에틸 2-피리딜 옥살레이트를 이용한 α-케토 에스터의 간편한 합성

Abstract

α-Keto esters have attracted interest as precursors of α-keto acids, which play important roles in the biosynthesis of amino acids and enzyme inhibitors. The general methods for the synthesis of α-keto esters involve direct coupling between Grignard or organolithium reagents and derivatives of oxalic esters. The reaction of triethoxyacetonitrile with organolithium reagents leads to the formation of α-keto esters after acidic hydrolysis, but Grignard reagents provide esters. The treatment of alkyl α-oxo-1H-imidazole-1-acetates or diethyl oxalate with Grignard reagents affords the corresponding α-keto esters in mild conditions. However, these imidazolides gave low yields when alkyl Grignard reagents were used and the reaction of diethyl oxalate with Grignard reagents required excess oxalate. The preparation of α-oxo alkynoates was successful by the reaction of monoethyloxalic acidN-methoxy-N-methylamide and alkynyl lithium reagents, but the corresponding reaction was fruitless when diethyl oxalate or ethyl α-oxo-1H-imidazole-1-acetate was used. The cross-coupling reaction of methyl oxalyl chloride with organocopper reagents and the addition of Grignard reagents to 1-[N(alkoxyoxalyl) -N-methylamino]-3-methylimidazolium iodides produce the corresponding α-keto esters, but the separation of products is often tedious and the availability of these imidazolium salts is limited. It has also been reported that oxidation of dimethyl hydrazone, ozonolysis of methyl acrylate/ reduction with Ph3P 10 or ethyl 3-hydroxy acrylate derivatives, and oxidative cleavage of cyanoketophosphoranes/subsequent trapping with alcohol could produce α-keto esters, but these routes require for multi-step. In this paper we wish to report that α-keto esters can be conveniently prepared by the treatment of ethyl 2-pyridyl oxalate with Grignard reagents in a one-step.