Rh( <scp>iii</scp> )-catalyzed cyclization of 5-amino-pyrazoles with maleimides to pyrazoloquinazolines

We report a novel Rh(III)-catalyzed [5+1] cycloaddition protocol for the one-step synthesis of functionalized spirocyclic pyrazolo[1,5-<i>a</i>]quinazoline derivatives (PZQZLs, 3) from 5-amino-1-aryl-pyrazoles (1) and maleimides. This method exploits the lone pair of electrons on the pyrazole ring of 1 as a traceless directing group, enabling <i>ortho</i> C-H activation followed by Michael addition and cyclization, circumventing the traditional need for pre-functionalization steps such as halogenation or alkylation. Notably, PZQZLs (4) bearing seven-membered rings were unexpectedly formed in certain cases. Furthermore, derivatives (3) were readily transformed into pyrazolo[1,5-<i>a</i>]quinazoline-5-carboxamides (5) upon heating with K₃PO₄ in DMSO. This work provides a representative example of utilizing 5-amino-1-aryl-pyrazoles (1) as C5 synthons. It lays the groundwork for future strategies to access diverse cyclic structures <i>via</i> [5+1], [5+2], and other cycloaddition reactions. These strategies can also be applied to the combinatorial and parallel synthesis of functionalized pyrazolines.