DOI: 10.1016/j.comptc.2016.06.020

Structure, binding energy and chiral discrimination in oxathiirane homodimers

Oxathiirane (XHCSO) homodimers bonded by hydrogen bonds (HB) and chalcogen bonds (YB) were studied at the Møller-Plesset (MP2) computational level. Binding energies obtained at the Coupled-Cluster level up to the Complete Basis Set limit [CCSD(T)/CBS] indicate that HB complexes present stronger binding modes than the YB complexes. In terms of chiral discrimination energy, R,S complexes are favored over R,Rcomplexes with the exceptions of SiCl₃ and SiF₃ derivatives. Natural Bond Orbital (NBO) results are in agreement with the interaction energies in the case of the HB complexes, but could not discriminate between R,R and R,S in the YB complexes. The lack of correlation between molecular electrostatic values on the 0.001 a.u. and binding energies, in addition to the discrepancies between Atoms in Molecules (AIM) and NBO results may suggest that the electrostatics is not the dominant term in the interaction energy. This was corroborated by the Localized Molecular Orbital Energy Decomposition Analysis (LMOEDA) calculations which showed that the exchange and dispersion terms are the most important attractive components for all the complexes studied, contributing up to 50.6% and 42.5% to the total attractive forces respectively.

DOI: 10.1007/s11224-015-0607-7

Researchgate

Essential versus accidental isochrony of diastereotopic nuclei in NMR spectroscopy

Compounds where a non-stereogenic sp 2 atom (for instance the C atom of a benzene ring) is linked to a stereogenic sp 3 atom (for instance CHFCl) have several conformations where two diastereotopic nuclei become isochronous. This also happens in some cases when the sp 3 atom is non-stereogenic, the difference being related to the weighted value of the difference of absolute shieldings. The results here described seem to be in contradiction with experimental results pointing out that all diastereotopic nuclei are anisochronous. Two examples of typical diastereotopic nuclei involving C(sp 3)–C(sp 3) bonds, a propane and an ethane, were also discussed.

DOI: 10.1002/anie.201412144

Observation of Diastereotopic Signals in 15N NMR Spectroscopy

The first example in the literature of a compound showing anisochronous ¹⁵N atoms resulting from diastereotopicity is described. Racemic 1,3-dimethyl-2-phenyloctahydro-1H-benzimidazole was prepared and studied by ¹H, ¹³C and ¹⁵N NMR spectroscopy. If convenient conditions were used (monitored by theoretical calculations of ²J_N-H spin–spin coupling constants), two ¹⁵N NMR signals were observed and corresponded to the diastereotopic atoms. GIAO/density-functional calculations of chemical shifts were not only in good agreement with the experimental values but also served as prediction tools. This study suggests that ¹⁵N NMR spectroscopy could be used to probe chirality.

DOI: 10.1002/chem.201402686

Static and Dynamic Properties of 1,1’-Bi-2-naphthol and Its Conjugated Acids and Bases

Several convergent techniques were used to characterize 1,1′-bi-2-naphthol (BINOL) and some of its properties. Its acidity in the gas-phase, from neutral species to monoanion, was measured by mass spectrometry. The conformation and structure of BINOL in the gas phase was determined by microwave rotational spectroscopy. NMR experiments in fluorosulfonic acid established that BINOL was monoprotonated on one of the hydroxyl oxygen atoms. The enantiomerization barriers reported in the literature for BINOL under neutral, basic, and acid conditions were analyzed with regard to the species involved. Finally, DFT calculations allowed all of these results to be gathered in a coherent picture of the BINOL structure.

DOI:  10.1016/j.tet.2014.09.018

A theoretical and experimental study of the racemization process of hexaaza[5]helicenes

A dynamic ¹H NMR study, together with DFT calculations, of bis-([1,2,3]triazolo)[1,5-a:5′,1′-k][1,10]phenanthroline 2 has allowed to identify the ring and open forms of a new example of ring/chain tautomerism, as well as their interconversion barriers (ring/ring and ring/open). The barrier of the exchange process between the chain forms and the ring form was found higher than the ‘racemization’ process in the closed form, so the ring opening does not contribute to the ‘racemization’. The di-1,10-methyl and di-1,10-iodo derivatives have been prepared and their properties calculated.shifts, ¹H–¹H coupling constants and electronic spectra reduced the 20 possible structures to only one, the 3,3′-Z,Z-anti-azopyrazole.

