Nickel-Catalyzed Synthesis of Quinazolinediones

Abstract

A nickel(0)-catalyzed method for the synthesis of quinazolinediones from isatoic anhydrides and isocyanates is described. High-throughput ligand screening revealed that XANTPHOS was the optimal ligand for this transformation. Subsequent optimization studies, supported by kinetic analysis, significantly expanded the reaction scope. The reaction exhibits a case of substrate inhibition kinetics with respect to the isocyanate. Preliminary results on an asymmetric synthesis of atropisomeric quinazolinediones are reported.

Ni(COD)(DQ): An Air‐Stable 18‐Electron Nickel(0)–Olefin Precatalyst

“…Lastly, we tested Ni(COD)(DQ) in the synthesis of quinazolinediones via a decarboxylative cycloaddition of isatoic anhydrides and isocyanates as reported by Beutner and colleagues at Bristol‐Myers Squibb. Ni(COD)(DQ) as catalyst afforded the desired product in good yield, albeit lower than that of the originally reported Ni(COD) 2 catalyst …”

“…We next tested Ni(COD)(DQ) in four emerging types of synthetic methodology with nickel: the borylation of aryl halides, C−H activation, alkene hydroarylation, and decarboxylative cycloaddition (Scheme ). Indeed, when we evaluated Ni(COD)(DQ) as a replacement for NiCl 2 (dppp) in the catalytic coupling of HBpin and an aryl chloride, we observed comparable yields to an original report by Murata .…”

Copper‐Mediated Direct Cyanatation of Benzamides: A New Approach to the Synthesis of Quinazolinediones

“…A copper mediated reaction of N ‐(2‐(pyridin‐2‐yl) phenyl) benzamide with formamide was reported by Zhao, as a single example, in the same year which leads to the formation of 3‐(2‐(Pyridin‐2‐yl)phenyl)quinazoline‐2,4(1 H ,3 H )‐dione, in 32 % yield (Equation 3) . Also, a nickel catalyzed synthesis of quinazolinediones from isatoic anhydrides and isocyanides was reported by Beutner in 2017 (Equation 4) . Very recently, Bathula and his co‐workers, reported a copper‐catalyzed domino C–C bond cleavage of 2,3‐unsubstituted indoles/indolines and oxindoles via oxidation and directed insertion of 2‐aminopyridines to access quinazolinediones (Equation 5) …”

“…[14] Also, a nickel catalyzed synthesis of quinazolinediones from isatoic anhydrides and isocyanides was reported by Beutner in 2017 (Equation 4). [15] Very recently, Bathula and his coworkers, reported a copper-catalyzed domino C-C bond cleavage of 2,3-unsubstituted indoles/indolines and oxindoles via oxidation and directed insertion of 2-aminopyridines to access quinazolinediones (Equation 5). [16] C-N bond forming reactions have been investigated extensively in recent years.…”

Facile Fabrication of Glycosylpyridyl-Triazole@Nickel Nanoparticles as Recyclable Nanocatalyst for Acylation of Amines in Water

“…Compelling environmental and economical demands are thus driving chemical researchers to use more earth-abundant metals such as Fe, Co, and Ni [17]. In particular, the application of nickel catalysts in cross-coupling reactions has received considerable attention [18][19][20][21][22][23][24][25][26][27], because nickel is cheaper and more abundant than other precious metals such as Pd, Pt, and Rh. In addition, nickel has several readily available oxidation states commonly shown in catalytic process and catalytic cycles can include Ni0/NiII and NiI/NiIII cycles [28].…”