Raul-Angel Orenes

Azodicarboxamides as template binding motifs for the building of hydrogen-bonded molecular shuttles.

Azodicarboxamides (R(2)NCON=NCONR(2)) are shown to act as new templates for the assembly of unprecedented azo-functionalized hydrogen-bond-assembled [2]rotaxanes. Moreover, these binding sites can be reversibly and efficiently interconverted with their hydrazo forms through a hydrogenation-dehydrogenation strategy of the nitrogen-nitrogen bond. This novel chemically switchable control element has been implemented in stimuli-responsive molecular shuttles that work through a reversible azo/hydrazo interconversion, producing large amplitude net positional changes with a good discrimination between the binding sites of the macrocycle in both states of the shuttle. These molecular shuttles are able to operate by two different mechanisms: in a discrete mode through two reversible and independent chemical events and, importantly, in a continuous regime through a catalyzed ester bond formation reaction in which the shuttle acts as an organocatalyst. In this latter, the incorporation of both states of the shuttle into this simple chemical reaction network promotes a dynamic translocation of the macrocycle between two nitrogen and carbon-based stations of the thread allowing an energetically uphill esterification process to take place.

Insertion of Benzynes into the P═N Bond of P-Alkenyl(alkynyl)-λ5-phosphazenes

Benzynes, generated from 2-(trimethylsilyl)phenyl triflates, have been found to react with P-Alkenyl-λ(5)-phosphazenes via a formal π-insertion into the P═N bond. A subsequent retro [2 + 2] cycloaddition/6π electrocyclization/protonation cascade explains the formation of the resulting 1,4-benzazaphosphorinium triflates. P-Alkynyl λ(5)-phosphazenes and phosphane sulfides undergo similar transformations.

[4 + 2] Cycloaddition Reaction of C-Aryl Ketenimines with PTAD as a Synthetic Equivalent of Dinitrogen. Synthesis of Triazolocinnolines and Cinnolines

C,C,N-Triaryl ketenimines and C-alkyl-C,N-diaryl ketenimines react with 2 equiv of PTAD to provide 1,2,4-triazolo[1,2-a]cinnolines with a pendant triazolidindione group by means of a Diels-Alder/ene sequence. The treatment of such adducts with potassium hydroxide affords 3-aminocinnolines.

Small-molecule recognition for controlling molecular motion in hydrogen-bond-assembled rotaxanes.

Di(acylamino)pyridines successfully template the formation of hydrogen-bonded rotaxanes through five-component clipping reactions. A solid-state study showed the participation of the pyridine nitrogen atom in the stabilization of the mechanical bond between the thread and the benzylic amide macrocycle. The addition of external complementary binders to a series of interlocked bis(2,6-di(acylamino)pyridines) promoted restraint of the back and forward ring motion. The original translation can be restored through a competitive recognition event by the addition of a preorganized bis(di(acylamino)pyridine) that forms stronger ADA-DAD complexes with the external binders.

Highly diastereoselective self-assembly of chiral tris(m-ureidobenzyl)amino capsules

The self-assembly of chiral tris(m-ureidobenzyl)amines to give dimeric capsules is a highly diastereoselective process in solution, while in the solid state, the formation of the corresponding capsules is not only diastereoselective but also regioselective.

Dampened circumrotation by CH···π interactions in hydrogen bonded [2]rotaxanes.

Establishment of CH···π interactions between the aliphatic axis and the benzylic amide macrocycle of hydrogen-bonded [2]rotaxanes causes a measurable interference in the pirouetting submolecular motion of these interlocked molecules.

New Applications of the Imine-Ketenimine Intramolecular [2+2] Cycloaddition Reaction: Highly Stereocontrolled Synthesis of Azeto[1,2-a]pyrimidines

Imino-ketenimines 7, in which the reactive functionalities are linked by an allylic tether connecting the imino and ketenimino nitrogen atoms, undergo a formal intramolecular [2+2] cycloaddition to yield azeto[1,2-a]pyrimidines 8. When enantiotopic ketenimine and imine fragments are combined, the resulting azeto[1,2-a]pyrimidines 8e−i contain two stereogenic carbon atoms C-6 and C-7, and the cycloaddition takes place with complete diastereoselectivity in favor of the cis diastereoisomers. This methodology has also been applied to the preparation of some azeto[1,2-a][1,3]thiazolo[4,5-d]pyrimidines 16, representative examples of a new fused heterocyclic system. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2002)

Palladium complexes derived from N,N-bidentate NH-iminophosphorane ligands: synthesis and use as catalysts in the Sonogashira reaction

The addition of primary amines to the C=C bond of diphenylalkenyl iminophosphoranes yielded a new subtype of N,N-bidentate ligands bearing N=P(V)-C-C-NH backbones. These donor ligands reacted with PdCl(2)(COD) to give the corresponding σN,σN-palladium complexes containing secondary amino groups, bearing an intrinsically chiral nitrogen atom, and iminophosphorane units. These new complexes have been fully characterized by the use of spectroscopic techniques and X-ray crystallography. The comparison of the data extracted from their solution NMR spectra with their solid state structures demonstrated the conformational stability of their six-membered chelate ring and also the configurational stability of the chiral nitrogen atom, thus ruling out an arm-off racemization process. The addition of the chiral, racemic α-methylbenzylamine to the prochiral P-alkenyl iminophosphoranes yielded mixtures of the two expected diasteroisomeric ligands in low diastereoisomeric ratios. One of these mixtures was resolved into their components, each one in turn giving rise to a pair of diasteromeric palladium complexes epimeric at the amino nitrogen atom. One selected example of the new complexes efficiently catalyzes the copper- and amine-free Sonogashira reaction of aryl halides with acetylenes.

Lewis acid catalyzed [3 + 2] annulation of ketenimines with donor–acceptor cyclopropanes: an approach to 2-alkylidenepyrrolidine derivatives

The [3 + 2] annulation reaction of C,C,N-trisubstituted ketenimines with donor-acceptor cyclopropanes bearing aryl, styryl and vinyl substituents at the C2 position, triggered by the Lewis acid Sc(OTf)3, supplies highly substituted pyrrolidines. Activated cyclopropanes fused to naphthalene and [1]benzopyrane nuclei are also suitable substrates in similar transformations, yielding partially saturated benz[g]indoles and [1]benzopyran[4,3-b]pyrroles. An intramolecular version of this ketenimine/cyclopropane [3 + 2] annulation has also been developed leading to the pyrrolo[2,1-a]isoindole framework.

Novel Capsular Aggregates from Flexible Tripodal Triureas with Cs Symmetry

Tris(2- and 3-ureidobenzyl)amines with C(s) symmetry self-assemble in solution forming mixtures of regioisomeric capsular aggregates, one of which is chiral and the other centrosymmetric. Under certain conditions, a predominance of the centrosymmetric regioisomer is found before equilibrium, that is, a mixture close to the statistical ratio of the two species is reached. In the solid state, there is a preference for the centrosymmetric capsules. Molecular models of both regioisomeric aggregates have been built and analyzed for comparison. Guests inside capsules formed by self-assembly of desymmetrized tris(3-ureidobenzyl)amines feel different magnetic environments, depending on whether they are inside a chiral or an achiral regioisomeric container. Of special significance are the experiments with a more flexible triurea endowed with an ureidopropylic arm, which self-assembles with the same efficiency as the more rigid tris(ureidobenzyl)amines.