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Stereoelectronic Effects: The #-Gauche Effect in Sulfoxides Sebastian Jung, and Joachim Podlech J. Phys. Chem. A, Just Accepted Manuscript • DOI: 10.1021/acs.jpca.8b03729 • Publication Date (Web): 12 Jun 2018 Downloaded from http://pubs.acs.org on June 20, 2018

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The Journal of Physical Chemistry

Stereoelectronic Effects: The γ-Gauche Effect in Sulfoxides Sebastian Jung, Joachim Podlech* Karlsruher Institut für Technologie (KIT), Institut für Organische Chemie, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany

ABSTRACT: 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 γgauche 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.

Introduction Chemical shifts in 13C NMR spectra are dependent from a functional group in α-, β-, γ-, etc. position. Charts with a large number of substituent chemical shifts (SCS) have been compiled, which are essential for the estimation of 13C shifts using incremental methods, e.g. used in software for the simulation and prediction of NMR spectra. It turned out that 13 C signals of carbons in γ-gauche position to a functional group are shifted upfield with respect to the parent compound, in which the functional group is replaced with a hydrogen atom (Figure 1).1 This γ-gauche effect has been investigated for different functional groups and this phenomenon is comprehensively described, though a general explanation has not been given. During our investigations on the influence of sulfoxide groups on structure, stability, reactivity, and spectroscopic properties of the respective compounds,2‒8 we realized that the γ-gauche effect in sulfoxides is not well understood and that a convincing and consistent explanation is still missing. It could be noted that the γ-gauche effect in sulfoxides actually occurs β to the S=O group. This extraordinary labelling is commonly used to allow for a comparison with other functional groups.

Figure 1. γ-Positions in functionalized substrates.

The effect has at first been observed in the quite related sulfites9‒12 and has later been identified in sulfoxides of 1,4oxathianes,13 thianes,14‒16 dithianes,17 other thia cycles,18‒21 and in compounds bearing further sulfur-related functional

groups.16,19,22,23 Compounds suitable for experimental investigations need to be cyclic and conformationally rigid to provide an unambiguous orientation of the functional group and the carbon atom. A variety of explanations has been given during the last 50 years. Archer et al. referred to steric reasons,18 which were widely accepted in the further course,13,15,20,24‒26 but seem to be less stressed inbetween. Other explanations considered a presumed magnetic anisotropy of the S‒O bond, as it is present in acetylenes.9‒12,23,27,28 Nevertheless, this anisotropy has never been investigated thoroughly. The possibility of stereoelectronic effects has been brought into equation by Fraser et al.19 and has occasionally been taken into account.17 Especially an interaction of the sulfur lone pair with the antibonding C‒C bond between the βand the γ-carbon atom (nS → σ*Cβ‒Cγ; positions are defined in Figure 1) was suggested by Rooney and Evans.21 Neither this effect was systematically examined. A further explanation considers that the C‒H bond is missing, when a functional group is present.29 To gain profound knowledge of the reasons of the γ-gauche effect, we decided to use a variety of theoretical methods.

Computational Details All structures were optimized at the B3LYP20‒32/6311++G(d,p)33‒35 level by using the Gaussian 09 software package.36 A very similar basis set was described to be suitable to describe intramolecular interactions that are responsible for trends in 13C chemical shifts.37 The NBO 3.1 program for natural bond orbital (NBO)38‒41 and natural chemical shielding (NCS) analyses42 was used as implemented in Gaussian 09. In conformational scans all conformers were optimized with one fixed dihedral angle followed by a single point calculation, where the atom of interest was placed in the origin of a cartesian system. Iso-chemical-shielding surfaces

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(ICSSs) based on the nucleus-independent chemical shifts (NICS) developed by von R. Schleyer et al.43 have been described by Kleinpeter et al.:44,45 Dummy atoms (5000 per run) were placed equidistantly on a 3D grid and their shielding tensors were calculated with Gaussian. The cube file prepared from the obtained values was visualized with Jmol.46 To visualize the paramagnetic and diamagnetic contributions to the total shielding, the utilized script was modified to calculate only one dummy atom per run, which was kept at the origin of the cartesian system with the molecule’s position changing. The isotropic shielding density was calculated as (σxx + σyy + σzz)/3. Gaussian standard NMR calculations result in checkpoint files, from which the densities can be extracted as cube files by using cubman (as delivered with Gaussian).47 Chemical shifts (relative to SiMe4) and paramagnetic and diamagnetic shieldings were calculated by means of the GIAO method48 (B3LYP/6-311++G(d,p)) in Gaussian 09. Magnetically induced currents were calculated using GIMIC,49‒51 where the required input files were obtained with the TURBOMOLE52,53 software package at the same level (using the GIMIC keyword). For adaptive natural density partitioning (AdNDP) analyses54,55 the tool MultiWFN56 was used. Plots were prepared with Gnuplot.57

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Chart 1. Investigated Sulfoxides and 13C NMR Dataa

