Electrochemical Chlorination of Physcion – An Approach to Naturally Occurring Chlorinated Secondary Metabolites of Lichens

The electrochemical chlorination of physcion (=1,8‐dihydroxy‐3‐methoxy‐6‐methylanthracene‐9,10‐dione; 1 ) in AcOH and CH 2 Cl 2 was investigated by cyclic voltammetry and prep.‐scale electrolysis. This approach provided access to a number of diverse biologically and pharmacologically interesting chlorinated secondary metabolites of lichen. Unlike the only previous literature report on the ‘classical’ chlorination of physcion ( 1 ), which allowed the preparation of 4‐chlorophyscion ( 2b ), 4,5‐dichlorophyscion ( 3b ), and 2,4,5‐trichlorophyscion ( 4 ), the present procedure also gave fragilin (=2‐chlorophyscion; 2a ) and 2,4‐dichlorophyscion ( 3a ), alongside the previously obtained 2b, 3b , and 4 . All of these compounds, except for 2a , were isolated by column chromatography and medium‐pressure liquid chromatography (MPLC) and characterized by spectral data. The preparative electrolysis with a 2 F⋅mol −1 charge consumption in AcOH and 10 F⋅mol −1 in CH 2 Cl 2 may have a practical synthetic utility, since the thus obtained product mixtures can be readily fractioned by column chromatography to afford pure 2b and 4 , respectively. The regioselectivity of the reaction is explained by the resonance stabilization of the corresponding arenium cations ‐ potential products of an electrophilic attack of a ‘positive’ Cl species on the physcion molecule.