Elucidation of the stereochemistry of octahydroisoquinoline derivatives by NMR spectroscopy

Complete H-1 and C-13 chemical shifts assignments for 12 octahydroisoquinoline derivatives, intermediates in the synthesis of morphine, were made based on 2D NMR spectroscopy. The stereochemistry of the compounds characterized by the decahydroisoquinoline skeleton was elucidated based on the value of the H-1-H-1 vicinal coupling constants, which were measured in the phase-sensitive DQCOSY spectrum. An approach based on the pattern of the relative intensity of the cross peaks in the NOESY spectrum was taken to determine the stereochemistry of the epoxides derived from octahydroisoquinoline. A pattern of coupling constants was identified in each of the series, allowing the assignment of the epoxide relative stereochemistry by means of the proton spectrum only. For each type of stereochemistry, x-ray data of representative compounds confirmed the configuration determined by NMR. Copyright (C) 1999 John Wiley & Sons, Ltd.