Electrochemical Intramolecular Oxytrifluoromethylation of N-Tethered Alkenyl Alcohols: Synthesis of Functionalized Morpholines

Abstract

An electrochemical intramolecular oxytrifluoromethylation of N-tethered alkenyl alcohols was developed providing straightforward access to CF3-containing morpholines derivatives. The method features mild reaction conditions with direct anodic oxidation of Langlois reagent as a cheap and easy to handle trifluoromethylating reagent. Variously substituted 2-(2,2,2-trifluoroethyl)­morpholines were obtained in moderate to high yields under constant current electrolysis in an undivided cell.

Electrifying green synthesis: recent advances in electrochemical annulation reactions

“…85 The reaction was performed under a constant current electrolysis of 6.7 mA in an undivided cell with a Pt plate as an electrode, MeCN : H 2 O (7 : 1) as a mixture of solvents, and HOAC (3 equiv.) as an additive at room temperature for 3 h. Both CF 2 Hand CF 3 -containing lactone products (84) were obtained in yields up to 93%. The mechanism was studied by cyclic voltammetry experiments.…”

“…Masson and co-workers developed an electrochemical intramolecular oxytrifluoromethylation of N-tethered alkenyl alcohols to access morpholine derivatives 76 (Scheme 20). 84 The authors applied mild reaction conditions with direct anodic oxidation of Langlois' reagent (CF 3 SO 2 Na) 75 as a cheap and easy method to handle the trifluoromethylation reagent. The reaction was performed from alken-6-ol 74 with 75 in an undivided cell, using a graphite carbon anode and a nickel cathode plate as electrodes under a constant current electrolysis of 15 mA, with LiClO 4 (0.2 M) as the electrolyte and MeCN as the solvent, 3.2 Fmol −1 at room temperature.…”

Electrochemical Generation and Use in Organic Synthesis of C‐, O‐, and N‐Centered Radicals

“…f) Cantillo's oxytrifluoromethylation of alkynes [107] . g) Masson's oxytrifluoromethylation of N ‐tethered alkenyl alcohols [109] . h) Hu's catalyst‐free, oxytrifluoromethylation of alkenes [110,111] .…”

Progress in Electrochemical Trifluoromethylation Reactions

“…CH 3 CN was found to be the best solvent along with the LiClO 4 electrolyte (Scheme 37). [35] Several N‐tethered alkene‐6‐ols successfully cyclized under the optimized conditions affording diversely functionalized morpholine derivatives including one seven‐membered 1,4‐ benzoxazepine derivative. However, the diastereoselectivity of the reaction, wherever applicable, was somewhat limited.…”