Results 13

C NMR Data of Sulfoxides During our investigations on sulfoxides2‒8 we obtained a number of 13C NMR data and found these to be not fully consistent with the proposed γ-gauche effect (Chart 1, measured 13C data are given in parenthesis15,58,59). To gain a deeper insight into this phenomenon we calculated chemical shifts for a wide selection of conformationally rigid thianederived sulfoxides together with data of substrates 1‒3, in which a rotation around S‒C bonds is possible. The analysis of all measured and calculated data revealed that only one of the two γ-gauche-positioned types of carbon atoms shows an upfield shift ‒ those carbons, which are in antiperiplanar orientation to sulfur lone pairs.21 These positions are labeled as antiperiplanar to the lone pair (aplp,60 Figure 1). Most convincing are the shift differences in the three conformers61 of ethyl methyl sulfoxide 1, in the isopropyl methyl sulfoxide conformers 2, and in tert-butyl methyl sulfoxide 3. These differences are only accessible by in silico methods, since the fast rotation leads to averaged signals in standard experiments. It is evident from the calculated NMR data of these compounds that only the γ-gauche carbons in ap-lp positions (marked in red) are additionally shielded, while the γ-gauche sc-lp carbons (synclinal to the lone pair, blue) virtually show the same shielding as the ap-SO carbon atoms (black). This finding is confirmed by the data of numerous thiane-derived sulfoxides: The ring carbons C-3 and C-5 are ap-SO-positioned in equatorial sulfoxides and ap-lporiented in the axial isomers. Only the latter suffer a significant shielding (upfield shift). In 2,2-dimethylsubstituted thiane S-oxides with equatorial S‒O bonds 5eq, 6eq and 7eq the axial methyl groups (ap-lp) show a shift difference around 14 ppm (upfield shift) as compared with the equatorial methyl groups (sc-lp).

a

Calculated 13C NMR data. Measured values are given in parenthesis.15,58,59 red: γ-gauche (ap-lp) positions; blue: γ-gauche (sclp).

Iso-Chemical-Shielding Surfaces (ICSSs) A magnetic anisotropy of sulfoxide bonds was considered a possible reason for the γ-gauche effect of sulfoxides during the last decades.9‒12,23 Calculation and visualization of the magnetic anisotropy is possible by application of a method described by Kleinpeter et al. for determination of the acetylene anisotropy.44,45 The obtained isosurfaces (isochemical-shielding surfaces ‒ ICSSs) show shielded and deshielded volumes, respectively. We calculated ICSSs for a selection of model compounds: the hypothetical dihydrogen sulfoxide (H2SO, Figure 2a), which would not suffer an aberration through further substituents at the sulfur, dimethyl sulfoxide (DMSO, Figure 2b), and the axial and equatorial thiane S-oxides (4ax and 4eq, Figure 2c and d). In H2SO, we found deshielded zones around the atoms and along the bonds and a weakly shielded volume of approximately toroidal shape around the S‒O bond together with a small bulge on the S‒O axis beyond the oxygen. The toroidal shape is quite similar to that observed for C≡C bonds in acetylenes (see Supporting Information).44,45 In DMSO the weakly shielded zone is partially countervailed by deshielded


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zones around the methyl groups. An argumentation based on the data for this molecule is thus not very meaningful. Thiane S-oxides 4 possibly would serve as appropriate models for the cyclic compounds depicted in Chart 1. Significantly deshielded volumes are present above and below the ring. Presuming that the anisotropy of the S‒O bond is observed virtually undisturbed in H2SO, we would expect a small additional deshielding at both γ-gauche positions instead of a strong shielding only at the ap-lp positions. We consequently come to the conclusion that the shielding of the ap-lp positions is not properly explained by the magnetic anisotropy of the S‒ O bond.

for an understanding of the shielding differences between ring member carbons and methyl substituents.

Figure 2. Iso-chemical-shielding surfaces (ICSSs) of (a) H2SO, (b) DMSO, and (c) equatorial and (d) axial thiane S-oxides 4; cutoffs: (a) 15 (shielded, mint), ‒0.10 (deshielded, salmon); (b‒d) 15, ‒0.15.

To supplement these findings, we calculated isoparamagnetic- and iso-diamagnetic-shielding surfaces for the conformers of ethyl methyl sulfoxide 1 (see Supporting Information). Although there is no obvious influence for the C-2 region, it can be deduced, that the paramagnetic deshielded volume around the oxygen turns into a paramagnetic shielded volume, when carbon C-2 is in proximity, what is true for both gauche conformations. Current Maps and Shielding Densities The conclusions drawn from the ICSSs are further supported by maps of magnetically induced currents (Figure 3). A significant current in H2SO is induced, when a magnetic field is applied with a vector along the S‒O bond. In DMSO local vortices are present around the S‒O bond and around the methyl groups irrespective of the applied magnetic field’s orientation (see Supporting Information). Dominating overall currents are possible in the thiane S-oxides’ rings, which allow

Figure 3. Magnetically induced currents in (a) H2SO, (b) DMSO, and in (c) equatorial and (d) axial thiane S-oxides 4.

It is quite demanding to deduce an influence of these complex arrangements of vortices on the shielding and deshielding of specific atoms. This becomes especially obvious, when the isotropic shielding density (accessible from the induced



current density) for C-2 in ethyl methyl sulfoxide (1) is visualized (Figure 4). The current density has no general shielding or deshielding effect but is higly location-dependant. The C-2 carbons of both γ-gauche conformers ap-lp-1 and sclp-1 are within an essentially shielding zone (blue). Pronounced deshielding currents (red) are located between C2 and C-1 and a less distinct deshielding influence appears in the vicinity of the S–O bonds.

