The origin of the anomeric effect has been reexamined in a coordinated experimental and computational investigation. The results of these studies implicate a number of different, but correlated, interactions that in the aggregate are responsible for the anomeric effect. No single factor is uniquely responsible for the axial preference of a substituent that is the hallmark of the anomeric effect. A CH···G nonbonded attraction between a polar axial substituent (G) and the syn-axial hydrogen(s) in the heterocycle has been demonstrated experimentally. The hyperconjugation model involving electron transfer from a ring heteroatom to an excited state of an axial C-G bond was shown to be, at most, a minor contributor because of the very small changes in charge density at the ring heteroatom(s): the main charge transfer is from hydrogen to G in the H-C-G unit. This appears to result from lengthening the C-G bond to minimize repulsion with the ring atom lone pair(s) and the advantage of having a more positive hydrogen that leads to a stabilizing Coulombic interaction with the ring heteroatom(s). In short, the anomeric effect arises mainly from two separate CH···G nonbonded Coulombic attractions.

The oxidation of primary amines using a stoichiometric quantity of 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1) in CH2Cl2-pyridine solvent at room temperature or at gentle reflux affords nitriles in good yield under mild conditions. The mechanism of the oxidation, which has been investigated computationally, involves a hydride transfer from the amine to the oxygen atom of 1 as the rate-limiting step.

A scalable, high yielding, rapid route to access an array of nitriles from aldehydes mediated by an oxoammonium salt (4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate) and hexamethyldisilazane (HMDS) as an ammonia surrogate has been developed. The reaction likely involves two distinct chemical transformations: reversible silyl-imine formation between HMDS and an aldehyde, followed by oxidation mediated by the oxoammonium salt and desilylation to furnish a nitrile. The spent oxidant can be easily recovered and used to regenerate the oxoammonium salt oxidant.

Synergism among several intertwined catalytic cycles allows for selective, room temperature oxidation of primary amines to the corresponding nitriles in 85-98% isolated yield. This metal-free, scalable, operationally simple method employs a catalytic quantity of 4-acetamido-TEMPO (ACT; TEMPO=2,2,6,6-tetramethylpiperidine N-oxide) radical and the inexpensive, environmentally benign triple salt oxone as the terminal oxidant under mild conditions. Simple filtration of the reaction mixture through silica gel affords pure nitrile products.

The multigram preparation and characterization of a novel TEMPO-based oxoammonium salt, 2,2,6,6-tetramethyl-4-(2,2,2-trifluoroacetamido)-1-oxopiperidinium tetrafluoroborate (5), and its corresponding nitroxide (4) are reported. The solubility profile of 5 in solvents commonly used for alcohol oxidations differs substantially from that of Bobbitt's salt, 4-acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium tetrafluoroborate (1). The rates of oxidation of a representative series of primary, secondary, and benzylic alcohols by 1 and 5 in acetonitrile solvent at room temperature have been determined, and oxoammonium salt 5 has been found to oxidize alcohols more rapidly than does 1. The rate of oxidation of meta- and para-substituted benzylic alcohols by either 1 or 5 displays a strong linear correlation to Hammett parameters (r > 0.99) with slopes (ρ) of -2.7 and -2.8, respectively, indicating that the rate-limiting step in the oxidations involves hydride abstraction from the carbinol carbon of the alcohol substrate.

This Concept highlights the discovery and developments in the oxidations of amines catalyzed by TEMPO (2,2,6,6‐tetramethylpiperidinyl‐N‐oxyl) and related catalytic systems. The most important feature of these systems is that, with slight modifications in the reaction media, amines are selectively oxidized to either an imine or nitrile. Progress made toward the oxidation of various benzylic, allylic, and aliphatic amines, and possible reaction mechanism pathways are discussed.

The development of a concise total synthesis of (±)‐phyllantidine (1), a member of the securinega family of alkaloids containing an unusual oxazabicyclo[3.3.1]nonane core, is described. The synthesis employs a unique synthetic strategy featuring the ring expansion of a substituted cyclopentanone to a cyclic hydroxamic acid as a key step that allows facile installation of the embedded nitrogen‐oxygen (N−O) bond. The optimization of this sequence to effect the desired regiochemical outcome and its mechanistic underpinnings were assessed both computationally and experimentally. This synthetic approach also features an early‐stage diastereoselective aldol reaction to assemble the substituted cyclopentanone, a mild reduction of an amide intermediate without N−O bond cleavage, and the rapid assembly of the butenolide found in (1) via use of the Bestmann ylide.

Oxidation reactions are critical components of the synthetic toolbox taught to undergraduate students during introductory organic chemistry courses. However, the oxidation reactions discussed in the undergraduate curriculum are often outdated as many organic chemistry textbooks emphasize chromium-based oxidants that are no longer in regular use by practitioners, which may limit an instructor’s time to allocate to discussion of other oxidants. Further, laboratory courses have since either removed oxidation experiments or replaced them with oxidative processes not discussed in lectures, thus leading to a disconnect between the two learning settings. As part of an effort to bridge this divide and modernize the oxidation reactions discussed in our curricula, we have developed a new laboratory experiment that uses a commercially available oxoammonium salt (Bobbitt’s salt) to cleanly oxidize cinnamyl alcohol to cinnamaldehyde. In addition to being a safe, convenient, colorimetric, and “green oxidant” suitable for use in the undergraduate teaching laboratory, the hydride-transfer mechanism allows for overlap with key course concepts presented in both introductory and advanced lecture courses. The procedure is well-suited for small and large organic I, II, or advanced laboratory sections alike and can be completed within a standard 3–4 h laboratory period. Aside from exposing students to a modern green oxidation protocol, the experiment contains expanded opportunities for interpretation of 1H NMR, 13C NMR, and IR spectra. An optional addendum for advanced students involving Hammett correlations was also developed.