[3 + 2] cycloaddition of quinazoline-derived azomethine imines with electron-deficient alkenes to access functionalized fused tricyclic tetrahydropyrazolo[1,5-c]quinazoline frameworks

Abstract

A classical Huisgen 1,3-dipolar cycloaddition reaction between quinazoline-derived azomethine imines and electron-deficient alkenes has been developed. This reaction offers a dearomatization strategy for the direct synthesis of functionalized fused tricyclic tetrahydropyrazolo[1,5-c]quinazoline frameworks, which contain two contiguous stereocenters. The reaction proceeds under mild conditions and achieves high yields (95–98 %), with excellent regio- and diastereoselectivity (up to >25:1 dr). Furthermore, this protocol is characterized by the use of easily available starting materials, a broad substrate scope, good functional group compatibility, straightforward operation, and 100 % atom economy. Additionally, the synthetic utility of this methodology was further demonstrated through synthetic transformations. The structure and relative configuration of the typical product were unambiguously established by single-crystal X-ray diffraction analysis.