Efficient One‐Pot Synthesis of N‐Containing Heterocycles by Multicomponent Coupling of Silicon‐Tethered Diynes, Nitriles, and Isocyanides through Intramolecular Cyclization of IminoacylZr Intermediates

Abstract

An efficient multicomponent synthesis of 5-azaindoles and dihydropyrrolo[3,2-c]azepines was achieved by zirconocene-mediated coupling of silicon-tethered diynes, nitriles, and isocyanides. The synthesis, structures, and intramolecular cyclization of mono- and bis(iminoacyl)--Zr intermediates were investigated to elucidate the reaction process. Upon hydrolysis, the isolated mono(iminoacyl)--Zr intermediates underwent intramolecular cyclization to afford tetrasubstituted 5-azaindoles, whereas intramolecular cyclization of bis(iminoacyl)--Zr intermediates led to the formation of dihydropyrrolo[3,2-c]azepines. The structure of a bis(iminoacyl)--Zr intermediate, formed through insertion of two molecules of CyNC into the Zr--C bond, and structures of two dihydropyrrolo[3,2-c]azepines were characterized by single-crystal X-ray structural analysis.

Synthesis of 4‐Aminoquinazolines by Palladium‐Catalyzed Intramolecular Imidoylation of N‐(2‐Bromoaryl)amidines

“…We have optimized the reaction with respect to the ligand, catalyst loading, base, temperature, and solvent. Easier to handle PdA C H T U N G T R E N N U N G (OAc) 2 , in comparison with [PdA C H T U N G T R E N N U N G (dba) 2 ], proved to be equally suited as the Pd source and generally allowed the use of the relatively inexpensive (compared with XPhos) ligand DCPB. An array of diversely substituted amidines can be combined with various aliphatic isocyanides to afford the target 4-aminoquinazolines in good to excellent yield, although fine-tuning of the reaction conditions was required for the more challenging substrates.…”

“…Interestingly, when we changed the palladium source to PdA C H T U N G T R E N N U N G (OAc) 2 (Ac = acetyl) in combination with the relatively www.chemeurj.org inexpensive ligand DCPB, amidine 3 a was fully converted and 1 a was isolated in 89 % yield ( source and the lower cost of DCPB versus XPhos, we decided to continue the optimization with the PdA C H T U N G T R E N N U N G (OAc) 2 /DCPB system. Changes in solvent, temperature, and the amount and type of base did not lead to further improvements in the isolated yield (Table 1, entries [8][9][10][11][12][13].…”

“…[1] Although isocyanides are isoelectronic with carbon monoxide, synthetic applications of Pd-catalyzed isocyanide insertion are extremely scarce. [2] These reactions would provide interesting opportunities for Pd-catalyzed cascade reactions. [3] On the other hand, isocyanide insertion into Pd À C bonds is a well-known phenomenon in coordination chemistry.…”

Multiple and Highly Selective Alkyne–Isonitrile C−C and C−N Couplings at Group 4 Metallocenes

“…This indicates that steric hindrance in 6 and 7 is high enough to impede rotation of the Xy groups. Notably, it is not only the type of Cp′ ligand that can influence the selectivity of insertion reactions; the steric demand of the isonitrile's substituent has also been shown to determine whether a single, double, or triple insertion occurs ,…”

“…Additionally, skeletal rearrangement and C−C or C−X bond formations have shown novel reactivity of certain substrates. Steric effects of metals and isocyanides are very important for the selectivity of these reactions . For example n ‐butyl isocyanide undergoes triple insertion into the Zr−C bond, owing to the small size of the substituent .…”