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significantly reduced (to 1.89 and 1.82, respectively), where the C‒S σ*-orbitals show the corresponding occupation. This can be expressed by a no bond ‒ double bond resonance with significant S‒O double bond character, though the reasoning that both oxygen p-orbitals participate in the resonance is not easy within this simplified picture (Figure 5, bottom). The relevant section of the NBO analysis is given in the Supporting Information. employed notations of sulfoxides:

O

O

O

S

S

S

double bond H3 C S H 3C

O

H 3C S H3 C

O no bond H 3C H3 C

H 3C H3C

S

O

H3 C H 3C

S

S

O

O

Figure 5. Possible representation of sulfoxides (top) and resonance formulae of DMSO (bottom).

Figure 4. Isosurfaces of isotropic shielding densities for C-2 for the gauche conformers ap-lp-1 (top) and sc-lp-1 (bottom) of ethyl methyl sulfoxide. Cutoffs: ‒0.1 (yellow) and 0.1 (aqua). The respective shielding densities are additionally given as contour plots in the C2-C1-S plane.

In adaptive natural density partitioning (AdNDP) analyses reasonable occupation numbers are achieved, when an S‒O triple bond is assumed. Figure 6 gives 13 localized orbitals as resulting from an AdNDP analysis, where neither an energetic order nor energetic distances are implied with this representation. The bottom molecular orbitals (MOs) show the localized lone pairs at the oxygen (left) and the sulfur (right). Above an overlay of the six C‒H bonds representing six MOs, in the third row from the bottom the S‒O σ-bond and then the two orthogonal S‒O π-bonds. In the top row two 4-center-2electron MOs including the carbons, the sulfur and the oxygen. The relevant section of the AdNDP output including the occupancies is given in the Supporting Information. The MOs in the second and third row from the top constitute the triple bond, while the 4-center-2-electron MOs are antibonding along the S‒O bond and reduce its bond order significantly.

Localized Orbitals of the S‒O Bond in Sulfoxides The character of the S‒O bond in sulfoxides (and other related compounds) is still in discussion and the special binding situation is reflected by the great number of possibilities for its notation (Figure 5, top). A profound knowledge of the bonding in the S=O group seems to be essential for an understanding, e.g., of its shielding or deshielding effect on vicinal carbon atoms. We performed a natural bond orbital (NBO) analysis of DMSO, where the output lists six localized C‒H σ-bonds, two C‒S σ-bonds, one S‒O σ-bond and four lone pairs. A mainly s-type lone pair is located at the sulfur atom and the oxygen is surrounded by one s-type and two orthogonal p-type lone pairs. Second order perturbation theory analysis indicates a strong delocalization of the oxygen’s p-type lone pairs with the C‒S σ*-orbitals. The occupancy of the lone pair orbitals is


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NCS Analyses We performed natural chemical shielding (NCS) analyses for three ethyl methyl sulfoxide (1) conformers allowing for the conclusion that shielding at C-2 is essentially an effect of the core orbitals of this atom. Nevertheless, the respective values are identical for all conformers. Deshielding however is related to the bonds attached to C-2 and is largely attributed to the paramagnetic contribution. Especially in the gauche conformers no differences in the total diamagnetic shielding can be detected, while the total paramagnetic shielding is significantly different for these isomers. Nevertheless, a general trend could not be traced back to specific bonds,63 neither for the paramagnetic shielding nor for shielding differences in the conformers. More details on the NCS analyses are given in the Supporting Information.

Figure 6. MOs as resulting from AdNDP analysis (no energetic order is implied).

The deduced triple bond character62 can further be rationalized by a schematic MO diagram, which was derived from a calculation of fragment orbitals (Figure 7): The MOs essentially arising from the two orthogonal S‒O π-bonds are bonding along the S‒O bond (ψ1, ψ2), while the highest occupied MOs built by symmetry-adapted linear combination of S‒O π*-orbitals with methyl sp3-hybrid orbitals are antibonding along the S‒O bond (ψ3, ψ4). This simple picture again allows for the conclusion that, though the S‒O moiety in sulfoxides has some triple bond character, its effective bond order is significantly smaller due to contributions of ψ3 and ψ4. The attenuation of the S‒C bonds becomes obvious from NBO analyses and is demonstrated by no bond ‒ double bond resonances as given in Figure 5. O O S H 3C

CH3

H 3C

CH3

H 3C

S

Dihedral Scans of Ethyl Methyl Sulfoxide Dihedral scans of ethyl methyl sulfoxide 1 were performed supplying information on dia- and paramagnetic shielding, partial charges, and orbital interactions in dependency of the dihedral angle. The conformations were optimized with one fixed parameter (the respective dihedral) and these partially optimized structures were used in further single point methods. To face the Eich invariance (gauge invariance) arising in calculation of the paramagnetic shielding, C-2 was always placed at the origin, the C-2–C-1 bond was set along the first axis and the C-2,C-1,S plane was positioned in the plane spanned by the first two axes. Figure 8 shows the diamagnetic, paramagnetic, and total shielding at carbon C-2 for all conformations. (Note the different scaling for these parameters.) Obviously the γ-gauche effect is a result of paramagnetic (de-)shielding. While the overall differences for the diamagnetic shielding span about 4.5 ppm, maxima are close to the minimum conformations of 1. The differences for these conformers are even smaller ‒ no significant contribution arises for any of the γ-gauche positions. Paramagnetic shielding varies within ~10 ppm and a significantly reduced deshielding emerges for the γ-gauche conformer ap-lp-1.

