LETTER 907

Desulfonylation of N-Sulfonyl Tetrahydroisoquinoline Derivatives by Fluoride on Alumina Under Microwave Irradiation: Selective Synthesis of 3,4-Dihydroisoquinolines and Isoquinolines

a a a b DesulfonylationClaudio of N-Sulfonyl-Tetrahydroisoquinolines with KF/Al2O3 C. Silveira,* Carmem R. Bernardi, Antonio L. Braga, Teodoro S. Kaufman* a Departamento de Quimica, Universidade Federal de Santa Maria, 97105.900, Santa Maria, RS, Brazil Fax +55(55)2208754; E-mail: [email protected] b Instituto de Química Orgánica de Síntesis (CONICET-UNR) and Facultad de Ciencias Bioquímicas y Farmacéuticas, Suipacha 531, (S2002LRK) Rosario, Argentina Fax +54(341)4370477; E-mail: [email protected] Received 9 April 2002

Spengler synthesis11,12 and in many variations of the Po- Abstract: In a solvent-free system, the microwave irradiation of 13 mixtures of N-sulfonyl tetrahydroisoquinolines and 37% potassium merantz–Fritsch sequence. Removal of the sulfonyl fluoride supported on alumina selectively furnished 3,4-dihydroiso- moiety by taking advantage of the different oxidation quinolines or isoquinolines, depending upon the reaction time. states of has been employed to broaden the scope of Key words: isoquinolines, 3,4-dihydroisoquinolines, KF on alumi- these synthetic protocols, but only a few methods have 11,13 na, microwave-assisted desulfonylation been described. Herein, we wish to report the selective elaboration of 3,4- dihydroisoquinolines and isoquinolines (Scheme 1) by Chemical transformations carried out with supported re- the microwave-assisted oxidative desulfonylation and agents under dry conditions have several significant ad- subsequent dehydrogenation (for isoquinolines) of N-sul- vantages over reactions traditionally run in solution; they fonyl tetrahydroisoquinolines with KF/Al2O3 as solid sup- offer easier separation of the products, new or better selec- ported reagent, in non-solvent conditions. tivities, faster processes or milder reaction conditions, less waste problems and the possibility of working in a contin- uous way.1

Potassium fluoride on alumina (KF/Al2O3) has been re- ported as a solid supported reagent for alkylation,2 elimi- 3 4 5 nation, addition, condensation, enolization, desilyl- Scheme 1 Reagents and Conditions: a) 37% KF/Al2O3, Micro- 6 7 ation, coupling and other useful reactions. It has been waves (time: t1 < t2). shown that during the impregnation-activation procedure, the salt reacts with oxide forming K3AlF6 and Starting tetrahydroisoquinolines consigned in Table 1 an active mixture of KOH and potassium aluminate on the were prepared employing a modified activated Pictet– surface of the solid support,8 which would contribute to Spengler procedure, by reaction of a-phenylchalcogen-a- explain its reactivity. halocarbonyls as aldehyde surrogates with conveniently On the other hand, the enhancement of chemical transfor- substituted N-tosyl-b-phenethylamines, under Lewis ac- 11b,12 mations by microwave irradiation of organic molecules ids promotion. supported on inorganic solids has experienced an enor- As shown in Table 1, submission of the N-sulfonyl hetero- mous growth in recent years,9 as this technique is manip- cycles to microwave irradiation (490 Watts) provided ulatively simple, can be conducted rapidly and provides good yields of the corresponding 3,4-dihydroisoquino- products in high yields employing solvent-free condi- lines upon a short reaction period (10–20 s), uncontami- tions. nated with the related isoquinolines; interestingly, Recent work informed that under microwave assistance however, increasing the irradiation time completely trans- formed the starting materials into the corresponding iso- KF/Al2O3 cleaves sulfonamides to the corresponding amines in dry conditions.10 However, the irradiation of quinolines, providing a highly selective and convenient mixtures of N-sulfonyl is