ATROPISOMERISM IN HINDERED NAPHTHYL SULFOXIDES - STRUCTURE, STEREODYNAMICS, AND CHIRAL RESOLUTION

Barriers for the EZ interconversion of atropisomers of 1-naphthyl sulf oxides (ArSOR) having a methyl group at position 2 of the naphthalene moiety were measured by variable-temperature NMR. Their values were fo und to cover the range 10.6-18.4 kcal mol-1, the extreme values corres ponding to derivatives 1 (R = Me) and 4 (R = Bu(t)), respectively. NOE and LIS measurements indicated that the Z atropisomer is more stable than the E but that the absence of the methyl group at position 2 of t he naphthalene moiety reverses this trend, rendering E more stable tha n Z. Solid-state NMR and X-ray diffraction of 4 established that only the more stable atropisomer (Z) is present in the crystalline state. M olecular mechanics calculations suggest that the Z,E interconversion p rocess might occur by a rotation pathway having an opposite direction in the case of the more hindered derivatives 3 and 4 (R = Pr(i) and Bu (t), respectively) with respect to the less hindered 1 and 2 (R = Me a nd Et, respectively). The enantiomers, which are due to the presence o f the asymmetric sulfur atom, were resolved on a chiral stationary pha se (DACH-DNB) having an SS configuration. Asymmetric oxidation reactio ns were employed to assign the absolute R configuration to the more re tained enantiomers of alkyl aryl sulfoxides. The opposite trend (S bei ng retained longer) was observed for diaryl sulfoxides such as 5 (R = Ph). In the case of the derivative with the largest interconversion ba rrier, sulfoxide 4, it was also possible to resolve (at -35-degrees-C) the two enantiomeric forms and their associated atropisomers. The use of on-line CD detection and the knowledge of the NMR assignments allo wed us to unambiguously assign the elution order of the four species a s ES, ER, ZS, ZR.