Vanesa Marcos

A switchable [2]rotaxane asymmetric organocatalyst that utilizes an acyclic chiral secondary amine.

A rotaxane-based switchable asymmetric organocatalyst has been synthesized in which the change of the position of the macrocycle reveals or conceals an acyclic, yet still highly effective, chiral organocatalytic group. This allows control over both the rate and stereochemical outcome of a catalyzed asymmetric Michael addition.

Allosteric initiation and regulation of catalysis with a molecular knot

Catalysis gets all tied up in knots Over the past decade, chemists have used metal ion templating to prepare a wide variety of knotted molecular strands. Marcos et al. now show that one such pentafoil knot can be applied to catalysis. When held taut by zinc ions, the knot can capture a chloride or bromide ion from a halocarbon, thereby unleashing the reactivity of the residual cation for applications such as Lewis acid catalysis. Removing the zinc ions lowers the knots affinity for the halides, offering a reversible modulation mechanism for the catalysis. Science, this issue p. 1555 Molecular knots, held taut by zinc ions, can capture bromide by cleavage of carbon-bromine bonds and thereby promote catalysis. Molecular knots occur in DNA, proteins, and other macromolecules. However, the benefits that can potentially arise from tying molecules in knots are, for the most part, unclear. Here, we report on a synthetic molecular pentafoil knot that allosterically initiates or regulates catalyzed chemical reactions by controlling the in situ generation of a carbocation formed through the knot-promoted cleavage of a carbon-halogen bond. The knot architecture is crucial to this function because it restricts the conformations that the molecular chain can adopt and prevents the formation of catalytically inactive species upon metal ion binding. Unknotted analogs are not catalytically active. Our results suggest that knotting molecules may be a useful strategy for reducing the degrees of freedom of flexible chains, enabling them to adopt what are otherwise thermodynamically inaccessible functional conformations.

Exploring the Activation Modes of a Rotaxane-Based Switchable Organocatalyst

The reactivity of a rotaxane that acts as an aminocatalyst for the functionalization of carbonyl compounds through HOMO and LUMO activation pathways has been studied. Its catalytic activity is explored for C-C and C-S bond forming reactions through iminium catalysis, in nucleophilic substitutions and additions through enamine intermediates, in Diels-Alder reactions via trienamine catalysis, and in a tandem iminium-ion/enamine reaction. The catalyst can be switched on or off, effectively controlling the rate of all of these chemical transformations, by the in situ change of the position of the macrocycle between two different binding sites on the rotaxane thread.

Enantioselective Cycloaddition of Münchnones onto [60]Fullerene: Organocatalysis versus Metal Catalysis

Novel chiral catalytic systems based on both organic compounds and metal salts have been developed for the enantioselective [3 + 2] cycloaddition of münchnones onto fullerenes and olefins. These two different approaches proved to be efficient and complementary in the synthesis of optically active pyrrolino[3,4:1,2][60]fullerenes with high levels of enantiomeric excess and moderate to good conversions. Further functionalization of the pyrrolinofullerene carboxylic acid derivatives has been carried out by esterification and amidation reactions.

Old tricks, new dogs: organocatalytic dienamine activation of α,β-unsaturated aldehydes

Here we outline and discuss the state-of-the-art in organocatalytic dienamine activation of enals, classifying examples according to different reactive activation pathways.

Switching Between Anion-Binding Catalysis and Aminocatalysis with a Rotaxane Dual-Function Catalyst

The off state for aminocatalysis by a switchable [2]rotaxane is shown to correspond to an on state for anion-binding catalysis. Conversely, the aminocatalysis on state of the dual-function rotaxane is inactive in anion-binding catalysis. Switching between the different states is achieved through the stimuli-induced change of position of the macrocycle on the rotaxane thread. The anion-binding catalysis results from a pair of triazolium groups that act together to CH-hydrogen-bond to halide anions when the macrocycle is located on an alternative (ammonium) binding site, stabilizing the in situ generation of benzhydryl cation and oxonium ion intermediates from activated alkyl halides. The aminocatalysis and anion-binding catalysis sites of the dual-function rotaxane catalyst can be sequentially concealed or revealed, enabling catalysis of both steps of a tandem reaction process.

Pyridyl-Acyl Hydrazone Rotaxanes and Molecular Shuttles

We report on rotaxanes featuring a pyridyl-acyl hydrazone moiety on the axle as a photo/thermal-switchable macrocycle binding site. The pyridyl-acyl E-hydrazone acts as a hydrogen bonding template that directs the assembly of a benzylic amide macrocycle around the axle to form [2]rotaxanes in up to 85% yield; the corresponding Z-hydrazone thread affords no rotaxane under similar conditions. However, the E-rotaxane can be smoothly converted into the Z-rotaxane in 98% yield under UV irradiation. The X-ray crystal structures of the E- and Z-rotaxanes show different intercomponent hydrogen bonding patterns. In molecular shuttles containing pyridyl-acyl hydrazone and succinic amide ester binding sites, the change of position of the macrocycle on the thread can be achieved through a series of light irradiation and heating cycles with excellent positional integrity (>95%) and switching fidelity (98%) in each state.

Molecular Machines with Bio-Inspired Mechanisms

The widespread use of molecular-level motion in key natural processes suggests that great rewards could come from bridging the gap between the present generation of synthetic molecular machines—which by and large function as switches—and the machines of the macroscopic world, which utilize the synchronized behavior of integrated components to perform more sophisticated tasks than is possible with any individual switch. Should we try to make molecular machines of greater complexity by trying to mimic machines from the macroscopic world or instead apply unfamiliar (and no doubt have to discover or invent currently unknown) mechanisms utilized by biological machines? Here we try to answer that question by exploring some of the advances made to date using bio-inspired machine mechanisms.