Spontaneous emergence of enantioenriched chiral aldol reaction products from Achiral precursors in solution and origin of biological homochirality of sugars: a first-principles study.

Experimental reports about observation of spontaneous mirror symmetry breaking and chiral amplification in stereoselective Mannich and aldol reactions, run under fully achiral initial conditions, have drawn a lot of attention, fuelled partly by the role these reactions could have played in chemical evolution as a cause for still puzzling observed homochirality of biomolecules, often considered a prerequisite for the origin of life. We have now revisited this still unresolved problem, using DFT computation of all combinatorially possible transition states and numerical solution of complete set of resulting coupled kinetic rate equations to model the aldol reaction rigorously "from the first principles" and without making any assumptions. Spontaneous mirror symmetry breaking in this autocatalytic, reversible, closed and homogenous system is explained by a supercritical pitchfork bifurcation, occurring in concentrations of enantiomers due to time-delayed kinetic instability of racemic composition of reaction mixture, when reactants are initially provided in non-stoichiometric quantities.

Disclosure of Ground-State Zimmerman-Möbius Aromaticity in the Radical Anion of [6]Helicene and Evidence for 4π Periodic Aromatic Ring Currents in a Molecular "Metallic" Möbius Strip.

In 1966, Zimmerman proposed a type of Möbius aromaticity that involves through-space electron delocalization; it has since been widely applied to explain reactivity in pericyclic reactions, but is considered to be limited to transition-state structures. Although the easily accessible hexahelicene radical anion has been known for more than half a century, it was overlooked that it exhibits a ground-state minimum and robust Zimmerman-Möbius aromaticity in its central noose-like opening, becoming, hence, the oldest existing Möbius aromatic system and with smallest Möbius cycle known. Despite its overall aromatic stabilization energy of 13.

Speeding up Viedma Deracemization through Water-catalyzed and Reactant Self-catalyzed Racemization.

Viedma deracemization is based on solution phase racemization, dissolution of racemic or scalemic conglomerates and crystal growth through autocatalytic cluster formation. With rate limiting racemization, its acceleration by appropriate catalysts may result in speeding up deracemization. A conglomerate-forming chiral compound may principally racemize directly, or via reverse of its formation reaction.

Hückel and Möbius Aromaticity in Charged Sigma Complexes.

In sigma complexes, intermediates in nucleophilic and electrophilic aromatic substitution and other reactions, delocalization in the aromatic ring is formally disrupted. Unexpectedly, computational evidence is presented that favorable processes contain aromatic sigma complexes. Tetracoordinated carbon therein surprisingly employs orbitals that are more similar to sp than to sp hybrids in sigma bonds with adjacent ring atoms.

Spin-paired solvated electron couples in alkali-ammonia systems.

Alkali metals form deep blue solutions of solvated electrons in liquid ammonia. To explain the diamagnetism of more concentrated solutions, DFT and ab initio computations have been used to show that spin-paired couples of electrons can overcome Coulomb repulsion, occupying a cavity formed by solvent molecules, comparable in size to that of single solvated electrons. Sluggish hydrogen evolution from the solutions is rationalized by a high activation barrier for reaction of the electron pair with an ammonia molecule.

Strict Correlation of HOMO Topology and Magnetic Aromaticity Indices in d-Block Metalloaromatics.

Magnetic aromaticity and antiaromaticity of closed shell metalloaromatics with 4d transition metals (Nb, Tc, Rh) is strictly correlated with the orbital topology (Möbius or Hückel) of their π-HOMO, investigated computationally with DFT methods. A surprisingly simple rule emerged: the metallacycle is aromatic (antiaromatic) when the number of π MOs is even and the π-HOMO is of Möbius (Hückel) topology-and vice versa when the number of π MOs is odd.

Iron-Catalyzed Olefin Metathesis with Low-Valent Iron Alkylidenes.

Inspired by recent reports of low-valent iron-complex-catalyzed formal [2+2] cycloaddition of olefins, we demonstrate computationally that with such low-valent iron complexes and with "strong" ligands, the olefin metathesis is also preferred over the undesired cyclopropanation side-reaction, competition already studied by Hoffmann and co-workers almost 40 years ago (J. Am. Chem.

