Supramolecular control on reactivity and selectivity inside the confined space of H-bonded hexameric capsules

The confinement of substrates inside the cavity of self-assembled capsules makes it possible to effectively catalyze organic reactions in a way that is analogous to how enzymes work in biological systems. Due to steric constraints, solvent exclusion, intermediates stabilization, and conformational control of substrates, chemical reactions taking place in a confined space may exhibit unique processes. As a result, the fundamental rules of organic reactivity are frequently broken. The hexameric capsule C_R, an intriguing supramolecular assembly formed by six resorcinarene 1 macrocycles and eight water molecules, is the subject of this review. This assembly has proven to be effective at catalyzing several chemical reactions by controlling reactivity and selectivity in its confined space.     

Crystallographic observation of an olefin photodimerization reaction that takes place via thermal molecular tumbling within a self-assembled host

In situ crystallography reveals that the solid state [2 + 2] photodimerization of acenaphthylene in a coordination cage takes place smoothly without preorganizaiton of reaction centers at a preferred geometry, because the substrate tumbles thermally in the large hollow of the cage.     

Development of a practical Buchwald-Hartwig amine arylation protocol using a conveniently prepared (NHC)Pd(R-allyl)Cl catalyst

Continuing efforts to establish a more general "user-friendly" protocol for the palladium-catalysed arylation of amines (Buchwald-Hartwig reaction) are described herein. Significant advances have been made through the use of the versatile (SIPr)Pd(methallyl)Cl complex in conjunction with the reliable base lithium hexamethyldisilazide (LHMDS).     

Facile one-step synthesis of bis(NHC) ruthenium benzylidene catalyst for ring-closing metathesis

Bis(NHC) ruthenium benzylidene complex (H₂IMe)₂(Cl)₂RuCHPh (9) [H₂IMe = 1,3-bis(2,6- dimethylphenyl)-4,5-dihydroimidazol-2-ylidene] was synthesized facilely by one-step reaction of (PPh₃)₂(Cl)₂RuCHPh (7) with N-heterocyclic carbene (NHC) H₂IMe (6). Complex 9 proved to exhibit remarkable catalytic activity for ring-closing metathesis (RCM) reaction at increased temperature.     

The first Negishi cross-coupling reaction of two alkyl centers utilizing a Pd-N-heterocyclic carbene (NHC) catalyst

The development of an NHC-based system capable of cross-coupling sp(3)-sp(3) centers in high yield has been a long-standing challenge. This communication describes the use of a Pd-NHC catalytic system that achieves room-temperature Negishi cross-couplings of unactivated, primary bromides and alkyl organozinc reagents with a variety of functionality. [reaction: see text]     

A G-octamer scaffold via self-assembly of a guanosine-based Au(I) isonitrile complex for Au(I)-Au(I) interaction

A guanosine-based Au(I) isonitrile complex was demonstrated to serve as the reliable scaffold via self-assembly, wherein the quartet and octamer were formed in the absence and presence of a potassium ion, respectively, exhibiting a switchable emission based on Au(I)-Au(I) interaction.     

Peptide recognition: encapsulation and alpha-helical folding of a nine-residue peptide within a hydrophobic dimeric capsule of a bowl-shaped host

A dimeric capsule of coordination bowl 1 encapsulated a nine-residue peptide (Trp-Ala-Glu-Ala-Ala-Ala-Glu-Ala-Trp; 2) within the large hydrophobic cavity in water, and stabilized the alpha-helical conformation of bound 2. An NMR titration experiment revealed that monomeric bowl 1 recognized two Trp residues at the both terminals of 2 through 1/2 = 1:1 to 2:1 complexation. The 1:1 and 2:1 species exist in equilibrium even in the presence of excess 1. It was found that the formation of the 2:1 complex, in which two bowls of 1 wrapped the whole of 2, became dominant by the addition of NaNO3 due to the fact that the enhanced ion strength increased the hydrophobic interaction between Trp residues and the cavity of 1. The alpha-helical conformation of 2 within the dimeric capsule of 1 was elucidated from detailed NOESY analysis.     

