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. (11th December 2012)

• Record Type: Journal Article
• Authors: Sulima, Agnieszka; Cheng, Kejun; Jacobson, Arthur E.; Rice, Kenner C.; Gawrisch, Klaus; Lee, Yong‐Sok
• Is Part Of: Magnetic resonance in chemistry. Volume 51:Number 2(2013:Feb.)
• Page Start: 82
• Page End: 88
• Publication Date: 2012-12-11
• Subjects: Nuclear magnetic resonance spectroscopy -- Periodicals; Chemistry, Organic -- Periodicals; Magnetic resonance -- Periodicals; 538.36
• DOI: 10.1002/mrc.3909
• Languages: English
• ISSNs: 0749-1581

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic>N</italic>‐Formyl‐1‐bromo‐4‐hydroxy‐3‐methoxymorphinan‐6‐one (compound <bold>2</bold>), an important intermediate in the NIH Opiate Total Synthesis, presumably exists as a mixture of two rotamers (<italic>Z</italic> and <italic>E</italic>) in both CHCl₃ and DMSO at room temperature due to the hindered rotation of its N‐C18 bond in the amide moiety. By comparing the experimental ¹H and ¹³C chemical shifts of a single rotamer and the mixture of compound <bold>2</bold> in CDCl₃ with the calculated chemical shifts of the geometry optimized <italic>Z</italic> and <italic>E</italic> rotamers utilizing density functional theory, the crystalline rotamer of compound <bold>2</bold> was characterized as having the <italic>E</italic> configuration. The energy barrier between the two rotamers was also determined with the temperature dependence of ¹H and ¹³C 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.</p> </abstract>