Antiperiplanar Orientation Research Articles

9-(Pyrrolidinium-1-yl)-9-boranuidabi-cyclo-[3.3.1]nona-ne.

The title compound, C12H24BN, is an adduct formed from 9-borabi-cyclo-[3.3.1]nonane (9-BBN) and pyrrolidine. It crystallizes in the triclinic space group P with three mol-ecules in the asymmetric unit, one of which has disorder of the pyrrolidine ring. The B-N bond lengths are between 1.631 (2) and 1.641 (2) Å. The boron and nitro-gen atoms are bound to one hydrogen atom each. These hydrogen atoms are in anti-periplanar orientation. Both six-membered rings of the 9-BBN unit are in a chair conformation in all three mol-ecules. Differences between the three crystallographic independent mol-ecules are found in the five-membered rings of the pyrrolidine unit. These adopt different twisted and envelope conformations.

The 2′-C-methylribonucleoside of 5-aza-7-deaza-7-iodoguanine: Hydrogen and halogen bonding in nucleoside crystals, synthesis and physical properties

The single-crystal X-ray structure of the 5-aza-7-deaza-7-iodoguanine 2′-C-methylribonucleoside 1 is described. The nucleoside was synthesized by stereoselective nucleobase anion glycosylation, yielding the protected nucleoside (70%), which was then deprotected to 1. By the same route, the non-iodinated 2′-C-methylribonucleoside 2 was obtained. In solution, the CD-spectrum of the iodinated 2′-C-methylribonucleoside 1 displays an almost mirror-like Cotton effect compared to the non-halogenated 2, revealing the strong impact of the iodo substituent to the molecule. Suzuki-Miyaura cross-coupling of 1 with pyrene boronic acid yielded a dye conjugate. The pyrene conjugate shows solvent dependent exciplex fluorescence. From the single-crystal X-ray structure of 1, conformational parameter were determined in solid state. The molecule shows anti conformation, a C3’-endo (N) sugar pucker and an antiperiplanar orientation of the 5′‑hydroxyl group. Apart from classical hydrogen bonds, nucleoside 1 possesses a halogen bond from the iodo substituent to the sugar oxygen O3’. A Hirshfeld surface analysis supports this finding. Nucleoside 1 forms a regular, tightly packed structure with stacking interactions between nucleobases and among sugar residues. A comparison of crystal packing of the iodinated 2′-C-methylribonucleoside 1 with the corresponding ribo- and 2′-deoxyribonucleosides demonstrates that halogen bonding depends on the sugar structure and determines the connectivity in crystal layers.

SYNTHESIS, CRYSTAL STRUCTURE, AND DFT STUDIES OF ETHYL 4-HYDROXY-2-(4-METHOXYPHENYL)-5-OXO- 1-PHENYL-2,5-DIHYDRO-1H-PYRROLE-3-CARBOXYLATE

An efficient method for the synthesis of a new highly substituted pyrrolidinone derivative is developed via a three-component one-pot reaction of aniline, diethyl acetylenedicarboxylate, and 4-anisaldehyde. The structure of ethyl 4-hydroxy-2-(4-methoxyphenyl)-5-oxo-1-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylate is confirmed by FTIR, 1H and 13C NMR spectroscopy. Unambiguous evidence for the structure of the synthesized product is obtained from the single crystal X-ray analysis. The comparison of both its molecular structure and intermolecular interactions with the previously known analogous compounds reveals that the mutual syn- or antiperiplanar orientation of ester C=O and pyrrolinone-bound OH is related to the type of molecular dimers formed in the solid state. The geometrical structure, the HOMO–LUMO analysis (electrophilicity index), 1H and 13C chemical shifts of the desired product are also calculated by DFT at the B3LYP level with the 6-31++G(d,p) basis set. The calculated chemical shifts are in compliance with the experimental data.