DOI: 10.1080/00268976.2013.851420

On the transferability of atomic contributions to the optical rotatory power of hydrogen peroxide, methyl hydroperoxide and dimethyl peroxide

The chirality of molecules expresses itself, for example, in the fact that a solution of a chiral molecule rotates the plane of linear polarised light. The underlying molecular property is the optical rotatory power (ORP) tensor, which according to time-dependent perturbation theory can be calculated as mixed linear response functions of the electric and magnetic dipole moment operators. Applying a canonical transformation of the Hamiltonian, which reformulates the magnetic dipole moment operator in terms of the operator for the torque acting on the electrons, the ORP of a molecule can be partitioned into atomic and group contributions. In the present work, we investigate the transferability of such individual contributions in a series of small, chiral molecules: hydrogen peroxide, methyl hydroperoxide and dimethyl peroxide. The isotropic atomic or group contributions have been evaluated for the hydrogen, oxygen and carbon atoms as well as for the methyl group at the level of time-dependent density functional theory with the B3LYP exchange-correlation functional employing a large Gaussian basis set. We find that the atomic or group contributions are not transferable among these three molecules.

DOI: 10.1016/j.tetasy.2014.02.015

Chiral self-assembly of enantiomerically pure (4S,7R)-campho[2,3-c]pyrazole in the solid state: a vibrational circular dichroism (VCD) and computational study

NH-Indazoles in solid phase usually form N-H⋯N hydrogen bonds between positions 1 and 2, which determine the secondary structure, forming dimers, trimers, or catemers (chains). Thus, the difficulty of the experimental analysis of the structure of the family of 1H-indazoles is clear. We have outlined a complete strategy by using different techniques of vibrational spectroscopy that are sensitive (VCD) and not sensitive (IR, FarIR, and Raman) to the chirality together with quantum chemical calculations. We have studied the chiral structure of (4S,7R)-campho[2,3-c]pyrazole both in solution (CCl₄) and in the solid phase (crystal). This compound crystallizes as a chiral trimer (LABHEB), with the monomer also being chiral. Herein, Far-IR, IR, and Raman spectra in solution and in the solid state are assigned using the support of B3LYP/6-31G(d) and B97D/6-31+G(d,p) calculations of (4S,7R)-campho[2,3-c]pyrazole monomers, dimers, and trimers, these last cyclamers being partially and fully optimized. Later, analysis of the vibrational circular dichroism (VCD) spectra allowed us to determine the chiral self-assembly of (4S,7R)-campho[2,3-c]pyrazole crystals (LABHEB). In the crystal, only the trimers are present while in solution, the monomer predominates. We have highlighted the importance of the analysis of the low frequency region (700–25 cm⁻¹) in the FT-Raman and Far-IR spectra, because it provides relevant information in order to confirm the presence of the trimers in the solid phase.

DOI: 10.1002/chem.201204197

A Facile Method to Determine the Absolute Structure of Achiral Molecules: Supramolecular-Tilt Structures

Achiral compounds 4-methoxy-4-(p-methoxyphenyl)cyclohexanoneethylene ketal (2), 4-hydroxy-4-(p-methoxy phenyl)cyclohexanoneethylene ketal (3), and 3,5-dimethyl-4-nitropyrazole (4) crystallized in chiral structures and the samples showed an enantiomeric excess. We have determined the absolute structures of these compounds by using X-ray diffraction with copper radiation at low temperatures. Moreover, we have also established the prevalent absolute structures in these samples, by comparing their calculated and solid-state vibrational circular dichroism (VCD) spectra. The consistency of this method was confirmed by using (R,R)-2,8-diiodo-4,10-dimethyl-6 H,12H-5,11-methano-dibenzo[b,f][1,5]diazocine, Tröger′s base, (R,R)-1, as a chiral compound of known absolute configuration.

