Synthesis of 4,5-Diazaspiro2.3hexanes and 1,2-Diazaspiro3.3heptanes as Hexahydropyridazine Analogues

摘要

4,5-Diazaspiro[2.3]hexanes are made by dihalocarbene addition across the exocyclic double bond of readily accessible 3-alkylidene-1,2-diazetidines. Using difluorocarbene, generated from TMSCF3/NaI, these spirocycles were produced in yields up to 97% by stereospecific addition across the alkene. Lower yields (up to 64%) were observed using more reactive dichlorocarbene, due to competitive insertion of the carbene into the N–N bond. Larger 1,2-diazaspiro[3.3]heptanes are produced by [2+2] cycloaddition of 3-alkylidene-1,2-diazetidines with tetracyanoethylene (TCNE) in up to 99% yield. These additions work with di-, tri- and tetrasubstituted alkenes, offering a practical route to rigidified analogues of the medicinally important hexahydropyridazines.