4N electron aromatic cycles in polycyclic hydrocarbons.

Polycyclic fully conjugated hydrocarbons in which aromatics are fused to aromatics - or aromatics to antiaromatics - are important as potential organic semiconductors. Herein we explore the only remaining fusion pattern of antiaromatics to antiaromatics. It is shown computationally that the central antiaromatic unit (cyclobutadiene or pentalene) in such a three-unit polycyclic hydrocarbon, generated by fusion of three antiaromatic molecules, turns aromatic according to magnetic shielding (NICS) criteria.

A new architecture for high spin organics based on Baird's rule of 4n electron triplet aromatics.

Due to the absence of open subshells (unlike transition metal compounds), stable high spin organic molecules are rare and are mostly limited to states of low multiplicity. As an alternative to high multiplicity polyradicals and polycarbenes, with their small energetic separation of different spin isomers, it is demonstrated that Baird's rule of 4n electron aromaticity in the triplet electronic state allows, in principle, the design of polycyclic high spin organics with high spin multiplicity in the electronic ground state and a large energetic separation for other spin states. Energy spacing between spin isomers is dictated here by the aromaticity or antiaromaticity of individual cycles (taking into account all π electrons), rather than by a spin Hamiltonian alone (accounting only for unpaired spin electrons).

Duality of Orbital-Symmetry-Allowed Transition States for Thermal Sigmatropic Hydrogen Shifts in Transition Metal Compounds.

Herein, the Zimmerman Möbius/Hückel concept is extended to pericyclic reactions involving transition metals. While sigmatropic hydrogen shifts in parent hydrocarbons are either uniquely antarafacial or suprafacial, we have shown by theoretical orbital topology considerations and quantum chemical computations at DFT level that both modes of stereoselectivity must become allowed in the same system as a consequence of Craig-Möbius-type orbital arrays, in which a transition metal d orbital induces a phase dislocation in metallacycles. This may have fundamental implications for the understanding of reactivity and bonding in organometallic chemistry.

Reversal of Orbital Symmetry Control in Electrocyclic Ring Closures through Craig-Möbius Aromaticity.

Experimentalists are challenged to find the organometallic thermal electrocyclizations that are computationally predicted to proceed with opposite stereoselectivity compared to their metal-free parent 4n and 4n+2 π-electron systems. While ring closure of, for example, s-cis-butadiene proceeds conrotatory, an iron alkyl complex formed by replacement of a (CH) unit by an [FeH] metal fragment results in a disrotatory electrocyclization.

Demonstration of "Möbius" aromaticity in planar metallacycles.

Möbius aromaticity, predicted by Edgar Heilbronner in 1964, is a stabilizing effect exhibited by 4n electron fully conjugated cyclic molecules (or transition states) with an odd number of orbital phase inversions. Although it has previously been suggested that this effect might also apply to planar metallacycles in which a transition metal employs a d orbital in delta-type binding mode, only very few examples of stable twisted molecules composed of main group elements are known. We report herein, the first computationally confirmed 4npi aromatic planar metallacyclic examples and their building principles.

Spontaneous mirror symmetry breaking in the aldol reaction and its potential relevance in prebiotic chemistry.

The origin of the single chirality of most biomolecules is still a great puzzle. Carbohydrates could form in the formose reaction, which is proposed to be autocatalytic and contains aldol reaction steps. Based on our earlier observation of organoautocatalysis and spontaneous enantioenrichment in absence of deliberate chiral influences in the aldol reaction of acetone and p-nitrobenzaldehyde we suggest that a similar effect might be present also in the aldol reactions involved in gluconeogenesis.

Autocatalytic enantiomerisation at the crystal surface in deracemisation of scalemic conglomerates.

Deracemisation of racemic or scalemic conglomerates of intrinsically chiral compounds appears to be a promising method of chiral resolution. By combining the established methods of asymmetric synthesis and the physical process of crystal growth, we were able to achieve a complete deracemisation (with 100% ee) of an asymmetric Mannich product conglomerate--vigorously stirred in its saturated solution--from a starting enantiomeric excess value of 15.8% in the presence of pyrrolidine (8 mol %) as an achiral catalyst for the CC bond-forming reaction.