DOI: 10.1002/poc.3017

A theoretical study of hemiacetal formation from the reaction of methanol with derivatives of CX₃CHO (X = H, F, Cl, Br and I)

A theoretical study of the hemiacetal formation reaction between methanol and CX₃CHO (X = H, F, Cl, Br, and I) has been carried out using density functional theory and Becke, three-parameter, Lee–Yang–Parr/6-311++G(d,p) computational methods. The stationary points of the reaction between the isolated molecules and the reaction catalyzed by an additional methanol molecule have been characterized. Because the final products present a stereogenic center, the potential autocatalysis of the reaction has been examined and also the possibility of spontaneous generation of chirality when the hemiacetal molecules are involved in the transition state structure. High barriers are found in the reaction between the isolated molecules that are reduced by the assistance of an additional molecule (methanol or hemiacetal product). The reactions catalyzed by the hemiacetal products show higher barriers than the one catalyzed by methanol. 

DOI: 10.1016/j.tet.2012.09.061

New C2-symmetry diols accumulating one stereogenic axis and two stereogenic centers

Herein we report a protocol for the enantioselective synthesis of the three stereoisomers of 1,1′-(1,1′-binaphthalene-2,2′-diyl)bis(2,2,2-trifluoroethanol) and their characterization. These compounds, that combine axial and central chirality, might present interesting properties for enantiorecognition. Different reduction processes were applied to racemic and enantiopure 1,1′-(1,1′-binaphthalene-2,2′-diyl)bis(2,2,2-trifluoroethanone) allowing the isolation of the corresponding ketols, 2,2,2-trifluoro-1-[2′-(2,2,2-trifluoro-1-hydroxyethyl)-1,1′-binaphthalen-2-yl]ethanone, and the named diols.

DOI: 10.1016/B978-0-12-396530-1.00001-2

Atropisomerism and Axial Chirality in Heteroaromatic Compounds

The chapter “Atropisomerism and axial chirality in heteroaromatic compounds” provides a summary of the present knowledge of this important topic. The structure of the chapter is: first a detailed description of the methods used to study atropisomerism, from X-ray diffraction to theoretical calculations (14 items), then the application to different compounds according to the nature of the central bond. Rotation about a C–C bond (5–5, 5–6 and 6–6 rings), rotation about a C–N bond (azoles, oxo- and thioxo-five-membered rings, azines), rotation about an N–N bond (5–5, 5–6 and 6–6 rings), rotation about ortho-ortho’-linked compounds, rotation about N-metal bonds, multiple rotations, to end with axial chiral synthesis. In conclusion, a phenomenon that was discovered in 1922 for diphenic acids and that was extended to heterocycles in 1931 by Adams shows eighty years later to be very active, being expected to grow in importance because it is related to asymmetric synthesis, to materials and to biological properties.

DOI: 10.1002/cphc.201100830

Intermolecular Weak Interactions in HTeXH Dimers (X=O, S, Se, Te): Hydrogen Bonds, Chalcogen-Chalcogen Contacts and Chiral Discrimination

A theoretical study of the HTeXH (X=O, S, Se and Te) monomers and homodimers was carried out by means of second-order Møller-Plesset perturbation theory (MP2) computational methods. In the case of monomers, the isomerization energy from HTeXH to H₂Te=X and H₂X=Te (X=O, S, Se, and Te) and the rotational transition-state barriers were obtained. Due to the chiral nature of these compounds, homo and heterochiral dimers were found. The electron density of the complexes was characterized with the atoms-in-molecules (AIM) methodology, finding a large variety of interactions. The charge transfer within the dimers was analyzed by means of natural bond orbitals (NBO). The density functional theory-symmetry adapted perturbation theory (DFT-SAPT) method was used to compute the components of the interaction energies. Hydrogen bonds and chalcogen–chalcogen interactions were characterized and their influence analyzed concerning the stability and chiral discrimination of the dimers.

DOI: 10.1063/1.3632086

Electric field effects on nuclear magnetic shielding of the 1:1 and 2:1 (homo and heterochiral) complexes of XOOX' (X, X' = H, CH3) with lithium cation and their chiral discrimination

The set of 1:1 and 2:1 complexes of XOOX′ (X, X′ = H, CH₃) with lithium cation has been studied to determine if they are suitable candidates for chiral discrimination in an isotropic medium via nuclear magnetic resonance spectroscopy. Conventional nuclear magnetic resonance is unable to distinguish between enantiomers in the absence of a chiral solvent. The criterion for experimental detection is valuated by the isotropic part of nuclear shielding polarisability tensors, related to a pseudoscalar of opposite sign for two enantiomers. The study includes calculations at coupled Hartree-Fock and density functional theory schemes for ¹⁷O nucleus in each compound. Additional calculations for¹H are also included for some compounds. A huge static homogeneous electric field, perpendicular to the magnetic field of the spectromer, as big as ≈1.7 × 10⁸ V m⁻¹ should be applied to observe a shift of ≈1 ppm for ¹⁷O magnetic shielding in the proposed set of complexes.

