Substituent Chemical Shifts Research Articles

Transmission of substituent effects in para-disubstituted benzenes: 13C chemical shift and Mulliken charge modeling of para carbon atoms via the Reynolds DSP model

The PM3 calculations of the Mulliken charge and the experimental 13C substituent chemical shifts (SCS) of para carbon for 17 para-disubstituted benzene series were investigated by correlation analysis. A significant correlation between the charge and the 13C SCS of the para carbon of the same series was observed. In mono-substituted benzene, the correlation of para13C SCS with Mulliken charges calculated by PM3 and Mulliken charge calculated by DFT(B3LYP) with basis set 6 311(dp)G of the same carbon is similar. All the substituent effects on the charge and 13C SCS were modeled by the Reynolds’ dual substituent parameter model (charge or 13C SCS = ρF σF + ρRσRo), where σF and σRo are the Reynolds’ field and resonance constants, respectively, and ρF and ρR are the field and resonance effects, respectively. The coefficients of determination for all series were significant. The concept of π-polarization was used to analyze variation in ρF. The interpretation of ρF showed parallels between the charge and 13C SCS. An enhanced ρF for a given series was attributed to the stabilization of the π-polarization charge at the para carbon. The ρR was a function of extended conjugation within the side chain. Parallelism of charge and 13C SCS of the ρR of the compared series were also observed, except in series with the reverse-substituent effect and the possession of a strong electronegative group, such as a nitro or azo group.

Seco B-Type Oligomers from Pinus massoniana Expand the Procyanidin Chemical Space and Exhibit Dental Bioactivity.

Investigation of a pine bark extract for bioactive proanthocyanidin oligomers resulted in the isolation of structurally related dimeric seco B-type procyanidin derivatives, 1-5. This includes scalemic mixtures of gambiriin A1 (1a) and A2 (2a) and their newly described optical antipodes, ent-gambiriin A1 (1b) and ent-gambiriin A2 (2b), respectively, as well as a racemic mixture of the newly described (ent-)gambiriin A5 (3a/3b). Furthermore, the study now fully characterizes the previously reported optically pure dimers gambiriin B1 (4) and gambirflavan D1 (5), and characterized the novel seco B-type procyanidin trimer, 6 (gambirifuran C1). Thermal conversion of catechin in aqueous solution provided further evidence for the structures of 1-6 and led to the purification of semisynthetic 1a and 2a as well as additional dimers 7-10. Elucidating the structures of the natural dimers, 1-5, from comprehensive NMR and ECD data and synthetic evidence provided crucial reference points for establishing the structure of the seco B-type procyanidin trimer, 6. Serving as assigned building blocks, data from the dimers supported the 3D structural assignment of 6 based on NMR substituent chemical shift differences (s.c.s., syn. ΔδC) and component-based empirical ECD calculations. Within the newly characterized series of PAC-related molecules, 5 exhibited high dentin biomodification potential. In addition, considering the nomenclature issues and plausible biosynthetic pathways of this group of compounds led to a consolidated nomenclature of all currently known seco B-type procyanidins. These findings, thereby, expand the chemical space of bioactive catechin oligomers, which have promise as agents for the natural enhancement of dental biomaterials. Finally, the current knowledge of the chemical space of seco B-type procyanidin derivatives was compiled to the level of absolute configuration.

Substituent Effect Study for 13Cβ SCS in a Meta-Styrene Series. Reynolds Dual Substituent Parameter Model Investigation.