Synthesis, crystal structure, and DFT studies of ethyl 4-hydroxy-2-(4-methoxyphenyl)-5-oxo-1-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylate

An efficient method for the synthesis of a new highly substituted pyrrolidinone derivative is developed via a three-component one-pot reaction of aniline, diethyl acetylenedicarboxylate, and 4-anisaldehyde. The structure of ethyl 4-hydroxy-2-(4-methoxyphenyl)-5-oxo-1-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylate is confirmed by FTIR, 1H and 13C NMR spectroscopy. Unambiguous evidence for the structure of the synthesized product is obtained from the single crystal X-ray analysis. The comparison of both its molecular structure and intermolecular interactions with the previously known analogous compounds reveals that the mutual syn- or antiperiplanar orientation of ester C=O and pyrrolinone-bound OH is related to the type of molecular dimers formed in the solid state. The geometrical structure, the HOMO—LUMO analysis (electrophilicity index), 1H and 13C chemical shifts of the desired product are also calculated by DFT at the B3LYP level with the 6-31++G(d,p) basis set. The calculated chemical shifts are in compliance with the experimental data.

Structural, Hirshfeld surface and in vitro cytotoxicity evaluation of five new N-aryl-N’-alkoxycarbonyl thiocarbamide derivatives

Five new compounds, N-(2, 4-dichlorophenyl)-N’-(methoxycarbonyl) thiocarbamide (1), N-(2, 4-dichlorophenyl)-N’-(ethoxycarbonyl) thiocarbamide (2), N-(2, 4-dichlorophenyl)-N’-(2, 2, 2-trichloroethoxycarbonyl) thiocarbamide (3), N-(2,4-dichlrophenyl)-N’-(pentoxycarbonyl) thiocarbamide (4) and N-(4-nitrophenyl)-N’-(pentoxycarbonyl) thiocarbamide (5), have been synthesized by the reaction of various alkoxy chloroformates with 2, 4-dichloroaniline/4-nitroaniline.The molecular structures of the compounds were elucidated by using spectroscopic methods (FT-IR, 1H and 13C NMR) and single-crystal X-ray structure analysis of compounds 2 and 5. Antiperiplanar orientation of C = O and C = S group across C–N bonds of thiocarbamide core may be due to the presence of intramolecular (N–H···O–C) hydrogen bond in the crystal structure of both the compounds. The presence of intermolecular interactions (C–H···S, C–H···O and N–H···S) in the molecular structure of the compounds has been studied in detail using Hirshfeld surfaces and their associated two-dimensional fingerprint plots. In vitro cytotoxicity screening of the synthesized compounds evaluated on a panel of seven human cancer cell lines (cervical carcinoma (2008, C13*), colorectal (HT29 and HCT116) and ovarian carcinoma (A2780, A2780/CP and IGROV-1)) demonstrated significant inhibitory properties.

7-Iodo-5-aza-7-deazaguanine ribonucleoside: crystal structure, physical properties, base-pair stability and functionalization.

The positional change of nitrogen-7 of the RNA constituent guanosine to the bridgehead position-5 leads to the base-modified nucleoside 5-aza-7-deazaguanosine. Contrary to guanosine, this molecule cannot form Hoogsteen base pairs and the Watson-Crick proton donor site N3-H becomes a proton-acceptor site. This causes changes in nucleobase recognition in nucleic acids and has been used to construct stable `all-purine' DNA and DNA with silver-mediated base pairs. The present work reports the single-crystal X-ray structure of 7-iodo-5-aza-7-deazaguanosine, C10H12IN5O5 (1). The iodinated nucleoside shows an anti conformation at the glycosylic bond and an N conformation (O4'-endo) for the ribose moiety, with an antiperiplanar orientation of the 5'-hydroxy group. Crystal packing is controlled by interactions between nucleobase and sugar moieties. The 7-iodo substituent forms a contact to oxygen-2' of the ribose moiety. Self-pairing of the nucleobases does not take place. A Hirshfeld surface analysis of 1 highlights the contacts of the nucleobase and sugar moiety (O-H...O and N-H...O). The concept of pK-value differences to evaluate base-pair stability was applied to purine-purine base pairing and stable base pairs were predicted for the construction of `all-purine' RNA. Furthermore, the 7-iodo substituent of 1 was functionalized with benzofuran to detect motional constraints by fluorescence spectroscopy.