DOI: 10.1016/j.tetasy.2011.06.010

Rates of enantiomerization in axially chiral 2,2'-bipyridines with restricted rotation: an ab initio study

Herein, we describe our findings concerning a 6,6′-bridged-2,2′-bipyridine derivative whose dynamic properties were described by Rebek and Trend in 1978. While the enantiomerization processes of the neutral molecule, the dication and the Zn complex were correctly described by DFT calculations, those of the monoprotonated cation were in disagreement. This led us to search for possible explanations, which led us to conclude that the experimental barrier corresponds to a N–H⋯O═CMe₂ hydrogen bonded complex between the cation and one solvent molecule.

DOI: 10.1016/j.tetasy.2011.06.003

Determination of the absolute configuration of 1,3,5-triphenyl-4,5-dihydropyrazole enantiomers by a combination of VCD, ECD measurements, and theoretical calculations

The enantiomers of 1,3,5-triphenyl-4,5-dihydropyrazole (an intense blue fluorescent compound) have been separated for the first time and their absolute configuration was established by a combination of VCD and ECD measurements and theoretical calculations. The enantiomers of 1,3,5-triphenyl-4,5-dihydropyrazole which are highly fluorescent both in solution (CH₂Cl₂) and in the solid state may find application in the very active field of enantioselective fluorosensors.

DOI: 10.1021/jp202912n

Theoretical Study of the 1:1 and 2:1 (Homo- and Heterochiral) Complexes of XOOX' (X, X' = H, CH3) with Lithium Cation

A theoretical study of the 1:1 and 2:1 complexes of XOOX′ (X, X′ = H, CH₃) with the lithium cation has been carried out by means of ab initio computational methods up to the MP2/aug-cc-pVTZ level. The optical rotatory power and NMR parameters (absolute chemical shielding and indirect coupling constants) have been calculated. In addition, the racemization barriers within the complexes formed have been evaluated. Special attention has been paid concerning the differences between the 2:1 homo- and heterochiral complexes.

DOI: 10.1002/poc.1686

Chiral recognition in self-complexes of diketopiperazine derivatives

The chiral discrimination in the self-association of 2,5-diketopiperazines derivatives has been studied using density functional theory (DFT) methods. Hence, clusters from dimers to tetramers have been considered. We have found a variety of linear and cyclic structures depending on the geometry of the monomers. In general, the heterochiral dimers (RR:SS or SS:RR) are more stable than the homochiral ones (RR:RR or SS:SS) with slight energetic differences. Nevertheless, most of the larger clusters (trimers and tetramers) show changes in stability, the homochiral cyclic structures being favored due to the better geometry of the hydrogen bond and/or the higher number of interactions. Some interesting correlations between the hydrogen bond geometrical descriptors and theoretical parameters obtained from the Natural Bond Orbital analysis (NBO), Natural energy decomposition analysis (NEDA), and the Atoms in Molecules theory (AIM) have been found. The chiral discrimination in the recognition process of these self-complexes has been evaluated. In addition, evidence of cooperative effects has been observed. 

DOI::10.1139/V09-177

Do corresponding coupling constants in hydrogen-bonded homo- and hetero-chiral dimers differ?

Ab initio equation-of-motion coupled cluster singles and doubles (EOM–CCSD) calculations have been carried out to evaluate spin–spin coupling constants in six pairs of homo- and hetero-chiral dimers: (HOOH)₂, (H₂NNH₂)₂, (FOOH)₂, (FHNNH₂)₂, (HOOOH)₂, and (FOOOH)₂. Corresponding spin–spin coupling constants in these isomeric pairs of C₂ and C_i symmetry may differ, but these differences are small and may not be detectable experimentally. For the complexes with O1–H···O and O1–H···F hydrogen bonds, ¹J(O1–H) has a larger absolute value in the C₂ isomer. For the same set of complexes, ¹J(O1–O2) has a larger absolute value in theC_i isomer. No distinguishable patterns could be discerned in the remaining spin–spin coupling constants in the C₂ and C_i isomers of these complexes, nor in complexes with N–H···N hydrogen bonds.

