STEM. This study utilizes meaningful learning and situated cognition as theoretical frameworks and phenomenography as a methodological framework, applied to data from semi-structured interviews with six students.

CoLab: A workshop-based undergraduate research experience for entering college students.

The goal of undergraduate chemistry laboratories is to allow students to learn about chemical systems and key laboratory skills. They should then apply this knowledge to solve problems and connect macroscopic observations in the laboratory with those occurring at the submicroscopic level. Unfortunately, these needs are not met through traditional confirmation labs.

Substituent and Solvent Effect Studies of N-Alkenylnitrone 4π Electrocyclizations.

The roles of substituent and solvent effects in promoting the 4π electrocyclization of N-alkenylnitrones to give azetidine nitrones have been investigated by experimental examination of relative rates, activation energies, and linear free energy relationships. These transformations are synthetically important because they favor the formation of a strained heterocyclic ring with imbedded functionality and stereochemical information for versatile derivatization. Mechanistic investigations, including Hammett studies, solvent-dependent Eyring studies, and solvent isotope effects, provide insight into the steric and electronic factors that control these electrocyclizations and identify trends that can be used to advance this approach towards the rapid synthesis of complex azetidines.

Cycloisomerization of Alkyne-Tethered N-Acyloxycarbamates to 2-(3H)Oxazolones through Nitrenoid-Mediated Carboxyamidation.

The cycloisomerization of alkyne-tethered N-benzoyloxycarbamates to 2-(3H)oxazolones is described. Two catalytic systems are tailored for intramolecular 5-exo-alkyne carboxyamidation and concomitant alkene isomerization. PtCl /CO (5 mol%, toluene, 100 °C) promotes both carboxyamidation and alkene isomerization but has a limited substrate scope.

Synthesis, Characterization, and X-ray Crystallography, of the First Cyclohexadienyl Trifluoromethyl Metal Complex (η-CH)Fe(CO)CF.

Fluorochemistry is a field of tremendous developments and advances in several areas of science including materials, pharmaceuticals and agriculture. This makes the design and synthesis of fluorine-containing substances highly desirable research targets. The sub-area of synthetic perfluorinated chemistry proportionately attracts widespread interest by applying to all areas of chemistry including organic and inorganic.

Rh(II)-Catalyzed Intermolecular -Aryl Aziridination of Olefins Using Nonactivated N Atom Precursors.

The development of the first intermolecular Rh(II)-catalyzed aziridination of olefins using anilines as nonactivated N atom precursors and an iodine(III) reagent as the stoichiometric oxidant is reported. This reaction requires the transfer of an -aryl nitrene fragment from the iminoiodinane intermediate to a Rh(II) carboxylate catalyst; in the absence of a catalyst only diaryldiazene formation was observed. This -aryl aziridination is general and can be successfully realized by using as little as 1 equiv of the olefin.

Counterion Control of t-BuO-Mediated Single Electron Transfer to Nitrostilbenes to Construct N-Hydroxyindoles or Oxindoles.

tert-Butoxide unlocks new reactivity patterns embedded in nitroarenes. Exposure of nitrostilbenes to sodium tert-butoxide was found to produce N-hydroxyindoles at room temperature without an additive. Changing the counterion to potassium changed the reaction outcome to yield solely oxindoles through an unprecedented dioxygen-transfer reaction followed by a 1,2-phenyl migration.

Ruthenabenzene: A Robust Precatalyst.

Metallaaromatics constitute a unique class of aromatic compounds where one or more transition metal elements are incorporated into the aromatic system, the parent of which is metallabenzene. One of the main concerns about metallabenzenes generally deals with the structural characterization related to their relative aromaticity compared to the carbon archetype. Transition metal-containing metallabenzenes are also implicated in certain catalytic processes such as alkyne metathesis polymerization; however, these transition metal-based metallaaromatic compounds have not been developed as a catalyst.

Synthesis of Spirocyclic 1-Pyrrolines from Nitrones and Arynes through a Dearomative [3,3']-Sigmatropic Rearrangement.