One-pot synthesis, spectroscopic characterizations, quantum chemical calculations, docking and cytotoxicity of 1-((dibenzylamino)methyl)pyrrolidine-2,5-dione

Abstract The investigations of stabilization energy, bond order, intra-molecular interactions and energy gap of pharmaceutical drugs are useful for understanding their behaviour. A new Mannich base molecule 1-((dibenzylamino)methyl)-pyrrolidine-2,5-dione (SBF) was synthesized through sequential Mannich reactions of an imide with an aldehyde and the intermediate obtained are reacted with secondary amine to get the desired product. The entire molecular geometry of the SBF molecule was confirmed by single crystal XRD studies. The crystal structure of SBF molecule was found symmetrical and planar with anti-periplanar orientation of C O group and nitrogen atom. The theoretical computations were performed using B3LYP/6-31G(d, p) level of basis set. The chemical environment of carbon and protons were shown with 13C and 1H NMR spectral analysis, respectively. The molecular weight of the title molecule was determined by mass spectrum. The thermal stability of the SBF molecule up to 270 °C was exposed by thermogravimetric (TG) and differential scanning analysis (DSC). The natural bonding orbital (NBO) analysis data revealed the highest stabilization value of E(2) for transfer of electron density from succinimide to the antibonding molecular orbital of the dibenzyl ring were found to be 51.51 and 50.31 kJ/mol. The energy of HOMO-LUMO, PDOS, OPDOS, RDG of the title molecule have also been carried out. The protein-ligand relationship was well revealed by molecular docking studies. The cytotoxic activity of the SBF molecule was evaluated by MTT assay on cell line A549.

Experimental and theoretical exploration of molecular structure and anticancer properties of two N, N′–disubstituted thiocarbamide derivatives

Two new compounds N-(2-chloro-4-nitrophenyl)-N'-(phenoxycarbonyl) thiocarbamide (1) and N-(2-chloro-4-nitrophenyl)-N'-(4-nitrobenzoyl) thiocarbamide (2), have been derived by the reaction of phenoxycarbonyl isothiocyanate/4-nitrobenzoyl isothiocyanate with 2-chloro-4-nitroaniline. The structures of these compounds were determined by spectroscopic (FT-IR, 1H and 13C NMR, UV–Visible) and single crystal X-ray studies. Both the crystal structures are symmetrical and planar with anti-periplanar orientation of CO and CS group. The molecular structure and vibrational properties of the compounds studied at B3LYP/6-311G ++ (d, p) level of density functional theory further concrete the experimental results. These compounds were screened for their in vitro cytotoxicity activity against seven human cancer cell lines; cervical (2008 and C13*), colorectal (HT29 and HCT116) and ovarian carcinoma (A2780, A2780/CP and IGROV-1). Compound 2 exhibited significant activity against all the cell lines whereas compound 1 demonstrated appreciable activity only against ovarian carcinoma cell lines.

Stereoelectronic Effects: The γ-Gauche Effect in Sulfoxides.

Reasons for the 13C NMR γ-gauche effect in sulfoxides, i.e., the distinct shielding of a carbon β to a gauche-oriented sulfoxide group were investigated. Several calculated and measured 13C NMR data of open chain or thiane-derived sulfoxides revealed that an upfield shift is only observed for that γ-gauche position, in which the respective carbon is anti to the sulfoxide's sulfur lone pair. Carbons in γ-gauche position, which are synclinal to the lone pair, are not affected. The magnetic anisotropy of the S═O group was examined by generation of iso-chemical-shielding surfaces (ICSSs) and magnetically induced current maps. Stereoelectronic interactions were determined with natural bond orbital (NBO) and natural chemical shielding (NCS) analyses. The γ-gauche effect is best described by stereoelectronic interactions, especially those of the sulfur's lone pair with antibonding orbitals to a β-carbon in antiperiplanar orientation. An explanation based on steric interactions, which has frequently been referred to, is not suitable to describe the observed shielding effects. Furthermore, a description of the bonding situation in the S═O group is given. It can be understood as S-O triple bond, where the bond order is significantly reduced by antibonding contributions in some of the occupied molecular orbitals.

