The radziszewski oxidation of (E)-3-aryl-2-(thiazol-2-yl)acrylonitriles: A convenient diastereoselective synthesis of (2S,3S)-3-aryl-2-(thiazol-2-yl)oxirane-2-carboxamides

Abstract

The oxidation of organic compounds with hydrogen peroxide in an alkaline medium is widely used in synthetic practice, in particular, for the preparation of catechol derivatives by the Dakin reaction, as well as for the epoxidation of activated olefins and the oxidative hydrolysis of nitriles [1‐3]. The latter transformation is known as the Radziszewski reaction [1, 4] and provides a convenient method for the conversion of nitriles into the corresponding amides [5‐7]. Hydroperoxy anion, which can be readily generated from hydrogen peroxide in the presence of a strong base, is one of the most available epoxidation agents and is often used for the oxidation of polar olefinic bonds according to the Weitz‐Scheffer procedure [2, 8, 9]. In this context, α , β unsaturated nitriles are of special interest as substrates for oxidation with peroxide since the hydroperoxide anion in this case can initially attack both the carbon atom of the nitrile group and the electron-deficient β carbon atom. In 1932, Murray and Cloke found that α , β -unsaturated nitriles underwent epoxidation under the Radziszewski reaction conditions to give the corresponding oxirane-2-carboxamides [10]. Payne and coworkers showed later for a series of other examples [5, 7] that this reaction is not always stereospecific and often is not regioselective: it is complicated by the side reaction of formation of oxirane-2-carbonitriles. In continuation of our studies in the field of cyanothioacetamide chemistry [11], we studied the behavior of its derivatives, ( E )-3-aryl-2-(thiazol-2-yl)acrylonitriles 1a ‐ 1d , under the Radziszewski reaction conditions. The treatment of suspensions of nitriles 1 in EtOH with an excess of 35% H 2 O 2 in the presence of 0.5 equiv. of 10% KOH upon short heating was found to produce substituted oxirane-2-carboxamides 2a ‐ 2d in high yields (87‐90%) (Scheme 1). It was revealed that the reaction proceeds slowly at ambient temperature; the use of larger amounts of KOH obviously increases the oxidation rate but generally leads to a decrease in the yield of amides 2 , presumably, on account of partial hydrolysis of both the initial reagents and the reaction products. It follows from the literature [5, 7, 10] that the initial attack of the hydroperoxide anion is directed preferably at the carbon atom of the nitrile group rather than at the β carbon atom. Resulting peroxycarboximidic acid 3 , containing a prochiral olefin moiety, undergoes intramolecular stereospecific epoxidation of the multiple bond with the retention of the initial E configuration to produce corresponding compound 2a ‐ 2d as a single diastereomer. Scheme 1.