O S

ψ4 CH3

O S H3 C

ψ3 CH3 O

1

ψ ,ψ

2

S

O S

CO

C

O

Me

Figure 7. Schematic MO diagram for DMSO. The energetic positions are not drawn to scale.

θ = 0°

O Me

60° (sc-lp-1)

C 120°

O Me

O Me

C 180° (ap-SO-1)

O C Me

240°

C Me

300° (ap-lp-1)

CO Me 360°

Figure 8. Dihedral scans of the dia- and paramagnetic shielding in ethyl methyl sulfoxide 1.



It has already concluded by Ramsey that shielding is linked to the occupancies of virtual orbitals at and around nuclei (and thus to their charges).64,65 Figure 9 gives the natural charges for carbon C-2 in ethyl methyl sulfoxide 1 resulting from NBO analyses, the summarized occupancies of the σ-orbitals adjacent to this atom, and the summarized occupancies of the adjacent σ*- and the eight lowest Rydberg (Ry) orbitals. (Note again the different and reversed scaling.) The σ-occupation is given relative to the maximum value, while the occupation of the virtual orbitals is given as relative deviation from the minimum. The σ-occupation is varying only within 1‰, while changes of the σ*-occupation are exceeding 20%. The σ*occupation and the herewith connected natural charges are close to the maximum values in the ap-lp conformation.

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Figure 10. Dihedral scans of virtual orbital occupancies at C-2 with and without deletion of stereoelectronic interactions in ethyl methyl sulfoxide 1. Newman projections of selected conformations are given in Figure 8.

Discussion

Figure 9. Dihedral scans of natural charges and σ- and σ*occupancies at C-2 in ethyl methyl sulfoxide 1. Newman projections of selected conformations are given in Figure 8. To determine the most relevant orbital interactions responsible for the significant occupancy of the virtual orbitals around carbon C-2, we performed NBO calculations in dihedral scans for the conformations of 1 with and without deletion of the respective orbital interactions (Figure 10). The off-diagonal elements for one (or several) donor orbitals and the relevant virtual orbitals around C-2 (σ*C2–C1, 3×σ*C2–H, 8×Ry*C2, and 3×Ry*H) were set to zero, thus preventing the respective set of stereoelectronic interactions. The occupancies of all virtual orbitals are summed up and compared with the occupation of these orbitals, when the respective orbital interactions are not disabled. The difference of the occupations with and without deletion of the stereoelectronic interaction with one or several donor orbitals is regarded as these donors’ contribution to the occupancy. Figure 10 gives the occupancy of virtual orbitals around C-2 without deletion (scale on the right) and the contributions to the occupancy arising from the nS → (C2)* and the (O) → (C2)* interactions, respectively (scale on the left). The term (O) → (C2)* is here used to describe a summation of all interactions between the donor(s) (here the σO‒S and lone pairs at the oxygen atom) and the acceptor(s) (here the σ*-bonds with participation of C-2 and Rydberg orbitals at C-2 and at the hydrogens at C-2). The main contribution for the (C2)* occupancy in the ap-lp conformer obviously arises from the nS → (C2)* interactions. The similarly significant (O) → (C2)* contributions are effective for both gauche conformations ap-lp and sc-lp and especially for the ap-SO conformation. Other interactions have only negligible influence on the (C2)* occupancies or are consistently effective in all conformations.

Though the γ-gauche effect is a well-established phenomenon and the shielding effect has been included into models for the prediction of NMR shifts,28 its origin remained obscure. Two explanations had been championed – the anisotropy theory and an argumentation based on steric reasons. Both theories have been discussed controversially, but to our opinion a concluding explanation has not been given. The herein presented investigations clearly show that the anisotropy theory is in contradiction with the determined ICSSs and with the calculated shielding densities. A putative similarity of the (diamagnetic) anisotropies in acetylenes and in the S‒O bond of sulfoxides has occasionally been emphasized.14 This would lead to additional shielding for both γ-gauche positions, what is in disagreement with measured and calculated data.66 An anisotropy similar to that in acetylenes would furthermore lead to an effect, which could be assumed to be much weaker ‒ Kleinpeter and Klod found the anisotropic influence of acetylenes to be negligible.45 Steric interactions seem at first glance to be consistent with the observed chemical shifts we calculated for the conformers of 1. Carbon C-2 in ap-lp-1 is gauche with respect to the S=O and the S‒Me group ‒ it is shielded. In conformer sc-lp-1 a gauche interaction arises only with the S=O and in ap-SO-1 only with the S‒Me group. Both conformers show similar shieldings at C-2. Nevertheless, the steric reasons are in contradiction with the analysis of the dihedral scan given in Figure 8: Steric interaction would be most significant not in the gauche ap-lp, but in the ecliptic conformations. Inspection of the scan in Figure 8 immediately reveals that the diamagnetic and paramagnetic shieldings are not highest for the ecliptic conformations; these are less than those of the aplp conformation. Further evidence against steric reasons and against effects arising from anisotropies can be deduced from related compounds: A substitution of the methyl with a methylene group leads to a significantly different curves for the diamagnetic and paramagnetic shieldings, while a replacement of the S=O group with C‒OH or C‒F groups gives rise to very similar curve shapes. The respective dihedral scans and those of further related compounds are given in the Supporting Information. The NCS analyses allow no unambiguous conclusion: The influence of isolated σ-bonds on the shielding at C-2 is not significant but at least it can be deduced that the effect of


