Intermolecular hydrogen bonding in calix[5]arene derived cavitands regulates the molecular recognition of fullerenes.

We present a readily available calix[5]arene derived cavitand receptor that is stabilized in the closed cone conformer through intermolecular hydrogen bonding with methanol molecules. The receptor features a highly spherical aromatic surface that binds C60 and C70 fullerenes effectively, and the binding event can be regulated allosterically by the addition of methanol.

Enantioselective Molecular Recognition in a Flexible Self-Folding Cavitand.

We report a chiral deep cavitand receptor based on calix[5]arene stabilized by a cooperative network of hydrogen bonds and having a highly flexible structure. The cavitand displays enantioselective molecular recognition with a series of chiral quaternary ammonium salts, providing unprecedented stability ratios between the corresponding diastereomeric host-guest complexes. Molecular dynamics simulations corroborate the higher flexibility of the new host and the emergence of superior induced-fit behavior with regards to resorcin[4]arene derived self-folding cavitands.

Comprehensive Characterization of the Self-Folding Cavitand Dynamics.

The conformational equilibria and guest exchange process of a resorcin[4]arene derived self-folding cavitand receptor have been characterized in detail by molecular dynamics simulations (MD) and 1 H EXSY NMR experiments. A multi-timescale strategy for exploring the fluxional behaviour of this system has been constructed, exploiting conventional MD and accelerated MD (aMD) techniques. The use of aMD allows the reconstruction of the folding/unfolding process of the receptor by sampling high-energy barrier processes unattainable by conventional MD simulations. We obtained MD trajectories sampling events occurring at different timescales from ns to s: 1) rearrangement of the directional hydrogen bond seam stabilizing the receptor, 2) folding/unfolding of the structure transiting partially open intermediates, and 3) guest departure from different folding stages. Most remarkably, reweighing of the biased aMD simulations provided kinetic barriers that are in very good agreement with those determined experimentally by 1 H NMR. These results constitute the first comprehensive characterization of the complex dynamic features of cavitand receptors. Our approach emerges as a valuable rational design tool for synthetic host-guest systems.

A Rh-Catalyzed Cycloisomerization/Diels-Alder Cascade Reaction of 1,5-Bisallenes for the Synthesis of Polycyclic Heterocycles.

A novel methodology to transform bisallenes into a variety of polycyclic derivatives employing rhodium(I) catalysis has been developed. This transformation encompasses an intramolecular Rh-catalyzed cycloisomerization of bisallenes 1 to deliver a reactive cycloheptadiene, which concomitantly undergoes a regioselective [4 + 2] cycloaddition with alkenes. A complete mechanistic study of this transformation has been undertaken including DFT calculations. Overall, the methodology presented here constitutes a new and straightforward entry to polycyclic dihydroazepine and dihydrooxepine derivatives employing catalytic methods.

Enhanced Open-Circuit Voltage in Perovskite Solar Cells with Open-Cage [60]Fullerene Derivatives as Electron-Transporting Materials.

The synthesis, characterization, and incorporation of open-cage [60]fullerene derivatives as electron-transporting materials (ETMs) in perovskite solar cells (PSCs) with an inverted planar (p-i-n) structure is reported. Following optical and electrochemical characterization of the open-cage fullerenes 2a-c, p-i-n PSCs with a indium tin oxide (ITO)/poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate (PEDOT:PSS)/perovskite/fullerene/Ag structure were prepared. The devices obtained from 2a-b exhibit competitive power conversion efficiencies (PCEs) and improved open-circuit voltage (Voc) values (>1.0 V) in comparison to a reference cell based on phenyl-C61-butyric-acid methyl-ester (PC61BM). These results are rationalized in terms of a) the higher passivation ability of the open-cage fullerenes with respect to the other fullerenes, and b) a good overlap between the highest occupied molecular orbital/lowest unoccupied molecular orbital (HOMO/LUMO) levels of 2a-b and the conduction band of the perovskite.

A flexible self-folding receptor for coronene.

We report a conformationally flexible deep cavitand receptor based on calix[5]arene and stabilized by a cooperative network of hydrogen bonds. The receptor binds coronene selectively over smaller polycyclic aromatic hydrocarbons, but is flexible enough to adapt to a smaller guest that presents a complementary electron deficient surface. The unique dynamic properties of this system have been thoroughly studied by NMR spectroscopy and molecular dynamics (MD) simulations.

