Synthesis of 1-tetrazolyl-1,2,3,4-tetrahydroisoquinoline bound-type bis-heterocycles via oxidative Ugi-azide reaction

A series of five novel 1-tetrazolyl-1,2,3,4-tetrahydroisoquinolines were synthesized in moderate yields (29-60%) by a two-step process. The first one involved a NH-CH₂ bond oxidation of the 1,2,3,4-tetrahydroisoquinoline to give the corresponding imine using IBX as oxidant. The second step was an oxidative Ugi-azide reaction using 3,4-dihydroisoquinoline, TMSN₃ and the corresponding isocyanides as starting reagents. Final bis-heterocycles may find application in medicinal chemistry because tetrazole and tetrahydroisoquinoline are present in a variety of bioactive products and drugs.