Fluorocyanation of Enamines

Abstract

A method for the fluorocyanation of enamines has been described. The reaction involves fluorination of the electron rich double bond with N-F reagent (Selectfluor or NFSI) accompanied by trapping of beta-fluoroiminium cationic intermediate with cyanide nucleophile.

Solvent‐Assisted Diastereoselective Tri­meth­ylsilyl Cyanide Additions to Cyclic α‐Fluoro Ketones

“…It has been established that the coupling constants of nitrile carbons with fluorine ( 3 J C,F ) are quite different in the cis (predicted J z = 8.0 Hz) and trans (predicted J z = 1.8 Hz) orientations (Figure 1). Based on our observed coupling constant, the major product for the cyclohexanone derivative (Table 2, entry 1) was the cis isomer ( 3 J C,F = 5.1 Hz), and the minor isomer had trans stereochemistry ( 3 J C,F = 2.1 Hz; Figure 1), which is consistent with previously published reports 9. The 19 F NMR spectra also showed a significant chemical shift difference between the cis and trans diastereomers.…”

“…The stereochemistries of the cyclic products were determined by examining their 13 C and 19 F NMR spectra 9. It has been established that the coupling constants of nitrile carbons with fluorine ( 3 J C,F ) are quite different in the cis (predicted J z = 8.0 Hz) and trans (predicted J z = 1.8 Hz) orientations (Figure 1).…”

One‐Pot Synthesis of α‐Amino Nitrile Units through Alkylative Strecker Cyanation from Formamides

“…3‐Methyl‐2‐(methyl(phenyl)amino)butanenitrile (35) : [27] Obtained as yellow oil (m=202.4 mg, 86 % yield). Purification by flash chromatography (Diethyl ether/Pentane: 1/99 to 2/98).…”

Introduction of Fluorine and Fluorine‐Containing Functional Groups

“…Activated alkenes such as enamines can be fluorinated without catalysts. For example, the fluorocyanation of enamines is hypothesized to occur by electrophilic fluorination of the enamine with NFSI followed by trapping of the iminium intermediate with cyanide (Scheme ) 51a…”