Z and E rotamers of N ‐formyl‐1‐bromo‐4‐hydroxy‐3‐methoxymorphinan‐6‐one and their interconversion as studied by 1 H/ 13 C NMR spectroscopy and quantum chemical calculations

N ‐Formyl‐1‐bromo‐4‐hydroxy‐3‐methoxymorphinan‐6‐one (compound 2 ), an important intermediate in the NIH Opiate Total Synthesis, presumably exists as a mixture of two rotamers ( Z and E ) in both CHCl 3 and DMSO at room temperature due to the hindered rotation of its N‐C18 bond in the amide moiety. By comparing the experimental 1 H and 13 C chemical shifts of a single rotamer and the mixture of compound 2 in CDCl 3 with the calculated chemical shifts of the geometry optimized Z and E rotamers utilizing density functional theory, the crystalline rotamer of compound 2 was characterized as having the E configuration. The energy barrier between the two rotamers was also determined with the temperature dependence of 1 H and 13 C NMR coalescence experiments, and then compared with that from the reaction path for the interconversion of the two rotamers calculated at the level of B3LYP/6‐31G*. Detailed geometry of the ground state and the transition states of both rotamers are given and discussed. Copyright © 2012 This article is a US Government work and is in the public domain in the USA.