Expeditious Preparation of Open-Cage Fullerenes by Rhodium(I)-Catalyzed [2+2+2] Cycloaddition of Diynes and C60 : An Experimental and Theoretical Study.

A novel methodology to transform C60 into a variety of open-cage fullerene derivatives by employing rhodium(I) catalysis has been developed. This transformation encompasses a partially intermolecular [2+2+2] cycloaddition reaction between diynes 1 and C60 to deliver a cyclohexadiene-fused fullerene, which concomitantly undergoes a formal [4+4]/retro-[2+2+2] rearrangement to deliver open-cage fullerenes 2. Most notably, this process occurs without the need of photoexcitation. The complete mechanism of this transformation has been rationalized by DFT calculations, which indicate that, after [2+2+2] cycloaddition, the cyclohexadiene-fused intermediate evolves into the final product through a Rh-catalyzed di-π-methane rearrangement followed by a retro-[2+2+2] cycloaddition. The obtained open-cage fullerenes can be derivatized by Suzuki-Miyaura cross-coupling or subjected to ring expansion to deliver a 12-membered ring orifice in the fullerene structure. Overall, the methodology presented constitutes a straightforward entry to functional open-cage C60 fullerene derivatives by employing catalytic methods.

A Computational Study of the Intermolecular [2+2+2] Cycloaddition of Acetylene and C60 Catalyzed by Wilkinson's Catalyst.

The functionalization of fullerenes helps to modulate their electronic and physicochemical properties, generating fullerene derivatives with promising features for practical applications. Herein, DFT is used to explore the attachment of a cyclohexadiene ring to C60 through a rhodium-catalyzed intermolecular [2+2+2] cycloaddition of C60 and acetylene. All potential reaction paths are analyzed and it can be concluded that the [2+2+2] cycloaddition of C60 and two acetylene molecules catalyzed by [RhCl(PPh3 )3 ], yielding a cyclohexadiene ring fused to a [6,6] bond of C60 , is energetically feasible.

Complementary Binding in Urea-Based Self-Folding Cavitands.

A new family of cavitands bearing urea groups has been prepared. The hosts display a fluxional behavior akin to that of amide analogues. The ureido functions serve a dual role, stabilizing the folded conformer of the receptor and providing stabilization to guests present in the cavity.

Dehydrogenative [2 + 2 + 2] Cycloaddition of Cyano-yne-allene Substrates: Convenient Access to 2,6-Naphthyridine Scaffolds.

A rhodium-catalyzed [2 + 2 + 2] cycloaddition of cyano-yne-allene scaffolds followed by a dehydrogenative process enabling the direct synthesis of unsaturated pyridine-containing compounds that can be conveniently converted to 2,6-naphthyridine derivatives is reported.

The Pauson-Khand reaction of medium sized trans-cycloalkenes.

Medium sized trans-cycloalkenes are unusually reactive in the intermolecular Pauson-Khand reaction (PKR) with regard to typical monocyclic alkenes. This is due to the ring strain imparted by the E stereochemistry. The PKR of these alkenes offers a modular, regioselective and straightforward entry to trans fused [n.3.0] bicyclic scaffolds (n = 6-8).

Tetramethylnorbornadiene, a versatile alkene for cyclopentenone synthesis through intermolecular Pauson-Khand reactions.

1,2,3,4-Tetramethyl-bicyclo[2.2.1]hepta-2,5-diene (TMNBD, for tetramethylnorbornadiene) has been prepared and used successfully as an acetylene equivalent in the synthesis of substituted cyclopentenones. TMNBD is easily accessible on a multigram scale and displays excellent reactivity toward the intermolecular Pauson-Khand reaction. Conjugate additions on the resulting tricyclic compounds proceed with exquisite diastereoselectivity. The retro-Diels-Alder reaction of these TMNBD derivatives occurs under much smoother conditions than those required for its norbornadiene homologues.

Deep cavitand receptors with pH-independent water solubility.

Pendant oligoethyleneglycol groups confer water solubility to a cavitand over a wide pH range. The kinetic stability of the host-guest complexes reveals an effective stabilization through hydrogen bonding even in the highly competitive aqueous environment.

Self-folding cavitands: structural characterization of the induced-fit model.

Deletion of structural elements in cavitand receptors is used to evaluate the thermodynamic and kinetic parameters of binding in these hosts. The use of a bulky guest showcases the importance of host-guest shape adaptations in the molecular recognition process.