This article investigates the transmission of the meta-substituent, X, effect to the carbon β (Cβ) of 17 different styrenes (X-C6H4-CH═CYZ) using the literature 13C substituent chemical shift (SCS) of Cβ. The 13C SCSs of Cβ were modeled by Reynolds substituent field σF and resonance σR constants. The model is considered a dual substituent parameter model, SCS = ρFσF + ρRσR. The coefficients of determination of the modeled 13C SCS for the 17 series fall between 0.9878 and 0.9983. The π-polarization concept was used to rationalize the field and resonance effects felt at Cβ. The ρF values of the meta-series were all lower than the para-series ρF values. The substituent field effect transmits to Cβ from Cipso. The substituent resonance effect transmits from Cipso to Cβ initially through the π-bond to Cortho and Cpara, next to the side chain, and then the generated charge will induce the vinyl group via π-polarization. The ρF felt at Cβ was almost double the ρR when compared with the short distance between Cmeta and Cβ, as opposed to Cortho and Cpara. Stabilization of the π-polarization of the vinyl group will increase, with the field and resonance effects felt at Cβ and vice versa.

Substituent Effects on NMR Spectroscopy of 2,2-Dimethylchroman-4-one Derivatives: Experimental and Theoretical Studies.

The attribution of 1H and 13C NMR signals of a library of 5-, 6- and 7-substituted 2,2-dimethylchroman-4-one derivatives is reported. Substituent effects were interpreted in terms of the Hammett equation, showing a good correlation for carbons para- to the substituent group, not for the meta- ones. Similarly, the Lynch correlation shows the additivity of the substituent chemical shifts in the case of both H and C nuclei, again with the exception of the carbons in the meta- position. Density Functional Theory (DFT)-predicted 1H and 13C chemical shifts correspond closely with experimentally observed values, with some exceptions for C NMR data; however, the correlation is valid only for the aromatic moiety and cannot be extended to the heterocyclic ring of the chroman-4-one scaffold.

Absolute configuration of the diterpenoids icetexone and conacytone from Salvia ballotaeflora.

Detailed literature inspections regarding the diterpenoids icetexone (1) and conacytone (3) reveal that the absolute configuration (AC) of these natural occurring compounds is not rigorously proven, despite they were originally isolated in 1976. This task is now completed by single-crystal X-ray diffraction Flack and Hooft parameters determination after processing data collected with Cu Kα graphite monochromated radiation. The AC of both compounds is further determined by vibrational circular dichroism measurements performed on icetexone acetate (2) and conacytone triacetate (4) since the solubility of 1 and 3 is limited. Comparison of the substituent chemical shifts (SCS) induced by acetylation of 1 and 3 to afford 2 and 4, respectively, reveals that in the case of icetexone, all six SCS values of the quinone ring are in excellent agreement with the expected values, while in the case of conacytone, three agree and three do not agree due to the presence of additional acetates near the quinone ring. Density functional theory calculations performed on 3-hydroxythymoquinone (6) and its tautomer 4-hydroxy-1,2-quinone 7, on 6-hydroxythymoquinone (8) and its tautomer ortho-quinone 9, and on icetexone (1) and the claimed natural occurring ortho-quinone tautomer romulogarzone (5) indicate that 2-hydroxy-1,4-quinones are more stable, by some 11-14kcal/mol, than their 4-hydroxy-1,2-quinone tautomers, and therefore, romulogarzone (5) is inexistent.

A Study of 13C Chemical Shifts for a Series of 2-(4-methoxyphenyl)-substituted-3-phenyl-1,3-thiazolidin-4-ones

