Unexpectedly formed amino ketones, stereochemistry and conformation

Abstract

AbstractBenzaldehyde adds to pyrrolidine enamines of cyclohexanone and 4‐tert‐butylcyclohexanone to form 1 and 4, respectively. The unstable ketones were reduced to afford stable alcohols 2 and 5. The stereochemistry of 2 was verified by X‐ray diffraction. Unambiguous structure elucidation of 5 was achieved by two‐dimensional NMR spectroscopy and by considering the system of vicinal and long‐range proton‐proton coupling constants determined at 400 MHz and analyzed by spin simulation. 13C‐T1 relaxation times proved the anisotropic motion of the subunits of 5. An intramolecular hydrogen bridge is observed both in the 1H‐NMR and in the IR spectrum. The relative stereochemistry of the chiral centers of 5 was determined by inter‐subunit nuclear Overhauser enhancements. The conformation in solution was predicted by NOE restrained nonbonded energy calculation and molecular modeling. The enhancements computed with the refined geometry are in good agreement with the observed NOE values.