A dearomative [3,3']-sigmatropic rearrangement that converts N-alkenylbenzisoxazolines into spirocyclic pyrroline cyclohexadienones has been developed by using the dipolar cycloaddition of an N-alkenylnitrone and an aryne to access these unusual transient rearrangement precursors. This cascade reaction affords spirocyclic pyrrolines that are inaccessible through dipolar cycloadditions of exocyclic cyclohexenones and provides a fundamentally new approach to novel spirocyclic pyrroline and pyrrolidine motifs that are common scaffolds in biologically-active molecules. Diastereoselective functionalization processes have also been explored to demonstrate the divergent synthetic utility of the unsaturated spirocyclic products.

Oxidation of Nonactivated Anilines to Generate -Aryl Nitrenoids.

A low-temperature, protecting-group-free oxidation of 2-substituted anilines has been developed to generate an electrophilic -aryl nitrenoid intermediate that can engage in C-NAr bond formation to construct functionalized -heterocycles. The exposure of 2-substituted anilines to PIFA and trifluoroacetic acid or 10 mol % Sc(OTf) triggers nitrenoid formation, followed by productive and selective C-NAr and C-C bond formation to yield spirocyclic- or bicyclic 3-indoles or benzazepinones. Our experiments demonstrate the breadth of these oxidative processes, uncover underlying fundamental elements that control selectivity, and demonstrate how the distinct reactivity patterns embedded in -aryl nitrenoid reactive intermediates can enable access to functionalized 3-indoles or benzazepinones.

C-H Insertion by Alkylidene Carbenes To Form 1,2,3-Triazines and Anionic [3 + 2] Dipolar Cycloadditions To Form Tetrazoles: Crucial Roles of Stereoelectronic and Steric Effects.

The synthesis of 1,2,3-triazines and bicyclic tetrazoles from α-azido ketones is described. The common intermediate generated from lithiated trimethylsilyldiazomethane and α-azido ketones diverges depending on the steric bulk of the substituents. The formation of 1,2,3-triazines via a C-H insertion of alkylidene carbene to form 3-azidocyclopropene, followed by its rearrangement, is supported by density functional theory calculations.

Silver-Catalyzed Selective Multicomponent Coupling Reactions of Arynes with Nitriles and Isonitriles.

Pathway selective aryne-based novel multicomponent coupling reactions with isonitriles and nitriles are described. Crucial to these reactions is the formation of a silver-aryne complex, which shows differential reactivity toward isonitriles and nitriles to form two different forms of -nitrilium organosilver arene species. Interception of the nitrilium of an aryne-isonitrile adduct with another isonitrile leads to the formation of benzocyclobutene-1,2-diimines, whereas the nitrilium of an aryne-nitrile adduct renders selective formation of 3-indol-3-imines or 3-iminoindolin-2-ol depending on the structure of the nitrile employed.

Silver-Catalyzed Annulation of Arynes with Nitriles for Synthesis of Structurally Diverse Quinazolines.

An efficient silver catalyzed annulation reaction of aryne with nitriles to generate quinazolines is described. Arynes generated from triynes or tetraynes through a hexadehydro Diels-Alder reaction readily participated in an [A + 2B] mode of annulation with nitriles in the presence of AgSbF catalyst. The mechanism was explored by DFT calculations, which supports the silver-catalyzed formation of nitrilium ion as a key intermediate.

Alder-ene reactions driven by high steric strain and bond angle distortion to form benzocyclobutenes.

A unique aryne-based Alder-ene reaction to form benzocyclobutene is described. In this process, the thermodynamic barrier to form a four-membered ring is compensated by the relief of the strain energy of an aryne intermediate. On the other hand, the driving force to overcome the high kinetic barrier is provided by the gearing effect of the bulky substituent at the -position of the ene-donor alkene.

Controlling the Selectivity Patterns of Au-Catalyzed Cyclization-Migration Reactions.

