No abstract

No abstract

No abstract

No abstract

Fused pyridine derivatives R 0450 Facile Regioselective Synthesis of Pyrazolo[5,1-a]isoquinolines via Ring-Opening Cyclization/Oxidation Reactions of Stable Aroyldiaziridines of 3,4-Tetrahydroisoquinoline with Alkynes. -Novel stable aroyldiaziridines (III) are prepared and their cycloaddition reaction with acetylenes is investigated. The product selectivity is found to depend on the reaction atmosphere since oxygen promotes the conversion of primary products (V) to pyrazoloisoquinolines [cf. (XII)]. -(ORTEGA, H.; AHMED, S.; ALPER*, H.; Synthesis 2007, 23, 3683-3691; Dep. Chem., Univ. Ottawa, Ottawa, Ont. K1N 6N5, Can.; Eng.) -Mais 16-165

Newly prepared, stable aroyldiaziridines of 3,4-tetrahydroisoquinolines undergo regioselective cycloaddition reactions with a number of both mono and disubstituted alkynes, affording five-membered ring products which, after oxidative aromatization of the pyrazoline ring, lead to the efficient preparation of pyrazolo[5,1-a]isoquinolines. The overall transformation is base-catalyzed and occurs more rapidly in the presence of oxygen, in halogenated solvents and in dioxane.The employment of three-membered-ring heterocycles for the synthesis of five-membered-ring heterocycles has been widely used as a strategy for the preparation of a large number of compounds including some that are biologically active. 1 This approach was also used by our group for catalyzed 2-6 as well as uncatalyzed 6 reactions employing 1,2-and 1,2,3-substituted aziridines, 2 2-vinyloxiranes, 3 2-vinylaziridines, 4 2-vinylthiiranes 5 and 1,2-diaroyldiaziridines. 6 As part of our ongoing interest in the study of three-membered-ring compounds containing two heteroatoms, we investigated the reaction of alkynes with new, stable aroyldiaziridines of 3,4-tetrahydroisoquinoline to form five-membered-ring compounds which, on oxidative aromatization of the pyrazoline ring, gave pyrazolo[5,1-a]isoquinolines. Some pyrazoloisoquinolines and their derivatives are known to possess biological activity, such as antibiotics, 7 kinase inhibitors and anticonvulsants. 8,9 Although there are some reports on the reaction of diaziridines with acetylenes, 10-13 the utility of this reaction for the synthesis of five-membered-ring heterocycles has not been fully described. Thus far, there are no publications on the reactions of alkynes with stable aroyldiaziridines of 3,4-tetrahydroisoquinoline leading to the regioselective formation of pyrazolo[5,1-a]isoquinolines.Aroyldiaziridines of 3,4-tetrahydroisoquinoline 3 were prepared according to a slightly modified procedure 6 (Scheme 1).1,2,3,7b-Tetrahydro-1,1a-diazacyclopropa[a]naphthalene (1) 14 reacts with aroyl chlorides 2 in pyridine-benzene to give the aroyldiaziridines of 3,4-tetrahydroisoquinoline 3.To our knowledge, this is the first time that the aroyldiaziridines of 3,4-tetrahydroisoquinoline 3 have been synthesized as very stable, easy-to-handle, crystalline materials that do not decompose for months at room temperature.We investigated the reaction of aroyldiaziridines of 3,4-tetrahydroisoquinoline 3 with alkynes 4 under a range of conditions (Scheme 2). We noted that the reaction was rather slow when employing equimolar amounts of reactants at room temperature; thus, we increased the temperature and the concentration of the alkyne 4a in order to accelerate the formation of 5a.Scheme 2 Cycloaddition reaction of 3,4-tetrahydroisoquinoline (3a) with phenylacetylene (4a) The structure of the cycloaddition product 5a was confirmed by single-crystal X-ray diffraction (Figure 1). 15 During handling of the colorless crystals of 5a, we noticed that some small but noticeable transformation to a light yellow compound was ta...