The effect of perfluorination on the aromaticity of benzene and heterocyclic six-membered rings.

Despite having six highly electronegative F's, perfluorobenzene C(6)F(6) is as aromatic as benzene. Ab initio block-localized wave function (BLW) computations reveal that both C(6)F(6) and benzene have essentially the same extra cyclic resonance energies (ECREs). Localized molecular orbital (LMO)-nucleus-independent chemical shifts (NICS) grids demonstrates that the F's induce only local paratropic contributions that are not related to aromaticity.

A preferred disrotatory 4n electron Möbius aromatic transition state for a thermal electrocyclic reaction.

Not forbidden: Thermal 4n electron electrocyclic reactions of Hückel topology structures proceed via "allowed" conrotatory pathways. However, for a Möbius topology, the Woodward-Hoffmann rules may be reversed and a "forbidden" disrotatory pathway can be preferred as shown theoretically for dodecahexaene 1 that transforms via a Heilbronner-Möbius aromatic transition structure 2 into a cyclic polyene 3.

Spontaneous emergence of homochirality via coherently coupled antagonistic and reversible reaction cycles.

Asymmetric synthesis aims at obtaining enantio-enriched products in stereoselective reactions under a chiral influence. We demonstrate both mathematically and numerically that, even under nominally achiral conditions, fully homochiral steady states can be obtained in open reactive systems by spontaneous mirror-symmetry breaking in the homogenous solution phase when the autocatalytic reaction network is closed in the form of coherently coupled antagonistic reversible reaction cycles which, paradoxically, allow for complete recycling of the reactant. We show that the fully reversible Frank mechanism for spontaneous mirror-symmetry breaking is closely related to the Lotka-Volterra system, which models predator-prey relations in ecosystems.

Demonstration of spontaneous chiral symmetry breaking in asymmetric Mannich and Aldol reactions.

Spontaneous symmetry breaking in reactive systems, known as a rare physical phenomenon and for the Soai autocatalytic irreversible reaction, might in principle also occur in other, more common asymmetric reactions when the chiral product is capable to promote its formation and an element of "nonlinearity" is involved in the reaction scheme. Such phenomena are long sought after in chemistry as a possible explanation for the biological homochirality of biomolecules. We have investigated homogeneous organic stereoselective Mannich and Aldol reactions, in which the product is capable to form H-bridged complexes with the prochiral educt, and found by applying NMR spectroscopy, HPLC analysis, and optical rotation measurements 0.

Investigation of a putative mobius aromatic hydrocarbon. The effect of benzannelation on mobius [4n]annulene aromaticity.

The first experimental example of a [4n]annulene derivative with one Mobius twist, 1, was synthesized recently [Ajami, D.; Oeckler, O.; Simon, A.

Aromaticity with a twist: Möbius [4n]annulenes.

Aromatic Möbius [4n]annulenes with 4n pi electrons, originally conceived by Heilbronner, are characterized computationally. These (CH)(12), (CH)(16), and (CH)(20) minima have nearly equal C-C bond lengths, small twist angles around the rings, and magnetic properties (NICS, nucleus-independent chemical shifts--see above at various positions in [16]annulene--and magnetic susceptibility exaltations) indicating significantly diatropic ring currents. The Möbius forms are not the most stable isomers but may contribute significantly to the chemistry of these annulenes.

Metal-mediated reactions modeled after nature.

The Collaborative Research Center (CRC) 436 'Metal-Mediated Reactions Modeled after Nature' was founded for the express purpose of analyzing the catalytic principles of metallo-enzymes in order to construct efficient catalysts on a chemical basis. The structure of the active center and neighboring chemical environment in enzymes serves as a focal point for developing reactivity models for the chemical redesign of catalysts. Instead of simply copying enzyme construction, we strive to achieve new chemical intuition based on the results of long-lasting natural evolution.