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Small rings that contain allenes are unconventional transient compounds that have been known since the 1960s. Despite being discovered around the same time as benzyne and offering a number of synthetically advantageous features, strained cyclic allenes have seen relatively little use in chemical synthesis. We report a concise total synthesis of the manzamine alkaloid lissodendoric acid A, which hinges on the development of a regioselective, diastereoselective, and stereospecific trapping of a fleeting cyclic allene intermediate. This key step swiftly assembles the azadecalin framework of the natural product, allows for a succinct synthetic endgame, and enables a 12-step total synthesis (longest linear sequence; 0.8% overall yield). These studies demonstrate that strained cyclic allenes are versatile building blocks in chemical synthesis.

We report a computational and experimental study of the reaction of oxadiazinones and strained alkynes to give polycyclic aromatic hydrocarbons (PAHs). The reaction proceeds by way of a pericyclic reaction cascade and leads to the formation of four new carbon-carbon bonds. Using M06-2X DFT calculations, we interrogate several mechanistic aspects of the reaction, such as why the use of non-aromatic strained alkynes can be used to access unsymmetrical PAHs, whereas the use of arynes in the methodology leads to symmetrical PAHs. In addition, experimental studies enable the rapid synthesis of new PAHs, including tetracene and pentacene scaffolds. These studies not only provide fundamental insight regarding the aforementioned cycloaddition cascades and synthetic access to PAH scaffolds, but are also expected to enable the synthesis of new materials.

Recently, it has been estimated that nearly 200 million people use marijuana with growing usage being attributed to the legalization and decriminalization of the drug around the world. A concerning implication of increased marijuana use is the alarming number of individuals who report driving under the influence of the drug, which has prompted the development of detection technologies. An electrochemical-based detection technology, akin to how the alcohol breathalyzer functions, would provide an attractive solution to this growing societal problem. The first step toward this goal is to develop a reaction that converts Δ(9)-tetrahydrocannabinol (Δ(9)-THC), the primary psychoactive substance in marijuana, to a derivative with diagnostic spectroscopic changes. We report the development of a mild electrochemical method for the oxidation of Δ(9)-THC to its corresponding p-quinone isomer. The photophysical and electrochemical properties of the resultant quinone show a dramatic shift in comparison to Δ(9)-THC. This simple protocol provides the foundation for the development of an electrochemical-based marijuana breathalyzer.

For over a century, the structures and reactivities of strained organic compounds have captivated the chemical community. Whereas triple-bond-containing strained intermediates have been well studied, cyclic allenes have received far less attention. Additionally, studies of cyclic allenes that bear heteroatoms in the ring are scarce. We report an experimental and computational study of azacyclic allenes, which features syntheses of stable allene precursors, the mild generation and Diels–Alder trapping of the desired cyclic allenes, and explanations of the observed regio- and diastereoselectivities. Furthermore, we show that stereochemical information can be transferred from an enantioenriched silyl triflate starting material to a Diels–Alder cycloadduct by way of a stereochemically defined azacyclic allene intermediate. These studies demonstrate that heteroatom-containing cyclic allenes, despite previously being overlooked as valuable synthetic intermediates, may be harnessed for the construction of complex molecular scaffolds bearing multiple stereogenic centres. Strained organic compounds have long fascinated the chemistry community. Heterocyclic allenes are particularly interesting strained intermediates, but their use in synthetic chemistry is rather scarce. Now, an experimental and computational study of azacyclic allenes demonstrates that heteroatom-containing cyclic allenes can be harnessed for the construction of complex molecular scaffolds, including those that bear multiple stereogenic centres.

An X-ray diffraction study of [6]cycloparaphenylene (1), crystallized under solvent-free conditions, revealed a unique solid state structure with tight packing of individual molecules that minimizes empty internal space. The controlled chemical reduction of this highly strained nanohoop with Group 1 metals resulted in the first isolation and structural characterization of its mono- and dianions, allowing for the evaluation of core transformations for the series ranging from 10 to 11- and 12-.

