Synthesis of Polysubstituted Quinolines from the Acetates of Baylis-Hillman Adducts: Aza-Claisen Rearrangement as the Key Step

Abstract

Recently, we have reported a variety of chemical transformations of the Baylis-Hillman adducts into useful heterocyclic compounds. Very recently, we published the synthesis of 3-benzylquinolin-2-ols from the Baylis-Hillman adducts of ethyl acrylate bearing aniline moiety at the secondary position. 3-Benzylquinolin-2-ols could be formed via the sequential aza-Claisen rearrangement of the adduct in PPA, amide bond formation, and the following isomerization with the aid of DBU as shown in Scheme 1. In this paper we would like to report our results on the synthesis of polysubstituted quinolines from the BaylisHillman adducts of alkyl vinyl ketones. As exemplified in Scheme 2, the required starting materials 2 were synthesized from the acetates of the Baylis-Hillman adducts of methyl vinyl ketone and ethyl vinyl ketone via the corresponding DABCO salts according to the reported procedure. In the reaction, however, cinnamyl amine derivatives 3 were isolated in variable yields (6-37%) depending upon the nature of anilines (Table 1) as side products. The formation of primary adducts 3 from 2 under the reaction conditions can be explained by sequential addition and elimination of aniline, presumably due to the higher electrophilicity of the β-carbon (marked with asterisk) of 2 than the cases of ethyl acrylate (Scheme 1). As can be seen easily in the ratios of 2 and 3 (Table 1), the amounts of primary products 3 were gradually increased according to the increase of the nucleophilicity of anilines. With the compound 2a in hand we examined the reaction in PPA at various reaction temperatures. Mixed solvent system of PPA and 1,2-dichloroethane was used in order to