Diastereoselective construction of a functionalized dihydro-pyridazine-based spirooxindole scaffold via C-3 umpolung of isatin N,N '-cyclic azomethine imine

摘要

Herein, functionalized spiro[indoline-3,5 '-pyrazolo[1,2-a]pyridazine]-7 '-carbonitrile containing two contiguous chiral stereocenters was efficiently synthesized in a satisfactory yield (up to 91% yield) and with excellent diastereoselectivity. We have reached this satisfactory yield by DABCO-catalyzed [3+3] annulation reactions of an isatin N,N '-cyclic azomethine imine 1,3-dipole with a Knoevenagel intermediate in dichloromethane (DCM) as solvent at ambient temperature; this was an entirely new strategy for creating one quaternary stereogenic center at the position-3 of an oxindole structure using an abnormal tandem Michael addition, N-cyclization, and a unique approach via the azomethine imine 1,3-dipole. Furthermore, in the proposed synthetic protocol, traditional chromatography and recrystallization purifications were avoided by washing away the crude products with cold diethyl ether such that the pure product could be obtained shortly and easily after the experiment. The X-ray crystallographic data confirmed the structure of the typical product.