Synthesis of novel 1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]- quinolines via benzotriazole methodology Rodrigo Abonia, a,p Andrea Albornoz, a Braulio Insuasty, a Jairo Quiroga, a Herbert Meier, b Angelina Hormaza, b Manuel Nogueras, c Adolfo Sa Ânchez, c Justo Cobo c and John N. Low d a Department of Chemistry, Grupo de Investigacio Ân de Compuestos Heterocõ Âclicos, Universidad del Valle, A.A. 25360 Cali, Colombia b Institute of Organic Chemistry, University of Mainz, Duesbergweg 10-14, 55099 Mainz, Germany c Departamento de Quõ Âmica Inorga Ânica y Orga Ânica, Universidad de Jae Ân, 23071 Jae Ân, Spain d Department of Chemistry, University of Aberdeen, Meston Walk, Old Aberdeen AB24 3UE, UK Received 19 February 2001; revised 2 April 2001; accepted 18 April 2001 Abstract ÐPyrroloquinolines have been synthesized reacting 1-benzotriazol-12)-ylmethyl)indolines with unactivated and electron-rich alkenesinthepresenceof p-toluenesulfonicacidcatalyst.Mixturesoftheexpecteddiastereomerswereobtainedandsomeofthemseparated intheirrespectivecomponents.X-Raydiffractionalongwithtwo-dimensionalNMRexperimentswasneededtoassistthedeterminationfor both the structures of the precursors and products. q 2001 Elsevier Science Ltd. All rights reserved. 1. Introduction Synthesis of highly hydrogenated polyheterocyclic systems isaninterestingtoolsincemanyofthemarecontainedinthe framework of naturally occurring products or in important compounds for practical applications. Thus, 1,2,5,6-tetra- hydro-4H-pyrrolo[3,2,1-ij]quinoline 1 known as lilolidine Fig. 1), 1 is present in the structure of the pyroquilone 2 2 and its derivatives 3,4 which have shown potent antifungal properties against rice blast disease. Additionally, the lilo- lidinic system has been found as part of the structure of some phenanthridine alkaloids 3 3a Assoanine, R, R 1 OMe, R 2 ,R 3 H; 3b Oxoassoanine, R, R 1 OMe, CR 2 R 3 O and 3c Anhydrolycorine, R1R 1 OCH 2 O, R 2 , R 3 H) isolated initially from Narcissus pseudonarcissus bulbs and aerial parts of N. assoanus. 5,6 Benzotriazole has been widely used as a synthetic auxiliary in organic synthesis, 7 and recently it has been found that N,N-disubstituted-benzotriazol-1-yl-methylaminesreact with electron-rich ole®ns under acid catalysis, which pro- videdusefulroutestothesynthesisoftetrahydroquinolines 8 and related compounds. 9 This work is part of our ongoing program concerning the synthesis of novel hydroquinoline-analogue systems with potential biological and pharmacological properties. This approach is based on the benzotriazole methodology, wherethereactionofbenzotriazolyl-derivativesoftheindo- lines 5a,b with terminal alkenes and p-toluenesulfonic acid as catalyst afforded the expected products 6 ± 10)a,b in good yields. 2. Results and discussion Using previous results as a starting point, the reaction was carried out starting with 5a in CH 2 Cl 2 at room temperature using ZnBr 2 as catalyst, but with poor results. Recently, these conditions were successfully used by us, 9 but in this case, an insoluble yellow solid was formed, corresponding to the complex 5a´ZnBr 2 10 and the expected product was not obtained. In a further experiment, the reaction was tried in THF at room temperature in the presence of ZnBr 2 , obtaining the expected products with low yields of 15± 25%. Some of that insoluble complex was also formed but slowly.Finally,thereactionofcompound 5a and1-vinyl-2- pyrrolidinone 2 equiv.) was carried out in methanol in the presence of catalytic amount of p-toluenesulfonic acid Tetrahedron 57 2001) 4933±4938 Pergamon TETRAHEDRON 0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved. PII:S0040-402001)00436-7 Figure 1. Structures of lilolidine and related pyrroloquinolines. Keywords: indolines; benzotriazole; alkenes; cyclization; 1,2,5,6-tetra- hydro-4H-pyrrolo[3,2,1-ij]quinolines; lilolidine. p Corresponding author. Fax: 157-2-3392440; e-mail: abonia@quimica.univalle.edu.co