One-pot reactions that combine non-enzymatic and biocatalytic transformations represent an emerging strategy in chemical synthesis. Some of the most powerful chemoenzymatic methodologies, although uncommon, are those that form a carbon–carbon (C–C) bond and a stereocenter at one of the reacting carbons, thereby streamlining traditional retrosynthetic disconnections. Here we report the one-pot, chemoenzymatic conversion of amides to enantioenriched alcohols. This transformation combines a nickel-catalyzed Suzuki–Miyaura coupling of amides in aqueous medium with an asymmetric, biocatalytic reduction to provide diarylmethanol derivatives in high yields and enantiomeric excesses. The synthetic utility of this platform is underscored by the formal syntheses of both antipodes of the pharmaceutical orphenadrine, which rely on ketoreductase enzymes that instill complementary stereoselectivities. We provide an explanation for the origins of stereoselectivity based on an analysis of the enzyme binding pockets.

Marijuana has long remained one of the most commonly used illicit drugs in the United States and other countries. Recently, it has been estimated that 55 million Americans use this psychoactive drug, with growing usage being attributed to the legalization of marijuana in several states. A concerning implication of increased marijuana use is the alarming number of individuals who report driving under the influence of the drug. It is estimated that nearly 12 million people in the US alone have driven a vehicle while being under the influence of marijuana. To counterbalance the growing use of marijuana and potential associated dangers, it is imperative to develop detection technologies for marijuana usage. An electrochemical-based detection technology, akin to the alcohol breathalyzer, would provide an attractive solution to this growing societal problem. The first step toward this goal is to develop a fundamental reaction that converts tetrahydrocannabinol (THC), the primary psychoactive substance in marijuana, to a derivative with diagnostic spectroscopic changes. We report the development of a mild electrochemical method for the oxidation of THC to its corresponding p-quinone isomer. The photophysical and electrochemical properties of the resultant quinone show a dramatic shift in comparison to THC. This exceedingly simple protocol provides a foundational step toward the development of an electrochemical-based marijuana breathalyzer.

We have synthesized a cycloparaphenylene containing a perylene motif that is a model for a carbon nanotube sidewall. The reactivity of the sidewall model towards a Diels–Alder reaction using a masked acetylene was examined and similar reactivity was observed between the macrocyclic and planar substrate. This study suggests that a Diels–Alder reaction is a viable method for carbon nanotube growth using an appropriate template.

We report a modular synthetic strategy for accessing heteroatom-containing polycyclic aromatic hydrocarbons (PAHs). Our approach relies on the controlled generation of transient heterocyclic alkynes and arynes. The strained intermediates undergo in situ trapping with readily accessible oxadiazinones. Four sequential pericyclic reactions occur, namely two Diels–Alder / retro-Diels–Alder sequences, which can be performed in a stepwise or one-pot fashion to assemble four new carbon–carbon (C–C) bonds. These studies underscore how the use of heterocyclic strained intermediates can be harnessed for the preparation of new organic materials.

We report a computational study of mesoscale morphology and charge-transport properties of radially π-conjugated cycloparaphenylenes ([ n]CPPs) of various ring sizes ( n = 5-12, where n is the number of repeating phenyl units). These molecules are considered structural constituents of fullerenes and carbon nanotubes. [ n]CPP molecules are nested in a unique fashion in the solid state. Molecular dynamics simulations show that while intramolecular structural stability (order) increases with system size, intermolecular structural stability decreases. Density functional calculations reveal that reorganization energy, an important parameter in charge transfer, decreases as n is increased. Intermolecular charge-transfer electronic couplings in the solid state are relatively weak (due to curved π-conjugation and loose intermolecular contacts) and are on the same order of magnitude (∼10 meV) for each system. Intrinsic charge-carrier mobilities were simulated from kinetic Monte Carlo simulations; hole mobilities increased with system size and scaled as ∼ n

Strained hydrocarbons are more than molecular curiosities — they often have promising materials properties, and even just making them offers challenges that push the limits of synthetic methods. Now, a short, efficient and room-temperature synthesis of [5]cycloparaphenylene, a carbon nanohoop with 119 kcal per mol of strain energy, is reported.

