Conformational Analysis of Functionalized Sultines by Nuclear Magnetic Resonance and X-Ray Crystallography. Application of a Generalized Karplus Equation

Article abstract of DOI:10.1021/ja00354a037

The solid-state conformation of β-amino-γ-sultine 2 was determined by X-ray crystallography, which allowed also the assignment of R configuration to the sulfinate sulfur atom.In addition the conformation of compounds 1 and 2 in solution is reported.This conformational analysis is based on the application of a new, empirical generalization of the classical Karplus equation.Application of eq 1 and 4 allowed the expression of vicinal coupling constants - obtained by 500-MHz NMR spectroscopy - in proton-proton torsion angles φ_HH.The puckering and conformation of the sultine ring of 1 and 2 are quantitatively described by using the concept of pseudorotation (eq 1, 2a-d).It appeared that in CDCl3 at 233 or 300 K compound 1 is present as a twist-chair conformer, which can be denoted as ⁴T₅ (Scheme I).In Me2SO-d6 compound 1 is engaged in an equiliblium between this ⁴T₅ conformer and another twist-chair conformer, denoted as ₂³T.Compound 2 in CDCl3 at 233 K is engaged in two conformational equilibria, a slow and fast one on the NMR time scale.The slow equilibrium between a major component and a minor component is due to hindered rotation in the urethane side chain.In the fast equilibrium the five-membered ring is engaged in an equilibrium between a twisted chair conformer (₃⁴T) and an envelope-shaped conformer (₁E, see Scheme II).The slow equilibrium is not observed in Me2SO-d6 at 300 K or in C2D2Cl4 at 383 K.The effects that might play a role in determining the conformation of 1 and 2 in solution are the gauche effect (Figure 7), the anomeric effect (Figure 8), and hydrogen bonding.Hydrogen bonding governs the solid-state conformation of 2, an envelope-shaped (₃E) conformer (Figure 3).Thus, a comparison of the solution conformer and the solid-state conformer of 2 (Scheme II and Figure 3, respectively) shows a remarkable difference.