5-(2-Hydroxybenzoyl)-2-(1H-indol-3-yl)pyridine-3-carbonitrile

In the title compound, C21H13N3O2, the indole and pyridine rings are planar. The pyridine ring is in an antiperiplanar (−ap) orientation with the indole ring system and an antiperiplanar (+ap) orientation with the hydroxyphenyl ring. An intramolecular O—H...O hydrogen bond stabilizes the molecular structure. In the crystal, N—H...N hydrogen bonds involving the indole NH group and the cyanide nitrogen atom lead to the formation of a two-dimensional supramolecular network lying parallel to (011).

Switching the Regioselectivity of a Cyclohexanone Monooxygenase toward (+)-trans-Dihydrocarvone by Rational Protein Design.

The regioselectivity of the Baeyer-Villiger monooxygenase-catalyzed oxidation is governed mostly by electronic effects leading to the migration of the higher substituted residue. However, in some cases, substrate binding occurs in a way that the less substituted residue lies in an antiperiplanar orientation to the peroxy bond in the Criegee intermediate yielding in the formation of the "abnormal" lactone product. We are the first to demonstrate a complete switch in the regioselectivity of the BVMO from Arthrobacter sp. (CHMOArthro) as exemplified for (+)-trans-dihydrocarvone by redesigning the active site of the enzyme. In the designed triple mutant, the substrate binds in an inverted orientation leading to a ratio of 99:1 in favor of the normal lactone instead of exclusive formation of the abnormal lactone in case of the wild type enzyme. In order to validate our computational study, the beneficial mutations were successfully transferred to the CHMO from Acinetobacter sp. (CHMOAcineto), again yielding in a complete switch of regioselectivity.

The conformation of acetaldehyde: a simple molecule, a complex explanation?

Consider acetaldehyde (ethanal for progressive nomenclaturists). What conformation does it adopt, and why? This question was posed of me by a student at the end of a recent lecture of mine. Surely, an easy answer to give? Read on … There really are only two possibilities, the syn and anti. Well, I have discovered it is useful to start with a search of the Cambridge data base. With R=H or C, X unspecified, acyclic and T ≤ 175K, two searches were performed. The first identified the torsion around O=C-C-H. This clearly shows a maximum at 120° (with twice the probability), and a smaller one at 0°. This matches syn; the anti conformation above would be expected to have peaks at 60° and 180°; the latter in particular is singularly missing. An alternative search is to define the distance between the oxygen and the H. For the syn conformer, distances of ~2.5 and 3.1Å are expected; for the anti conformer, 2.7 and 3.3Å. Again, syn matches better. Remember, searches based on the position of a hydrogen are less reliable than most, so these distributions provide only a statistical indication. Now for a (ωB97XD/6-311G(d,p) calculation of the rotational barrier. The minima occur at torsions of 0, 120 and 240°, matching syn, although the barrier is very low. Now to try to find explanations. The standard one finds this in three effects: Donation from two C-H bonds (R=H above) into the π*C=O NBO orbital (in the manner that was used to explain the cis-orientation of the two methyl groups in cis-butene). Donation from the single co-planar C-H bond into the σ*C=O NBO orbital (blue bonds above) Pauli bond-bond repulsions between two filled NBOs. Effect 1 has an NBO perturbation energy E(2) of 7.0 kcal/mol for the syn conformer and 6.45 for the anti. The explanation is the π*C=O NBO “leans outward”, overlapping better with the C-H bonds in the syn than in the anti. the One up to the syn! Effect 2 has values of 1.3 for the syn and 4.1 for the anti. The latter now has the edge. But wait, there are other (smaller) interactions. The syn has an antiperiplanar orientation of the two C-H bonds shown above (X=H,red), E(2) = 3.3 vs 0.6 for the corresponding syn-planar orientation in the anti-conformation. It’s now a tie; neck-and-neck. Effect three suggests that the disjoint NLMO steric exchange energy is 54.34 for the anti and 53.88 (i.e. lower) for the syn. It is vaguely disappointing that no absolutely clear-cut explanation emerges. But then the difference (in total free energy) is only 1.4 kcal/mol. But even this small difference in energy can manifest in fairly clear-cut conformational preferences obtained from crystal structures. Ultimately of course, all effects in chemistry are reducible to the sum of lots of small effects (in other words unpredictable until one does the sum). I cannot end without mentioning the largest of all the NBO interactions, namely the in-plane lone pair on the oxygen as donor and the aldehyde proton C-H as acceptor (X=H). This has values of 29.3 for syn and 28.8 kcal/mol for anti. This manifest (inter alia) in a greatly reduced C-H vibrational wavenumber (ν 2982 for syn, 2900 cm-1 for anti) compared to the methyl C-H values (~3043-3164). So this tiny little molecule ended up a little less obvious than might have seemed at the outset. One can find interesting things in even the tiniest of things! HC…C-H alignment. Click for 3D. O=C*…C-H alignment. Click for 3D.

