Conformational Studies by Dynamic NMR. 60.¹ Structure and Stereomutation of the Enantiomers of Dialkoxy Disulfides

Abstract

The structure of dialkoxy disulfides ROSSOR has been established by single-crystal X-ray diffraction of 1, ArCH2OSSOCH2Ar (Ar = 4-nitrophenyl). The gauche conformation (OSSO dihedral angle = 85.4°) observed in the solid state entails the existence of M and P enantiomers that were actually detected in solution, in the case of MeOSSOMe, t-BuOSSOBu-t, and t-BuOSSOMe (3, 4, 5, respectively), by means of NMR spectroscopy in a chiral environment. The activation parameters (ΔG ⧧, ΔH ⧧, and ΔS ⧧) for the stereomutation of this type of enantiomers, brought about by the S−S bond rotation at high temperature (50−110 °C), were measured by computer line shape simulation of the dynamic NMR spectra of appropriate derivatives bearing alkyl substituents with potentially diastereotopic geminal groups. The free energies of activation for such a process (18−19 kcal mol-1, depending on the compound) were found to be much higher than for the corresponding disulfides (RSSR), owing to the larger S−S double-bond character, as indicated by the shorter S−S bond length (1.957 vs 2.057 Å, respectively).

Conformational Studies by Dynamic NMR. 63.1Stereodynamics of Dialkylamino Ethoxy Disulfides: S−S and S−N Rotation Processes

“…The enantiomerization barriers (Table ) measured for 1−3 (14.5−11.9 kcal mol -1 ) have indeed, as anticipated, values intermediate between those of RSSR (7−9.4 kcal mol -1 ) 6 and of ROSSOR (18−19 kcal mol -1 ) …”

“…In the case of 2 the Δ H ⧧ and Δ S ⧧ values were also determined, the latter (0.3 ±2 eu) being negligible within the errors. This often occurs in conformational processes as it was observed, for instance, in the analogous dialkoxy disulfides 1 Experimental (left) 1 H NMR signal (at 300 MHz) of the OCH 2 hydrogens of 2 (decoupled at the frequency of the corresponding methyl triplet) as a function of temperature, displaying the effect due to the exchange of the M and P stereolabile enantiomers whose structures are reported on the top.…”

“…This often occurs in conformational processes as it was observed, for instance, in the analogous dialkoxy disulfides. 15 The exchange process which makes diastereotopic, at low temperature, the otherwise enantiotopic OCH 2 hydrogens is the rotation about the S-S bond, interconverting the M,P stereolabile enantiomers, the structures of the latter being displayed in Figure 1 for derivative 2. Also the NCH 2 hydrogens in 2, and the isopropyl methyl groups in 3, became diastereotopic for the same reason, although the separation of their NMR shifts is extremely small.…”

“…This model (sometimes referred to as negative hyperconjugation) 10,11a,b parallels the one proposed to account for the barrier of the S−N, N−C(O)X, and P−N rotation processes. Such an approach also explains the observation that in dialkoxy disulfides (ROSSOR) the S−S bond length is shorter , and the S−S rotational barrier higher , than in dialkyl disulfides (RSSR). Therefore, the more electronegative a substituent X in a XSSX derivative, the lower the energy of the X−S antibonding σ* orbital is expected to be, ,11b, thus making the π-type bond stronger, due to the more efficient n,σ* overlapping.…”

Inherently Hindered Rotation about a Disulfide Bond

“…The experimental and theoretical barrier maxima agree extremely well with one another and require that the Thompson dialkoxy disulfide barrier 2,10 be adjusted upward by 9.2 kcal/mol. The results likewise confirm that Seel's measurement is in fact an S−S torsional barrier. ,, …”