The <sup>13</sup>C substituent chemical shifts C-2, C-4 and C-5 (with a particular focus at C-2) for disubstituted 2,3-diphenylthiazolidin-4-ones with one substituent in each phenyl ring are systematically being investigated. The substituents in question are <em>p</em>-NO<sub>2</sub>, <em>m</em>-NO<sub>2</sub>, <em>p</em>-F, <em>m</em>-F, <em>p</em>-Cl, <em>m</em>-Cl, <em>p</em>-Br, <em>m</em>-Br, H, <em>p</em>-CH<sub>3</sub>, <em>m</em>-CH<sub>3</sub>, <em>p</em>-OCH<sub>3</sub> and <em>m</em>-OCH<sub>3</sub>. This combination of substituents leads to a 13 x 13 matrix array of compounds with the fixed substituents in the 2-phenyl ring constituting the columns and the fixed substituents in the 3-phenyl rings constituting the rows. Including this present study, 81 of the total 169 compounds in the matrix have been analyzed. A single <em>para</em>-methoxy group interacting with another fixed substituent, as measured by <sup>13</sup>C substituent chemical shift values at C-2 in either the C-2 phenyl or N-3 phenyl rings, shows little deviation. This changes however when the moiety is either an alkyl group at N-3 or when a <em>para</em>-methoxy group is the fixed substituent on the N-3 phenyl ring. This present study shows that a <em>para</em>-methoxy group on a C-2 phenyl ring shows a similar deviation in the efficacy in the transmission of electronic effects witnessed in this set of matrix compounds and mimics the issues seen with a previously studied <em>para</em>-methoxy substituted system with the <em>para</em>-methoxy group on the N-3 phenyl ring. Reasons for these aberrations are discussed.

The Substituent Effect of 1‐Arylazonaphthen‐2‐ols on Azo‐hydrazone Tautomerization According to NMR Analysis

AbstractThe substituent effect on azo‐hydrazone tautomerization of 1‐arylazonaphthen‐ols is studied by means of NMR analysis. Among the 13C chemical shifts, the C(2) of this series compound is the most sensitive to the variation in the nature of substituent on the phenyl ring. Therefore, the variation in the chemical shifts of C(2) is used to probe the substituent effect by using the substituent chemical shifts and free energy vs. Hammett’s constant (χρ+). Both methods give a negative correlation slope, indicating the electron‐with‐ drawing groups favor the hydrazone tautomer form. The effect on the chemical shifts of C(2) of compound 8 in ten solvents can be classified as the solvent with a proton‐donor, proton‐acceptor and arenes system. The substituent with electron‐donating character is more sensitive to the nature of solvent and it favors the hydrazone form. Free energy obtained from the dynamic NMR technique indicates the tautomerization favors the hydrazone‐form for the substituent with electron‐withdrawing character.

2-Substituted and 2,2-disubstituted adamantane derivatives as models for studying substituent chemical shifts and C–Hax⋯Yax cyclohexane contacts—results from experimental and theoretical NMR spectroscopic chemical shifts and DFT structures

The complete 1H and 13C NMR chemical shifts assignment for various 2-substituted and 2,2-disubstituted adamantane derivatives 1–38 in CDCl3 solution was realized on the basis of NMR experiments combined with chemical structure information and DFT-GIAO (B3LYP/6-31+G(d,p)-GIAO) calculations of chemical shifts in solution. Substituent-induced 13C NMR chemical shifts (SCS) are discussed. C–Hax⋯Yax contacts are a textbook prototype of steric hindrance in organic chemistry. The nature of these contacts will be further investigated in this work on basis of new adamantane derivatives, which are substituted at C-2 to provide models for 1,4-C–Hax⋯Yax and 1,5-C–Hax⋯Yax contacts. The B3LYP/6-31+G(d,p) calculations predicted the presence of NBO hyperconjugative attractive interactions between C–Hax and Yax groups along C–Hax⋯Yax contacts. The 1H NMR signal separation, Δδ(γ-CH2), reflects the strength of the H-bonded C–Hax⋯Yax contact.

Complexes of peracetylated cyclodextrin in a non-aqueous aprotic medium: the role of residual water.