Matrix isolation study of the conformations and photochemistry of S-ethyl fluorothioformate, FC(O)SCH2CH3.

The IR spectra of S-ethyl fluorothioformate, FC(O)SCH2CH3, were recorded in the vapor phase and compared with the Raman spectrum in the liquid state. Additional IR spectra of the compound isolated in argon and nitrogen matrices at ca. 12 K were also recorded. The title compound exhibits rich conformational equilibria at room temperature being C1 the most stable symmetry with a synperiplanar orientation of the carbonyl double bond (C═O) with respect to the S-C(sp(3)) single bond, while the C-C bond of the ethyl group presents a gauche orientation with respect to the C-S single bond. Several bands assigned to a second conformer were also observed in the IR matrix spectra. This second rotamer presents a planar skeleton (Cs point group) retaining the prevalent syn orientation of the FC(O)SCH2CH3 molecule with an antiperiplanar orientation of the C-C bond of the ethyl group with respect to the C-S bond. The variation of the nozzle temperature before matrix gas deposition gives rise to different conformer ratios. With these data an enthalpy difference of 0.45 kcal mol(-1) can be calculated between the more stable C1 and the Cs conformers. A third form, corresponding to the anti-gauche conformer, is also detected when the matrix is exposed to broad-band UV-visible irradiation. Moreover, the photochemistry of the Ar and N2 matrix-isolated species is studied. Conformational interconversion is observed at short irradiation times, whereas a decarbonylation process with the concomitant formation of a HC(S)CH3:HF molecular complex dominates the photochemistry of FC(O)SCH2CH3 of longer irradiation times. The new ethyl fluoro sulfide, FSCH2CH3, is proposed as an intermediate species.

The Ant‐Pro Reverse‐Turn Motif. Structural Features and Conformational Characteristics

AbstractThis article details the characteristic conformational features of the Ant‐Pro reverse turn ― a folded pseudo β‐turn motif that displays a closed nine‐membered‐ring hydrogen‐bonded network involving just two amino acid residues, namely anthranilic acid (Ant; a constrained β‐amino acid), and proline (Pro; a constrained α‐amino acid). The results from the extensive investigation of ten crystal structures and their NMR conformations in the solution state provide a clear idea about the conformational characteristics of the Ant‐Pro reverse turn. The Ant and Pro residues, which form the turn segment, maintain a perfect antiperiplanar orientation throughout, leaving little possibility for the formation of the otherwise possible six‐membered hydrogen‐bonding that requires a coplanar disposition of the two amino acid residues, as clearly evident from investigation of several crystal structures. The closed hydrogen‐bonded network observed in the Ant‐Pro reverse turn motif, formed in the forward direction of the sequence (1→2 amino acid interactions) involving only two amino acid residues, is in stark contrast to the native β‐turns that involve four residues to form hydrogen‐bonded network featuring backward 1←4 amino acid interactions. The readily available two‐residue Ant‐Pro motif raises the possibility of a practical utility, particularly in the application of rigidifying flexible peptide backbones by inserting the robust Ant‐Pro reverse turn motifs into their backbone.