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distant bonds is negligible. NBO analyses turned out to be much more meaningful: A reasoning with donor/acceptor interactions (stereoelectronic effects), which lead to an occupation of σ*-bonds and Rydberg orbitals at selected atoms is very instructive and can result in a conclusive understanding of the γ-gauche effect in sulfoxides: The oxygen lone pairs act as donors, transferring electron density through space into acceptor orbitals at C-2 when close enough, which is possible in both gauche conformations. Nevertheless, a strong interaction of the sulfur lone pair with the unoccupied C-2 orbitals is possible only in the ap-lp gauche conformation. Any shielding resulting from stereoelectronic effects in the other gauche conformation sc-lp is considerably smaller. Investigations of Della, Contreras et al. on 1-substituted bicyclo[1.1.1]pentanes showed that the interaction of donors (bonds or lone pairs) with unoccupied bonds adjacent to a carbon are clearly related with a shielding of this carbon, while the respective interaction of bonds adjacent to a carbon with acceptors come along with a deshielding effect for this carbon.37,67 It can be assumed that these findings are similarly applicable to sulfoxides. The coexistence of other influences like steric or geometric effects cannot be ruled out, but steric effects have been stated to have a deshielding effect68 and a geometric effect can be expected to be negligible for this type of carbon atoms since their shielding tensor shows only a small anisotropy. It could be mentioned in passing that the shielding tensors of oxygen and sulfur atoms show a significantly higher anisotropy; their eigenvectors are strongly affected by conformational changes (see Supporting Information).

Conclusions While the γ-gauche effect in sulfoxides has previously mainly been explained with steric interactions or with the diamagnetic anisotropy of the S–O bond, we identified an nS → σ*C1–C2 stereoelectronic interaction to be the main foundation for the reduction of the paramagnetic deshielding at ap-lp positions. This is in agreement with investigations, where the influence of stereoelectronic interactions on chemical shifts caused by other functional groups has been examined,67 and is related with other stereoelectronic effects on NMR-spectroscopic properties like the Perlin effect observed for 1JC‒H or 1JC‒F coupling constants.69‒72 A generalization of this model for other functional groups is not permissible without further examinations, but an adoption of the herein applied methods to other compound families seems to be very promising. A presented instructive model for the bonding in sulfoxide’s S=O groups based on AdNDP analysis turned out to be helpful in these investigations and might lead to a better understanding of spectroscopic properties and the reactivity of sulfoxides. Supporting Information. Enlarged figures, iso-paramagneticshielding surfaces for the conformers of ethyl methyl sulfoxide 1 and tert-butyl methyl sulfoxide 3, additional dihedral scans, details on the NBO, AdNDP, and NCS analyses, and shell scripts and input files for calculations described in this paper. This material is available free of charge via the Internet at http://pubs.acs.org.

AUTHOR INFORMATION

Corresponding Author * [email protected]

Author Contributions The manuscript was written through contributions of all authors.

ACKNOWLEDGMENT We are deeply indebted to Florian Weigend, Kevin Reiter, and Willem Klopper for continuous support and helpful discussions. We thank Heike Fliegl for her helpful advice on GIMIC. Dedicated to Prof. Dr. Dr. h.c. Dieter Seebach on the occasion of his 80th birthday.

ABBREVIATIONS AdNDP, adaptive natural density partitioning; DMSO, dimethyl sulfoxide; GIAO, gauge-including atomic orbitals; GIMIC, gauge-including magnetically induced currents; ICSS, isochemical-shielding surface; lp, lone pair; MO, molecular orbital; NBO, natural bond orbital; NCS, natural chemical shielding; NICS, nucleus-independent chemical shifts; NMR, nuclear magnetic resonance; Ry, Rydberg (orbital); SCS, substituent chemical shielding.

REFERENCES (1) Duddeck, H., Substituent Effects on Carbon-13 Chemical Shifts in Aliphatic Molecular Systems. Dependence on Constitution and Stereochemistry. Top. Stereochem. 1986, 16, 219–324. (2) Wedel, T.; Müller, M.; Podlech, J.; Goesmann, H.; Feldmann, C., Stereoelectronic Effects in Cyclic Sulfoxides, Sulfones, and Sulfilimines: Application of the Perlin Effect to Conformational Analysis. Chem. Eur. J. 2007, 13, 4273–4281. (3) Wedel, T.; Gehring, T.; Podlech, J.; Kordel, E.; Bihlmeier, A.; Klopper, W., Nucleophilic Additions to Alkylidene Bis(sulfoxides) ‒ Stereoelectronic Effects in Vinyl Sulfoxides. Chem. Eur. J. 2008, 14, 4631–4639. (4) Ulshöfer, R.; Podlech, J., Stereoelectronic Effects in Vinyl Sulfoxides. J. Am. Chem. Soc. 2009, 131, 16618–16619. (5) Podlech, J., Stereoelectronic Effects in α-Carbanions of Conformationally Constrained Sulfides, Sulfoxides, and Sulfones. J. Phys. Chem. A 2010, 114, 8480–8487. (6) Ulshöfer, R.; Wedel, T.; Süveges, B.; Podlech, J., Conformationally Constrained Oxides of 1,3-Dithiane: Synthesis and NMR Spectroscopic Investigations. Eur. J. Org. Chem. 2012, 6867–6877. (7) Süveges, B. D.; Podlech, J., Dependence of Stereoelectronic and Charge Effects on pKa Values of 1,3-Dithiane-derived Sulfides, Sulfoxides, and Sulfones: An Experimental and Computational Investigation. Eur. J. Org. Chem. 2015, 987–994. (8) Süveges, B. D.; Podlech, J., Stereoelectronic Effects in Conformations of Sulfide, Sulfoxide, and Sulfone α-Carbanions. Tetrahedron 2015, 71, 9061–9066. (9) Pritchard, J. G.; Lauterbur, P. C., Proton Magnetic Resonance, Structure and Stereoisomerism in Cyclic Sulfites. J. Am. Chem. Soc. 1961, 83, 2105–2110. (10) Arbouzov, B. A.; Samitov, Y. Y., Conformation and Anisotropy of Chemical Bonds in Cyclic Ethers Investigated by N.M.R. Spectroscopy. Tetrahedron Lett. 1963, 4, 473–476. (11) Edmundson, R. S., Structure of the Cyclic Sulphite and Sulphate from 2,2-Dimethylpropane-1,3-diol. Tetrahedron Lett. 1965, 6, 1649–1652. (12) Green, C. H.; Hellier, D. G., Chemistry of the S=O Bond. Part I. Nuclear Magnetic Resonance and Infrared Studies on Trimethylene Sulphite. J. Chem. Soc., Perkin Trans. 2 1972, 458–463. (13) Szarek, W. A.; Vyas, D. M.; Sepulchre, A.-M.; Gero, S. D.; Lukacs, G., 13C Nuclear Magnetic Resonance Spectra of 1,4Oxathiane Derivatives. Can. J. Chem. 1974, 52, 2041–2047.



