Stereochemistry of aldols: Configuration and conformation of aldols derived from cycloalkanones and aldehydes

The structures of cycloalkanone-based threo and erythro aldols were investi gated by systematic introduction of stereo-determining factors. The combina tion of single-crystal X-ray analysis and cryoscopic measurement and soluti on NMR and IR studies elucidated the detailed geometry of these typical ald ols. Currently, X-ray diffraction is the only reliable spectroscopic method to determine the relative configuration of aldol,, Empirical NAM analysis can be safely applied in only limited cases. In hydrocarbon solvents, many aldols exist as monomers with an intramolecular OH . . .O=C hydrogen bond, but some compounds are in an equilibrium with higher aggregates via intermo lecular hydrogen bonds. The aldols take various staggered conformers, where the relative stabilities are controlled largely by torsional strain affect ed by the size and nature of substituents. The intramolecular and intermole cular hydrogen bonds, gauche interactions between the vicinal. substituents , and sometimes CH/pi attractions significantly influence the distribution of conformers. The preferred structure in solution often differs greatly fr om the crystalline-state geometry.