Synthetic Studies for the 1,3‐Iterative Organoiron Approach to the Synthesis of Siculinine: Efficient Arylation Using a Diarylcuprate Reagent

Abstract

Disubstituted (cyclohexadienyl)iron(1+) complex 2b is prepared by an improved route that starts from 1,2‐dimethoxycyclohexa‐1,4‐diene 3. In five steps, the synthesis of 2b is achieved by complexation with Fe(CO)5, hydride abstraction, hydrolysis, addition of EtO2CCH2ZrBr, and reaction with HBF4. In the presence of dimethyl sulfide, the reaction of 2b with 2‐[CH2N(CH2CH=CH2)2]‐functionalized diarylcuprate reagent 7 gave the 5α‐arylcyclohexadiene complex 1b in 88 % yield. A DFT study compared diarylzinc and diarylcuprate reagents containing chelating CH2NMe2 substituents.

Selective Iron-Mediated C- and O-Addition of Phenolic Nucleophiles to a Cyclohexadiene Scaffold Using Renewable Precursors

“…12,13 Other advantages of this methodology are the mild reaction conditions used, and the fact that the tailoring of reaction conditions for each class of nucleophile is generally not required. Applications of this method include the synthesis of natural products, such as siculinine 14 and clausine K; 15 antiviral compounds, such as oseltamivir phosphate (Tamiflu); 16,17 probes for infrared spectroscopy; 18 as well as parallel synthesis applications. 19 While anilines have been widely shown to react as nucleophiles via selective C-or Naddition, 20−23 the analogous reactivity of phenols has not been examined to the same extent.…”

“…Subsequent nucleophilic addition then takes place stereoselectively, to the opposite face of the coordinated iron carbonyl moiety. , Other advantages of this methodology are the mild reaction conditions used, and the fact that the tailoring of reaction conditions for each class of nucleophile is generally not required. Applications of this method include the synthesis of natural products, such as siculinine and clausine K; antiviral compounds, such as oseltamivir phosphate (Tamiflu); , probes for infrared spectroscopy; as well as parallel synthesis applications . While anilines have been widely shown to react as nucleophiles via selective C - or N -addition, − the analogous reactivity of phenols has not been examined to the same extent. , Considering also that phenols can potentially be sourced from lignin or other biomass sources, we have investigated their application as nucleophiles using the cationic iron carbonyl methodology.…”