Supramolecular structures of poly(γ-benzyl-L-glutamate) self-assembled on mica surface

This article reports the results of structural studies of poly (γ-benzyl-L -glutamate) (PBLG) layers self-assembled from dilute solutions in organic solvents on mica surface. Polarized dynamic light scattering and atomic force microscopy were used to study polymer properties in solutions and on the surface. The hierarchy of self-assembly from PBLG solutions in different solvents was investigated as a function of polymer concentration and solvent polarity. We show that the surface–polymer interaction is suppressed in polar solvents that is interpreted in terms of suppressed charge–dipole interaction. The transformation of the PBLG surface structure occurs upon addition of different amounts of trifluoroacetic acid to polymer solution in dioxane. Rigid-rod PBLG molecules experience rod–globular transition while assembling on nonmodified mica from the very dilute solutions. A scheme is proposed describing different stages of PBLG fibrogenesis on a charged surface. © 1998 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 36: 1567–1577, 1998     

A self-assembled cage as a non-covalent protective group: regioselectivity control in the nucleophilic substitution of aryl-substituted allylic chlorides

Aryl-substituted allylic chlorides are accommodated by a self-assembled cage in such a restricted orientation that the internal reaction sites are shielded while the external ones are exposed. This non-covalent protection enhances terminal regioselectivity in the allylic substitution.     

Molecular encapsulation via metal-to-ligand coordination in a Cu(I)-folded molecular basket

A molecular basket, composed of a semirigid C3v symmetric tris-norbornadiene framework and three pyridine flaps at the rim, has been shown to coordinate to a Cu(I) cation and thereby fold in a multivalent fashion. The assembly was effective (Ka = 1.73 +/- 0.08 x 10(5) M(-1)) and driven by enthalpy (DeltaH(o) = -7.2 +/- 0.1 kcal/mol, DeltaS(o) = -0.25 eu). Variable temperature (1)H NMR studies, assisted with 2D COSY and ROESY investigations, revealed the existence of Cu(I)-folded basket 10b with a molecule of acetonitrile occupying its interior and coordinated to the metal. Interestingly, 10b is in equilibrium with Cu(I)-folded 10a , whose inner space is solvated by acetone or chloroform. The incorporation of a molecule of acetonitrile inside 10a was found to be driven by enthalpy (DeltaH(o) = -3.3 +/- 0.1 kcal/mol), with an apparent loss in entropy (DeltaS(o) = -9.4 +/- 0.4 eu); this is congruent with a complete immobilization of acetonitrile and release of a "loosely" encapsulated solvent molecule during 10a/b interconversion. From an Eyring plot, the activation enthalpy for incorporating acetonitrile into 10a was found to be positive (DeltaH(double dagger) = 6.5 +/- 0.5 kcal/mol), while the activation entropy was negative (DeltaS(double dagger) = -20 +/- 2 eu). The results are in agreement with an exchange mechanism whereby acetonitrile "slips" into an "empty" basket through its side aperture. In fact, DFT (BP86) calculations are in favor of such a mechanistic scenario; the calculations suggest that opening of the basket's rim to exchange guests is energetically demanding and therefore less feasible.     

Tuning of redox properties of iron and iron oxides via encapsulation within carbon nanotubes

We report the tuning of the redox properties of iron and iron oxide nanoparticles by encapsulation within carbon nanotubes (CNTs) with varying inner diameters. Raman spectroscopy was employed to investigate the interaction of the encapsulated nanoparticles with the CNTs. A red shift of the Fe-O mode is observed in the nanoparticles deposited on the outer CNT surfaces with respect to bulk Fe2O3. However, this mode is found to be stepwise blue-shifted with decreasing inner diameter in the CNT-encapsulated Fe2O3 nanoparticles, suggesting an enhanced interaction of Fe2O3 with the inner CNT surface as its curvature increases. The autoreduction of the encapsulated Fe2O3 is significantly facilitated inside CNTs with respect to the outside nanoparticles. Interestingly, it becomes more facile with decreasing CNT channel diameter as evidenced by temperature programmed reaction, in situ XRD, and Raman spectroscopy. The oxidation of encapsulated metallic Fe nanoparticles on the other hand is retarded in comparison to that of the outside Fe particles as shown by in situ XRD and gravimetrical measurements with an online microbalance. We attribute this tunable redox behavior of transition metal nanoparticles inside CNTs to a particular electronic interaction of the encapsulates with the interior CNT surface, which stabilizes the metallic state of Fe.     