Cycloparaphenylenes (CPPs) have optoelectronic properties that are unique when compared to their acyclic oligoparaphenylene counterparts. The synthesis and characterization of two bent heptaphenyl-containing macrocycles has been achieved in order to probe the effects of bending and cyclic conjugation on the properties of the CPPs. The study suggests that both bending and cyclic conjugation play a role in the novel properties of the CPPs.

Constrained macrocyclic scaffolds are recognized as challenging synthetic motifs with few general macrocyclization methods capable of accessing these types of systems. Although palladium catalyzed oxidative homocoupling of aryl boronic acids and esters to biphenyls has been recognized as a common byproduct in Suzuki-Miyaura cross-couplings for decades, this reactivity has not been leveraged for the synthesis of challenging molecules. Here we report an oxidative boronic ester homocoupling reaction as a mild method for the synthesis of strained and conformationally restricted macrocycles. Higher yields and better efficiencies are observed for intramolecular diboronic ester homocouplings when directly compared to the analogous intramolecular Suzuki-Miyaura cross-couplings or reductive Yamamoto homocouplings. Substrates included strained polyphenylene macrocycles, strained cycloalkynes, and a key macrocyclic intermediate toward the synthesis of acerogenin A. Notably, this oxidative homocoupling reaction is performed at room temperature, open to atmosphere, and without the need to rigorously exclude water, thus representing an operationally simple alternative to traditional cross-coupling macrocyclizations. The mechanism of the reaction was investigated indicating that 1-5 nm palladium nanoparticles may serve as the active catalyst.

Quantum confinement of two-dimensional surface electronic states has been explored as a way for controllably modifying the electronic structures of a variety of coinage metal surfaces. In this Letter, we use scanning tunneling microscopy and spectroscopy (STM/STS) to study the electron confinement within individual ring-shaped cycloparaphenylene (CPP) molecules forming self-assembled films on Ag(111) and Au(111) surfaces. STM imaging and STS mapping show the presence of electronic states localized in the interiors of CPP rings, inconsistent with the expected localization of molecular electronic orbitals. Electronic energies of these states show considerable variations correlated with the molecular shape. These observations are explained by the presence of localized states formed due to confinement of surface electrons by the CPP skeletal framework, which thus acts as a molecular electronic "corral". Our experiments suggest an approach to robust large-area modification of the surface electronic structure via quantum confinement within molecules forming self-assembled layers.

A highly-strained, nitrogen-doped cycloparaphenylene (CPP), aza[6]CPP, was synthesized and then converted to a donor–acceptor nanohoop, N-methylaza[6]CPP, via alkylation of the nitrogen center. The energy levels of the lowest unoccupied molecular orbital (LUMO) and the highest occupied molecular orbital (HOMO) for both molecules were then probed by cyclic voltammetry (CV), which revealed that the donor–acceptor nanohoop had a significantly lower LUMO energy relative to [6]CPP and aza[6]CPP. Density functional theory (DFT) revealed that the donor–acceptor nanohoop underwent a redistribution of the frontier molecular orbital (FMO) density such that a significant portion of the LUMO density resided upon the electron-deficient nitrogen-containing ring. This localization of LUMO density caused a large lowering in the LUMO energy of nearly a full electron volt, while the HOMO energy was less affected due to a large centralization of the FMO on the electron-rich phenylene backbone. This ultimately resulted in a net lowering of the HOMO–LUMO energy gap which was observed both experimentally and computationally. In addition, N-methylaza[6]CPP has a significantly lower energy LUMO than N-methylaza[8]CPP, illustrating that the FMO levels of donor–acceptor nanohoops can be tuned by adjusting the hoop size.

Review: [data and discussion on the optical, electronic, and solid-state structure of [5]—[12]cycloparaphenylenes; 55 refs.].