Computational reexamination of the eclipsed conformation in cis-2-tert-butyl-5-(tert-butylsulfonyl)-1,3-dioxane

The conformational free energy differences, ΔG° values, for the methyl sulfide, methyl sulfoxide, methyl sulfone, tert-butyl sulfide, tert-butyl sulfoxide, and tert-butyl sulfone groups at C(5) in the 1,3-dioxane ring have been calculated at two different levels, B3LYP/6-31G(d) and B3LYP/6-311++G(d,p). There is good agreement between experimental and calculated values, particularly in the case of data obtained at the lower level of theory, B3LYP/6-31G(d). In order to get information that could help understand the nature of the effects present in the molecules of interest, the charge distribution in representative compounds was analyzed by means of the natural bond orbital (NBO) analysis. NBO calculations indicate the existence of substantial negative charges at oxygen and significant positive charge at sulfur. This observation seems to support the argument the existence of electrostatic, attractive interactions between the endocyclic oxygens and the axial sulfonyl group. From the second order perturbation theory analysis of Fock matrix, two σ C–C → σ*S–O delocalizing interactions are observed in the methyl-inside conformer of cis-2-tert-butyl-5-(methylsulfonyl)-1,3-dioxane derivative cis-7. These results are in line with anti-periplanar σ C–C → σ*S–O hyperconjugative interactions that help stabilize the methyl-inside conformation of cis-7, as previously found by 1H NMR analysis. By contrast, NBO analysis does not provide evidence for the existence of σ C–C → σ*S–O hyperconjugative interactions that might help stabilize the eclipsed tert-butyl—outside conformation previously found in the solid-state crystallographic structure of analog cis-1. Because of the threshold value of the NBO calculations, if present such syn-periplanar stereoelectronic interaction should be less than 0.5 kcal mol−1. This observation suggests that an anti-periplanar orientation of the interacting orbitals is more effective relatively to the corresponding syn-periplanar orientation.

Ballistic energy transport via perfluoroalkane linkers

Intramolecular energy transport in a series of perfluoroalkane oligomers with various chain lengths of 3, 5, 7, 9, and 11 carbon atoms terminated by a carboxylic acid moiety on one end and –CF2H group on another end is studied by relaxation-assisted two-dimensional infrared spectroscopy. Perfluoroalkane oligomers adopt an extended structure with antiperiplanar orientation of the neighboring carbon atoms. The energy transport initiated by exciting the CO stretching mode of the acid was recorded by measuring a cross-peak amplitude between the CO stretch and the C–H bending mode as a function of the waiting time between the excitation and probing. A linear dependence of energy transport time vs. chain length is found, which suggests a ballistic energy transport mechanism. The energy transport speed, measured from the chain-length dependence of the half-rise time, T½, was found to be ca. 1150m/s, which is close to the longitudinal speed of sound in Teflon polymers.

Synthesis, Duplex Stabilization and Structural Properties of a Fluorinated Carbocyclic LNA Analogue

DNA oligonucleotides modified with nucleoside monomers which have an electron withdrawing group (EWG) at the 2'-position of the furanose ring form more stable duplexes with complementary RNA as compared to unmodified DNA. Here we show that an anti-periplanar orientation of the nucleobase and the 2'-EWG is important for optimal duplex stabilization even for nucleic acid analogues with conformationally locked furanose rings.