Supramolecular enantiodifferentiating photoisomerization of cyclooctene with modified beta-cyclodextrins: critical control by a host structure

Enantiodifferentiating photoisomerization of (Z)-cyclooctene included and sensitized by m-methoxybenzoyl-beta-cyclodextrin gave chiral (E)-isomers in up to 46% enantiomeric excess, which is the highest value ever reported for supramolecular photochirogenesis with analogous hosts, thus demonstrating the crucial role of the sensitizer-spacer moiety in supramolecular photochirogenic systems.     

The precise editing of surface sites on a molecular-like gold catalyst for modulating regioselectivity

It is extremely difficult to precisely edit a surface site on a typical nanoparticle catalyst without changing other parts of the catalyst. This precludes a full understanding of which site primarily determines the catalytic properties. Here, we couple experimental data collection with theoretical analysis to correlate rich structural information relating to atomically precise gold clusters with the catalytic performance for the click reaction of phenylacetylene and benzyl azide. We also identify a specific surface site that is capable of achieving high regioselectivity. We further conduct site-specific editing on a thiolate-protected gold cluster by peeling off two monomeric RS–Au–SR motifs and replacing them with two Ph₂P–CH₂–PPh₂ staples. We demonstrate that the surface Au–Ph₂P–CH₂–PPh₂–Au motifs enable extraordinary regioselectivity for the click reaction of alkyne and azide. The editing strategy for the surface motifs allows us to exploit previously inaccessible individual active sites and elucidate which site can explicitly govern the reaction outcome.

Editing surface motifs on gold cluster catalysts achieves high regioselectivity for the click reactions of azides and alkynes.     

Chemical reactivity of D3h C78 (metallo)fullerene: regioselectivity changes induced by Sc3N encapsulation

We report here for the first time a full comparison of the exohedral reactivity of a given fullerene and its parent trinitride template endohedral metallofullerene. In particular, we study the thermodynamics and kinetics for the Diels-Alder [4 + 2] cycloaddition between 1,3-butadiene and free D3h'-C78 fullerene and between butadiene and the corresponding endohedral D3h-Sc3N@C78 derivative. The reaction is studied for all nonequivalent bonds, in both the free and the endohedral fullerenes, at the BP86/TZP//BP86/DZP level. The change in exohedral reactivity and regioselectivity when a metal cluster is encapsulated inside the cage is profound. Consequently, the Diels-Alder reaction over the free fullerene and the endohedral derivative leads to totally different cycloadducts. This is caused by the metal nitride situated inside the fullerene cage that reduces the reactivity of the free fullerene and favors the reaction over different bonds.     

New free-radical halogenations of alkanes, catalysed by N-hydroxyphthalimide. Polar and enthalpic effects on the chemo- and regioselectivity

Reactions of alkanes with different halogenating systems are compared in order to explore the reactivity of phthalimido-N-oxyl radical in hydrogen abstraction; the importance of polar effects is emphasised.     

Accelerating the insertion reactions of (NHC)Cu–H via remote ligand functionalization

Most ligand designs for reactions catalyzed by (NHC)Cu–H (NHC = N-heterocyclic carbene ligand) have focused on introducing steric bulk near the Cu center. Here, we evaluate the effect of remote ligand modification in a series of [(NHC)CuH]₂ in which the para substituent (R) on the N-aryl groups of the NHC is Me, Et, ^tBu, OMe or Cl. Although the R group is distant (6 bonds away) from the reactive Cu center, the complexes have different spectroscopic signatures. Kinetics studies of the insertion of ketone, aldimine, alkyne, and unactivated α-olefin substrates reveal that Cu–H complexes with bulky or electron-rich R groups undergo faster substrate insertion. The predominant cause of this phenomenon is destabilization of the [(NHC)CuH]₂ dimer relative to the (NHC)Cu–H monomer, resulting in faster formation of Cu–H monomer. These findings indicate that remote functionalization of NHCs is a compelling strategy for accelerating the rate of substrate insertion with Cu–H species.

Remote modification of an N-heterocyclic carbene ligand with bulky or electron-rich groups in [(NHC)Cu(μ-H)]₂ increases the rate of substrate insertion, which kinetics studies suggest arises from changes in the Cu–H monomer–dimer equilibrium.