Facile Access to 6-Methoxy-1,2,3,6-tetrahydro- and 4-Hydroxy-1,2,3,4-tetrahydropyridines by Electrochemical Haloalkoxylation-Dehydrohalogenation Sequence as a Key Operation

Article abstract of DOI:10.1055/s-1987-27901

A facile procedure for the synthesis of N-ethoxycarbonyl-6-methoxy-1,2,3,6-tetrahydropyridines 6 and N-ethoxycarbonyl-4-hydroxy-1,2,3,4-tetrahydropyridines 7 from piperidines 1 is described.The electrochemical halomethoxylation of N-ethoxycarbonyl-1,2,3,4-tetrahydropyridines 4 (easily accessible from 1 by ethoxycarbonylation followed by electrooxidative methoxylation and acid-catalyzed elimination of methanol) in a CH3OH-NR4X (X=Cl, Br, I)-(Pt)-(Pt) system provides N-ethoxycarbonyl-3-halo-2-methoxypiperidines 5 in 74-90percent yields.Dehydrohalogenation of iodides 5 (X=I)with 1,8-diazabicyclo<5.4.0>undec-7-ene (DBU) in toluene gave the desired olefin 6, which was isomerized in aqueous acetic acid to afford the alcohol 7 in 34-55percent yields (from 5).The procedure is also applicable to the synthesis of seven membered derivatives 6f and 7f from 1f.