Fernando Sancassan

Conformational analysis—III: A lanthanide induced shift (LIS) NMR investigation of benzaldehyde, and thiophen- and furan-2-aldehyde

Abstract A rigorous error analysis of LIS is described which avoids the use of any normalising atom. This analysis is used to investigate the LIS of benzaldehyde and thiophen- and furan-2-aldehyde. The non pseudo-contact components of theYb(fod)3 induced shifts are isolated and found to be appreciable at the carbonyl carbon and the ortho and para carbons. Estimation of the diamagnetic contribution to these shifts withLa(fod)3 allows a precise analysis of the1H and13C LiS of these aldehydes without the need to invoke any contact shifts. The lanthanide-complex geometry found is essentially one-site, i.e. 100% population on the unhindered exo side of the carbonyl. The lanthanide is in the molecular plane of the aldehydes with Ln O and Ln.O.C. parameters ofca 2.5A˚and 140°, respectively. This procedure also gives the percent population of the O-cis conformer of furfural asca 70–75% in CDCl3 solution.

A lanthanide induced shift (LIS) investigation of the conformation of cyclohexanones in solution

Abstract The solution conformations of cyclohexanone 1 and 4- t -butyl cyclohexanone 2 have been obtained by the use of the LIS given by Yb(fod) 3 . A starting geometry for the substrates was obtained by molecular mechanics calculations. The use of a two-site model for lanthanide-substrate complexing, together with iteration on the 1 H and 13 C induced shifts allowed the angle of pucker of the cyclohexanone rings to be determined. In contrast, a one-site model gave no acceptable solutions. The cyclohexanone ring is somewhat flatter at the carbonyl end than cyclohexane, the angle of pucker (α) being reduced from 51° to 49° i.e. the dihedral angle (ω 12 ) is reduced trom 56 to 51°. In 4- t -butyl-cyclohexanone the angle of pucker at the carbonyl end is further reduced. The solution conformation of 1 agrees closely with that deduced by MM calculations; interestingly, the conformation of 2 is essentially identical with the geometry found in the crystal.

Conformational analysis-V.: A lanthanide induced shift (L.I.S.) N.M.R. investigation of conformational isomerism in aromatic aldehydes and ketones

Abstract An L.I.S. N.M.R. investigation of conformational isomerism in meta-nitrobenzaldehyde and furan- and thiophene-3-aldehydes, and of the conformation of acetophenone has been carried out. With the diamagnetic (complexation) contributions to the observed shifts removed by means of experiments with La (fod)3 and the application of our previously-described lanthanide ion complexing model, the pseudo-contact shifts have been used to obtain the precise conformational preferences of the aldehydes. They exist to the extent of 45%, 100% and 80% respectively in the O - trans conformation, findings which are good agreement with the previously-reported values. The L.I.S.s for acetophenone are in best agreement with a planar molecule, although the definition is not as good in this case. These examples suggest that the L.I.S. technique is of general applicability in the determination of conformer populations and the conformations of aromatic aldehydes and ketones.

Conformational analysis—II1: A lanthanide-induced shift nmr and theoretical study of bicyclo [3.1.0] hexan-3-one and adamantanone

Abstract The solution conformation of bicyclo [3.1.0] hexan-3-one has been obtained by the use of the shifts induced in its 1H and 13C NMR by Yb(fod)3. Refinement of the angle of pucker, ∝, of the 5-membered ring indicates that the molecule adopts a flattened boat conformation with ∝ = 195°. This prediction is supported by ab initio, STO-3G, calculations on the isolated molecule. Use of a two- or four-site model for lanthanide-substrate complexing adequately reproduces the experimental data whereas a one-site binding model is unsatisfactory. The importance of multi-site binding is further emphasised by results for the C2v-symmetric ketone, adamantanone, where only a four-site model gives satisfactory agreement between observed and calculated lanthanide-induced shifts.

Ring-Opening/Ring-Closing Protocols from Nitrothiophenes: Six-Membered versus Unusual Eight-Membered Sulfur Heterocycles through Michael-Type Addition on Nitrobutadienes

When Ar is a low-aromaticity homo- or heterosystem, the sulfonyl-stabilized anion of nitrobutadienes 4 (which derive from the initial ring opening of 3-nitrothiophene) undergoes a rather surprising addition onto the aromatic ring itself, thereby leading to the construction of an unusual eight-membered sulfur heterocycle condensed with the original Ar ring. The competitiveness of such a pathway with respect to the formation of the thiopyran ring (i.e., addition onto the nitrovinyl moiety) is favored at low temperatures, thus revealing its nature as a kinetically controlled process.

On the nature of resonance interactions in substituted benzenes. Part 3. A 13C nuclear magnetic resonance study of substituent effects in 4-substituted benzamides and methyl benzoates in dimethyl sulphoxide

The substituent effect on the carbonyl-carbon chemical shift in 4-X-benzamides 2 and in 2,6-dimethyl-4-X-benzamides 2′ has been studied in (CD3)2SO. Comparison of the results with those obtained from the corresponding methyl 4-X-benzoates 1 and 1′ in the same solvent and their analysis by both the dual-substituent parameter (DSP) and Exner-Budesinsky′s methods suggest that in the less hindered benzamides 2 the carbamoyl-carbon chemical shift is not significantly affected by through-conjugation with the para-substituent, π-polarization appearing to be the prevalent resonance effect.

