We have previously reported on the reaction of 2-methylthioquinolinium salts with active methylene compounds for the formation of a carbon-carbon bond.1) Additionally, various methods for the synthesis of indolizine derivatives have been reported.2) In view of the recent report by Iwao and Kuraishi.2) on the novel total synthesis of the marine alkaloid lamellarins, which contain the pyrrolo[2,1-a]isoquinoline skeleton (Chart 1), 3) functionalized pyrrolo-[2,1-a]isoquinolines would function as very useful synthetic intermediates toward their syntheses. The conventional methods for preparing the substituted pyrrolo[2,1-a]isoquinoline derivatives are either via Michael condensation of Reissert compounds, 4) or via 1,3-and 1,5-dipolar cycloaddition reactions. 5,6) In this paper, we report a novel method for the synthesis of a pyrrolo[2,1-a]isoquinoline skeleton using the cyclization of 2-benzyl-1-(substituted methylene) isoquinolines, which are readily prepared by the reaction of 2-benzyl-1-alkylthioisoquinolinium iodides with active methylene compounds.Reaction of 1-Alkylthioisoquinolinium Iodides with Active Methylene Compounds Initially, the reaction of active methylene compounds with isoquinolinium salts that have a methylthio group as a leaving group at the 1-position was examined under mild conditions in the presence of sodium hydride (Chart 2, Table 1). 2-Methyl-and 2-benzyl-1(2H)-thioisoquinolones (3, 7) 4) were prepared from 2-methyl-and 2-benzyl-1(2H)-isoquinolones (1, 8) 2) in excellent yields, respectively. The reaction of thioisoquinolones (3, 4) with methyl iodide (5a) afforded 2-methyl-and 2-benzyl-1-methylthioisoquinolinium iodides (6a, 9) 7) in 99 and 77% yields, respectively. The reactions of 6a with straight-chain active methylene compounds (8a-c) in the presence of sodium hydride for 1.5 h at room temperature afforded 2-methyl-1-(substituted methylene)isoquinolines (9a, 88%; 9b, 81%; 9c, 85%, respectively) in high yields. However, reactions of 6a with straight-chain active methylene compounds (8d-f) afforded 9d-f in moderate yields. Reactions of 6a with cyclic active methylene compounds (8g, h) at 90°C for 3 h gave 2-methyl-1-(substituted methylene)isoquinolines (9g, h) in 92% and 61% yields, respectively. Similarly, the reaction of 7 with 8a-e produced 2-benzyl-1-(substituted methylene)-isoquinolines (10a, 95%; 10b, 98%; 10c, 99%; 10d, 88%; 10e, 53%, respectively). To examine the effects of the alkylthio group at the 1-position, the experiments were repeated using other alkyl iodides. In comparison to methyl iodide, the reaction of 3 with ethyl iodide (5b) and isopropyl iodide (5c) afforded low yields of the corresponding 1-alkylthioisoquinolinium salts (6b, 75%; 6c, 52%). Furthermore, the reactions of 6b, c with 8a and with 8g gave products [9a ( 65%, 65%); 9g (42%, 40%)] in lower yields than that of 6a with 8a, g ( Table 1). These results can be explained by assuming that the enol form arising from the active methylenes (8d-f) would be more stable than the corresponding keto form, and would te...