Recognition and organocatalysis with a synthetic cavitand receptor.

The cyclization reaction of an epoxyalcohol is catalyzed by a synthetic cavitand receptor with an inwardly directed carboxylic acid function. The receptor features a hydrophobic pocket in which the substrate is bound and positioned to react in a regioselective manner. The nature of this substrate-catalyst complex and its dynamic properties were investigated by NMR methods and with the aid of a model compound lacking the epoxide function. The kinetic parameters of the cyclization reaction were also studied. A catalytic cycle is proposed and diverse inhibition mechanisms are identified that parallel those encounterd in enzymology.

Pseudo-capsule assemblies characterized by 19F NMR techniques.

The formation of capsule-like dynamic assemblies which do not rely on attractions between host subunits was achieved via specific interactions with fluorinated guests. Characterization of these three component assemblies was accomplished by applications of (19)F NMR spectroscopy.

Theoretical and experimental studies on the mechanism of norbornadiene Pauson-Khand cycloadducts photorearrangement. Is there a pathway on the excited singlet potential energy surface?

The intermolecular Pauson-Khand reaction (PKR), a carbonylative cycloaddition between an alkyne and an alkene, is a convenient method to prepare cyclopentenones. Using norbornadiene as alkene, a myriad of tricyclo[5.2.1.0(2,6)]deca-4,8-dien-3-ones 1 can be easily prepared. The mechanism of the photochemical rearrangement of these adducts 1 into tricyclo[5.2.1.0(2,6)]deca-3,8-dien-10-ones 2 has been studied. The ground state (S(0)) and the three lowest excited states ((3)(pi pi*), (1)(n pi*), and (3)(n pi*)) potential energy surfaces (PESs) concerning the prototypical rearrangement of 1a (the cycloadduct of the PK carbonylative cycloaddition of norbornadiene and ethyne) to 2a have been thoroughly explored by means of CASSCF and CASPT2 calculations. From this study, two possible nonadiabatic pathways for the photochemical rearrangement arise: one starting on the (3)(pi pi*) PES and the other on the (1)(n pi*) PES. Both involve initial C-C gamma-bond cleavage of the enone, which leads to the formation of a bis-allyl or an allyl-butadienyloxyl diradical, respectively, that then decays to the S(0) PES through a (3)(pi pi*)/S(0) surface crossing or a (1)(n pi*)/S(0) conical intersection, each one lying in the vicinity of the corresponding diradical minimum. Once on the S(0) PES, the ring-closure to 2a occurs with virtually no energy barrier. The viability of both pathways was experimentally studied by means of triplet sensitization and quenching studies on the photorearrangement of the substituted Pauson-Khand cycloadduct 1b (R = TMS, R' = H) to 2b. Using high concentrations of either piperylene as a triplet quencher, or benzophenone as a triplet sensitizer, the reaction rate significantly slowed down. A Stern-Volmer type plot of product 2b concentration vs triplet quencher concentration showed an excellent linear correlation, thus indicating that only one excited state is involved in the photorearrangement. We conclude that, though there is a nonadiabatic pathway starting on the (1)(n pi*) PES, the reaction product is formed through the (3)(pi pi*) state because the energy barrier involved in the initial C-C gamma-bond cleavage of the enone is much lower in the (3)(pi pi*) PES than in the (1)(n pi*) PES.

The conjugate addition-Peterson olefination reaction for the preparation of cross-conjugated cyclopentenone, PPAR-gamma ligands.

5-Alkylidenecyclopent-2-enones 15a-q may be prepared via a conjugate addition-Peterson olefination sequence, best achieved in one-pot, using exo-2-trimethylsilyl-3a,4,7,7a-tetrahydro-4,7-methanoinden-1-one 12, followed by a retro-Diels-Alder reaction. The geometry of the exocyclic alkene may be controlled according to the use of organometallic species in the conjugate addition step; organocuprate reagents are found to selectively lead to the formation of E-exocyclic alkene adducts, whereas Grignard reagents favour the formation of Z-alkenyl isomers. The use of enantiomerically enriched 12, accessed from an asymmetric Pauson-Khand reaction, affords the corresponding enantioenriched 5-alkylidenecyclopent-2-enones and this approach is exemplified by the short, stereoselective total syntheses of two cyclopentenone phytoprostanes 51 and 13,14-dehydrophytoprostane J1 65. The ability of this family of synthetic compounds to activate the peroxisome proliferator activated receptor-gamma is reported.