Efficient Introduction of Aryl Acetylenes to Quinolinium and Pyridinium Salts: Synthesis of 1-Acyl-1,2-dihydroquinolines and 1-Acyl-1,2-dihydropyridines

Abstract

Recently, we reported the alkynylation of N-tosylimines with aryl acetylenes promoted by ZnBr2 and N,N-diisopropylethylamine (DIEA) in acetonitrile. In the reaction, in situ generated zinc acetylide was added to N-tosylimine to afford the corresponding N-tosyl propargylamines in good yields. As a continuing work we presumed that we could synthesize 1-acyl-1,2-dihydroquinolines and 1-acyl-1,2dihydropyridines when we used 1-acylquinolinium salts or 1-acylpyridinium salts as the electrophile. Synthesis of 1-acyl-1,2-dihydroquinolines and 1-acyl-1,2dihydropyridines have received much attention due to the usefulness of them for the synthesis of natural products and as useful building blocks for alkaloid synthesis. The most straightforward method for the synthesis of substituted dihydroquinolines and dihydropyridines is the addition of Grignard reagents to 1-acylquinolinium and 1-acylpyridinium salts. Besides organomagnesium reagents, other organometallic reagents involving indium, tin, silver, copper, and zinc were reported as the efficient reagents for the reaction. However, the addition of alkynyl moiety to 1-acylquinolinium or 1-acylpyridinium salts was rather limited. Initially, we tried the reaction of 1-ethoxycarbonylquinolinium chloride and phenylacetylene in acetonitrile in the presence of ZnBr2 and DIEA (N,N-diisopropylethylamine, Hunig’s base) as shown in Scheme 1. The starting material 1-ethoxycarbonylquinolinium chloride was generated in situ instantaneously by simply mixing quinoline (1a) and ethyl chloroformate in acetonitrile at room temperature. As expected we obtained 1-ethoxycarbonyl-1,2-dihydroquinoline derivative 2a in 70% isolated yield. Encouraged by the successful results we tried other entries as shown in Table 1 and obtained moderate to good yields of products. As the substrates, we examined quinoline (entries 1-4), pyridine (entries 5-6), and isoquinoline (entry 7). We used ethyl chloroformate (entries 1-3, 5, 7) and benzoyl chloride (entries 4 and 6) as the activators. As the acetylenes, we chose phenylacetylene (entries 1, 4-7), 4-ethynyltoluene (entry 2), and 1-ethynyl-4-methoxybenzene (entry 3) as the representative examples. As shown in Table 1, we obtained the desired products 2a-g in 63-79% isolated yields. Identification of the structure of 2a-g was carried out by their IR, H and C NMR spectra, mass, and/or by comparison with the reported data. The H and C NMR spectra showed broad peaks in some cases presumably due to the line broadening effect of nitrogen atom as easily can be seen in a similar system. In summary, we disclosed in this paper that the combination of aryl acetylene, ZnBr2, and DIEA could be used for the efficient introduction of acetylene moiety toward activated pyridines, quinolines, and isoquinolines.