DOI:10.1016/j.tetasy.2010.05.032

Distinction between homochiral and heterochiral dimers of 1-aza[n]helicenes (n = 1-7) with alkaline cations

A theoretical study of the chiral distinction between the homochiral and heterochiral dimers of the 1-aza[n]helicenes, with n = 1–7, glued with lithium, sodium, and potassium cations has been carried out by means of DFT calculations up to M05-2x/6-311+G(d) computational level. The electronic characteristic of the isolated helicenes has been explored. The chiral distinction is dependent on the size of the helicene and the cation used with the largest values obtained for the 1-aza[6]helicene bound to lithium cation.

DOI: 10.1007/978-90-481-2687-3_3

This review summarizes the literature survey on chiral recognition from a theoretical view point. Nevertheless, experimental results in the gas phase are reported when they are relevant for the theoretical calculations. The review is divided into the following sections: general considerations; experiment vs. theory; pure theoretical results; solvent effects; metals as glue; optical rotatory power; and conclusions.

DOI:10.1007/s11224-009-9463-7

Chiral distinction in square planar Pt and Pd complexes of 2,2'-bipyridine derivatives

A computational study of square planar organometallic complexes formed by the ligand 2,2′-bipyridine and all its possible difluoro derivatives in analogous position of the aromatic rings (n,n′-difluoro-2,2′-bipyridine, where n = n′ = 3, 4, 5, and 6) and two M–X₂ (M = Pd and Pt and X = F, Cl, Br, and I) fragments has been carried out amounting to a total of 80 complexes. Relationships have been found between the chiral distinction energy and the different chemical moieties present. Using the statistical Free-Wilson method, the relative energies between the diastereomeric complexes have been correlated with the position of the substituent, the counter anion, and the central metal cation.

 DOI:10.1135/cccc2008169

Chiral recognition in bicyclic guanidines

A theoretical study of chiral recognition in bicyclic guanidines has been carried out by means of B3LYP/6-31+G(d,p) DFT calculations. A series of complexes between protonated 4,8-dimethyl-1,5,7-triazabicyclodecene (DTBD) and 2,5-disubtituted chiral cyclopentanones have been evaluated for chiral recognition, both in the gas phase and in benzene solution as per the polarizable continuum model (PCM) and analyzed by AIM and NBO methodologies. An inversion in the sense of chiral recognition has been observed between gas phase and solvated results for cyclopentanone complexes. Among the different correlations found (i.e. between electron density, hydrogen bond distance, second-order perturbation energy), a linear correlation has been established between thechiral recognition energy and different molecular parameters.

DOI:10.1063/1.2826351

Atomic partition of the optical rotatory power of methylhydroperoxide

We applied a methodology capable of resolving the optical rotatory power into atomic contributions. The individual atomic contributions to the optical rotatory power and molecular chirality of the methylhydroperoxide are obtained via a canonical transformation of the Hamiltonian by which the electric dipolar moment operator is transformed to the acceleration gauge formalism and the magnetic dipolar moment operator to the torque formalism. The gross atomic isotropic contributions have been evaluated for the carbon, the nonequivalent oxygen, and the nonequivalent hydrogen atoms of methylhydroperoxide, employing a very large Gaussian basis set which is close to theHartree-Fock limit.

DOI: 10.1016/j.tetlet.2007.11.099

From theoretical calculations to the enantioselective synthesis of a 1,3,4-trisubstituted Gly-derived 2-azetidinone

Theoretical calculations on the transition states of the cyclization of 2S-chloropropionyl amino acid derivatives to the corresponding β-lactams have served to explain the high stereoselectivity of the reaction, and have been the driving force to extend the procedure to the preparation of a Gly-derived 1,3,4-trisubstituted 2-azetidinone in enantiopure form.