This paper describes the interaction between aromatic esters and peracetylated cyclodextrins (CDs) studied by NMR spectroscopy in deuterochloroform (CDCl3). The observed chemical shift changes highlight the existence of interactions between an aromatic alkyl ester, water and peracetylated CDs. In some cases, substituent chemical shift determination was influenced by the low water content of CDCl3 and/or the host molecule. Higher CD concentrations resulted in water signal drifts in all studied cases. It was not possible to obtain a completely dry sample of peracetyl γCD: ∼1 mol of water remained and the water signal showed reversed movement, with respect to the other two CD analogues, upon increasing host concentration. The estimated 1 : 1 stability constants for the water : peracetyl CD complexes are in the 50-150 M(-1) range in CDCl3, but show a relatively large calculation error. The calculated 1 : 1 stability constants for the peracetyl CD : ester complexes are also in this range, but 1 : 2 and 2 : 1 complex compositions are also possible. Overall, our results highlight dynamic aspects of water nanoconfined in a highly hydrophobic environment, thus mimicking biological recognition where a few water molecules often play a pivotal role.

An Anomalous Hammett Correlation for a Series of Substituted 3-Benzyl-2-phenyl-1,3-thiazolidin-4-ones

A series of 3-benzyl-2-phenyl-1,3-thiazolidin-4-one derivatives, with substituents at the N-benzyl site, was synthesized and characterized. Excluding the p -MeO and m -Br derivatives, distinct correlations between Hammett constant ? and 13 C substituent chemical shifts were observed in the C2, C4, and C5 carbons in the thiazolidin-4-one ring. This was unexpected because the transmission of substituent effects appears to be occurring via the sp 3 hybridized N-benzyl carbon. No discernible correlation was seen for the N-benzyl carbon; the carbon through which the effects were occurring. Correlations for substituent chemical shifts to Swain Lupton substituent parameters r and f constants were also attempted. Similar to the Hammett correlations, C2, C4, and C5 showed a reasonable degree of correlation with minimal to no improvement over Hammett constants; similarly, as with the Hammett correlations, the benzyl carbon exhibited no correlation with Swain Lupton parameters. Normal 0 7.8 ? 0 2 false false false EN-US ZH-CN X-NONE

NMR Analysis of Substituent Effect of Arymethylene‐malononitriles and Malonates

AbstractA series of arylmethylene‐malononitriles and malonates were prepared from the condensation of arylaldehydes and malononitriles and malonates, respectively. The function of substituents on the carbon‐13 chemical shifts of the Cα and Cβ was studied. The correlation between Hammett's constants and the substituent chemical shifts demonstrates a negative slope for Cα and positive for Cβ (1, Cα:ρ = ‐3.877, r2 = 0.979; Cβ:ρ = 6.899, r2 = 0.984; 2, Cα:ρ = ‐2.817, r2 = 0.926; Cβ:ρ = 5.355, r2 = 0.950). The large slopes for Cβ for both series compounds resemble our previous studies on the arylcyclopropanes.The relaxation time of both proton and carbon are slightly affected by the size of substituents. In the viscosity study, an inverse‐law relationship between relaxation time and viscosity was observed.

Verifying the Predictability of 13C Chemical Shifts for a Series of Substituted-2-(4-Chlorophenyl)-3-Phenyl-1,3-Thiazolidin-4-Ones

Previously, an “additivity” equation relating experimental 13C chemical shift data for two monosubstituted diphenyl-1,3-thiazolidin-4-one series was developed to predict chemical shifts for a similarly substituted bis-disubstituted thiazolidinone series. The sites of interest in the 1,3-thiazolidin-4-one are at the C-2, C-4, and C-5 carbons. The empirically derived equation for predicting the chemical shifts is dXY = dH + (dX-dH) + (dY-dH) where dXY is the predicted chemical shift for the disubstituted thiazolidinone: dH is the experimental chemical shift for the unsubstituted thiazolidinone, dX is the experimental chemical shift for substituent in the 2-phenyl ring, and dY is the experimental chemical shift for substituent in the N-(3)-phenyl ring. This article discusses the application of the aforementioned equation with respect to a new series of 2-(p-chlorophenyl)-phenyl-substituted-3-phenyl-1,3-thiazolidin-4-oneswith a comparison of both experimental and predicted 13C chemical shifts for the C-2, C4 and C-5 sites in the thaizolidinone ring. Utilization of the equation showed a level of chemical shift predictability with a degree of accuracy in concert with a previously reported series. The degree of predictability again showed a dependency on the particular substituent and the chemical shift for the site being predicted. This was ±0.06 ppm for C-2, ±0.2 ppm for C-4 and ±0.09 ppm for C5. Finally, there was a correlation between Hammett s values and the substituent chemical shifts using 13C values at C-2. The r value was -0.86 indicating that the C-2 carbon preferred a positive charge.