The excited state properties of two nitrogen-doped cycloparaphenylene molecules, or carbon nanohoops, have been studied using steady-state and time-resolved absorption and emission spectroscopies. Quantum yield of fluorescence (Φf = 0.11 and 0.13) and intersystem crossing (Φisc = 0.45 and 0.32) were determined for aza[8]CPP and 1,15-diaza[8]CPP, respectively. We also present the proton transfer reaction between trifluoroacetic acid and the nitrogen-doped nanohoops, which resulted in significant modifications to the steady-state absorption and emission spectra as well as the triplet-triplet absorption spectra. From fluorescence quenching data we determine the equilibrium constant for the proton transfer reaction between aza[8]CPP (Keq = 1.39 × 10(-3)) and 1,15-diaza[8]CPP (Keq = 2.79 × 10(-3)) confirming that 1,15-diaza[8]CPP is twice as likely to be protonated at a particular concentration of trifluoroacetic acid.

[n]Cycloparaphenylenes (or "carbon nanohoops") are cyclic fragments of carbon nanotubes that consist of n para linked benzene rings. These strained, all sp(2) hybridized macrocycles, have size-dependent optical and electronic properties that are the most dynamic at the smallest size regime where n = 5-12. This review highlights the unique physical phenomena surrounding this class of polycyclic aromatic hydrocarbons, specifically emphasizing the novel structural, optical, and electronic properties of [5]-[12]CPPs.

Cycloparaphenylene molecules, commonly known as "carbon nanohoops", have the potential to serve as building blocks in constructing carbon nanotube architectures. The singlet and triplet excited-state characteristics of [9]-cycloparaphenylene ([9]CPP) and [12]-cycloparaphenylene ([12]CPP) have now been elucidated using time-resolved transient absorption and emission techniques. The fluorescence quantum yields (Φ) of [9]CPP and [12]CPP were determined to be 0.46 and 0.83, respectively. Rates of nonradiative recombination (knr), radiative recombination (kr), and intersystem crossing (kisc) determined in this study indicate that radiative decay dominates in these nanohoop structures. The triplet extinction coefficient was determined through energy transfer with biphenyl, and the triplet quantum yield (ΦT) was calculated to be 0.18 and 0.13 for [9]CPP and [12]CPP, respectively. The rate of triplet state quenching by oxygen was measured to be 1.7 × 10(3) ([9]CPP) and 1.9 × 10(3) s(-1) ([12]CPP). The excited-state dynamics established in this study enable us to understand the behavior of a carbon nanotube-like structure on a single subunit level.

The divergent, selective syntheses of [7]–[12]cycloparaphenylenes have been accomplished utilizing sequential, orthogonal Suzuki–Miyaura cross-coupling reactions from two late-stage intermediates. Quantum yields decrease dramatically as cycloparaphenylene size decreases, highlighting the unique photophysical behavior of the smaller cycloparaphenylenes.

We find evidence for the surprising formation of polymeric phases under high pressure for conjugated nanohoop molecules was found. This paper represents one of the unique cases, in which the molecular‐level effects of pressure in crystalline organic solids is addressed, and provides a general approach based on vibrational Raman spectroscopy combining experiments and computations. In particular, we studied the structural and supramolecular chemistry of the cyclic conjugated nanohoop molecule [5]cyclo‐para‐phenylene ([5]CPP) under high pressures up to 10 GPa experimentally and up to 20 GPa computationally. The theoretical modeling for periodic crystals predicts good agreements with the experimentally obtained Raman spectra in the molecular phase. In addition, we have discovered two stable polymeric phases that arise in the simulation. The critical pressures in the simulation are too high, but the formation of polymeric phases at high pressures provides a natural explanation for the observed irreversibility of the Raman spectra upon pressure release between 6 and 7 GPa. The geometric parameters show a deformation toward quinonoid structures at high pressures accompanied by other deformations of the [5]CPP nanohoops. The quinonoidization of the benzene rings is linked to the systematic change of the bond length alternation as a function of the pressure, providing a qualitative interpretation of the observed spectral shifts of the molecular phase.