(14) Buck, K. W.; Foster, A. B.; Pardoe, W. D.; Qadir, M. H.; Webber, J. M., Observations on the N.M.R. Spectra of Some Derivatives of 1,4-Oxathian S-Oxide. Anisotropy of the S→O Bond. Chem. Commun. 1966, 759–761. (15) Buchanan, G. W.; Durst, T., A New Approach to the Determination of Sulfoxide Stereochemistry: Carbon-13 Nuclear Magnetic Resonance. Tetrahedron Lett. 1975, 16, 1683–1686. (16) Barbarella, G.; Dembech, P.; Garbesi, A.; Fava, A., 13C NMR of Organosulphur Compounds: The Effects of Sulphur Substituents on the 13C Chemical Shifts of Alkyl Chains and of S-Heterocycles. Org. Magn. Reson. 1976, 8, 108–114. (17) Carey, F. A.; Dailey, O. D., Jr.; Hutton, W. C., Structural Dependence of Carbon-13 Chemical Shifts in Oxides of 1,3-Dithiane. J. Org. Chem. 1978, 43, 96–101. (18) Archer, R. A.; Cooper, R. D. G.; Demarco, P. V.; Johnson, L. R. F., Structural Studies on Penicillin Derivatives: 13C Nuclear Magnetic Resonance Studies of Some Penicillins and Related Sulphoxides J. Chem. Soc. D: Chem. Commun. 1970, 1291–1293. (19) Fraser, R. R.; Schuber, F. J., Assignments of Configuration by Nuclear Overhauser Effects in Some Dibenzthiepin Derivatives. Can. J. Chem. 1970, 48, 633–640. (20) Wiseman, J. R.; Krabbenhoft, H. O.; Anderson, B. R., Carbon13 Nuclear Magnetic Resonance Spectra of 9Thiabicyclo[3.3.1]nonanes. J. Org. Chem. 1976, 41, 1518–1521. (21) Rooney, R. P.; Evans, S. A., Jr., Carbon-13 Nuclear Magnetic Resonance Spectra of trans-1-Thiadecalin, trans-1,4-Thiadecalin, trans-1,4-Oxathiadecalin, and the Corresponding Sulfoxides and Sulfones. J. Org. Chem. 1980, 45, 180–183. (22) Freeman, F.; Angeletakis, C. N., 13C NMR Chemical Shifts of Thiols, Sulfinic Acids, Sulfinyl Chlorides, Sulfonic Acids and Sulfonic Anhydrides. Org. Magn. Reson. 1983, 21, 86–93. (23) Tanaka, S.; Sugihara, Y.; Sakamoto, A.; Ishii, A.; Nakayama, J., The Thiosulfinyl Group Serves as a Stereogenic Center and shows Diamagnetic Anisotropy Similar to That of the Sulfinyl Group. J. Am. Chem. Soc. 2003, 125, 9024–9025. (24) Quin, L. D.; Breen, J. J., Steric Effects in 31P NMR Spectra: ‘Gamma’ Shielding in Aliphatic Phosphorus Compounds. Org. Magn. Reson. 1973, 5, 17–19. (25) Wilson, N. K.; Stothers, J. B., Stereochemical Aspects of 13C NMR Spectroscopy. Top. Stereochem. 1974, 8, 1–158. (26) Seidman, K.; Maciel, G. E., Proximity and Conformational Effects on 13C Chemical Shifts at the γ Position in Hydrocarbons J. Am. Chem. Soc. 1977, 99, 659–671. (27) Kovács, J.; Tóth, G.; Simon, A.; Lévai, A.; Koch, A.; Kleinpeter, E., 1H, 13C, 17O NMR and Quantum-chemical Study of the Stereochemistry of the Sulfoxide and Sulfone Derivatives of 3Arylidene-1-thioflavan-4-one Epoxides. Magn. Reson. Chem. 2003, 41, 193–201. (28) Abraham, R. J.; Byrne, J. J.; Griffiths, L., 1H Chemical Shifts in NMR. Part 27: Proton Chemical Shifts in Sulfoxides and Sulfones and the Magnetic Anisotropy, Electric Field and Steric Effects of the SO Bond. Magn. Reson. Chem. 2008, 46, 667–675. (29) Beierbeck, H.; Saunders, J. K., A Reinterpretation of Beta, Gamma, and Delta Substituent Effects on 13C Chemical Shifts. Can. J. Chem. 1976, 54, 2985–2995. (30) Lee, C.; Yang, W.; Parr, R. G., Development of the ColleSalvetti correlation-energy formula into a functional of the electron density. Phys. Rev. B 1988, 37, 785–789. (31) Becke, A. D., Development of the Colle-Salvetti CorrelationEnergy Formula into a Functional of the Electron Density. J. Chem. Phys. 1993, 98, 5648-5652. (32) Koch, W.; Holthausen, M. C., A Chemist's Guide to Density Functional Theory. Wiley-VCH: Weinheim, 2002. (33) McLean, A. D.; Chandler, G. S., Contracted Gaussian Basis Sets for Molecular Calculations. I. Second Row Atoms, Z=11–18. J. Chem. Phys. 1980, 72, 5639–5648.