An Experimental and Theoretical Conformational Study of a Series of Substituted 3-cyclohexyl-2-phenyl-1,3-thiazolidin-4-ones

A series of novel 3-cyclohexyl-2-phenyl-1,3-thiazolidin-4-one derivatives with substituents on the 2-phenyl ring were synthesized, and a study of their solid state and solution conformations was effected. In solution the thiazolidin-4-one ring preferred the C2 phenyl in a pseudo-equatorial orientation and the solid state indicated a preference for the C2 phenyl being in a pseudo-axial orientation. Less robust substituent chemical shift (SCS) correlations utilizing 13C NMR were observed in this instance than in prior studies. Molecular modeling studies using Moller-Plessett second-order perturbation theory (MP2) indicate that the thiazolidinone ring and cyclohexyl ring conformations exhibit a global minimum consistent with the solution studies.

Synthesis and NMR Studies of (E)-1-Aryl-3-(2-pyrrolyl)-2-propenones and (E)-3-Aryl-1-(2-pyrrolyl)-2-propenones

Series of (E)-1-aryl-3-(2-pyrrolyl)-2-propenones, that were aldol condensation products between pyrrole-2-carbaldehyde and m- and p-substituted acetophenones, were prepared and their <TEX>$^1H$</TEX> and <TEX>$^{13}C$</TEX> NMR spectra were examined to obtain the information on the conformation of the enone system. Similar studies were carried out with (E)-3-aryl-1-(2-pyrrolyl)-2-propenones that were prepared from 2-acetylpyrrole and m- and p-substituted benzaldehydes. The substituent chemical shifts were studied by applying the Hammett relationship.

1H NMR spectra. Part 30: 1H chemical shifts in amides and the magnetic anisotropy, electric field and steric effects of the amide group

The (1)H spectra of 37 amides in CDCl(3) solvent were analysed and the chemical shifts obtained. The molecular geometries and conformational analysis of these amides were considered in detail. The NMR spectral assignments are of interest, e.g. the assignments of the formamide NH(2) protons reverse in going from CDCl(3) to more polar solvents. The substituent chemical shifts of the amide group in both aliphatic and aromatic amides were analysed using an approach based on neural network data for near (≤3 bonds removed) protons and the electric field, magnetic anisotropy, steric and for aromatic systems π effects of the amide group for more distant protons. The electric field is calculated from the partial atomic charges on the N.C═O atoms of the amide group. The magnetic anisotropy of the carbonyl group was reproduced with the asymmetric magnetic anisotropy acting at the midpoint of the carbonyl bond. The values of the anisotropies Δχ(parl) and Δχ(perp) were for the aliphatic amides 10.53 and -23.67 (×10(-6) Å(3)/molecule) and for the aromatic amides 2.12 and -10.43 (×10(-6) Å(3)/molecule). The nitrogen anisotropy was 7.62 (×10(-6) Å(3)/molecule). These values are compared with previous literature values. The (1)H chemical shifts were calculated from the semi-empirical approach and also by gauge-independent atomic orbital calculations with the density functional theory method and B3LYP/6-31G(++) (d,p) basis set. The semi-empirical approach gave good agreement with root mean square error of 0.081 ppm for the data set of 280 entries. The gauge-independent atomic orbital approach was generally acceptable, but significant errors (ca. 1 ppm) were found for the NH and CHO protons and also for some other protons.