Hyperconjugation-Mediated Solvent Effects in Phosphoanhydride Bonds

Density functional theory and natural bond orbital analysis are used to explore the impact of solvent on hyperconjugation in methyl triphosphate, a model for "energy rich" phosphoanhydride bonds, such as found in ATP. As expected, dihedral rotation of a hydroxyl group vicinal to the phosphoanhydride bond reveals that the conformational dependence of the anomeric effect involves modulation of the orbital overlap between the donor and acceptor orbitals. However, a conformational independence was observed in the rotation of a solvent hydrogen bond. As one lone pair orbital rotates away from an optimal antiperiplanar orientation, the overall magnitude of the anomeric effect is compensated approximately by the other lone pair as it becomes more antiperiplanar. Furthermore, solvent modulation of the anomeric effect is not restricted to the antiperiplanar lone pair; hydrogen bonds involving gauche lone pairs also affect the anomeric interaction and the strength of the phosphoanhydride bond. Both gauche and anti solvent hydrogen bonds lengthen nonbridging O-P bonds, increasing the distance between donor and acceptor orbitals and decreasing orbital overlap, which leads to a reduction of the anomeric effect. Solvent effects are additive with greater reduction in the anomeric effect upon increasing water coordination. By controlling the coordination environment of substrates in an active site, kinases, phosphatases, and other enzymes important in metabolism and signaling may have the potential to modulate the stability of individual phosphoanhydride bonds through stereoelectronic effects.

Two-Dimensional Infrared Spectroscopy Reveals the Structure of an Evans Auxiliary Derivative and Its SnCl4Lewis Acid Complex

Determining the structure of reactive intermediates is the key to understanding reaction mechanisms. To access these structures, a method combining structural sensitivity and high time resolution is required. Here ultrafast polarization-dependent two-dimensional infrared (P2D-IR) spectroscopy is shown to be an excellent complement to commonly used methods such as one-dimensional IR and multidimensional NMR spectroscopy for investigating intermediates. P2D-IR spectroscopy allows structure determination by measuring the angles between vibrational transition dipole moments. The high time resolution makes P2D-IR spectroscopy an attractive method for structure determination in the presence of fast exchange and for short-lived intermediates. The ubiquity of vibrations in molecules ensures broad applicability of the method, particularly in cases in which NMR spectroscopy is challenging due to a low density of active nuclei. Here we illustrate the strengths of P2D-IR by determining the conformation of a Diels-Alder dienophile that carries the Evans auxiliary and its conformational change induced by the complexation with the Lewis acid SnCl(4), which is a catalyst for stereoselective Diels-Alder reactions. We show that P2D-IR in combination with DFT computations can discriminate between the various conformers of the free dienophile N-crotonyloxazolidinone that have been debated before, proving antiperiplanar orientation of the carbonyl groups and s-cis conformation of the crotonyl moiety. P2D-IR unequivocally identifies the coordination and conformation in the catalyst-substrate complex with SnCl(4), even in the presence of exchange that is fast on the NMR time scale. It resolves a chelate with the carbonyl orientation flipped to synperiplanar and s-cis crotonyl configuration as the main species. This work sets the stage for future studies of other catalyst-substrate complexes and intermediates using a combination of P2D-IR spectroscopy and DFT computations.

Palladium-catalyzed formation of oxazolidinones from biscarbamates: a mechanistic study

Oxazolidinones can be synthesized starting from cyclic biscarbamates via a palladium-catalyzed reaction. To test the proposed mechanism of this reaction, first, bicyclonorcarene endoperoxides derived from cyano and carbomethoxy cycloheptatrienes were synthesized and converted into the corresponding diols. The reaction of diols with toluenesulfonyl isocyanate followed by a palladium catalyzed reaction furnished oxazolidinone derivatives in similar yields. It was shown that, if one face of the double bond is blocked by substituents such as H or CN, the reaction also takes place. On the basis of these results, it was assumed that an antiperiplanar orientation of the metal and nucleophile is not necessary to form oxazolidinones. The metal is probably bonded to the allylic system from the same face as the nucleophile.