Iron‐Catalyzed [3+3]‐Annulation of 3‐Amino‐1,2,4‐Triazoles and Cyclopropanols: A General Synthesis of 1,2,4‐Triazolo[1,5‐a]Pyrimidines

Abstract

Although several synthetic approaches for constructing 1,2,4‐triazolo[1,5‐a]pyrimidines have been established, their production from cyclopropanols and 3‐amino‐1,2,4‐triazoles remains unexplored. Herein, a general method for synthesizing 1,2,4‐triazolo[1,5‐a]pyrimidines via iron‐catalyzed [3 + 3] annulation of cyclopropanols and 3‐amino‐1,2,4‐triazoles is presented. This protocol features no acid or base conditions, but has a broad substrate scope, high regioselectivity, and good functional group tolerance. The utility of this approach is demonstrated via the late‐stage modification of marketed drug molecules and natural products. Furthermore, the reaction mechanisms of iron‐catalyzed [3 + 3] annulation of cyclopropanols with 3‐amino‐1,2,4‐triazoles have been investigated using control experiments and density functional theory calculations.