Hypervalent Iodine(III) Promoted Direct Synthesis of Imidazo[1,2‐a]pyrimidines

Abstract

An efficient and mild synthesis of imidazo[1,2‐a]pyrimidine derivatives has been developed from readily available pyrimidyl arylamines or enamines through a hypervalent iodine‐promoted intramolecular C–H bond cycloamination reaction. This protocol allows for the facile construction of biologically active bicyclic imidazo[1,2‐a]pyrimidine skeletons as well as other imidazo[1,2‐a]‐type fused heterocycles.

Benzimidazopurine nucleosides from N6-aryl adenosine derivatives by PhI(OAc)2-mediated C–N bond formation, no metal needed

“…5–7 Of relevance to the present work are the approaches to synthesis of benzimidazoles and azabenzimidazoles using hypervalent iodine reagents. Examples include cyclizations of appropriate precursors with PhI/CH 3 CO 3 H, 8 PhI(OAc) 2 or PhI(OTFA) 2 , 9–11 PhI(OAc) 2 / m -CPBA/ p -TsOH or Koser’s reagent, 12 and rearrangements of N -benzyl-2-aminopyridines. 13 …”

Transition Metal-Participated Synthesis and Utilization of N-containing Heterocycles: Exploring for Nitrogen Sources

“…Furthermore, we hypothesized that the nitrogen atoms in pyrimidines could be used as good nucleophiles, besides taking the role as directing groups 25. During our research on the synthesis of isatins 5 ,8 substrate 4 , with a pyrimidyl group, was found to transform into the unexpected product 11 H ‐pyrimido[2,1‐ b ]quinazolin‐11‐one 25 using similar reaction conditions 30.…”

“…Furthermore, we hypothesized that the nitrogen atoms in pyrimidines could be used as good nucleophiles, besides taking the role as directing groups. [25] During our research on the synthesis of isatins 5, [8] substrate 4, with a pyrimidyl group, was found to transform into the unexpected product 11H-pyrimido[2,1-b]quinazolin-11-one 25 using similar reaction conditions. [30] This copper-catalyzed tandem reaction provides a direct approach for the domino synthesis of a vast array of tricyclic-or tetracyclic-fused quinazolinone alkaloid structures, and features a novel protocol for sequential chemical bond formation and cleavage of arylacetamides involving sequential aerobic benzylic oxidation, intramolecular cyclization, and decarbonylation processes (Scheme 18).…”

“…Given their great importance in many research fields, pyrimidines have been investigated widely as a class of ideal directing group for C–H bond activation 20. Notably, in the past few years, C–H functionalization reactions directed by pyrimidines have been reported by our group, such as Pd‐catalyzed regioselective mono‐halogenation,21 hydroxylation or acetoxylation of arylpyrimidines,22 Pd‐ or Rh‐catalyzed cyanation of arenes,23 Ru‐catalyzed double alkoxycarbonylation,24 and iodine(III)‐promoted intramolecular cyclization25 (Figure ). Besides, the insertion of isocyanides to N–H bonds of less active secondary arylamines was realized with the assistance of a pyrimidyl directing group 26…”

Nitrenium Ions from Amine‐Iodine(III) Combinations

“…An intramolecular C−H cycloamination for the synthesis of imidazo[1,2‐ a ]pyrimidines 91 from anilines 90 in acetonitrile and from pyrimidyleneamines 92 in ethanol (Figure ) was explored by Xu and co‐workers using an iodine(III) reagent . The nitrenium ion 94a was in equilibrium with another electrophilic species 94b which led to nucleophilic attack from the nitrogen of the pyrimidyl/pyridine ring on to the benzene ring followed by deprotonation to gain aromaticity thus affording 91 or 93 .…”