Reductive Lactonization of Strategically Methylated Quinone Propionic Acid Esters and Amides

Article abstract of DOI:10.1021/jo00275a012

It has been shown that the reduction of quinone propionic acid esters or amides bearing three methyl groups in the so-called "trialkyl lock" positions (o-, β-, β-positions) is accompanied by spontaneous lactonization with the release of alcohol or amine, respectively.A new convenient method is reported for introducing the β,β-dimethylpropionic acid side chain onto an appropriate hydroquinone nucleus via alkylative cyclization in methanesulfonic acid.Oxidation of the resulting lactone gives the quinone propionic acid, which can be converted by normal techniques to the corresponding ester or amide derivative.Initial model studies were carried out on pentamethylated systems 6 and 7.In order to make available quinones of varying redox potential or enhanced solubility in physiological media, methoxy- and amino-substituted quinones 10a, 10b, and 17a,b were synthesized.Upon reduction under mild conditions (Na2S2O4), all model esters or amides underwent reductive cyclization with loss of alcohol or amine.In the case of 7a the intermediate hydroquinone 19 could be isolated and its conversion to 4 with ejection of diethylamine followed by NMR techniques