Page 8 of 23

(34) Krishnan, R.; Binkley, J. S.; Seeger, R.; Pople, J. A., Selfconsistent Molecular Orbital Methods. XX. A Basis Set for Correlated Wave Functions. J. Chem. Phys. 1980, 72, 650–654. (35) Clark, T.; Chandrasekhar, J.; Spitznagel, G. W.; von R. Schleyer, P., Efficient Diffuse Function-augmented Basis Sets for Anion Calculations. III. The 3-21+G Basis Set for First-Row Elements, Li–F. J. Comput. Chem. 1983, 4, 294–301. (36) Gaussian 09, Revision A.02, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; et al. Gaussian, Inc.: Wallingford CT, 2009. (37) Contreras, R. H.; Esteban, A. L.; Díez, E.; Della, E. W.; Lochert, I. J., Influence of σ-Hyperconjugative Interactions on 13C Substituent Chemical Shifts: Experimental and Theoretical Study in 1-X,3-CH3-Bicyclo[1.1.1]pentanes. Magn. Reson. Chem. 2004, 42, S202–S206. (38) NBO, Version 3.1, Glendening, E. D.; Reed, A. E.; Carpenter, J. E.; Weinhold, F., Theoretical Chemistry Institute, University of Wisconsin: Madison, WI, 2001. (39) Reed, A. E.; Weinhold, F., Natural Localized Molecular Orbitals. J. Chem. Phys. 1985, 83, 1736–1740. (40) Reed, A. E.; Curtiss, L. A.; Weinhold, F., Intermolecular Interactions from a Natural Bond Orbital, Donor-Acceptor Viewpoint. Chem. Rev. 1988, 88, 899–926. (41) Weinhold, F., Natural Bond Orbital Methods. In Encyclopedia of Computational Chemistry (Vol. 3); von R. Schleyer, P.; Allinger, N. L.; Clark, T.; Gasteiger, J.; Kollman, P. A.; Schaefer III, H. F.; Schreiner P. R., Eds.; Wiley: Chichester, 1998; p 1792–1811. (42) Bohmann, J. A.; Weinhold, F.; Farrar, T. C., Natural Chemical Shielding Analysis of Nuclear Magnetic Resonance Shielding Tensors from Gauge-including Atomic Orbital Calculations. J. Chem. Phys. 1997, 107, 1173–1184. (43) von R. Schleyer, P.; Maerker, C.; Dransfeld, A.; Jiao, H.; van Eikema Hommes, N. J. R., Nucleus-independent Chemical Shifts: A Simple and Efficient Aromaticity Probe. J. Am. Chem. Soc. 1996, 118, 6317–6318. (44) Klod, S.; Kleinpeter, E., Ab Initio Calculation of the Anisotropy Effect of Multiple Bonds and the Ring Current Effect of Arenes ‒ Application in Conformational and Configurational Analysis. J. Chem. Soc., Perkin Trans. 2 2001, 1893–1898. (45) Kleinpeter, E.; Klod, S., Separation of Anisotropic and Steric Substituent Effects − Nuclear Chemical Shielding Analysis of H-4 and C-4 in Phenanthrene and 11-Ethynylphenanthrene. J. Am. Chem. Soc. 2004, 126, 2231–2236. (46) Jmol: an open source Java viewer for chemical structures in 3D. http://www.jmol.org/ (47) Jameson, C. J.; Buckingham, A. D., Nuclear Magnetic Shielding Density. J. Phys. Chem. 1979, 83, 3366–3371. (48) Ruud, K.; Helgaker, T.; Bak, K. L.; Jørgensen, P.; Jensen, H. J. A., Hartree–Fock Limit Magnetizabilities from London Orbitals. J. Chem. Phys. 1993, 99, 3847–3859. (49) Jusélius, J.; Sundholm, D.; Gauss, J., Calculation of Current Densities Using Gauge-including Atomic Orbitals. J. Chem. Phys. 2004, 121, 3952–3963. (50) Fliegl, H.; Taubert, S.; Lehtonen, O.; Sundholm, D., The Gauge Including Magnetically Induced Current Method. Phys. Chem. Chem. Phys. 2011, 13, 20500–20518. (51) Sundholm, D.; Fliegl, H.; Berger, R. J. F., Calculations of Magnetically Induced Current Densities: Theory and Applications. Wiley Interdiscip. Rev.: Comput. Mol. Sci. 2016, 6, 639–678. (52) TURBOMOLE V7.0 2015, a development of University of Karlsruhe and Forschungszentrum Karlsruhe GmbH, 1989–2007, TURBOMOLE GmbH, since 2007; available from http://www.turbomole.com. (53) Furche, F.; Ahlrichs, R.; Hättig, C.; Klopper, W.; Sierka, M.; Weigend, F., Turbomole. Wiley Interdiscip. Rev.: Comput. Mol. Sci. 2014, 4, 91–100.


