|Title||Regiocontrolled and Stereoselective Syntheses of Tetrahydrophthalazine Derivatives using Radical Cyclizations|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Zhang, W, Mo, JYi, He, W, Kennepohl, P, Sammis, GM|
|Journal||CHEMISTRY-A EUROPEAN JOURNAL|
|Date Published||JAN 18|
Tetrahydrophthalazine derivatives have found important applications in pharmaceutical research, but existing synthetic methods are unable to access them regio- and stereoselectively. Here, a new approach is presented that addresses these challenges by utilizing a 6-endo-trig radical cyclization in the key step. The desired tetrahydrophthalazines can be accessed in high yields (55-98 %) and high diastereoselectivities for the trans-product (>95:5) starting either from readily accessible hydrazones, or from the corresponding aldehydes and substituted Boc-hydrazides in a one-pot process. The synthetic versatility of the tetrahydrophthalazine core was demonstrated by its straightforward conversion to dihydro-phthalazines, phthalazines, or pyrazolo dione derivatives. Furthermore, the N-N bond was reduced to afford a new route to 1,4-diamines.