Position of Coordination of the Lithium Ion Determines the Regioselectivity of Demethylations of 3,4-Dimethoxymorphinans with L-Selectride

Abstract

[reaction: see text] L-Selectride is an efficient agent for the 3-O-demethylation of opioids and is known to cleave the least hindered methoxyl group in a molecule. The treatment of a 3,4-dimethoxymorphinan containing a 6-ketal with L-Selectride gave selective 4-O-demethylation, rather than cleavage of the less hindered 3-methoxyl. In contrast, a 3,4-dimethoxymorphinan lacking a 6-ketal gave selective 3-O-demethylation, suggesting that the regiochemistry of L-Selectride-mediated O-demethylation can be manipulated through altering the position of coordination of the lithium ion.

Isolation, semisynthesis, covalent docking and transforming growth factor beta-activated kinase 1 (TAK1)-inhibitory activities of (5Z)-7-oxozeaenol analogues

“…The main reason for methylating the phenol was to verify the prior hypothesis that the phenol hydrogen bonds to the carbonyl of nearby residue Pro160. 14 The use of diazomethane 19 or iodomethane with sodium hydride 20 did not result in the methylation of the hydroxy at carbon 17, as indicated by 1 H NMR spectroscopy. Instead, macrolactone 1 either decomposed or was unreactive under those conditions.…”

1,1′‐Diaryl‐Substituted Ferrocenes: Up to Three Hinges in Oligophenyleneethynylene‐Type Molecular Wires

“…Such ether cleavages might not only be realized by Lewis acids such as BCl 3 , which would presumably give rise to undesired side-reactions, but also under reducing reaction conditions with -Selectride. [36,37] As redox-active systems the corresponding hydroquinone/quinone subunits would be conjugated to the ferrocene hinges, which are also redox-active, and therefore allow electronic interactions to be observed by cyclic voltammetry. Although the proximity of the methoxy groups to the ferrocene hydrogen atoms might lead to some deviation from coplanarity, this is expected to be less so in the demethylated hydroquinone or quinone products.…”

Synthesis of Both Enantiomers of Protoberberines via Laterally Lithiated (S)-4-Isopropyl-2-(o-tolyl)oxazolines

“…The absolute configuration of 24a was determined to be S by converting it to 25 (Scheme 7). 19 The specific rotation of 25 was identical with that of 8a. Scheme 7…”

“…The hydroxyl group of commercially available vanillin (16) was protected by isopropyl ether to give O-isopropylvanillin (17) in 99% yield. Henry reaction of the resulting aldehyde (17) with nitromethane afforded β-nitrostyrene (18) which was reduced by LiAlH 4 to give 2-arylethylamine (19).…”

“…The amine (19) (4.19 g, 20.0 mmol) was dissolved in ethyl formate (10.6 mL) and the solution was refluxed for 14 h. The reaction mixture was then cooled to rt and evaporated under reduced pressure.…”