Page 9 of 23 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(54) Zubarev, D. Y.; Boldyrev, A. I., Developing Paradigms of Chemical Bonding: Adaptive Natural Density Partitioning. Phys. Chem. Chem. Phys. 2008, 10, 5207–5217. (55) Zubarev, D. Y.; Boldyrev, A. I., Revealing Intuitively Assessable Chemical Bonding Patterns in Organic Aromatic Molecules via Adaptive Natural Density Partitioning. J. Org. Chem. 2008, 73, 9251– 9258. (56) Lu, T.; Chen, F., Multiwfn: A Multifunctional Wavefunction Analyzer. J. Comp. Chem. 2012, 33, 580–592. (57) gnuplot: www.gnuplot.info/ 58 Claus, P. K.; Rieder, W.; Vierhapper, F. W.; Willer, R. L.; Kenan, W. R., Equatorial Preference of the Sulfimide Functionality in Cyclic N-Aryl Sulfimides. Tetrahedron Lett. 1976, 17, 119–122. (59) Jalsovszky, I.; Ruff, F.; Kajtár-Peredy, M.; Kövesdi, I.; Kucsman, Á., Stereoselective Synthesis of cis and trans N-Tosyl Sulphilimines and Sulphoxides from 2-Alkylthianes and 2Alkylthiolanes Assignments of Configurations. Tetrahedron 1986, 42, 5649–5656. (60) We use the Klyne-Prelog system for denomination of the conformers: Klyne, W.; Prelog, V., Description of Steric Relationships Across Single Bonds. Experientia 1960, 16, 521–523. (61) We use the term conformation for any possible dihedral, while conformers are minimum conformations: Moss, G. P., Basic Terminology of Stereochemistry. Pure Appl. Chem., 1996, 68, 2193–2222. (62) Reed, A. E.; von R. Schleyer, P., Chemical Bonding in Hypervalent Molecules. The Dominance of Ionic Bonding and Negative Hyperconjugation over d-Orbital Participation. J. Am. Chem. Soc. 1990, 112, 1434–1445. (63) This has similarly been reported for cyclohexane: Klod, S.; Koch, A.; Kleinpeter, E., Ab-Initio Quantum-mechanical GIAO Calculation of the Anisotropic Effect of C‒C and X‒C Single Bonds ‒ Application to the 1H NMR Spectrum of Cyclohexane. J. Chem. Soc., Perkin Trans. 2 2002, 1506–1509. (64) Ramsey, N. F., Magnetic Shielding of Nuclei in Molecules. Phys. Rev. 1950, 78, 699–703 (65) The Ramsey formula describes the paramagnetic shielding as contributions from MO/MO* pairs coupled magnetically by the angular momentum operator.64 A more sophisticated strategy based on propagators within the RPA framework is given in Ref. 68. Both pictures allow to deduce that the paramagnetic part of the shielding tensor is driven by occupancies, overlap, and by the energy gap of the respective orbital pairs. (66) Sataty, I., Configurational Assignments in Some Dihydrobenzo[c]thiophenes by NMR Solvent Effects. Correlation of the Relative Chemical Shifts of α-Methyl Groups with Sulphoxide Stereochemistry. Org. Magn. Reson. 1974, 6, 8–10. (67) Della, E. W.; Lochert, I. J.; Peralta, J. E.; Contreras, R. H., A DFT/GIAO/NBO and Experimental Study of 13C SCSs in 1-XBicyclo[1.1.1]pentanes. Magn. Reson. Chem. 2000, 38, 395–402. (68) High Resolution NMR Spectroscopy: Understanding Molecules and Their Electronic Structures; Contreras, R. H., Ed.; Elsevier: Amsterdam, 2013; pp 327. (69) Notario, R.; Roux, M. V.; Cuevas, G.; Cárdenas, J.; Leyva, V.; Juaristi, E., Computational Study of 1,3-Dithiane 1,1-Dioxide (1,3Dithiane Sulfone). Description of the Inversion Process and Manifestation of Stereoelectronic Effects on 1JC‒H Coupling Constants. J. Phys. Chem. A 2006, 110, 7703‒7712. (70) Juaristi, E.; Cuevas, G., Manifestations of Stereoelectronic Interactions in 1JC–H One-Bond Coupling Constants. Acc. Chem. Res. 2007, 40, 961‒970. (71) Freitas, M. P., Simultaneous gauche and Anomeric Effects in α-Substituted Sulfoxides. J. Org. Chem. 2012, 77, 7607‒7611. (72) Freitas, M. P.; Bühl, M., Density Functional Study of the OneBond C–F Coupling Constant in α-Fluorocarbonyl and αFluorosulfonyl Compounds. J. Fluor. Chem. 2012, 140, 82‒87.



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