title: Z and E rotamers of N-formyl-1-bromo-4-hydroxy-3-methoxymorphinan-6-one and their interconversion as studied by 1H/13C NMR spectroscopy and quantum chemical calculations.
abstract: 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.
authors.affiliation: Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Sulima
authors.forename: Kejun
authors.initials: K
authors.lastname: Cheng
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Jacobson
authors.forename: Kenner C
authors.initials: KC
authors.lastname: Rice
authors.forename: Klaus
authors.initials: K
authors.lastname: Gawrisch
authors.forename: Yong-Sok
authors.initials: YS
authors.lastname: Lee
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009019:Morphinans / Q000737:chemistry* / Q000145:classification; D011789:Quantum Theory; D013237:Stereoisomerism
chemical_list: D009019:Morphinans; C582022:N-formyl-1-bromo-4-hydroxy-3-methoxymorphinan-6-one