1 H NMR spectra. Part 29§: proton chemical shifts and couplings in esters-the conformational analysis of methyl γ-butyrolactones

The (1)H NMR spectra of 35 cyclic and acyclic esters are analysed to give the (1)H chemical shifts and couplings. The substituent chemical shifts of the ester group were analysed using three-bond (γ) effects for near protons and the electric field, magnetic anisotropy and steric effect of the ester group for more distant protons. The electric field is calculated from the partial atomic charges on the O⋅C = O atoms, and the asymmetric magnetic anisotropy of the carbonyl group acts at the midpoint of the C = O bond. The values of the anisotropies Δχ(parl) and Δχ(perp) were for the aliphatic esters 10.35 and -18.84 and for the conjugated esters 7.33 and -15.75 (×10(-6) Å(3)/molecule). The oxygen steric coefficients found were 104.4 (aliphatic C = O), 45.5 (aromatic C = O) and 16.0 (C-O) (×10(-6) Å(6)/molecule). After parameterisation, the overall RMS error for the data set of 280 entries was 0.079 ppm. The strongly coupled (1) H NMR spectra of the 2-methyl, 3-methyl and 4-methyl γ-butyrolactones were analysed and the methyl conformational equilibrium obtained from the observed couplings. The observed versus calculated density functional theory (DFT) ΔG(ax-eq) was 1.0 (1.01), 0.34 (0.54) and 0.65 (0.71) kcal/mol res. The shielding effect of a methyl cis to a proton in the five-membered lactone rings is -0.40 ±0.05 ppm and deshielding trans effect 0.12 ±0.05 ppm, which is common to both five and six membered rings. The cis/trans isomerism in the vinyl esters methyl acrylate, crotonate and methacrylate and methyl furoate was examined using the (1)H chemical shifts. The calculated shifts of both the cis and trans isomers were in good agreement with the observed shifts.

NMR Landscapes for Chemical Shift Prediction

The ability to reliably predict NMR chemical shifts plays an important role in elucidating the structure of organic molecules. Additionally, an intriguing question is how the multitude of variable factors (structural, electronic, and environmental) correlate with the actual electromagnetic shielding effect that determines the chemical shift value. This work presents NMRscape as a new tool for understanding these correlations by constructing the landscape that describes the relationship between the chemical shift value and the moieties bonded to a molecular scaffold. The scaffold may be as small as a single atom probed by NMR or a larger molecular framework containing the probed atom. NMRscape operates with only a list of the chemical moieties bonded to the scaffold, without utilizing any potentially biasing chemometric descriptors. The corresponding chemical shift landscape is constructed based on fundamental physical principles, which makes NMRscape a credible chemical shift prediction and analysis tool. As an illustration, we demonstrate that NMRscape can predict (13)C chemical shifts with an accuracy exceeding the substituent chemical shift (SCS) increment, hierarchical organization of spherical environments (HOSE), and neural networks (NN), methods for three distinct families of molecules sharing a common scaffold structure with moieties placed at two variable sites. The constructed NMR landscapes confirmed known empirical rules relating chemical shift values to the variation of chemical moieties on a scaffold, as well as uncovered hitherto hidden relationships. The practical importance of NMRscape is discussed.

1 H NMR Spectra. Part 28: Proton chemical shifts and couplings in three-membered rings. A ring current model for cyclopropane and a novel dihedral angle dependence for 3 JHH couplings involving the epoxy proton