As little as 2 mol % of (XPhos)AuNTf catalyzes the transformation of a broad range of o-acetylene-substituted styrenes into 1,2-dihydronaphthalenes. Our data suggests that this transformation occurs via a gold-stabilized cyclopropyl carbinyl cation, which triggers either a [1,2] carboxylate shift or a less favorable [1,2] aryl shift. The relative rates of these migrations can be controlled by the identity of the ligand or by stabilizing the mesomeric cation.

Catalyst-controlled cascade synthesis of bridged bicyclic tetrahydrobenz[b]azepine-4-ones.

A catalyst-controlled cascade reaction has been developed for the synthesis of bridged bicyclic tetrahydrobenz[b]azepin-4-ones from N-arylnitrones and allenes. This method expands the accessible structural diversity of a synthetically challenging heterocyclic scaffold and tunes a catalyst-sensitive process in a new direction.

Generation and Rearrangement of N,O-Dialkenylhydroxylamines for the Synthesis of 2-Aminotetrahydrofurans.

A new diastereoselective route to 2-aminotetrahydrofurans has been developed from N,O-dialkenylhydroxylamines. These intermediates undergo a spontaneous C-C bond-forming [3,3]-sigmatropic rearrangement followed by a C-O bond-forming cyclization. A copper-catalyzed N-alkenylation of an N-Boc-hydroxylamine with alkenyl iodides, and a base-promoted addition of the resulting N-hydroxyenamines to an electron-deficient allene, provide modular access to these novel rearrangement precursors.

Cascade Synthesis of 3-Functionalized Indoles from Nitrones and Their Conversion to Cycloheptanone-Fused Indoles.

A cascade reaction of N-aryl-α,β-unsaturated nitrones and electron-deficient allenes has been discovered that allows single-step access to 3-functionalized indoles that usually require preformation and alkylation of an indole precursor. The heterocycles prepared through the hydrogen bond donor catalyzed cascade reaction are poised to undergo a McMurry coupling to form previously synthetically elusive cycloheptanone-fused indoles. The scope of these transformations is discussed as well as mechanistic experiments describing proposed intermediates of the cascade reaction and an initial catalytic asymmetric example that generates a carbon stereocenter during the cascade process.

Synthesis and Properties of New N-Heteroheptacenes for Solution-Based Organic Field Effect Transistors.

A series of N-heteroheptacenes was synthesized from ortho-thiophene-substituted aryl azides using a Rh -catalyzed C-H bond amination reaction to construct the thienoindole moieties. This reaction tolerated the presence of electron-donating or withdrawing groups on the aryl azide without adversely affecting the yield of the amination reaction. The central thiophene ring was created from two thienoindole pieces through a Pd-catalyzed Stille reaction to install the thioether followed by a Cu-mediated Ullman reaction to trigger the cyclization.

Achieving Site Selectivity in Metal-Catalyzed Electron-Rich Carbene Transfer Reactions from N-Tosylhydrazones.

Catalyst control of the site-selectivity of electron-rich alkyl, aryl disubstituted carbenes generated in situ from o-alkenyl-substituted N-tosylhydrazones was achieved in this study. Exposure of these substrates to copper iodide triggered the formation of α-alkoxy 2H-naphthalenones. This investigation established that changing the catalyst to a rhodium(II) carboxylate turned off cyclization and migration of the electron-rich metal carbene with the β-carboxylate and turned on allylic C-H bond functionalization to diastereoselectively afford 1H-indenes.

Facile Synthesis of Azetidine Nitrones and Diastereoselective Conversion into Densely Substituted Azetidines.

An electrocyclization route to azetidine nitrones from N-alkenylnitrones was discovered that provides facile access to these unsaturated strained heterocycles. Reactivity studies showed that these compounds undergo a variety of reduction, cycloaddition, and nucleophilic addition reactions to form highly substituted azetidines with excellent diastereoselectivity. Taken together, these transformations provide a fundamentally different approach to azetidine synthesis than traditional cyclization by nucleophilic displacement and provide novel access to a variety of underexplored strained heterocyclic compounds.