Conformational analysis, Part 31.1 A theoretical and lanthanide induced shift (LIS) investigation of the conformations of some epoxides

An improved LIS technique, using Yb(fod)3 to obtain the paramagnetic induced shifts of all the spin ½ nuclei in the molecule, together with complexation shifts obtained by the use of Lu(fod)3, has been used to investigate the conformations of a group of epoxides. These are cis (1) and trans (2) stilbene oxide, cyclopentene oxide (3), cyclohexene oxide (4), cycloheptene oxide (5), propene oxide (6) and styrene oxide (7).The LIRAS3 complexation model involving two symmetric lone pairs on the oxygen atom was used for the symmetric compounds but, for the unsymmetric compounds, a more complex unsymmetric complexation model (HARDER) was found to be necessary. The calculated LIS for styrene oxide and cis- and trans-stilbene oxide were in excellent agreement with the observed data for both the molecular mechanics (MM) and the ab initio geometries with the phenyl ring dihedral angles optimised.In styrene oxide and trans-stilbene oxide the phenyl rings are approximately perpendicular to the oxirane ring, in agreement with the conformation in the solid state and with the theoretical calculations. In cis-stilbene oxide steric repulsions between the phenyl rings splay them apart so that they are now exo to the oxirane ring. Again the LIS analysis is in good agreement with the theoretical calculations.Both the LIS data and the modelling studies agree that cyclopentene oxide is in a boat conformation with an angle of pucker of ca. 30° and that cyclohexene oxide is in a half-chair conformation with C4 and C5 displaced from the ring plane.The LIS analysis of cycloheptene oxide gave good agreement for two equilibrating chair conformations with an endo/exo ratio of 70∶30, in excellent agreement with low temperature NMR data.The accurate reproduction of the LIS data provides an unambiguous method of assigning the proton chemical shifts of the individual methylene protons in the cyclic epoxides, which are not easily available by any other technique.

Conformational analysis. Part 30. The conformational analysis of some lactones by the lanthanide induced shift (LIS) technique

An improved LIS technique, using Yb(fod)3to obtain the paramagnetic induced shifts of all the spin 1/2 nuclei in the molecule, together with complexation shifts obtained by the use of Lu(fod)3, has been used to investigate the conformations of several lactones. The appropriate complexation model was obtained by investigations on the planar well-defined structures of isocoumarin (1) and coumarin (2). This complexation model was then used to investigate the conformations and conformational equilibria in 3,4-dihydrocoumarin (3), β-butyrolactone (4), γ-valerolactone (5), δ-valerolactone (6) and Iµ-caprolactone (7).3,4-Dihydrocoumarin is puckered with both C2 and C3 displaced from the benzene ring plane. β-Butyrolactone is planar. γ-Valerolactone interconverts between the two envelope conformations with C4 out of the plane of the other ring atoms with 70% of the conformer with a pseudo-equatorial methyl group. For δ-valerolactone the two interconverting conformations are the half-chair and the boat form and analysis of the data suggests that there is ca. 20% of the boat form. In Iµ-caprolactone the LIS data gives a well-defined minimum for 100% of the chair form with no other significantly populated conformer. The LIS results agree with both the ab initio and MM optimised geometries and the observed and calculated conformer energies are in reasonable agreement to give ΔG (ax–eq) 0.6 kcal mol-1 for γ-valerolactone, ΔG (boat–half-chair) 0.9 kcal mol-1 for δ-valerolactone and ΔG (boat–chair) > 3.5 kcal mol-1 for Iµ-caprolactone.

ipso- and tele-Substitution pathways in the reactions of 1,3-dimethyl-2,4-dinitro- and 1,3-dimethyl-2-nitro-4-phenylsulphonylnaphthalene with sodium arenethiolates in dimethyl sulphoxide

1,3-Dimethyl-2,4-dinitronaphthalene (4) reacts with sodium 2,4,6-trimethylbenzenethiolate in dimethyl sulphoxide at 120 °C giving a mixture of an ipso-substitution product, 1,3-dimethyl-2-nitro-4-(2,4,6-trimethylphenylthio)naphthalene (6a), and of two tele-substitution products, viz. 3-methyl-2-nitro-1-(2,4,6-trimethylphenylthiomethyl)-(7a) and 1-methyl-2-nitro-3-(2,4,6-trimethylphenylthiomethyl)-naphthalene (8a). Lower relative yields of tele-substitution products were obtained when the reaction temperature was decreased and when the less bulky sodium benzenethiolate was used as nucleophile. The reaction of 1,3-dimethyl-2-nitro-4-phenylsulphonylnaphthalene (5) with sodium 2,4,6-trimethylbenzenethiolate (Me2SO, 120 °C) gave only the tele-substitution products (7a) and (8a). The obtained results show that among the possible ipso- and tele-substitution products only those deriving from the departure of the nucleofugic group present in the α-position are formed. Probable mechanisms accounting for the experimental results are discussed.

Lanthanum-induced 13C-n.m.r. shifts: a novel probe of π-electron delocalisation

La(fod)3(fod = 6,6,7,7,8,8,8-heptafluoro-2,2-dimethyloctane-3,5-dionato) diamagnetic complexation shifts can be used as a sensitive probe of the extent and pattern of π-electron delocalisation in aromatic and olefinic aldehydes and ketones and hence as a tool for the assignment of 13C-n.m.r. signals in complex, unsaturated molecules.