Synthesis and Selenation of Tandem Multicomponent Condensation Adducts

Abstract

A number of four-component condensation adducts, which were readily obtained from one-pot reaction of aryl carboxylic acids, arylaldehydes, arylamines and chexylisocyanide, were treated with two equivalents of Woollins' reagent leading to the formation of a series of novel selenoamides with one or two C=Se groups, or heterocyclic compounds such as 1,3-selenazole and 1,3-selenazolidin-5-one. [15][16][17][18][19] to generate structural diversity and a high degree of complexity in a minimal number of reaction steps. To our knowledge, however, there is no protocol for the synthesis of chalcogenated amides in such condensation adducts so far. Thus, the development of an efficient approach for the synthesis of chalcoginated adducts remains a challenge.2,4-Bis(phenyl)-1,3-diselenadiphosphethane-2,4-diselenide [{PhP(Se)(µ-Se)} 2 ] (Woollins' reagent), a selenium counterpart of the well-known Lawesson's reagent, has been well documented as an efficient phosphorus-selenium building block or selenation reagent in organic synthetic chemistry in recent years. 20 The reaction of Woollins' reagent with a variety of organic substrates exhibits a diverse spectrum ranging from simple oxygen-selenium exchange to the formation of complex phosphorus-selenium small-and macro-heterocycles as well as the surprising phosphorus-selenium-free products. [21][22][23][24][25][26][27][28][29][30][31][32][33] In light of our continuing interest in the application of Woollins' reagent in organic synthesis, herein, we report the synthesis of a series of new adducts via tandem four-component condensation, and their corresponding selenation derivatives.It has been well known that a highly flexible multicomponent reaction between aldehydes, amines, carbonyl compounds, and isocyanides to form N-aryl amines. 34,35 While searching for new acidic substituents in the Ugi reaction, we thought that a suitable electron-withdrawing group on a carbonyl group could trigger both the imine activation and the irreversible rearrangement in the key step of the reaction.Indeed, we found that phenylglyoxylic acid reacting with an equivalent of cyclohexyl isocyanide, p-chloroaniline and substituted benzaldehydes such as 2,3-dimethoxybenzaldehyde or 3-methoxybenzaldehyde or 4-chlorobenzaldehyde is a very straightforward and efficient four-component reaction. This reaction proceeded smoothly at room temperature in methanol medium within 18 hours to provide the desired N-aryl amines 1 -3 in excellent yields (Scheme 1). 36Scheme 1 Formation of four-component condensation adducts 1 -3The high yield, simple reaction protocol, and originality of this tandem process prompted us to explore the reaction more widely with a variety of substrates. Phenylacetic acid and benzoic acid are proved to be good substrates for this process and reacted with various amines, isocyanides and arylaldehydes. The reaction of phenylacetic acid with one equivalent of cyclohexylisocyanide, 2,3-dimethoxybenzaldehyde and 4-bromoaniline gave rise to the expected adduct 4 in 99% yield under ...