Orthogonal and Auto-Tandem Catalysis:  Synthesis of Dipyrido[1,2-a:2‘,3‘-d]imidazole and Its Benzo and Aza Analogues via Inter- and Intramolecular C−N Bond Formation

Abstract

[reaction: see text] The synthesis of dipyrido[1,2-a:2',3'-d]imidazole and hitherto unknown benzo and aza analogues is described. These relatively complex polycyclic heterocycles could be smoothly prepared in one step from commercially available building blocks. Mechanistically, the developed procedure involves orthogonal (Pd and Cu catalyst) or auto-tandem (Pd catalyst) catalysis via regioselective inter- and intramolecular C-N bond formation.

Dipyrido[1,2-a;3′,4′-d]imidazole systems

“…Synthetic procedures for the construction of dipyridoimidazole motifs are very rare 10 and recent publications describe syntheses involving reaction of 2-aminopyridine derivatives with an appropriate dihalogenated pyridine system catalysed by palladium acetate or palladium acetate/copper (I) iodide in Buchwald-Hartwig type processes. 11,12 Alternatively, annelation of imidazo[1,2-a]pyridine systems has allowed the synthesis of some functionalised systems, albeit in low yield. 10,13,14 In all cases, further functionalisation of the heterocyclic core scaffolds to provide analogue systems has not been reported because, in part, the multi-step synthesis of functionalised dibrominated pyridine starting materials can be very difficult indeed.…”

Phosphonylation of 2‐Amino‐ and 2‐Amido‐3‐bromopyridines and 2‐Amino‐3‐chloroquinoxalines with Triethyl Phosphite

“…[29] 1e was synthesized by Pd-catalyzed monoarylation of 2,3-dibromopyridine with 2-aminopyridine. [30] The acylation of 1a to 2a-f was carried out in analogy to the syntheses of the respective 2-amido-3-bromo isomers. [31] NMR spectra were measured at 25°C on a multinuclear FT-NMR spectrometer Bruker ARX300 or AVANCE300 at 300.1 ( 1 H), 75.5 ( 13 C), and 121.5 ( 31 P) MHz.…”

(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis-[diphenylphosphine](Xantphos)

“…37, 38 Polycyclic aza heteroaromatic skeletons, such as dipyrido-[1,2-a:2 ,3 -d]imidazole, result from orthogonal tandem (Pd-Cu-Xantphos) or auto-tandem (Pd-Xantphos) catalyzed inter-and intramolecular C-N coupling, starting with 2,3-dibromopyridine and aminopyridine frames. 39 The chemoselective amination of 5-bromo-2-chloro-3-fluoropyridine in the 5-position can be realized with a Pd-Xantphos catalyst in 82-95% isolated yield. 40 Furthermore, Pd-Xantphos is the catalyst of choice for the Buchwald-Hartwig coupling of deactivated aminothiophenes with substituted halopyridines.…”