Doi: 10.1016/j.tetasy.2004.03.021

Chiral discrimination and isomerization processes in monomers, dimers and trimers of sulfoxides and thioperoxides

The chiral discrimination in cyclic dimers and trimers of mono-substituted sulfoxides and thioperoxides has been studied by means of DFT (B3LYP/6-31+G**) and ab initio (MP2/6-311+G**) calculations. In addition, the inter- and intramolecular proton transfer processes that interconvert these two classes of compounds have been considered for the isolated molecules and clusters. The thioperoxide clusters are more stable than the corresponding sulfoxides even though the strongest hydrogen bonds are found in the latter complexes. Correlations have been found between the relative energies of the sulfoxide versus the thioperoxide compounds and the transition state barriers. The geometry of the hydrogen bonds has been analyzed using a Steiner–Limbach relationship.

Doi: 10.1016/j.theochem.2004.04.030

Theoretical study of peptide model dimers. Homo versus heterochiral complexes

The study of possible chiral recognition of a series of peptide models (For-Gly-NH₂, For-Ala-NH₂ and four of their fluoro substituted derivatives) has been carried out by means of DFT calculations. Homo (L,L) and heterochiral (L,D) dimers formed by hydrogen bond (HB) complexation have been considered. Initially, the conformational preferences of the monomers have been calculated and used to generate all the possible homo and heterochiral dimers. The energetic results show that in most cases, the β monomers are the most stable while in the dimers, the γ–γ complexes show the strongest interaction energies. In three of the four chiral cases studied, a heterochiral dimer is the most stable one. In addition, the electron density and nuclear shielding of the complexes have been studied.

Doi: 10.1021/jo035026y

Large Chiral Recognition in Hydrogen-Bonded Complexes and Proton Transfer in Pyrrolo[2,3-b]pyrrole Dimers 

The chiral recognition in the formation of hydrogen-bonded (HB) dimers of 1,6a-dihydropyrrolo[2,3-b]pyrrole derivatives as well as in their proton-transfer processes have been studied by means of ab initio calculations. The heterochiral dimers are in general the most stable ones, but amphiprotic substituents that are able to form attactive interactions with twin groups revert this tendency. Energy differences up to 4.0 kcal/mol have been found favoring the homo- or heterochiral complexes. Two possible proton-transfer processes have been studied, the concerted one and the nonconcerted one. The compresion of the systems in the transition structures produce an increase in the energetic differences when compared to the corresponding minima complexes. A Steiner−Limbach relationship has been found for the geometrical properties of the HB in the minima and transition states calculated here. The electron density and its Laplacian at the bond critical point have been found to correlate with the HB distance.

Doi: 10.1021/ja011348c 

Self-Discrimination of Enantiomers in Hydrogen-Bonded Dimers

The homochiral and heterochiral hydrogen-bonded (HB) dimers of a set of small model molecules (alfa-amino alcohols) have been studied by means of ab initio methods. The gas-phase calculations have been carried out with the hybrid HF/DFT B3LYP method and the 6-311++G** basis set. The electron density of the complexes has been analyzed using the atoms in molecules (AIM) methodology, which allows characterization of the HB interactions and additional intermolecular contacts. To take into account the water solvation effect, the polarized continuum model (PCM) method has been used to evaluate the deltaGsolv. The gas-phase results show that the heterochiral dimers are the most stable ones for each case studied, while in solution for several cases, the relative stability is reversed and the homochiral dimers become more stable. The AIM analysis shows the typical bond critical points characteristic of the HB and additional bond critical points denoting, in this case, destabilization of intermolecular interaction as CF3...F3C and CH3...H3C contacts.

Doi: 10.1063/1.1504710

Discrimination of hydrogen-bonded complexes with axial chirality

The chiral self-discrimination of twelve molecules showing axial chirality has been studied. They included peroxides, hydrazines, carboxylic acids, amides, and allenes. The homo and heterochiral dimers of the selected compounds, that present two hydrogen bonds, have been studied by means of density functional theory (B3LYP/6-31+G**) and ab initio (MP2/6-31+G** and MP2/6-311++G**) methods. The energetic differences found for the complexes of each compound have been rationalized based on their electron density maps and the natural bond orbital analysis. In some cases, intermolecular oxygen-oxygen interactions have been found and interpreted as additional stabilizing contacts.