2016
DOI: 10.1002/ejoc.201600153
|View full text |Cite
|
Sign up to set email alerts
|

Direct Synthesis of Noroxymorph­one from Thebaine: Unusual CeIV Oxidation of a Methoxydiene‐Iron Complex to an Enone‐γ‐Nitrate

Abstract: Noroxymorphone was prepared from thebaine in seven operations. The key steps involved the successive N‐ and O‐demethylations of an iron tricarbonyl complex of thebaine followed by the unusual ceric ammonium nitrate oxidation of the methoxydiene moiety to the corresponding enone‐γ‐nitrate during the decomplexation of the iron tricarbonyl functionality.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1
1

Citation Types

0
13
0

Year Published

2016
2016
2021
2021

Publication Types

Select...
6

Relationship

0
6

Authors

Journals

citations
Cited by 12 publications
(13 citation statements)
references
References 28 publications
0
13
0
Order By: Relevance
“…[2][3][4] These opiate therapeutic agents are typically synthesized from 1 a or 2 a, which are converted to oxycodone 7 a or oxymorphone 8 a through C14 hydroxylation and hydrogenation, before N-demethylation and subsequent functionalization. [1,[3][4][5][6] However, 1 a is preferred over 2 a as starting compound due to its considerably higher natural abundance. [3,7] The most challenging step in the reaction sequence, from natural opiates to opiate-like therapeutics, is the selective N-demethylation of the highly functionalized morphinan structure.…”
Section: Introductionmentioning
confidence: 99%
“…[2][3][4] These opiate therapeutic agents are typically synthesized from 1 a or 2 a, which are converted to oxycodone 7 a or oxymorphone 8 a through C14 hydroxylation and hydrogenation, before N-demethylation and subsequent functionalization. [1,[3][4][5][6] However, 1 a is preferred over 2 a as starting compound due to its considerably higher natural abundance. [3,7] The most challenging step in the reaction sequence, from natural opiates to opiate-like therapeutics, is the selective N-demethylation of the highly functionalized morphinan structure.…”
Section: Introductionmentioning
confidence: 99%
“…In the course of the investigation of iron decomplexation with ammonium cerium(IV) nitrate (CAN), we have discovered that decomplexation performed with five equivalents of CAN furnished 80% yield of nitrate ester 29 (Scheme 6). 39 This unprecedented formation of a nitrate ester from the methoxydiene provided an opportunity for the preparation of noroxymorphone without relying on TMANOmediated decomplexation, considered to be the bottle neck of nororipavine synthesis (vide supra).…”
Section: Methodsmentioning
confidence: 99%
“…The mechanism for the formation of the nitrate ester may be postulated as shown in Scheme 7 and previously reported in the preliminary communication. 39 Hydrogenation of nitrate ester 29 in ethyl acetate, somewhat sluggish because of the steric hindrance at C-14, provided hydroxy ketone 28, whose acid-catalyzed hydrolysis furnished the desired noroxymorphone 30 in good yield. 39 Hydrogenation under milder conditions (3% wt.…”
Section: Methodsmentioning
confidence: 99%
See 2 more Smart Citations