The (1) H chemical shifts of selected three-membered ring compounds in CDCl(3) solvent were obtained. This allowed the determination of the substituent chemical shifts of the substituents in the three-membered rings and the long-range effect of these rings on the distant protons. The substituent chemical shifts of common substituents in the cyclopropane ring differ considerably from the same substituents in acyclic fragments and in cyclohexane and were modelled in terms of a three-bond (γ)-effect. For long-range protons (more than three bonds removed), the substituent effects of the cyclopropane ring were analysed in terms of the cyclopropane magnetic anisotropy and steric effect. The cyclopropane magnetic anisotropy (ring current) shift was modelled by (a) a single equivalent dipole perpendicular to and at the centre of the cyclopropane ring and (b) by three identical equivalent dipoles perpendicular to the ring placed at each carbon atom. Model (b) gave a more accurate description of the (1) H chemical shifts and was the selected model. After parameterization, the overall root mean square error for the dataset of 289 entries was 0.068 ppm. The anisotropic effects are significant for the cyclopropane protons (ca 1 ppm) but decrease rapidly with distance. The heterocyclic rings of oxirane, thiirane and aziridine do not possess a ring current. (3) J(HH) couplings of the epoxy ring proton with side-chain protons were obtained and shown to be dependent on both the H-C-C-H and H-C-C-O orientations. Both density functional theory calculations and a simple Karplus-type equation gave general agreement with the observed couplings (root mean square error 0.5 Hz over a 10-Hz range).

A 1H NMR and theoretical investigation of the conformations of some monosubstituted cyclobutanes

The complete analysis of the complex (1)H NMR spectra of some monosubstituted cyclobutanes was achieved to give all the (1)H chemical shifts and (n)J(HH) (n = 2, 3 and 4) coupling constants in these molecules. The substituent chemical shifts of the substituents in the cyclobutane ring differ significantly from those in acyclic systems. For example, the OH and the NH(2) groups in cyclobutanol and cyclobutylamine produce a large shielding of the hydrogens of the opposite CH(2) group of the ring compared with little effect on the comparable methylene protons of butane. These effects and the other (1)H shifts in the cyclobutanes were modelled successfully in the CHARGE program. The RMS error (calculated vs observed shifts) for the 34 (1)H shifts recorded was 0.053 ppm. The conformational equilibrium in these compounds between the axial and the equatorial conformers was obtained by comparing the observed and the calculated (4)J(HH) couplings. These couplings in cyclobutanes, in contrast to the corresponding (3)J(HH) couplings, show a pronounced orientation dependence; (4)J(eq-eq) is ca 5 Hz and (4)J(ax-ax) ca 0 Hz. The couplings in the individual conformers were calculated at the B3LYP/EPR-III level. The conformer energy differences ΔG(ax-eq) vary from 1.1 kcal mol(-1) for OH to 0.2 kcal mol(-1) for the CH(2)OH substituent. The values of the conformer energy differences are compared with the previous IR data and the corresponding theoretical values from molecular mechanics (MM) and DFT theory. Generally, good agreement is observed although both the MM and the DFT calculations deviate significantly from the observed values for some substituents.

ChemInform Abstract: Transmission of Polar Substituent Effects in the Adamantane Ring System as Monitored by 19F NMR: Hyperconjugation as a Stereoinductive Factor.

A limited series of (E)- and (Z)-5-substituted adamant-2-yl fluorides 8 and 9, respectively, has been synthesized and characterized, and the 19 F chemical shifts have been measured in several solvents. A wide range of 19 F substituent chemical shifts (SCS, ppm) are obtained for the former system (ca. 9.1 (c-C 6 H 12 ), 9.6 (CDCl 3 ), and 11.8 (HFIP)) compared to the latter (ca. 0.6 (c-C 6 H 12 ), 0.7 (CDCl 3 ), and 2.3 (HFIP)). Factorization of the 19 F SCS into polar field (ρ F σ F ) and residual contributions ( 19 F SCS-ρ F σ F ) reveals the predominance of the latter solvent-independent component for the E fluorides (8). Comparison of 8 with a similar dissection of the 19 F SCS of 4-substituted bicyclo[2.2.]oct-1-fluorides 2 strongly suggests that the origin of the large residual contributions for 8 is «through-three-bond] electron delocalization or double hyperconjugation. The importance of this long-range electronic mechanism as a factor governing π-facial diastereoselection in 2,5-disubstituted adamantanes is discussed