Synthesis of Nitrogen-Containing Macrocycles with Reductive Intramolecular Coupling of Aromatic Diimines

Article abstract of DOI:10.1021/jo00118a013

Reductive intramolecular coupling of aromatic diimines is an effective method for the synthesis of a variety of nitrogen-containing macrocycles. 1,4-Diazacrown ethers 3 were effectively synthesized by intramolecular coupling of bis(imino ethers) 9 promoted by electroreduction (method A) or chemical reduction with zinc powder (method B) in the presence of methanesulfonic acid.In spite of the formation of macrocycles, the yields of 3 were relatively high.This can be explained by the formation of proton-bridged intermediates 14, in which intramolecular hydrogen bonds are formed between hydrogen and oxygen atoms of diiminium salts.Method B was more effective in the formation of 1,4-diaza-12-crown-4 derivatives 3 (n = 1) due to the template effect of Zn(2+).Optically active macrocyclic bislactones 4 were synthesized stereoselectively by reductive intramolecular coupling of bis(imino esters) 20 with zinc powder (method B).The high stereoselectivity is explained by considering proton-bridged intermediate 23.The resultant compounds 4 were transformed to optically active 1,2-diarylethylenediamines 7.Various sizes of macrocyclic bislactams 5 were synthesized by reductive intramolecular coupling of bis(imino amides) 26 with zinc powder (method B).Reduction of 5 gave the corresponding macrocyclic polyamines 6.